Reduction of Recurrence Risk of Pancreatitis in Cystic Fibrosis with Ivacaftor: Case Series.

The effect of ivacaftor in cystic fibrosis (CF) patients with recurrent pancreatitis is unknown. We conducted a multicenter retrospective study of CF patients taking ivacaftor who had a history of recurrent pancreatitis. During the first three months of therapy, only one of the six patients had an episode of pancreatitis, which was managed on an outpatient basis. Between three and twelve months on ivacaftor therapy, none of the patients had recurrence of pancreatitis or required hospitalization. The use of ivacaftor was associated with a reduced frequency and recurrence rate of pancreatitis in CF patients. (C) 2017 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology,

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Choice of Endoscopic Procedure in Children With Clinically Suspected Gastrointestinal Graft-Versus-Host Disease.

Objectives: Gastrointestinal graft-versus-host disease (GI-GVHD) is a potentially life-threatening complication after hematopoietic stem cell transplantation. Symptoms indicating GI-GVHD motivates endoscopy with biopsy sampling and histopathological confirmation. However, optimal extent of endoscopy in children is presently unknown. Therefore, we aimed to evaluate if biopsies from the rectosigmoid area versus the rest of the colon/ileocolon with or without biopsies from simultaneous upper endoscopy, were equally reliable for detection of GI-GVHD and relevant differential diagnoses. Methods: Retrospective multicentre study based on histopathological re-evaluation of biopsies and hospital record data, collected from children with suspected GI-GVHD. Results: Forty-four children with 51 endoscopic occasions (81 procedures) were included. Thirty-nine of 51 (76.5%) were diagnosed as GI-GVHD, 14 (27.4%) received a differential diagnosis and 7 (13.7%) had normal histology findings. Co-morbidity, i.e. simultaneous detection of a differential diagnosis and GI-GVHD, was observed in 9 (23.1%) cases. CMV infection was the most frequent differential diagnosis, 6/7 were detected in biopsies from rectosigmoid- and esophagogastroduodenal areas. Sensitivity for detection of GI-GVHD in biopsies collected from rectosigmoid-ileocolonic-, rectosigmoid-, or esophagogastroduodenal areas were 97.4%, 84.6%, 83.3%, respectively, and 97.4% when the latter two were merged. The difference, non-detected GI-GVHD in the rectosigmoid area versus detected elsewhere in the GI tract, was statistically significant (p = 0.03). Conclusions: Biopsies collected from the rectosigmoid area solely, were not optimal for detection of paediatric GI-GVHD. However, when biopsy sampling from rectosigmoid- and upper GI tract areas were combined, the sensitivity for GI-GVHD was equally high as for ileocolonoscopy or full upper and lower endoscopy. (C) 2017 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology,

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Male-specific Association Between Fat Free Mass Index and Faecal Microbiota in 2 to 3 Year Old Australian Children.

Objectives: Maturation of the gut microbiota has been shown to influence childhood growth while alterations in microbiota composition are proposed to be causally related to the development of overweight and obesity. The objective of this study is to explore the association between microbiota profile, body size and body composition in young children. Methods: Faecal microbiota was examined by 16S rRNA gene sequencing while body composition was assessed using the deuterium oxide dilution technique in a cohort of 37 well-nourished 2 to 3 year old Australian children. Results: Microbiota composition (weighted UniFrac distance) was shown to be significantly associated with FFMI (Fat Free Mass Index) Z score (p = 0.027, adonis) in boys but not girls. In boys, FFMI Z score was significantly correlated with the relative abundance of an OTU belonging to the Ruminococcaceae family (Rho = 0.822, p

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Donor Human Milk and Fortifier use in United States level 2, 3, and 4 Neonatal Care Hospitals.

Objective: In 2011 the United States Surgeon General issued a call to action to "identify and address obstacles to greater availability of safe banked donor milk for fragile infants." The purpose of this study is to analyze patterns in donor human milk (DHM) and fortifier use in level 2, 3, and 4 neonatal facilities in 2015 and to identify factors associated with non-use. Methods: Data from the 2015 Maternity Practices in Infant Nutrition and Care survey, conducted by the Center for Disease Control and Prevention, was analyzed for questions about feeding practices within neonatal hospitals. Results: The percentage of neonatal facilities that reported using DHM in 2015 was 38.3%, up 74% from 2011. The majority of level 3 and level 4 facilities reported using DHM (65.7% and 73.3% respectively) and fortifiers (96.1% and 91.9% respectively). Within DHM-using facilities, a wide range of DHM feeding patterns were reported. The prevalence of DHM use was higher in facilities that had the highest rates of mother's own milk feedings (P

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Awareness and Implementation of the 2014 ESPGHAN/NASPGHAN Guideline for Childhood Functional Constipation.

Objective: To assess if physicians approach children with functional constipation according to the 2014 ESPGHAN/NASPGHAN guideline. Methods: We invited pediatricians and pediatric gastroenterologists in the Netherlands and the U.S. to participate in this anonymous survey using a self-developed questionnaire containing 19 multiple-choice questions concerning evaluation and treatment of children with constipation. Results: We included 328 physicians (67% from the U.S., 34% from the Netherlands). The majority of U.S. responders (53%) worked in primary care whereas all Dutch responders worked in a hospital. In total, 31% of responders were not familiar with the guideline, (38% U.S. responders vs. 16% Dutch responders, p =1 year). Conclusions: Many responders were not familiar with the ESPGHAN/NASPGHAN guideline for functional constipation. Nonetheless, therapeutic decisions correlated fairly well with recommendations from the guideline, especially for children >=1 year. Guideline awareness and adherence remain to be improved. Future studies should focus on exploring strategies to improve guideline implementation through the development of digital learning tools. (C) 2017 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology,

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Impact of Race and Ethnicity on Outcomes for Children Waitlisted for Pediatric Liver Transplantation.

Objective: African Americans and other minorities are known to face barriers to health care influencing their access to organ transplantation but it is not known whether these barriers exist among pediatric liver transplant waitlist candidates. We sought to determine whether outcomes on the waitlist (i.e., mortality, deceased donor liver transplantation (DDLT), and living-donor liver transplantation (LDLT)) varied by race/ethnicity. Methods: National registry data were studied to estimate the race/ethnicity-specific risk of waitlist mortality, DDLT and LDLT in children (

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Impaired IL-10 Receptor Mediated Suppression in Monocyte from Patients with Crohn's Disease.

Objectives: Interleukin-10 (IL-10) is an immunoregulatory cytokine that has a central role in suppressing pro-inflammatory responses. Patients with deleterious mutations in IL-10 or IL-10 receptor (IL-10R) genes develop severe colitis and perianal disease in the first months of life. Whether IL-10R expression and signaling in pediatric- or adult-onset Crohn's disease (CD) are altered is unknown. The objective of this study was to characterize IL-10R expression and IL-10R-mediated suppression in patients with CD. Methods: Monocytes were sorted from peripheral blood mononuclear cells of patients with CD and control subjects. IL-10R expression was determined by flow cytometry. Monocytes were stimulated with lipopolysaccharide (LPS) for 3 hours in the presence of different concentrations of IL-10 in order to determine IL-10-mediated suppression of TNF[alpha] production. Signaling through the IL-10R was evaluated by quantifying STAT3 phosphorylation in response to IL-10 stimulation. Results: Forty-two subjects were enrolled in this study: 19 with CD and 23 controls. Stimulation of monocytes with LPS markedly increased IL-10R expression in both groups but to a much lower extent in patients with CD. In addition, IL-10-mediated suppression of TNF[alpha] production upon LPS stimulation, and IL-10-induced STAT3 phosphorylation were attenuated in patients with CD vs. controls. Finally, LPS-stimulated monocytes from patients with CD secreted significantly lower quantities of IL-10, compared with control monocytes. Conclusions: IL-10R expression and signaling are decreased in monocytes from patients with CD. Additional studies are required to assess whether similar patterns occur in other innate immune cells, especially in the gut, and whether disease activity, medical therapy and genetic factors modulate these findings. (C) 2017 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology,

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The Case for Thoughtful prescribing of PPIs in Infants.

No abstract available

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Trends of Cholecystectomies for Presumed Biliary Dyskinesia in Children in the United States.

Background: Biliary dyskinesia is a controversial clinical entity. Standardized diagnostic test and management guidelines are lacking in children. Published data suggest that long-term outcomes of surgical and medical management are similar. We sought to determine national population-based trends of cholecystectomies performed in children for biliary dyskinesia and associated healthcare expenditure in the US over a 10-year period. Methods: Using Nationwide Inpatient Sample and the International Classification of Diseases, the 9th revision clinical modification codes, we identified children who had a cholecystectomy for biliary dyskinesia from 2002-2011 in the United States. Results: A total of 66,380 cholecystectomies were identified as primary procedural diagnosis using weighted analysis from 2002 to 2011 in children. Biliary dyskinesia was the primary indication for cholecystectomy in 6,674 (10.8%) of the patients. Over the study period, the number of cholecystectomies performed for biliary dyskinesia in children increased from 6.6% in 2002 to 10.6% in 2011, a majority were adolescent white Caucasian females. The annual health care expenditure for surgical management of biliary dyskinesia for children in the U.S. was estimated to almost $16 million/year. Conclusion: Despite lack of standardized diagnostic criteria and variable outcomes of surgical intervention reported in pediatric literature, cholecystectomies are commonly performed for children with biliary dyskinesia in the United States. Consensus guidelines for the diagnosis and management of this controversial disorder in children are needed. (C) 2017 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology,

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Chronic curcumin treatment improves spatial working memory but not recognition memory in middle-aged rhesus monkeys

Abstract

Studies of both humans and non-human primates have demonstrated that aging is typically characterized by a decline in cognition that can occur as early as the fifth decade of life. Age-related changes in working memory are particularly evident and mediated, in part, by the prefrontal cortex, an area known to evidence age-related changes in myelin that is attributed to inflammation. In recent years, several nutraceuticals, including curcumin, by virtue of their anti-inflammatory and antioxidant effects, have received considerable attention as potential treatments for age-related cognitive decline and inflammation. Accordingly, we assessed for the first time in a non-human primate model of normal aging the efficacy of dietary intervention using the natural phenol curcumin to ameliorate the effects of aging on spatial working and recognition memory. Results revealed that monkeys receiving daily administration of curcumin over 14–18 months demonstrated a greater improvement in performance on repeated administration of a task of spatial working memory compared to monkeys that received a control substance.

