Plasmacytoid dendritic cells drive acute exacerbations of asthma

Publication date: Available online 17 October 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Aikaterini-Dimitra Chairakaki, Maria-Ioanna Saridaki, Katerina Pyrillou, Marios-Angelos Mouratis, Ourania Koltsida, Ross P. Walton, Nathan W. Bartlett, Athanasios Stavropoulos, Louis Boon, Nikoletta Rovina, Nikolaos G. Papadopoulos, Sebastian L. Johnston, Evangelos Andreakos
BackgroundAlthough acute exacerbations, mostly triggered by viruses, account for the majority of hospitalizations in asthma, there is still very little known about the pathophysiological mechanisms involved. Plasmacytoid DCs (pDCs), prominent cells of antiviral immunity, exhibit pro-inflammatory or tolerogenic functions depending on the context, yet their involvement in asthma exacerbations remains unexplored.ObjectivesWe sought to investigate the role of pDCs in allergic airway inflammation and acute exacerbations of asthma.MethodsAnimal models of allergic airway disease (AAD) and virus-induced AAD exacerbations were employed to dissect pDC function in vivo and unwind potential mechanisms involved. Sputum from asthma patients with stable disease or acute exacerbations was further studied to determine pDC presence and correlation with inflammation.Results: pDCs were key mediators of the immuno-inflammatory cascade that drives asthma exacerbations. In animal models of AAD and RV-induced AAD exacerbations, pDCs were recruited to the lung during inflammation and migrated to the draining lymph nodes to boost Th2-mediated effector responses. Accordingly, pDC depletion post-allergen challenge or during RV infection abrogated exacerbation of inflammation and disease. Central to this process was IL-25, induced by allergen challenge or RV infection that conditioned pDCs for pro-inflammatory function. Consistently, in asthma patients pDCs were markedly increased during exacerbations, and correlated with the severity of inflammation and the risk for asthmatic attacks.ConclusionsOur studies uncover a previously unsuspected role of pDCs in asthma exacerbations with potential diagnostic and prognostic implications. They also propose the therapeutic targeting of pDCs and IL-25 for the treatment of acute asthma.

Graphical abstract

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Cholecystokinin receptor antagonist alters pancreatic cancer microenvironment and increases efficacy of immune checkpoint antibody therapy in mice

Abstract

Advanced pancreatic ductal adenocarcinoma (PDAC) has typically been resistant to chemotherapy and immunotherapy; therefore, novel strategies are needed to enhance therapeutic response. Cholecystokinin (CCK) has been shown to stimulate growth of pancreatic cancer. CCK receptors (CCKRs) are present on pancreatic cancer cells, fibroblasts, and lymphocytes. We hypothesized that CCKR blockade would improve response to immune checkpoint antibodies by promoting influx of tumor-infiltrating lymphocytes (TILs) and reducing fibrosis. We examined the effects of CCKR antagonists or immune checkpoint blockade antibodies alone or in combination in murine models of PDAC. Monotherapy with CCKR blockade significantly decreased tumor size and metastases in SCID mice with orthotopic PDAC, and in C57BL/6 mice, it reduced fibrosis and induced the influx of TILs. Immune-competent mice bearing syngeneic pancreatic cancer (Panc02 and mT3-2D) that were treated with the combination of CCK receptor antagonists and immune checkpoint blockade antibodies survived significantly longer with smaller tumors. Tumor immunohistochemical staining and flow cytometry demonstrated that the tumors of mice treated with the combination regimen had a significant reduction in Foxp3+ T-regulatory cells and an increase in CD4+ and CD8+ lymphocytes. Masson's trichrome stain analysis revealed 50% less fibrosis in the tumors of mice treated with CCKR antagonist compared to controls and compared to checkpoint antibody therapy. CCKR antagonists given with immune checkpoint antibody therapy represent a novel approach for improving survival of PDAC. The mechanism by which this combination therapy improves the survival of PDAC may be related to the decreased fibrosis and immune cells of the tumor microenvironment.

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Glial cells are functionally impaired in juvenile neuronal ceroid lipofuscinosis and detrimental to neurons

The neuronal ceroid lipofuscinoses (NCLs or Batten disease) are a group of inherited, fatal neurodegenerative disorders of childhood. In these disorders, glial (microglial and astrocyte) activation typically o...