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Professional identity, career choices, and working conditions of future and young dentists in Germany – study design and methods of a nationwide comprehensive survey

Abstract

Background

Little is known regarding young and future dentists' career choices, professional identity, and working conditions in Germany. While the dental healthcare environment and demands in treatment are changing, it remains unclear what job perceptions young dentists have developed at the beginning of their work life and if and how these perceptions change during the subsequent years. The aim of this study was to survey future and young dentists regarding their professional identity, planned career paths, and working conditions and strains to understand career decisions and choices and enable policy makers to include future dentists' views and expectations in their decisions.

Methods/design

This study is a longitudinal nationwide survey over a time span of 4 years of dental students and young dentists in Germany and is comprised of three waves. The first wave focuses on dental students in their final year before the state examination and is composed of a qualitative pre-study in the form of focus groups and a quantitative main survey in the form of a questionnaire. The end points were established to analyse (1) the professional identity of the young future dentists; (2) their career paths, preparation for a career, and basic career conditions; and (3) perceived conditions and strains. The aim of the overall survey was to depict the development of these three aspects during the first years of work life. All of the questions were evaluated with a descriptive univariate analysis. The analysed subgroups were grouped according to gender, target working condition (employed/self-employed), and primary socialisation (parents dentists/parents not dentists).

Discussion

To our knowledge, this is the only study which focuses on career choices, professional identity, and working conditions of future and young dentists in Germany. The longitudinal observation provides information that is essential for professional and purposive dental health care planning, and to meet the oral health demands and needs of the German population appropriately over the long term.

Trial registration

German Health Services Research Data Bank VfD_Y-Dent_14_003759.

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Planned secondary wound closure at the circular stapler insertion site after laparoscopic gastric bypass reduces postoperative morbidity, costs, and hospital stay

Abstract

Purpose

The aims of the present study were to assess whether planned secondary wound closure at the insertion site of the circular stapler reduces wound infection rate and postoperative morbidity after laparoscopic Roux-en-Y gastric bypass (RYGB) and to identify independent predictive factors increasing the risk for wound infections after RYGB.

Methods

This paper is a retrospective single-center analysis of a prospectively collected database of 1400 patients undergoing RYGB surgery in circular technique between June 2000 and June 2016. Planned secondary wound closure at the circular stapler introduction site was performed at postoperative day 3 in 291 (20.8%) consecutive patients and compared to a historical control of 1109 (79.2%) consecutive patients with primary wound closure. Independent predictive factors for wound infection were assessed by multivariable analysis.

Results

Secondary wound closure significantly decreased wound infection rate from 9.3% (103/1109) to 1% (3/291) (p < 0.001) leading to a shorter hospital stay (mean 9 (SD8) vs. 7 days (SD2), p < 0.001), lower costs (p = 0.039), and reduced postoperative morbidity (mean 90-day Comprehensive Complication Index (CCI) 7.4 (SD14.0) vs. 5.1 (SD11.1) p = 0.008) when compared to primary wound closure. Primary wound closure, dyslipidemia, and preoperative gastritis were independent predictive risk factors for developing wound infections both in the univariate (p < 0.001; p = 0.048; p = 0.003) and multivariable analysis (p < 0.001; p = 0.040; p = 0.012). Further, on multivariable analysis, the female gender was a predictive factor (p = 0.034) for wound infection development.

Conclusions

Secondary wound closure at the circular stapler introduction site in laparoscopic RYGB significantly reduces the overall wound infection rate as well as postoperative morbidity, costs, and hospital stay when compared to primary wound closure.

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Comparison of posterior retroperitoneal and transabdominal lateral approaches in robotic adrenalectomy: an analysis of 200 cases

Abstract

Background

Although numerous studies have been published on robotic adrenalectomy (RA) in the literature, none has done a comparison of posterior retroperitoneal (PR) and transabdominal lateral (TL) approaches. The aim of this study was to compare the outcomes of robotic PR and TL adrenalectomy.

Methods

This is a retrospective analysis of a prospectively maintained database. Between September 2008 and January 2017, perioperative outcomes of patients undergoing RA through PR and TL approaches were recorded into an IRB-approved database. Clinical and perioperative parameters were compared using Student's t test, Wilcoxon rank-sum test, and χ ² test. Multivariate regression analysis was performed to determine factors associated with total operative time.

Results

188 patients underwent 200 RAs. 110 patients were operated through TL and 78 patients through PR approach. Overall, conversion rate to open was 2.5% and 90-day morbidity 4.8%. The perioperative outcomes of TL and PR approaches were similar regarding estimated blood loss, rate of conversion to open, length of hospital stay, and 90-day morbidity. PR approach resulted in a shorter mean ± SD total operative time (136.3 ± 38.7 vs. 154.6 ± 48.4 min; p = 0.005) and lower visual analog scale pain score on postoperative day #1 (4.3 ± 2.5 vs. 5.4 ± 2.4; p = 0.001). After excluding tumors larger than 6 cm operated through TL approach, the difference in operative times persisted (136.3 ± 38.7 vs. 153.7 ± 45.7 min; p = 0.009). On multivariate regression analysis, increasing BMI and TL approaches were associated with longer total operative time.

Conclusion

This study shows that robotic PR and TL approaches are equally safe and efficacious. With experience, shorter operative time and less postoperative pain can be achieved with PR technique. This supports the preferential utilization of PR approach in high-volume centers with enough experience.

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Modified peroral endoscopic myotomy: a “Push and Pull” technique

Abstract

Background

Peroral endoscopic myotomy (POEM) is a minimally invasive yet challenging procedure for achalasia. Additional technological innovations and improvements are important for simplifying the procedure.

Methods

We report the successful use of a modified POEM procedure, which utilized a "Push and Pull" technique, on a patient with achalasia.

Results

Our modifications resulted in a short operation time of only 35 min. No complications arose during or after the procedure, up to a follow-up period of 6 months, and symptoms were significantly and quickly improved.

Conclusions

This modified procedure shortens operation time and lowers the difficulty of the operation, while leaving the safety and efficacy uncompromised.

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Minimally invasive liver resection for primary and metastatic liver tumors: influence of age on perioperative complications and mortality

Abstract

Background

As minimally invasive technique becomes more popular, an increasing number of elderly patients were considered for minimally invasive liver resection (MILR). Limited physiologic reserve remains a major concern, which frequently leads surgeons to recommend nonresectional alternatives. We sought to evaluate complications and outcomes of elderly patients undergoing MILR.

Methods

Eight hundred and thirty-one patients who underwent MILR were classified into groups A, B, and C based on age [(< 70, n = 629), (70–79, n = 148), (≥ 80, n = 54) years old, respectively].

Results

Gender distribution, BMI, and cirrhotic status were comparable among all groups. Groups B and C had higher MELD (p = 0.047) and ASA (p = 0.001) scores. Operative time (170, 157, 152 min; p = 0.64) and estimated blood loss (145, 130, 145 ml; p = 0.95) were statistically equal. Overall postoperative complications were greater in groups B and C (12.9 and 9.3 vs. 6.5%, respectively). Complications in group C were all minor. Clavien–Dindo grade III–IV complications were higher in group B when compared to group A (6.8 vs. 2.7%, p = 0.43). There was no significant difference in cardiopulmonary complications, thromboembolic events, ICU admissions, and transfusion rates seen in groups B and C when compared to group A. Duration of hospital stay was statistically longer in groups B and C (3.6, 3.5 vs. 2.5 days, p = 0.0012). 30- and 90-day mortality rates were comparable among the groups, irrespective of age.

Conclusions

In spite of greater preoperative comorbidities and ASA score, there was no significant increase in postoperative morbidity after minimally invasive liver resection in patients ≥ 70 years of age.

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Endoscopic submucosal dissection for undifferentiated-type early gastric cancer: short- and long-term outcomes

Abstract

Background and aims

Application of endoscopic submucosal dissection (ESD) for undifferentiated-type early gastric cancers (EGCs) remains controversial owing to limited data regarding long-term outcomes. We aimed to evaluate the feasibility of ESD for undifferentiated-type EGCs that meet the expanded criteria (EC).

Methods

We performed a retrospective analysis of 66 patients who underwent ESD for undifferentiated-type EGC between January 2005 and December 2014. We evaluated the rates of en bloc, complete, and curative resections along with overall survival (OS), disease-specific survival (DSS), and recurrence-free survival (RFS).

Results

Of the 66 patients, the EC group included 38 patients and the beyond-EC group included 28 patients. The overall rates of en bloc, complete, and curative resection of the 66 lesions were 92.4% (61/66), 65.2% (43/66), and 48.5% (32/66), respectively. Of the 34 patients with non-curative resection, 18 underwent additional surgery. Local remnant cancer was detected in 1 patient (1/18, 5.6%), and none of the 18 patients had lymph node metastasis. On multivariate analysis, tumors > 2 cm [odd ratio (OR) 6.183, 95% confidence interval (CI) 1.279–29.880, p = 0.023) and submucosal invasion depth (OR 6.226, 95% CI 1.881–20.606, p = 0.003) were independent predictors of incomplete resection. All 26 patients with more than 1 year of follow-up after curative resection survived without any evidence of local or distant recurrences over a median follow-up period of 36 months. The OS, DSS, and RFS rates of patients with curative ESD were 93.8, 100, and 100%, respectively.

Conclusions

ESD may have favorable long-term outcomes in patients with undifferentiated-type EGC after curative resection.

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Heller myotomy versus Heller myotomy with Dor fundoplication for achalasia: long-term symptomatic follow-up of a prospective randomized controlled trial

Abstract

Background

Our prior randomized controlled trial of Heller myotomy alone versus Heller plus Dor fundoplication for achalasia from 2000 to 2004 demonstrated comparable postoperative resolution of dysphagia but less gastroesophageal reflux after Heller plus Dor. Patient-reported outcomes are needed to determine whether the findings are sustained long-term.

Methods

We actively engaged participants from the prior randomized cohort, making up to six contact attempts per person using telephone, mail, and electronic messaging. We collected patient-reported measures of dysphagia and gastroesophageal reflux using the Dysphagia Score and the Gastroesophageal Reflux Disease-Health-Related Quality of Life (GERD-HRQL) instrument. Patient-reported re-interventions for dysphagia were verified by obtaining longitudinal medical records.

Results

Among living participants, 27/41 (66%) were contacted and all completed the follow-up study at a mean of 11.8 years postoperatively. Median Dysphagia Scores and GERD-HRQL scores were slightly worse for Heller than Heller plus Dor but were not statistically different (6 vs 3, p = 0.08 for dysphagia, 15 vs 13, p = 0.25 for reflux). Five patients in the Heller group and 6 in Heller plus Dor underwent re-intervention for dysphagia with most occurring more than five years postoperatively. One patient in each group underwent redo Heller myotomy and subsequent esophagectomy. Nearly all patients (96%) would undergo operation again.

Conclusions

Long-term patient-reported outcomes after Heller alone and Heller plus Dor for achalasia are comparable, providing support for either procedure.

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Laparoscopic choledochoduodenostomy as a reliable rescue procedure for complicated bile duct stones

Abstract

Background

Endoscopic retrograde cholangiopancreatography (ERCP) with stone extraction is generally accepted as first line management for common bile duct (CBD) stones. CBD exploration, either by open or laparoscopic approach nowadays, is usually reserved for ERCP failures, complicated stone locations, along with altered anatomical situations. The aim of this study was to highlight the increasing role of laparoscopic choledochoduodenostomy which is not only a reliable but also as a rescue procedure for those failed ERCP cases due to complicated bile duct stones.

Materials and methods

It is a retrospective review of the database, from a tertiary care teaching institution from India, from Jan 2012 up to December 2016.

Results

Out of total 30 patients who underwent laparoscopic choledochoduodenostomy, 28 had failed ERC stone clearance while two patients were directly offered drainage in view of unfavorable anatomy. The major reasons for failed ERC stone clearance were as follows—multiple large calculi (42.8%), recurrent stones (21.4%), and associated stricture (21.4%). Mean operating time was 130 (± 27) minutes with mean blood loss of 60 (± 19) ml. Stone extraction was successful, primarily by milking in 13 (43.33%) patients, rest required augmentation by Dormia basket/balloon. Two patients (6.66%) developed controlled bile leak which resolved with conservative treatment. The median length of hospital stay was 5 days (IQR 3–9). Mean duration of follow-up was 17 (± 3.2) months.

Conclusion

Laparoscopic common bile duct exploration with choledochoduodenostomy has been shown to be a safe, reliable, and efficient method for treating complex CBDS, especially after failed ERCP procedures.

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Telomerase reverse transcriptase (TERT) promoter mutations are rare in urachal cancer

High rates of telomerase reverse transcriptase (TERT) promoter mutations have recently been described in urothelial carcinoma (UC). Unlike UC in the bladder, adenocarcinomas account for the majority of urachal cancer (UrC) cases. As data in UrC is unclear, we analyzed TERT promoter mutations in a large cohort of UrC for its differential diagnostic, clinicopathological and prognostic significance. UrC cases from six academic centers were analyzed for c.-146C>T (C250T) and c.-124C>T (C228T) TERT promoter mutations by PCR and Sanger sequencing. Clinicopathological and survival data were collected. The cohort consisted of 15 men (56%) and 12 women (44%) with a median age of 50 years including 23 adenocarcinomas, two squamous cell carcinomas (SCC), one UC and one undifferentiated carcinoma. In one case of (mucinous) urachal adenocarcinoma a C228T mutation was detected (1/23; 4%), like in a case of SCC in addition to one C250T mutation in the UC case. TERT promoter mutations are very rare in urachal adenocarcinomas (unlike in UC) with differential diagnostic implications. Additionally, the low TERT promoter mutation rate in urachal adenocarcinomas is more comparable to colorectal adenocarcinomas than to UC, giving further support to recent genetic findings and therapeutic considerations.

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Relationship between gastric lanthanum deposition and Helicobacter pylori-associated chronic gastritis: is it rare or common?

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Ral signaling pathway in health and cancer

Abstract

The Ral (Ras-Like) signaling pathway plays an important role in the biology of cells. A plethora of effects is regulated by this signaling pathway and its prooncogenic effectors. Our team has demonstrated the overactivation of the RalA signaling pathway in a number of human malignancies including cancers of the liver, ovary, lung, brain, and malignant peripheral nerve sheath tumors. Additionally, we have shown that the activation of RalA in cancer stem cells is higher in comparison with differentiated cancer cells. In this article, we review the role of Ral signaling in health and disease with a focus on the role of this multifunctional protein in the generation of therapies for cancer. An improved understanding of this pathway can lead to development of a novel class of anticancer therapies that functions on the basis of intervention with RalA or its downstream effectors.

Ral signaling pathway as an important effector pathway downstream of Ras plays an important role in health and diseases.

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A comprehensive genome-wide analysis of long noncoding RNA expression profile in hepatocellular carcinoma

Abstract

Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide, especially in East Asia and China. Long noncoding RNAs (lncRNAs) are emerging as critical regulators that may be involved in the development and progression of cancers in humans. However, the contributions of lncRNAs to HCC development, metastasis, and recurrence remain largely unknown. In this study, we comprehensively investigated lncRNA expression profile in HCC and normal tissues using TCGA RNA sequencing data, one RNA sequencing dataset, and two microarray datasets from GEO. By analyzing these four datasets, we identified hundreds of expression-dysregulated lncRNAs in HCC tissues compared with normal tissues. Genomic copy number variation analysis showed that many of those lncRNAs disorder are related to the copy number amplification or deletion. Moreover, several lncRNAs expression levels are associated with HCC patients' overall and recurrence-free survival, such as RP1-228H13.5, TMCC1-AS1, LINC00205, and RP11-307C12.11. Furthermore, we identified two lncRNAs termed PVT1 and SNHG7 that may be involved in HCC cells metastasis by comparing lncRNAs expression profiles between early recurrence HCC tissues with metastasis and late recurrence HCC tissues without metastasis. Finally, loss-of-function assays confirmed that knockdown of SNHG7 and PVT1 impaired HCC cells invasion. Taken together, these findings may provide a valuable resource for further identification of novel biomarkers and therapeutic targets for HCC patients.

lncRNAs are emerging as critical regulators that are involved in the development and progression of cancers in humans. We comprehensively investigated lncRNA expression profiling in HCC and normal tissues; these findings may provide a valuable resource to further identify novel biomarkers and therapeutic targets of HCC.

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Different Contributions of Primary Motor Cortex, Reticular Formation and Spinal Cord to Fractionated Muscle Activation

Coordinated movement requires patterned activation of muscles. In this study we examined differences in selective activation of primate upper limb muscles by cortical and sub-cortical regions. Five macaque monkeys were trained to perform a reach and grasp task, and electromyogram (EMG) was recorded from 10-24 muscles while weak single-pulse stimuli were delivered through microelectrodes inserted in the motor cortex (M1), reticular formation (RF) or cervical spinal cord (SC). Stimulus intensity was adjusted to a level just above threshold. Stimulus-evoked effects were assessed from averages of rectified EMG. M1, RF and SC activated 1.5±0.9, 1.9±0.8 and 2.5±1.6 muscles per site (mean±SD); only M1 and SC differed significantly. In between recording sessions, natural muscle activity in the home cage was recorded using a miniature data logger. A novel analysis assessed how well natural activity could be reconstructed by stimulus-evoked responses. This provided two measures: normalized vector length L, reflecting how closely aligned were natural and stimulus-evoked activity, and normalized residual R, measuring the fraction of natural activity not reachable using stimulus-evoked patterns. Average values for M1, RF and SC were L=119.1±9.6, 105.9±6.2 and 109.3±8.4 and R=50.3±4.9, 56.4±3.5 and 51.5±4.8 respectively. RF was significantly different from M1 and SC on both measures. RF is thus able to generate an approximation to the motor output with less activation than required by M1 and SC, but M1 and SC are more precise in reaching the exact activation pattern required. Cortical, brainstem and spinal centers likely play distinct roles as they cooperate to generate voluntary movements.

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Paired corticospinal-motoneuronal stimulation increases maximal voluntary activation of human adductor pollicis

Paired corticospinal-motoneuronal stimulation (PCMS), which delivers repeated pairs of transcranial magnetic stimuli (TMS) and maximal motor nerve stimuli, can alter corticospinal transmission to low threshold motoneurones in the human spinal cord. To determine whether similar changes occur for high threshold motoneurones, we tested whether maximal voluntary activation and force can be affected by PCMS in healthy individuals. On two separate days, healthy participants (n=14) performed brief thumb adduction MVCs before and after a control protocol (TMS only) or PCMS designed to facilitate corticospinal transmission to adductor pollicis. Peripheral nerve stimulation alone was not performed. During each MVC, a superimposed twitch was elicited by a supramaximal stimulus delivered to the ulnar nerve. With muscles relaxed following the maximal contraction, a similar stimulus elicited a resting twitch. Voluntary activation was calculated as (1- superimposed twitch/resting twitch)*100%. While voluntary activation decreased over time in both conditions, the decrease was less after PCMS (-0.4 ± 4.1%) than after the control protocol (-4.9 ± 4.9%, p = 0.007). This was supported by a greater increase in EMG after PCMS than control (7 ± 13% vs. -3 ± 10%; p = 0.043). However, maximal force was not affected. The findings indicate a modest effect of PCMS on maximal neural drive to adductor pollicis, suggesting that PCMS can affect corticospinal transmission to high threshold motoneurones.

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Carotid chemoreceptors tune breathing via multipath routing: Reticular chain and loop operations supported by parallel spike train correlations

We tested the hypothesis that carotid chemoreceptors tune breathing through parallel circuit paths that target distinct elements of an inspiratory neuron chain in the ventral respiratory column (VRC). Microelectrode arrays were used to monitor neuronal spike trains simultaneously in the VRC, peri-nucleus tractus solitarius-medial medulla (p-NTS-MM), the dorsal parafacial region of the lateral tegmental field (FTL-pF), and medullary raphé nuclei together with phrenic nerve activity during selective stimulation of carotid chemoreceptors or transient hypoxia in 19 decerebrate, neuromuscularly-blocked, and artificially ventilated cats. Of 994 neurons tested, 56% had a significant change in firing rate. A total of 33,422 cell pairs were evaluated for signs of functional interaction; 63% of chemoresponsive neurons were elements of at least one pair with correlational signatures indicative of paucisynaptic relationships. We detected evidence for post-inspiratory neuron inhibition of rostral VRC I-Driver (preBötzinger) neurons, an interaction predicted to modulate breathing frequency, and for reciprocal excitation between chemoresponsive p-NTS neurons and more downstream VRC inspiratory neurons for control of breathing depth. Chemoresponsive peri-columnar tonic expiratory neurons, proposed to amplify inspiratory drive by disinhibition, were correlationally linked to afferent and efferent "chains" of chemoresponsive neurons extending to all monitored regions. The chains included coordinated clusters of chemoresponsive FTL pF neurons with functional links to wide-spread medullary sites involved in the control of breathing. The results support long-standing concepts on brain stem network architecture and a circuit model for peripheral chemoreceptor modulation of breathing with multiple circuit loops and chains tuned by tegmental field neurons with quasi-periodic discharge patterns.