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Targeting the ubiquitin-proteasome system for cancer treatment: discovering novel inhibitors from nature and drug repurposing

Abstract

In the past 15 years, the proteasome has been validated as an anti-cancer drug target and 20S proteasome inhibitors (such as bortezomib and carfilzomib) have been approved by the FDA for the treatment of multiple myeloma and some other liquid tumors. However, there are shortcomings of clinical proteasome inhibitors, including severe toxicity, drug resistance, and no effect in solid tumors. At the same time, extensive research has been conducted in the areas of natural compounds and old drug repositioning towards the goal of discovering effective, economical, low toxicity proteasome-inhibitory anti-cancer drugs. A variety of dietary polyphenols, medicinal molecules, metallic complexes, and metal-binding compounds have been found to be able to selectively inhibit tumor cellular proteasomes and induce apoptotic cell death in vitro and in vivo, supporting the clinical success of specific 20S proteasome inhibitors bortezomib and carfilzomib. Therefore, the discovery of natural proteasome inhibitors and researching old drugs with proteasome-inhibitory properties may provide an alternative strategy for improving the current status of cancer treatment and even prevention.

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Evidence-based interventions of dichotic listening training, compensatory strategies and combined therapies in managing pupils with auditory processing disorders

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Brain MRI in a patient with classical galactosemia: acute event of unilateral hemispheric cerebral edema

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Time-to-event analysis of surgically treated posthemorrhagic hydrocephalus in preterm infants: a single-institution retrospective study

Abstract

Purpose

The purpose of this study is to report time points relevant to the neurosurgical management of posthemorrhagic hydrocephalus (PHH).

Methods

Data were collected retrospectively on 104 preterm infants with intraventricular hemorrhage (IVH) who received neurosurgical intervention for PHH at St. Louis Children's Hospital from 1994 to 2016. Kaplan-Meier curves were constructed for various endpoints.

Results

IVH grade on head ultrasound obtained through routine clinical care was II, III, and IV in 5 (4.8%), 33 (31.7%), and 66 (63.5%) of the patients, respectively. Neither IVH size nor location appeared to affect development of PHH. Days from birth to IVH, ventriculomegaly, temporizing neurosurgical procedure (TNP), and permanent neurosurgical intervention were 2.0 (95% CI 1.7–2.3), 3.0 (2.5–3.5), 24.0 (22.2–25.8), and 101.0 (90.4–111.6), respectively. Grades III and IV IVH did not differ in age at IVH diagnosis (Χ ² (1 d.f.) = 1.32, p = 0.25), ventriculomegaly (Χ ² = 0.73, p = 0.40), TNP (Χ ² = 0.61, p = 0.43), or permanent intervention (Χ ² = 2.48, p = 0.17). Ventricular reservoirs and ventriculosubgaleal shunts were used in 71 (68.3%) and 30 (28.8%), respectively. Eighty (76.9%) of the patients ultimately received a VPS. Five (4.8%) underwent a primary endoscopic third ventriculostomy (ETV), and two (1.9%) had ETV for a revision procedure. Four of the seven ETVs had choroid plexus cauterization.

Conclusions

Although most infants who develop IVH and ventriculomegaly will do so within a few days of birth, at-risk infants should be observed for at least 4 weeks with serial head ultrasounds to monitor for PHH requiring surgery.

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Giant occipital aneurysmal bone cyst caused to hydrocephalus in a child

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Erratum to: Notomelia and related neural tube defects in a baby born in Niger: case report and literature review

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Successful multimodal treatment of a gigantic choroid plexus carcinoma (CPC) in an 8-year-old girl

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LIN28A, a sensitive immunohistochemical marker for Embryonal Tumor with Multilayered Rosettes (ETMR), is also positive in a subset of Atypical Teratoid/Rhabdoid Tumor (AT/RT)

Abstract

Introduction

CNS embryonal tumors comprise a group of highly malignant neoplasms with a wide spectrum of histomorphological entities that includes Medulloblastoma (MB), Atypical Teratoid/Rhabdoid Tumor (AT/RT), Neuroblastoma (NB), Ganglioneuroblastoma (GNB), Embryonal Tumor with Multilayered Rosettes (ETMR), and the embryonal tumor—Not Otherwise Specified (NOS). The entity ETMR includes previously described histopathologic patterns—Embryonal Tumor with Abundant Neuropil and True Rosettes (ETANTR), Ependymoblastoma (EBL), and Medulloepithelioma (MEPL). Based on the histopathological similarities (multilayered rosettes) among ETANTR, EBL, and MEPL, as well as uniform clinical behavior and common molecular genetic characteristics, the WHO revision has created a new entity, "ETMR." Immunoreactivity of LIN28A has been identified as a sensitive tool for the diagnosis of this entity. Since there is a paucity of literature regarding immunoreactivity of LIN28A across all embryonal CNS tumors, the present study was undertaken.