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Spatio-temporal characteristics of retinal response to network-mediated photovoltaic stimulation

Subretinal prostheses aim at restoring sight to patients blinded by photoreceptor degeneration using electrical activation of the surviving inner retinal neurons. Today, such implants deliver visual information with low-frequency stimulation, resulting in discontinuous visual percepts. We measured retinal responses to complex visual stimuli delivered at video rate via a photovoltaic subretinal implant and by visible light. Using a multielectrode array to record from retinal ganglion cells (RGCs) in the healthy and degenerated rat retina ex-vivo, we estimated their spatio-temporal properties from the spike-triggered average (STA) responses to photovoltaic binary white noise stimulus with 70μm pixel size at 20Hz frame rate. The average photovoltaic receptive field size was 194±3μm (S.E.M.), similar to that of visual responses (221±4μm), but response latency was significantly shorter with photovoltaic stimulation. Both visual and photovoltaic receptive fields had an opposing center-surround structure. In the healthy retina, ON RGCs had photovoltaic OFF responses, and vice versa. This reversal is consistent with depolarization of photoreceptors by electrical pulses, as opposed to their hyperpolarization under increasing light, although alternative mechanisms cannot be excluded. In degenerate retina, both ON and OFF photovoltaic responses were observed, but in the absence of visual responses, it is not clear what functional RGC types they correspond to. Degenerate retina maintained the antagonistic center-surround organization of receptive fields. These fast and spatially localized network-mediated ON and OFF responses to subretinal stimulation via photovoltaic pixels with local return electrodes raise confidence in the possibility of providing more functional prosthetic vision.

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Phosphorylation of Connexin 43 Induced by Traumatic Brain Injury Promotes Exosome Release

Traumatic brain injury (TBI) caused by the external force leads to the neuronal dysfunction and even death. TBI has been reported to significantly increase the phosphorylation of glial gap junction protein connexin 43 (Cx43), which in turn propagates damages into surrounding brain tissues. However, the neuroprotective and anti-apoptosis effects of glia-derived exosomes have also been implicated in recent studies. Therefore, we detected whether TBI-induced phosphorylation of Cx43 would promote exosome release in rat brain. To generate TBI model, adult male Sprague-Dawley rats were subjected to lateral fluid percussion injury. Phosphorylated Cx43 protein levels and exosome activities were quantified using western blot analysis following TBI. Long-term potentiation (LTP) was also tested in rat hippocampal slices. TBI significantly increased the phosphorylated Cx43 and exosome markers expression in rat ipsilateral hippocampus, but not cortex. Blocking the activity of Cx43 or ERK, but not JNK, significantly suppressed TBI-induced exosome release in hippocampus. Furthermore, TBI significantly inhibited the induction of LTP in hippocampal slices, which could be partially but significantly restored by pretreatment with exosomes. The results implicated that TBI-activated Cx43 could mediate a nociceptive effect by propagating the brain damages, as well as a neuroprotective effect by promoting exosome release.

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Passive sensorimotor stimulation triggers long lasting alpha-band fluctuations in visual perception

Movement planning and execution rely on the anticipation and online control of the incoming sensory input. Evidence suggests that sensorimotor processes may synchronize visual rhythmic activity in preparation of action performance. Indeed, we recently reported periodic fluctuations of visual contrast sensitivity which are time-locked to the onset of an intended movement of the arm. However, the origin of the observed visual modulations has so far remained unclear due to the endogenous (and thus temporally undetermined) activation of the sensorimotor system that is associated with voluntary movement initiation. Here, we activated the sensorimotor circuitry involved in the hand control in an exogenous and controlled way by means of peripheral stimulation of the median nerve and characterized the spectrotemporal dynamics of the ensuing visual perception. The stimulation of the median nerve triggers robust and long-lasting (1 s) alpha-band oscillations in visual perception, whose strength is temporally modulated in a way that is consistent with the changes in alpha power described at the neurophysiological level after sensorimotor stimulation. These findings provide evidence in support of a causal role of the sensorimotor system in modulating oscillatory activity in visual areas with consequences for visual perception.

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The intrinsic physiology of inhibitory neurons changes over auditory development

During auditory development, changes in membrane properties promote the ability of excitatory neurons in the brainstem to code aspects of sound, including the level and timing of a stimulus. Some of these changes coincide with hearing onset, suggesting that sound-driven neural activity produces developmental plasticity of ion channel expression. While it is known that the coding properties of excitatory neurons are modulated by inhibition in the mature system, it is unknown whether there are also developmental changes in the membrane properties of brainstem inhibitory neurons. We investigated the primary source of inhibition in the avian auditory brainstem, the superior olivary nucleus (SON). The present studies test the hypothesis that, as in excitatory neurons, the membrane properties of these inhibitory neurons change following hearing onset. We examined SON neurons at different stages of auditory development: embryonic days 14-16 (E14-16), a time at which cochlear ganglion neurons are just beginning to respond to sound, later embryonic stages (E18-19), and after hatching (P0-P2). We used in vitro whole-cell patch electrophysiology to explore physiological changes in SON. Age-related changes were observed at the level of a single spike and in multi-spiking behavior. In particular, tonic behavior, measured as a neuron's ability to sustain tonic firing over a range of current steps, became more common later in development. Voltage-clamp recordings and biophysical models were employed to examine how age-related increases in ion currents enhance excitability in SON. Our findings suggest that concurrent increases in sodium and potassium currents underlie the emergence of tonic behavior.

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The fate of non-selected activity in saccadic decisions: distinct goal-related and history-related modulation.

The Global Effect (GE) traditionally refers to the tendency of effectors (e.g. hand, eyes) to first land in between two nearby stimuli - forming a unimodal distribution. By measuring a shift of this distribution, recent studies used the GE to assess the presence of decision-related inputs on the motor map for eye movements. However, this method cannot distinguish whether one stimulus is inhibited or the other is facilitated and could not detect situations where both stimuli are inhibited or facilitated. Here, we detect deviations in the bimodal distribution of landing positions for remote stimuli, and find that this bimodal GE reveals the presence, location and polarity (facilitation or inhibition) of history-related and goal-related modulation of the non-selected activity (e.g. the distractor activity in correct trials, and the target activity in error trials). We tested, for different inter-stimulus distances, the effect of the rarity of double-stimulus trials, and the difference between performing a discrimination task compared to free choice. Our work shows that the effect of rarity is symmetric and decreases with inter-stimulus distances, while the effect of goal-directed discrimination is asymmetric - occurring only when the distractor is selected for the saccade - and maintained across inter-stimulus distances. These results suggest that the former effect changes the response property of the motor map, while the latter specifically facilitates the target location.

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Path Perturbation Detection Tasks Reduce MSTd Neuronal Self-Movement Heading Responses

We presented optic flow and real movement heading stimuli while recording MSTd neuronal activity. Monkeys were alternately engaged in three tasks: visual detection of optic flow heading perturbations, vestibular detection of real movement heading perturbations, and auditory detection of brief tones. Push-button RTs were fastest for tones, and slower for visual and vestibular heading perturbations, suggesting that the tone detection task was easier. Neuronal heading selectivity was strongest during the tone detection task, and weaker during the visual and vestibular heading perturbation detection tasks. Heading selectivity was weaker during visual and vestibular path perturbation detection, despite our presented heading cues only in the visual and vestibular modalities. We conclude that focusing on the self-movement transients of path perturbation distracted the monkeys from their heading and reduced neuronal responsiveness to heading direction.

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Esophageal lesions following button-battery ingestion in children: Analysis of causes and proposals for preventive measures

Publication date: Available online 18 October 2017
Source:European Annals of Otorhinolaryngology, Head and Neck Diseases
Author(s): J. Lahmar, C. Célérier, E.N. Garabédian, V. Couloigner, N. Leboulanger, F. Denoyelle
ObjectivesTo study recent cases of esophageal injury due to button-battery ingestion in children presenting in pediatric ENT emergency departments of the Paris area of France (Île-de-France region), in order to propose appropriate preventive measures.Material and methodA retrospective descriptive single-center study included all children under 15 years of age, presenting in pediatric ENT emergency departments between January 2008 and April 2014 for button-battery ingestion with esophageal impaction requiring emergency removal.ResultsTwenty-two boys and 4 girls, with a median age of 25 months, were included. Twenty-five of the 26 batteries had diameters of 20mm or more. Median esophageal impaction time was 7 hours 30 minutes (range, 2 to 72 hours). The complications rate was 23%. Mean hospital stay cost was €38,751 (range, €5130–119,737). The origin of the battery was known in 23 of the 26 cases: remote control without screw-secured compartment (42.3%), open battery pack (15.4%), children's toy (15.3%), camera (7.7%), watch (1 case) and hearing aid without screw-secured compartment (1 case).ConclusionEsophageal lesions due to ingestion of button-batteries in children are almost always due to batteries larger than 20mm in diameter, mostly from devices with a poorly protected compartment, or batteries that are not individually packaged. These lesions cause serious complications in a quarter of cases and their management entails high health costs. Legislation requiring screw-secured compartments and individual blisters for batteries could have prevented 69.2% of the ingestions.



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Understanding middle-aged and older adults’ first associations with the word ‘cancer’: a mixed methods study in England

Abstract

Objective

Cancer is still widely feared and often associated with death. Fatalistic beliefs adversely affect help-seeking for cancer symptoms and engagement in cancer prevention. This study aims to understand middle-aged and older adults' first association with the word 'cancer', and their relationship with sociodemographic factors, cancer fear, and cancer information avoidance.

Methods

We conducted a cross-sectional survey of 1464 community-based adults aged 50 to 70 living in England in April 2015. First associations with cancer were measured qualitatively and analysed using content analysis. We used binary logistic regression to analyse associations between the most common first association of cancer and sociodemographic characteristics, cancer fear and cancer information avoidance.

Results

Cancer was most commonly associated with 'death' (26%). Respondents with lower levels of education, living in the Midlands or North of England where cancer mortality is higher, or with close friends or family members with a cancer history, were more likely to associate cancer with death. Cancer fear was significantly associated with death associations, but cancer information avoidance was not.

Conclusions

Despite improved cancer outcomes, middle-aged and older adults often associate cancer with death. Further efforts to decrease fatalistic associations in this age group may be needed.

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Locus of control, optimism, and recollections of depression and self-reported cognitive functioning following treatment for colorectal cancer

Abstract

Objective

To investigate the effects of disposition (locus of control, optimism, depression) on recollections of cognitive functioning following cancer treatment.

Methods

Participants were survivors of colorectal cancer (n = 88) and their spouses (n = 40). Survivors retrospectively rated their cognitive functioning and depression, as experienced following treatment; and currently rated their dispositions for optimism and locus of control. Survivors' spouses likewise provided their recollections of survivors' cognitive functioning and depression at time following treatment.

Results

Correlations between survivors' and spouses' ratings for cognitive functioning were statistically significant but not for depression. Results supported validity of survivors' longer-term retrospective reports. Although internal locus of control correlated positively with retrospectively self-reported cognitive functioning, and negatively with retrospectively self-reported depression, moderated hierarchical multiple regression found independent contribution of internal locus of control was limited to predicting quality of life; and that, among variables tested, depression correlated strongest with cognitive functioning.

Conclusions

Neither internal locus of control nor optimism in colorectal cancer survivors influences correlation between cognition and depression. Health care providers should note individual differences in responses to treatment and be alert to the impact of depression on perceived everyday functioning.

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Identification of a novel torque teno mini virus in cerebrospinal fluid from a child with encephalitis

Abstract

Anelloviruses are single-strand circular DNA viruses and ubiquitous within the human population. Although there is no direct evidence, many studies have suggested the anelloviruses may be associated with a variety of diseases. In this study, a novel torque teno mini virus (TTMV) was detected in a child with unexplained encephalitis. The detected virus had a circular genome of 2943 nt in length and 3 open reading frames. It shared 45.4% – 35.9% nucleotide identities with known TTMV species and < 35% with the other species of anellovirus, which suggested it might belong to a new species within the genus Betatorquevirus. Phylogenetic analysis based on the amino acid sequences of ORF1 showed that this virus represented a distinct branch within the diversity of anellovirus. Whether this novel anellovirus strain is associated with encephalitis requires further study.

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Cathepsin B is dispensable for cellular processing of cathepsin B-cleavable antibody-drug conjugates

Antibody-drug conjugates (ADCs) are designed to selectively bind to tumor antigens via the antibody and release their cytotoxic payload upon internalization. Controllable payload release through judicious design of the linker has been an early technological milestone. Here, we examine the effect of the protease-cleavable valine-citrulline (VC(S)) linker on ADC efficacy. The VC(S) linker was designed to be cleaved by cathepsin B, a lysosomal cysteine protease. Surprisingly, suppression of cathepsin B expression via CRISPR-Cas9 gene deletion or shRNA knockdown had no effect on the efficacy of ADCs with VC(S) linkers armed with a monomethyl auristatin E (MMAE) payload. Mass spectrometry studies of payload release suggested that other cysteine cathepsins can cleave the VC(S) linker. Also, ADCs with a non-protease-cleavable enantiomer, the VC(R) isomer, mediated effective cell killing with a cysteine-VC(R)-MMAE catabolite generated by lysosomal catabolism. Based on these observations, we altered the payload to a pyrrolo[2,1-c][1,4]benzodiazepine dimer (PBD) conjugate that requires linker cleavage in order to bind its DNA target. Unlike the VC-MMAE ADCs, the VC(S)-PBD ADC is at least 20-fold more cytotoxic than the VC(R)-PBD ADC. Our findings reveal that the VC(S) linker has multiple paths to produce active catabolites, and that antibody and intracellular targets are more critical to ADC efficacy. These results suggest that protease-cleavable linkers are unlikely to increase the therapeutic index of ADCs and that resistance based on linker processing is improbable.

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PP2A inactivation mediated by PPP2R4 haploinsufficiency promotes cancer development

Protein phosphatase 2A (PP2A) complexes counteract many oncogenic kinase pathways. In cancer cells, PP2A function can be compromised by several mechanisms, including sporadic mutations in its scaffolding A and regulatory B subunits or more frequently through overexpression of cellular PP2A inhibitors. Here we identify a novel genetic mechanism by which PP2A function is recurrently affected in human cancer, involving haploinsufficiency of PPP2R4, a gene encoding the cellular PP2A activator PTPA. Notably, up to 70% of cancer patients showed a heterozygous deletion or missense mutations in PPP2R4. Cancer-associated PTPA mutants exhibited decreased abilities to bind the PP2A-C subunit or activate PP2A and failed to reverse the tumorigenic phenotype induced by PTPA suppression, indicating they function as null alleles. In Ppp2r4 gene-trapped (gt) mice showing residual PTPA expression, total PP2A activity and methylation were reduced, selectively affecting specific PP2A holoenzymes. Both PTPAgt/gt and PTPA+/gt mice showed higher rates of spontaneous tumors, mainly hematologic malignancies and hepatocellular adenomas and carcinomas. These tumors exhibited increased c-Myc phosphorylation and increased Wnt or Hedgehog signaling. We observed a significant reduction in lifespan in PTPA+/gt mice compared to wildtype mice. Additionally, chemical induced skin carcinogenesis was accelerated in PTPA+/gt compared to wildtype mice. Our results provide evidence for PPP2R4 as a haploinsufficient tumor suppressor gene, defining a high-penetrance genetic mechanism for PP2A inhibition in human cancer.

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Evidence for the presence in rainbow trout brain of amino acid sensing systems involved in the control of food intake

To assess the existence of central amino acid sensing systems in fish we carried out two experiments in rainbow trout. In the first one, we injected ICV two different branched-chain amino acids (BCAA), leucine and valine, and assessed food intake up to 48 h later. Leucine decreased and valine increased food intake. In a second experiment, 6h after similar ICV treatment we determined changes in parameters related to putative amino acid sensing systems. Amino acid sensing systems respond to leucine in hypothalamus and telencephalon, and to valine in telencephalon. The decreased food intake observed in fish treated ICV with leucine could relate to changes in mRNA abundance of hypothalamic neuropeptides (POMC, CART, NPY and AgRP). These in turn could relate to amino acid sensing systems present in the same area, related to BCAA and glutamine metabolism, as well as mechanistic target of rapamycin (mTOR), taste receptors and general control non-derepressible 2 (GCN2) kinase signalling. The treatment with valine did not affect amino acid sensing parameters in hypothalamus. These responses are comparable to those characterized in mammals. However, clear differences arise when comparing rainbow trout and mammals, in particular with respect to the clear orexigenic effect of valine, which could relate to the finding that valine partially stimulated two amino acid sensing systems in telencephalon. Another novel result is the clear effect of leucine on telencephalon, in which amino acid sensing systems, but not neuropeptides, were activated as in hypothalamus

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Vasoactivity of nitrite in the iliac artery of the toad, Rhinella marina

Nitrite (NO₂^-) causes vasodilation in mammals due to the formation of (nitric oxide) NO by endogenous NO₂^- reduction in the vascular wall. In this study, we determined if a similar mechanism operates in amphibians. Dual-wire myography of the iliac artery from Rhinella marina showed that applied NO₂^- caused a concentration-dependent vasodilation in normoxia (21% O₂; EC₅₀ 438 µM). Hypoxia (0.63% O₂) significantly increased the maximal dilation to NO₂^- by 5 % (P = 0.0398). The addition of oxyhemoglobin significantly increased the EC₅₀ (P = 0.0144; EC₅₀ 2236 µM), but did not affect the maximal vasodilation. In contrast, partially deoxygenated hemoglobin (90% desaturation) did not affect the EC₅₀ (P = 0.1189) but significantly (P = 0.0012) increased the maximal dilation to NO₂^- by 11%. The soluble guanylyl cyclase inhibitor, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) completely abolished the response to NO₂- (P < 0.0001), and of the nitric oxide synthase inhibitors, only vinyl-L-NIO (P = 0.0028) significantly reduced the NO₂^- vasodilation. The xanthine oxidoreductase inhibitor, allopurinol (P = 0.927), the NO-scavenger C-PTIO (P = 0.478), and disruption of the endothelium (P = 0.094) did not affect the NO₂^- vasodilation. Incubation of iliac arteries with 1 mM NO₂^- did not a cause a change in cGMP concentration (P = 0.407). Plasma NO₂^- was found to be 0.86 ± 0.20 µmol.L^-1, while nitrate (NO₃^-) was 19.55 ± 2.55 µmol.L^-1. Both cygb and ngb mRNAs were expressed in the iliac artery and it is possible that these globins facilitate NO₂^- reduction in hypoxia. In addition, NO₂^- intracellular disproportionation processes could be important in the generation of NO from NO₂^-.

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Sex Differences in Maternal Gestational Hypertension-Induced Sensitization of Angiotensin II Hypertension in Rat Offspring: the Protective Effect of Estrogen

Recent studies demonstrate that maternal hypertension during pregnancy sensitizes an angiotensin (ANG) II-induced increase in blood pressure (BP) in adult male offspring that was associated with upregulation of mRNA expression of several renin-angiotensin-aldosterone system (RAAS) components and NADPH oxidase in the lamina terminalis (LT) and paraventricular nucleus (PVN). The purpose of the present study was to test whether there are sex differences in the maternal hypertension-induced sensitization of ANG II hypertension, and whether sex hormones are involved in the sensitization process. Male offspring of hypertensive dams showed an enhanced hypertensive response to systemic ANG II when compared to male offspring of normotensive dams and to female offspring of either normotensive or hypertensive dams. Castration did not alter the hypertensive response to ANG II in male offspring. Intact female offspring had no upregulation of RAAS components and NADPH oxidase in the LT and PVN. Whereas, ovariectomy (OVX) upregulated mRNA expression of several RAAS components and NADPH oxidase in these nuclei and induced a greater increase in the pressor response to ANG II in female offspring of hypertensive dams compared to female offspring of normotensive dams. This enhanced increase in BP was partially attenuated by E2 replacement in the OVX offspring of hypertensive dams. The results suggest that maternal hypertension induces a sex-specific sensitization of ANG II-induced hypertension and mRNA expression of brain RAAS and NADPH oxidase in offspring. Female offspring are protected from maternal hypertension-induced sensitization of ANG II hypertension and female sex hormones are partially responsible for this protective effect.