Materials and methods

During the 5-year study period (2012 to 2016), all the embryonal tumors (MB, AT/RT, other embryonal tumors—ETANTR, MEPL, PNET) that had been earlier diagnosed in the department of neuropathology (cases operated in our institute as well as received as referral) were reviewed. The archived Hematoxylin and Eosin (H&E) and the available immunohistochemistry (IHC) sections were studied. Further, for the other embryonal tumors where the paraffin blocks were available, an extended panel of IHC was performed for confirming the diagnosis of embryonal tumor and only confirmed cases were included in the study. The demographic details of the study cohort were noted. IHC for LIN28A was performed on conventional sections.

Results

A total of 396 cases of embryonal tumors including 302 MB, 72 AT/RT, and 22 other embryonal tumors were diagnosed during the study period. Among these, 80 MB, 35 AT/RT, 4 ETANTR, 1 MEPL, 4 NB, 2 GNB, and 1 CNS embryonal tumor-NOS (total—127) were included for the study. LIN28A immunoreactivity was absent in all MB, GNB, NB, and CNS embryonal tumors-NOS whereas all cases of ETMR (4 ETANTR, 1 MEPL) and 8/35 (23%) of AT/RT showed immunopositivity for LIN28A, which was patchy and distinct in most of the cases of ETMR.

Conclusion

Our study reiterates that LIN28A is a sensitive IHC marker for the diagnosis of ETMR. We also show that among CNS embryonal tumors, LIN28A is not specific to ETMRs and such immunoreactivity can also be seen in a proportion of AT/RTs.

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Letter to the Editor: Presentation of extrapontine myelinolysis associated with hypernatremia in an infant: a case report

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Diagnostic Accuracy of Nasal Endoscopy as Compared to Computed Tomography in Chronic Rhinosinusitis

Abstract

The study was done with the aims to evaluate the accuracy of nasal endoscopy as compared to computed tomography (CT) in diagnosing chronic rhinosinusitis (CRS) and to evaluate the correlation between Endoscopy Score and CT Score. It was a cross sectional study. Every consecutive, symptomatic patient of CRS who fulfilled the criteria of American Academy of Otolaryngology—Head and Neck Surgery Task Force were included in the study. Rigid diagnostic nasal endoscopy (DNE) was done and Lund-Kennedy scoring system was used. Plain CT of paranasal sinuses was done on the same day and severity was assessed using Lund-Mackay scoring system. Results were analysed considering CT as a gold standard. Out of 54 study patients, 45 (83.33%) had abnormal endoscopic examination while 50 (92.59%) were showing positive CT scan. Sensitivity and specificity of DNE against CT scan were 94% (95% CI 81.43–98.33%) and 75% (95% CI 42–99.24%), respectively. The positive predictive value was 98% and negative predictive value was 67%. Correlation between Lund-Mackay overall CT and Lund-Kennedy Endoscopy Score was high [Pearson's correlation coefficient (r) = 0.881, p value < 0.0001]. The conclusion was drawn that, endoscopy is valuable in individuals with symptoms consistent with CRS and can be used to confirm the diagnosis and to know the severity of the disease. CT scan can be advised in those with high clinical suspicion of CRS but negative endoscopy and in those having persistent symptoms after optimum medical management requiring Functional Endoscopic Sinus Surgery.

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Female gonadal shielding with automatic exposure control increases radiation risks

Abstract

Background

Gonadal shielding remains common, but current estimates of gonadal radiation risk are lower than estimated risks to colon and stomach. A female gonadal shield may attenuate active automatic exposure control (AEC) sensors, resulting in increased dose to colon and stomach as well as to ovaries outside the shielded area.

Objective

We assess changes in dose–area product (DAP) and absorbed organ dose when female gonadal shielding is used with AEC for pelvis radiography.