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Central serotonin and the control of arterial blood pressure and heart rate in infant rats: influence of sleep state and sex

Sudden Infant Death Syndrome (SIDS) is associated with serotonin (5-HT) neuron abnormalities. There is evidence of autonomic dysfunction during sleep in infants eventually succumbing to SIDS, as well as cardiovascular collapse prior to death. Neonatal rodents deficient in central 5-HT display hypotension and bradycardia. We hypothesized that central 5-HT reduces cardiac vagal tone and increases sympathetic vascular tone and, given the firing pattern of 5-HT neurons, that these effects are greater in quiet sleep (QS) than in active sleep (AS). We tested these hypotheses using two week-old, male and female rat pups lacking tryptophan hydroxylase 2 (TPH2-/-) and wildtype littermates (WT). Arterial blood pressure (ABP) and HR were measured over 3 hr, during periods of QS and AS. We also gave atropine or atenolol (each 1 mg/kg i.v.), or phentolamine (5, 50 and 500 ug/kg, i.v.) to separate groups to assess the effects 5-HT deficiency on autonomic tone to the heart or sympathetic vascular tone, respectively. Compared to WT, male and female TPH2-/- pups had reduced ABP in QS, but not in AS. Atropine induced a greater HR increase in female TPH2-/- compared to female WT pups, an effect absent in male TPH2-/- pups. Both genotypes experienced the same atenolol-induced drop in HR. In males only, phentolamine induced a smaller decrease in the ABP of TPH2-/- pups compared to WT. These data suggest that central 5-HT maintains ABP in QS, and HR in both states. In males, central 5-HT facilitates sympathetic vascular tone and in females, reduces cardiac vagal drive.

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Dicarbonyl Stress and Glyoxalase Enzymatic System Regulation in Human Skeletal Muscle

Skeletal muscle insulin resistance is a hallmark of Type II Diabetes (T2DM) and may be exacerbated by protein modifications by methylglyoxal (MG), known as dicarbonyl stress. The glyoxalase enzyme system composed of glyoxalase 1/2 (GLO1/GLO2) is the natural defense against dicarbonyl stress, yet its protein expression, activity and regulation remain largely unexplored in skeletal muscle. Therefore, this study investigated dicarbonyl stress and the glyoxalase enzyme system in the skeletal muscle of subjects with T2DM (age: 56 ± 5 yrs; BMI: 32 ± 2 kg/m²) compared to lean healthy control subjects (LHC; age: 27 ± 1 yrs; BMI: 22 ± 1 kg/m²). Skeletal muscle biopsies obtained from the vastus lateralis at basal and insulin-stimulated states of the hyperinsulinemic (40 mU/m²/min) -euglycemic (5 mM) clamp were analyzed for proteins related to dicarbonyl stress and glyoxalase biology. At baseline, T2DM had increased carbonyl stress and lower GLO1 protein expression (-78.8%, p<0.05), which inversely correlated with BMI, percent body fat and HOMA-IR while positively correlating with clamp derived glucose disposal rates. T2DM also had lower NRF2 protein expression (-31.6%, p<0.05), which is a positive regulator of GLO1, while Keap1 protein expression, a negative regulator of GLO1, was elevated (207%, p<0.05). Additionally, insulin stimulation during the clamp had a differential effect on NRF2, Keap1 and MG-modified protein expression. These data suggest that dicarbonyl stress and the glyoxalase enzyme system are dysregulated in T2DM skeletal muscle and may underlie skeletal muscle insulin resistance. Whether these phenotypic differences contribute to the development of T2DM warrants further investigation.

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Activity of Muscle Sympathetic Neurons during Normotensive Pregnancy

In pathological populations, elevated sympathetic activity is associated with increased activity of individual sympathetic neurons. We used custom action potential detection software to analyze multi-unit sympathetic activity in 18 normotensive pregnant women (third trimester; 33 ± 5 weeks) and 19 non-pregnant women at rest and a subset (10 and 13 respectively) during a cold pressor challenge. Although the number of action potentials per burst, and number of active amplitude based "clusters" were not different between groups the total number of sympathetic action potentials per minute was higher in pregnant women at rest. Individual clusters were active predominately once per burst suggesting they represent single neurons. Action potentials occurred in closer succession in normotensive pregnant (inter-spike interval 36 ± 10 ms) versus non-pregnant women (50 ± 27 ms; P<0.001) at rest. Pregnant women had a lower total peripheral resistance (11.7 ± 3.0 mmHg/L/min) than non-pregnant women (15.1 ± 2.7 mmHg/L/min; P<0.001) indicating a blunted neurovascular transduction. The cold pressor reduced the number of action potentials per burst in both groups due to shortening of the R-R interval in conjunction with increased burst frequency, total neural firing per minute was unchanged. Thus, elevated sympathetic activity during normotensive pregnancy is specific to increased incidence of multi-unit bursts. This is likely due to decreased central gating of burst output as opposed to generalized increases in central drive. These data also reinforce the concept that pregnancy appears to be the only healthy state of chronic sympathetic hyperactivity that we are aware of.

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Relaxin mediated renal vasodilation in the rat is associated with falls in glomerular blood pressure

Relaxin (RLX) is a pleiotropic peptide hormone with marked renal vasodilatory actions which are physiologically important during pregnancy. RLX also has potent antifibrotic actions and is being tested therapeutically in various fibrotic diseases including chronic kidney disease (CKD). Since renal vasodilation may expose the glomerulus to increased blood pressure (P_GC), which exacerbates progression of CKD, we assessed the glomerular hemodynamic actions of RLX when administered acutely (75 min; 0.89 µg/100g body weight/hr, iv) and chronically (1.5µg/100g body weight/hr, sc). Both acute and chronic RLX produced marked renal vasodilation and increased renal plasma flow (RPF) in euvolemic, anesthetized male rats. GFR also increased with RLX but the magnitude of the rise was much less than the increase in RPF, due to concomitant falls in filtration fraction (FF). The fall in FF was the result of significant falls in glomerular blood pressure (P_GC) which occurred despite a slight rise in mean arterial blood pressure (MAP) with acute RLX, and no net change in MAP with chronic RLX. This fall in P_GC occurred because of the "in-series" arrangement of the afferent and efferent arteriolar resistance vessels (RA and RE) which can regulate P_GC independently of MAP. With both acute and chronic RLX RE relaxed to a greater extent than RA, thus producing falls in P_GC. Based on this finding, RLX has a beneficial hemodynamic impact on the kidney, which together with the antifibrotic actions suggest a strong therapeutic potential for use in CKD.

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Respiratory dysfunction following neonatal sustained hypoxia exposure during a critical window of brainstem extracellular matrix formation

The extracellular matrix (ECM) modulates brain maturation and plays a major role in regulating neuronal plasticity during critical periods of development. We examined: 1) whether there is a critical postnatal period of ECM expression in brainstem cardio-respiratory control regions; and 2) if the attenuated hypoxic ventilatory response (HVR) following neonatal sustained (5 days) hypoxia exposure (SH, 11% O₂, 24hrs/day) is associated with altered ECM formation. The nucleus tractus solitarius (nTS), dorsal motor nucleus of the vagus (DMNV), the hypoglossal motor nucleus (XII), the cuneate nucleus (CN) and area postrema (AP) were immunofluorescently processed for aggrecan and Wisteria floribunda (WFA) agglutinin, a key proteoglycan of the ECM and the perineuronal net. From postnatal age 5 days (P5), aggrecan and WFA expression increased postnatally in all regions. Aggrecan expression in the nTS, a region that integrates and receives afferent inputs from the carotid body, increased abruptly between P10-15 followed by a distinct and transient plateau between P15-20. WFA expression in the nTS exhibited an analogous transient plateau, but it occurred earlier (plateauing between P10-P15). SH exposure between this period (P11-15) attenuated the HVR (assessed at P16) and increased aggrecan (but not WFA) expression in the nTS, DMNV and AP. An intracisternal micro-injection of chondroitinase ABC (ChABC), an enzyme that digests chondroitin sulfate proteoglycans, rescued the HVR and the increased aggrecan expression. These data indicate there are important stages of ECM formation that take place in key brainstem respiratory neural control regions that appear to be associated with a heightened vulnerability to hypoxia.

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Combined Gluteus and Pudendal Thigh Flap Reconstruction of Vaginal Defects following Robotic Abdominoperineal Resection

Summary: Low-lying rectal cancers are being treated more frequently with robotic-assisted abdominoperineal resection, obviating the need for laparotomy and the ability to raise vertical rectus abdominis musculocutaneous flaps. For female patients, posterior vaginectomy often accompanies the resection. Combined pudendal thigh flaps as an extension of bilateral gluteus advancement flaps allow for posterior vaginal resurfacing with thin pliable fasciocutaneous flaps, which rest on the gluteal flap soft-tissue bulk that obliterates the pelvic dead space. For patients with advanced cancers who have had neoadjuvant chemoradiation, the pudendal skin paddle can be planned more laterally to bring in healthier medial thigh skin. The donor incisions lie within the gluteal cleft and crease and groin creases recapitulating normal perineal anatomy and aesthetics.

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Optimizing Nipple Position following Nipple-Sparing Mastectomy

Background: The best treatment for nipple malposition following nipple-sparing mastectomy is prevention. This article reviews basic elements for success in nipple-sparing mastectomy and offers an option to patients with grade 2–3 breast ptosis who strongly desire to preserve the nipple. Methods: Retrospective review identified patients undergoing nipple-sparing mastectomy and immediate reconstruction. Results: Patient selection centered on realistic goals for postoperative breast size, nipple position, and when not to save the nipple. The choice of device considered projection and nipple centralization as equal components and led to wider, lower profile devices selectively for the first stage of reconstruction. In severe grade 2–3 nipple ptosis, an inferior vertical incision or wedge excision was used to enhance nipple position postoperatively. Eighteen consecutive patients underwent 32 implant-based breast reconstructions following nipple-sparing mastectomy with the vertical incision. The average age was 45 years old, and the average body mass index was 26.7. Direct-to-implant reconstruction was performed in 25%, whereas 75% had tissue expander-implant reconstruction. Overall complications included infection (3%) and nipple necrosis (3%) leading to explant in 1 reconstruction. Conclusions: The final nipple position following nipple-sparing mastectomy can be optimized with preoperative planning. The vertical incision, combined with proper patient selection and choice of device, may increase eligibility for nipple-sparing procedures in patients with grade 2–3 ptosis who desire nipple preservation.

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Macroglossia During Awake Craniotomy: A Near Miss.