Materials and methods

We imaged adult and 5-year-old equivalent dosimetry phantoms using pelvis radiograph technique with AEC in the presence and absence of a female gonadal shield. We recorded DAP and mAs and measured organ absorbed dose at six internal sites using film dosimetry.

Results

Female gonadal shielding with AEC increased DAP 63% for the 5-year-old phantom and 147% for the adult phantom. Absorbed organ dose at unshielded locations of colon, stomach and ovaries increased 21–51% in the 5-year-old phantom and 17–100% in the adult phantom. Absorbed organ dose sampled under the shield decreased 67% in the 5-year-old phantom and 16% in the adult phantom.

Conclusion

Female gonadal shielding combined with AEC during pelvic radiography increases absorbed dose to organs with greater radiation sensitivity and to unshielded ovaries. Difficulty in proper use of gonadal shields has been well described, and use of female gonadal shielding may be inadvisable given the risks of increasing radiation.

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Correction to: Contribution of the MRPS22 variant and a Down mosaic to the phenotype

Abstract

In the original publication of the article, the title was incorrectly written as "The cerebellum is a common site of affection in Leigh syndrome." The correct title is "Contribution of the MRPS22 variant and a Down mosaic to the phenotype."

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Proline dehydrogenase gene (PRODH) polymorphisms and schizophrenia susceptibility: a meta-analysis

Abstract

Previous studies have been conducted to explore the association between proline dehydrogenase gene (PRODH) polymorphisms and schizophrenia (SZ) susceptibility, but providing the controversial results. Here we performed this meta-analysis to determine whether PRODH variants were associated with SZ risk. Relevant studies were screened by retrieving online database PubMed, Web of Science, Embase, China National Knowledge Infrastructure (CNKI) and SZGene from inception to December 2016. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated based on genotype data or allele frequency to evaluate the strength of this association. For rs372055, eleven studies with 3398 SZ patients and 3171 controls were included and the results indicated that people carrying the T allele was not associated with SZ risk in allele frequency model (C vs T, OR = 1.12, 95%CI = 0.96–1.32). However, results from subgroup analysis showed a significant relationship between rs372055 and SZ risk in dominant genetic model (CC + CT vs TT, OR = 1.26, 95% CI = 1.05–1.50) and heterogeneous model (CT vs TT, OR = 1.26, 95% CI = 1.05–1.52) in Asian, but not in Caucasian. For polymorphisms rs383964, rs450046, rs385440 and rs2870983, no associations were found between these polymorphisms and SZ susceptibility in allele frequency. This meta-analysis suggests that rs372055 (C/T) polymorphism in PRODH gene is associated with increased SZ risk only in Asian.

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Issue Information

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Dynamic Risk Stratification in Stage I Papillary Thyroid Cancer Patients Younger Than 45 Years of Age

Thyroid , Vol. 0, No. 0.


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Rebuttal to Smith and Janssen

Thyroid , Vol. 0, No. 0.


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Risk Factors for Mild Traumatic Brain Injury and Subsequent Post-Traumatic Stress Disorder and Mental Health Disorders among United States Army Soldiers

Journal of Neurotrauma , Vol. 0, No. 0.


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Extensive nail changes in a toddler with multisystemic Langerhans cell histiocytosis

Abstract

Langerhans cell histiocytosis (LCH) is a multisystem disorder involving various organs. Nail changes in LCH are extremely rare. We present this case report of extensive nail changes in an 18-month-old child with multisystem LCH.

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Methotrexate treatment in a case of juvenile pityriasis rubra pilaris

Abstract

An 8-year-old boy who was initially diagnosed with plaque psoriasis failed management with topical therapies and skin biopsy confirmed the suspected diagnosis of juvenile pityriasis rubra pilaris (PRP). Pityriasis rubra pilaris is a rare inflammatory disorder of the skin characterized by follicular keratotic papules coalescing into plaques, along with palmoplantar keratoderma. Treatment modalities include topical and systemic therapies, although previous studies have not shown much benefit with methotrexate in children. We present a case in which methotrexate led to significant improvement of the skin findings in a child with type IV juvenile pityriasis rubra pilaris.

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Risk Factors for Mild Traumatic Brain Injury and Subsequent Post-Traumatic Stress Disorder and Mental Health Disorders among United States Army Soldiers

Journal of Neurotrauma , Vol. 0, No. 0.


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Desmoplastic Small Round Cell Tumor Presenting as an Ocular Mass: Unusual Localization and Remarkable Surgical Approach

Abstract

Desmoplastic small round cell tumor (DSRCT) is a rare tumor that was first described by Gerald and Rosai in 1989 as a mesenchymal entity. This tumor has a unique translocation t (11:22) (p:13, q:12) resulting in EWS/WT1 gene fusion that is diagnostic for DSCRT. The overall prognosis for desmoplastic small round cell tumor remains extremely poor, with reported rates of death as high as 90%. Although the majority of patients undergo chemotherapy following surgery, the prognosis has been shown to be independent of whether the surgical process preceded or followed chemotherapy. In this review, we provide insights for the management of DSCRT that requires aggressive multimodality therapy.

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Renal cell -like carcinoma of the nasal cavity: a case report and review of the literature

Sinonasal renal cell-like carcinoma (SRCLC) is an extremely rare low malignant tumor arising in the sinonasal tract, with histological mimicry of renal cell carcinoma.

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SOCS1 gene therapy improves radiosensitivity and enhances irradiation-induced DNA damage in esophageal squamous cell carcinoma

STAT3 has been implicated recently in radioresistance in cancer. In this study, we investigated the association between STAT3 and radioresistance in esophageal squamous cell carcinoma (ESCC). Strong expression of activated phospho-STAT3 (p-STAT3) was observed in 16/22 ESCC patients with preoperative chemoradiotherapy (CRT), compared to 9/24 patients with surgery alone, where the prognosis of those with CRT was poor. Expression of p-STAT3 and the anti-apoptotic proteins Mcl-1 and survivin was strongly induced in ESCC cells by irradiation. Ectopic STAT3 expression increased radioresistance, whereas expression of the STAT3 negative regulator SOCS1 via an adenoviral vector improved radioresponse. Inhibiting the STAT3-Mcl-1 axis by SOCS1 enhanced DNA damage after irradition and induced apoptosis. Combining SOCS1 with radiotherapy enhanced antitumor responses in a murine xenograft model compared to the individual therapies. Tumor repopulation occurred transiently after treatment by irradiation but not the combination SOCS1/radiotherapy. Tumors subjected to this combination expressed high levels of γ-H2AX and low levels of Ki-67, which was maintained after cessation of treatment. Overall, we demonstrated that inhibiting the STAT3-Mcl-1 signaling axis by ectopic SOCS1 improved radiosensitivity by inducing apoptosis and enhancing DNA damage after radiotherapy, offering a mechanistic rationale for a new ESCC treatment.

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Restoration of natural killer cell anti-metastatic activity by IL-12 and checkpoint blockade

Immune checkpoint therapies target tumor antigen-specific T cells, but less is known about their effects on natural killer (NK) cells, which help control metastasis. In studying the development of lung metastases, we found that NK cells lose their cytotoxic capacity and acquire a molecular signature defined by the expression of co-inhibitory receptors. In an effort to overcome this suppressive mechanism, we evaluated NK cell responses to the immunostimulatory cytokine IL-12. Exposure to IL-12 rescued the cytotoxicity of NK cells but also led to the emergence of an immature NK cell population which expressed high levels of the co-inhibitory molecules PD-1, Lag-3 and TIGIT, thereby limiting NK cell-mediated control of pulmonary metastases. Notably, checkpoint blockade therapy synergized with IL-12 to fully enable tumor control by NK cells, demonstrating that checkpoint blockers are not only applicable to enhance T cell-mediated immunotherapy, but also to restore the tumor-suppressive capacity of NK cells.