No abstract available

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The effect of phasic alertness on temporal precision

Abstract

Many previous studies have found that there is a close relationship between attention and temporal precision. As a mechanism that regulates the intensity of attention, alertness has beneficial influences on perceptual processing. However, little is known regarding whether and how phasic alertness affects temporal precision. Experiment 1 and Experiment 2 used visual and auditory warning cues in a visual temporal order judgment (TOJ) task and a simultaneity judgment (SJ) task to investigate the phasic alerting effect on temporal precision. Participants in the TOJ and SJ tasks were required to make judgments of two successive and synchronous stimuli at various stimulus onset asynchronies (SOAs). Because of dissension regarding the SJ task, Experiment 3 adopted a dual SJ and TOJ task to create a new indicator of participant performance. Although these tasks may differ in the cognitive mechanism they involve, they all produced consistently decreased just noticeable difference (JND) scores and unaltered point of subjective simultaneity (PSS). This suggests that phasic alertness could significantly improve participants' temporal precision (reduced JNDs) of visual perception, without affecting temporal accuracy (unaltered PSS). We then discuss that the alerting effect on temporal sensitivity might be attributed mainly to transient arousal rather than temporal expectancy. Furthermore, the analysis of response ratios at each SOA could distinguish a heightened temporal precision from a reduction of attentional lapses. According to the previous and present studies, phasic alertness might simultaneously benefited the early perceptual processing and late motor execution of responses.

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Representational momentum and anisotropies in nearby visual space

Abstract

The possibility of anisotropies in visual space in and near the final location of a moving target was examined. Experiments 1 and 2 presented a moving target, and after the target vanished, participants indicated the final location of the leading or trailing edge of the target. Memory for both edges was displaced forward from the actual final locations, and the magnitude of displacement was smaller for the leading edge. Experiments 3 and 4 also presented stationary objects in front of and behind the final location of the target, and participants indicated the location of the nearest or farthest edge of one of the stationary objects. Memory for the near or far edge of an object in front of the target was displaced backward, and memory for the near or far edge of an object behind the target was displaced forward; the magnitude of displacement was larger for objects in front of the target and when the edge was farther away. The findings (a) suggest representational momentum is associated with an anisotropy of visual space that extends across and outward from the moving target and (b) are consistent with previous findings regarding estimation of time-to-contact, anorthoscopic perception, and memory psychophysics.

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Phase I study of the combination of crizotinib (as a MET inhibitor) and dasatinib (as a c-SRC inhibitor) in patients with advanced cancer

Summary

Background Both MET and c-SRC are important mediators of cancer progression and there is cross talk between the two molecules. Preclinical studies have demonstrated combination of MET and c-SRC inhibitors is effective in multiple cancer types. Methods We analyzed the safety and efficacy of administering a c-SRC inhibitor (dasatinib) in combination with a MET inhibitor (crizotinib) in a two-arm concurrent phase I study. Arm A consisted of crizotinib fixed at 250 mg twice per day with escalation of dasatinib. Arm B consisted of dasatinib fixed at 140 mg daily with escalation of crizotinib. Endpoints included dose-limiting toxicities (DLTs), recommended phase II dose (RP2D), and response (RECIST 1.1). Results We enrolled 61 patients (arm A: 31, arm B: 30). The most common cancers were sarcoma (21%) and prostate cancer (16%). In Arm A, at dose level 2 (DL2), 40% (2/5) experienced DLTs. In the expanded DL1, 21% (4/19) experienced DLTs (all grade 3). In Arm B, at DL2, 50% (2/4) experienced DLTs. In the expanded DL1, 22% (4/18) experienced DLTs (all grade 3). RP2D was determined to be arm A, DL1 (250 mg crizotinib orally twice per day plus 50 mg dasatinib orally daily). Partial response (N = 1) and stable disease for ≥6 months (N = 3) were seen. Conclusions The combination of crizotinib and dasatinib is safe to administer but tolerability is limited given the high rate of adverse events. Responses and durable stable disease were limited. Further precision therapy approach using this specific combination may be difficult given the toxicity.

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Correlation between computed tomography imaging and histopathology in pleomorphic adenoma of parotid gland

The purpose of this study was to correlate the CT imaging features and histopathological findings of pleomorphic adenomas (PA), and also try to identify its clinical significance.

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Baseline asthma burden, comorbidities, and biomarkers in omalizumab-treated patients in PROSPERO

Patients included in clinical trials do not necessarily reflect the real-world population.

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Diplomacy Review Course/Exam December 1-2, 2017 in Phoenix, AZ With Dr. Rudi Ferrate, MD and Dr. Kevin Mueller, DDS

The American Sleep and Breathing Academy is an organization dedicated to enriching our members' knowledge and skill in the treatment of sleep disordered breathing. Our goal is to provide current evidence based information to our members and enable them to provide optimal treatment for their patients. The Academy offers certification to its members as a confirmation of their knowledge, skill and experience.

On December 1-2, 2017, in Phoenix, AZ the ASBA will be holding a review course and exam that is offered to Dentists who wish to attain diplomacy with the American Sleep and Breathing Academy. The review course will be taught by Board Certified ASBA instructors Dr. Kevin Mueller DMD and Dr. Rudi Martinez-Ferrate MD.

Diplomate Review/Exam

Friday–Saturday, December 1-2, 2017
Embassy Suites by Hilton Phoenix Airport
2333 East Thomas Road
Phoenix, AZ 85016 United States

Registration For The Review

Registration For The Exam

Link For The Hotel Booking With Special Rate

For questions please email info@myasba.com

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Uncommon Initial Presentation of Gastric Cancer with Bone Metastases: a Case Report

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The Effects of Exposure to Environmental Cigarette Smoke on the Vocal Folds of Rats

This study aimed to investigate histopathologically and immunohistochemically the effects of environmental smoke on the vocal folds.

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Evaluation of facial blood flow using three-dimensional scanning

The Vectra X3 3-dimensional face scanner allows us to visualise the erythema of superficial layers of skin in addition to its regular scanning functions. The aim of our study was to find out whether changes we provoked in the circulation of the skin would be registered and displayed by the face scanner. We measured the circulation in the skin of the cheeks of 20 volunteers with a face scanner, a laser Doppler device, and a skin pigmentation analyser before and after the application of a nitric oxide cream.

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Bleomycin electrosclerotherapy: new treatment to manage vascular malformations

Venous malformations are congenital anomalies of the vascular system. The injection of bleomycin (a cytotoxic, antitumour drug) into the lesion is a safe and effective treatment for low-flow (venous and lymphatic) malformations, but its use systemically has been associated with pulmonary fibrosis. Intralesional injection of bleomycin is considered to have a lower risk, but caution should be used when planning treatment, with particular regard to respiratory function. Electroporation is the temporary application of an electrical field across a tissue to increase (briefly) the permeability of the cell membrane in that tissue.

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Prescription of antibiotics: does it alter the outcome for patients who have fractures of the angle of the mandible?

We retrospectively studied 708 consecutive patients at the Queen Elizabeth Hospital, Birmingham, to find out whether one of the four antibiotic protocols in use conferred any advantage (or disadvantage) on a patient who had a fractured angle of the mandible, and there was none. However, the time from initial injury until the time of the first dose of antibiotic was important. Clinically, if patients waited more than 72hours after the injury before the first dose of antibiotic was given, they had a three times higher rate of postoperative infection than patients who were given their first dose between 24 and 72hours after the injury.

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Surgical and social implications of extraction of mandibular third molars as a separate procedure before bilateral sagittal split osteotomy

In some units, lower wisdom teeth are extracted in a separate procedure before bilateral sagittal split osteotomy (BSSO), whereas in others they are removed at the time of the osteotomy. We identified 57 patients who had BSSO at Salisbury Hospital between October 2013 and September 2015, 40 of whom had their wisdom teeth extracted at the same time. The remaining 17 did not have wisdom teeth. Patients who have these teeth extracted as a separate procedure require at least one day off work, which can result in a loss of earnings.

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A single-centre retrospective proof of concept review of salvage of infected or exposed implant breast reconstructions with explantation and one-stage free flap replacement

Implant-based breast reconstruction has relatively high complication rates. Removal of infected implants and immediate autologous reconstruction is a safe single stage procedure that preserves the native breast skin envelope.

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Effects of infraorbital nerve's anatomical course on fracture pattern of the orbital floor

In this study, details of the infraorbital nerve's (ION's) anatomical course variants were compared using computed tomography (CT) and relationships between the variants and fracture patterns in the orbital floor were investigated. Fifty-two normal individuals and 50 patients with unilateral isolated orbital floor fractures were enrolled in this study. Four measurements in normal individuals and 5 measurements in fracture patients were obtained in parasagittal sections. The anatomical variations of the ION were categorized into 3 types based on the classification by Ferences et al.

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Endoscopic anti-reflux devices (with videos)

The American Society for Gastrointestinal Endoscopy (ASGE) Technology Committee provides reviews of existing, new, or emerging endoscopic technologies that have the potential to affect the practice of GI endoscopy. Evidence-based methodology is used, with a MEDLINE literature search to identify pertinent preclinical and clinical studies on the topic and a MAUDE (Food and Drug Administration Center for Devices and Radiological Health) database search to identify the reported adverse events of a given technology.

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My Path from Hiroshima to Houston

Publication date: Available online 14 October 2017
Source:Practical Radiation Oncology
Author(s): Ritsuko Komaki




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Behavioral Animal Model of the Emotional Response to Tinnitus and Hearing Loss

Abstract

Increased prevalence of emotional distress is associated with tinnitus and hearing loss. The underlying mechanisms of the negative emotional response to tinnitus and hearing loss remain poorly understood, and it is challenging to disentangle the emotional consequences of hearing loss from those specific to tinnitus in listeners experiencing both. We addressed these questions in laboratory rats using three common rodent anxiety screening assays: elevated plus maze, open field test, and social interaction test. Open arm activity in the elevated plus maze decreased substantially after one trial in controls, indicating its limited utility for comparing pre- and post-treatment behavior. Open field exploration and social interaction behavior were consistent across multiple sessions in control animals. Individual sound-exposed and salicylate-treated rats showed a range of phenotypes in the open field, including reduced entries into the center in some subjects and reduced locomotion overall. In rats screened for tinnitus, less locomotion was associated with higher tinnitus scores. In salicylate-treated animals, locomotion was correlated with age. Sound-exposed and salicylate-treated rats also showed reduced social interaction. These results suggest that open field exploratory activity is a selective measure for identifying tinnitus distress in individual animals, whereas social interaction reflects the general effects of hearing loss. This animal model will facilitate future studies of the structural and functional changes in the brain pathways underlying emotional distress associated with hearing dysfunction, as well as development of novel interventions to ameliorate or prevent negative emotional responses.

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Desmin expression profile in reactive astrocytes in the 3-nitropropionic acid–lesioned striatum of rat: Characterization and comparison with glial fibrillary acidic protein and nestin

Publication date: Available online 18 October 2017
Source:Acta Histochemica
Author(s): Jeong-Heon Choi, Tae-Ryong Riew, Hong Lim Kim, Xuyan Jin, Mun-Yong Lee
Desmin, a muscle-specific, type-III intermediate-filament protein, is reportedly expressed in astrocytes in the central nervous system. These cells become reactive astrocytes in response to brain injuries. To elucidate whether desmin is involved in this process, we examined the spatiotemporal expression profiles of desmin and their relationship with two astroglial intermediate filaments, glial fibrillary acidic protein (GFAP) and nestin, in the striatum of rats treated with the mitochondrial toxin 3-nitropropionic acid (3-NP). Weak, constitutive immunoreactivity for desmin was observed in astrocytes generally, and in reactive astrocytes in the peri-lesional area, its expression increased in parallel with that of GFAP over 3 d post-lesion and was maintained until at least day 28. Desmin, GFAP, and nestin showed characteristic time-dependent expression patterns in reactive astrocytes forming the astroglial scar; delayed and long-lasting induction of desmin and GFAP, and rapid but transient induction of nestin. In the lesion core, desmin was expressed in two categories of perivascular cells: nestin-negative and nestin-positive. These findings show that desmin, together with GFAP and nestin, is a dynamic component of intermediate filaments in activated astroglia, which may account for the dynamic structural changes seen in these cells in response to brain injuries.



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Behavioral Animal Model of the Emotional Response to Tinnitus and Hearing Loss

Abstract

Increased prevalence of emotional distress is associated with tinnitus and hearing loss. The underlying mechanisms of the negative emotional response to tinnitus and hearing loss remain poorly understood, and it is challenging to disentangle the emotional consequences of hearing loss from those specific to tinnitus in listeners experiencing both. We addressed these questions in laboratory rats using three common rodent anxiety screening assays: elevated plus maze, open field test, and social interaction test. Open arm activity in the elevated plus maze decreased substantially after one trial in controls, indicating its limited utility for comparing pre- and post-treatment behavior. Open field exploration and social interaction behavior were consistent across multiple sessions in control animals. Individual sound-exposed and salicylate-treated rats showed a range of phenotypes in the open field, including reduced entries into the center in some subjects and reduced locomotion overall. In rats screened for tinnitus, less locomotion was associated with higher tinnitus scores. In salicylate-treated animals, locomotion was correlated with age. Sound-exposed and salicylate-treated rats also showed reduced social interaction. These results suggest that open field exploratory activity is a selective measure for identifying tinnitus distress in individual animals, whereas social interaction reflects the general effects of hearing loss. This animal model will facilitate future studies of the structural and functional changes in the brain pathways underlying emotional distress associated with hearing dysfunction, as well as development of novel interventions to ameliorate or prevent negative emotional responses.

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Puerto Rico Audiology Program Requests Help

In the aftermath of Hurricane Irma's destruction, the University of Puerto Rico Audiology Program would like to make a heartfelt request for the following items:

Tweet

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A single-centre retrospective proof of concept review of salvage of infected or exposed implant breast reconstructions with explantation and one-stage free flap replacement

Publication date: Available online 18 October 2017
Source:Journal of Plastic, Reconstructive & Aesthetic Surgery
Author(s): Russell J. Bramhall, Izaro Hernan, Paul A. Harris
IntroductionImplant-based breast reconstruction has relatively high complication rates. Removal of infected implants and immediate autologous reconstruction is a safe single stage procedure that preserves the native breast skin envelope.MethodsA single-centre retrospective proof of concept review of all salvage procedures performed for acute/chronic infected or exposed implant-based reconstructions by a single surgeon over a 6 year period.ResultsWe present 13 cases of a particularly difficult subgroup over a 6 year period that were for acute/chronic infection/extrusion. All were successfully salvaged in one procedure by implant removal and immediate free flap reconstruction with no significant complications. All patients had a change of pocket from subpectoral to subcutaneous and partial capsulectomies. 4 patients had unilateral DIEP flaps for unilateral reconstruction, 3 bi-pedicle DIEP flaps for unilateral reconstruction, 2 bilateral TUG flaps for unilateral reconstruction, 3 bilateral DIEP flaps for bilateral reconstruction and 1 patient had a unilateral DIEP and implant for unilateral reconstruction.ConclusionsThese patients are often slim with limited donor sites and pose technical challenges, often requiring double free flap reconstructions. Single stage implant removal and autologous reconstruction preserves the breast skin envelope to maximise cosmesis in a single procedure. The introduction of healthy, well vascularised tissue may also help to treat the infection.



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Effects of infraorbital nerve's anatomical course on fracture pattern of the orbital floor

Publication date: Available online 18 October 2017
Source:Journal of Plastic, Reconstructive & Aesthetic Surgery
Author(s): Junhyung kim, Sang Woo Park, Jaehoon Choi, Woonhyeok Jeong, Ryeolwoo kim
In this study, details of the infraorbital nerve's (ION's) anatomical course variants were compared using computed tomography (CT) and relationships between the variants and fracture patterns in the orbital floor were investigated. Fifty-two normal individuals and 50 patients with unilateral isolated orbital floor fractures were enrolled in this study. Four measurements in normal individuals and 5 measurements in fracture patients were obtained in parasagittal sections. The anatomical variations of the ION were categorized into 3 types based on the classification by Ferences et al. Among the normal individuals, 42 orbits were classified as type 1 ION, 48 orbits as type 2 and 14 orbits as type 3. The distance from the inferior orbital rim to the upper border of the inferior orbital foramen and the length of descension portion of the ION in type 1 ION were significantly shorter than in type 2 and type 3 IONs. In patients with orbital floor fractures, the distance from the inferior orbital rim to the upper border of the inferior orbital foramen was positively correlated with herniation level of bone and soft tissue. The ION had 3 anatomical variants based on the degree of descension in the anterior portion of the orbit. When fracture of the orbital floor occurs in patients with type 1 ION, inferior displacement of the fractured orbital bone and orbital soft tissue may be less severe than in patients with other ION types.



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Issue Information

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Development and evaluation of novel biodegradable chitosan based metformin intrapocket dental film for the management of periodontitis and alveolar bone loss in a rat model

Publication date: January 2018
Source:Archives of Oral Biology, Volume 85
Author(s): Deepak Kumar Khajuria, Omprakash Nandikamba Patil, David Karasik, Rema Razdan
ObjectiveThe aim of this study was to develop a chitosan-metformin based intrapocket dental film (CMIDF) for applications in the treatment of periodontitis and alveolar bone loss in an rat model of periodontitis.DesignCMIDF inserts were fabricated by the solvent casting technique. The fabricated inserts were evaluated for physical characteristics such as folding endurance, surface pH, mucoadhesive strength, metformin content uniformity, and release. X-ray diffraction analysis indicates no crystallinity of metformin in presence of chitosan which confirmed successful entrapment of metformin into the CMIDF. Fourier-transform infrared spectroscopy revealed stability of CMIDF and compatibility between metformin and chitosan. Periodontitis was induced by a combination of Porphyromonas gingivalis- lipopolysaccharide injections in combinations with ligatures around the mandibular first molar. We divided rats into 5 groups (8 rats/group): healthy, untreated periodontitis; periodontitis plus CMIDF-A (1.99±0.09mg metformin; total mass-4.01±0.05mg), periodontitis plus CMIDF-B (2.07±0.06mg metformin; total mass-7.56±0.09mg), and periodontitis plus chitosan film (7.61±0.08mg). After four weeks, mandibles were extracted to evaluate alveolar bone loss by micro-computerized tomography and histological techniques.ResultsAlveolar bone was intact in the healthy group. Local administration of CMIDF resulted in significant improvements in the alveolar bone properties when compared to the untreated periodontitis group. The study reported here demonstrates that novel CMIDF showed good antibacterial activity and effectively reduced alveolar bone destruction in a rat model of experimental periodontitis.ConclusionsNovel CMIDF showed good antibacterial activity and improved alveolar bone properties in a rat model.

Graphical abstract

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Individual Alpha Peak Frequency Predicts 10 Hz Flicker Effects on Selective Attention

Rhythmic visual stimulation ("flicker") is primarily used to "tag" processing of low-level visual and high-level cognitive phenomena. However, preliminary evidence suggests that flicker may also entrain endogenous brain oscillations, thereby modulating cognitive processes supported by those brain rhythms. Here we tested the interaction between 10 Hz flicker and endogenous alpha-band (~10 Hz) oscillations during a selective visuospatial attention task. We recorded EEG from human participants (both genders) while they performed a modified Eriksen flanker task in which distractors and targets flickered within (10 Hz) or outside (7.5 or 15 Hz) the alpha band. By using a combination of EEG source separation, time-frequency, and single-trial linear mixed-effects modeling, we demonstrate that 10 Hz flicker interfered with stimulus processing more on incongruent than congruent trials (high vs low selective attention demands). Crucially, the effect of 10 Hz flicker on task performance was predicted by the distance between 10 Hz and individual alpha peak frequency (estimated during the task). Finally, the flicker effect on task performance was more strongly predicted by EEG flicker responses during stimulus processing than during preparation for the upcoming stimulus, suggesting that 10 Hz flicker interfered more with reactive than proactive selective attention. These findings are consistent with our hypothesis that visual flicker entrained endogenous alpha-band networks, which in turn impaired task performance. Our findings also provide novel evidence for frequency-dependent exogenous modulation of cognition that is determined by the correspondence between the exogenous flicker frequency and the endogenous brain rhythms.

SIGNIFICANCE STATEMENT Here we provide novel evidence that the interaction between exogenous rhythmic visual stimulation and endogenous brain rhythms can have frequency-specific behavioral effects. We show that alpha-band (10 Hz) flicker impairs stimulus processing in a selective attention task when the stimulus flicker rate matches individual alpha peak frequency. The effect of sensory flicker on task performance was stronger when selective attention demands were high, and was stronger during stimulus processing and response selection compared with the prestimulus anticipatory period. These findings provide novel evidence that frequency-specific sensory flicker affects online attentional processing, and also demonstrate that the correspondence between exogenous and endogenous rhythms is an overlooked prerequisite when testing for frequency-specific cognitive effects of flicker.

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