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Limitations of high throughput methods for miRNA expression profiles in non-functioning pituitary adenomas

Abstract

Microarray, RT-qPCR based arrays and next-generation-sequencing (NGS) are available high-throughput methods for miRNA profiling (miRNome). Analytical and biological performance of these methods were tested in identification of biologically relevant miRNAs in non-functioning pituitary adenomas (NFPA). miRNome of 4 normal pituitary (NP) and 8 NFPA samples was determined by these platforms and expression of 21 individual miRNAs was measured on 30 (20 NFPA and 10 NP) independent samples. Complex bioinformatics was used. 132 and 137 miRNAs were detected by all three platforms in NP and NFPA, respectively, of which 25 were differentially expressed (fold change > 2). The strongest correlation was observed between microarray and TaqMan-array, while the data obtained by NGS were the most discordant despite of various bioinformatics settings. As a technical validation we measured the expression of 21 selected miRNAs by individual RT-qPCR and we were able to validate 35.1%, 76.2% and 71.4% of the miRNAs revealed by SOLiD, TLDA and microarray result, respectively. We performed biological validation using an extended number of samples (20 NFPAs and 8 NPs). Technical and biological validation showed high correlation (p < 0.001; R = 0.96). Pathway and network analysis revealed several common pathways but no pathway showed the same activation score. Using the 25 platform-independent miRNAs developmental pathways were the top functional categories relevant for NFPA genesis. The difference among high-throughput platforms is of great importance and selection of screening method can influence experimental results. Validation by another platform is essential in order to avoid or to minimalize the platform specific errors.

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An Unusual Progression of Signet-Ring Cell Carcinoma of the Appendix in a Caucasian Woman

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Multi-site lymphatic venous anastomosis using echography to detect suitable subcutaneous vein in severe lymphedema patients

The method of lymphatic venous anastomosis (LVA), including its indications or pre-operative examinations, has not been established. The purpose of this study is to reveal the possible application of pre-operative echography in surgical LVA outcome.

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Three-stage folded forehead flap for nasal reconstruction: objective and subjective measurements of aesthetic and functional outcomes.

This three-stage folded forehead flap (FFF) proved to be a simple and readily available method of lining replacement. To date, no clinical trial has evaluated the outcomes of the FFF the nose shape and function.

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Removable rigid dressings for postoperative management of transtibial amputations: a review of published evidence

Forty years of clinical experience and peer reviewed research studies support the use of non-weight bearing removable rigid dressings (RRD) as an effective means of post-operative management of transtibial amputations. We reviewed the published medical evidence regarding the use of RRDs as a postoperative management strategy, culminating in an evidence-based practice recommendation. Published peer reviewed literature on the topic was searched and classified by level of evidence based on the research design utilizing the scale recommended by the PM&R Journal (level I through V).1 The search uncovered a total of 15 articles, including 5 level I randomized controlled trials (RCT), 6 level III retrospective matched controlled trials, and 4 level V case reports.

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Impact of Critical Illness Polyneuromyopathy in Rehabilitation: A Prospective Observational Study

Critical illness polyneuromyopathy (CIPNM) is increasingly recognized as a source of disability in patients requiring intensive care unit (ICU) admission. The prevalence and impact of CIPNM on patients in the rehabilitation setting has not been established.

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Kidney Transplantation and the Impact on Health-Related Quality of Life in Frail Patients.

No abstract available

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Breast Reduction: Decreasing Complications and Improving Long-Term Aesthetic Results with Parenchymal Sutures

Background: The inverted T/keyhole pattern is commonly used for large breast reductions. This technique relies on the breast skin to retain the shape. With the passage of time "fallout" (pseudoptosis) occurs impairing the cosmetic result. A technique is described that uses parenchymal sutures and inframammary fold (IMF) reinforcement sutures to maintain the intraoperative shape. Methods: A retrospective study of 25 consecutive patients (50 breasts) where the IMF was reinforced and parenchymal sutures were inserted. The patients were followed up and the nipple to notch and nipple to IMF distance was measured and compared with that marked preoperatively and set intraoperatively. Complications, especially T junction breakdown, were also recorded. Results: The mean age was 38 years (range, 16–62 years) with a mean follow-up of 12 months. The mean body mass index was 31 (range, 22–41). The mean mass of tissue excised was 925 g (range, 340–1,800 g) per side. The distance from the suprasternal notch to the nipple remained unchanged. The distance from the nipple to the IMF remained the same as that marked preoperatively except in 3 patients who developed pseudoptosis. Only 3 patients had wound dehiscence. Conclusion: Parenchymal and superficial fascial system sutures combined with IMF reinforcement contributes to maintaining the aesthetic result and decreasing complications, in weight stable patients.

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Extraction of mandibular third molars: proposal of a new scale of difficulty

We evaluated the accuracy of a new scale of surgical difficulty for the extraction of impacted mandibular third molars, which includes consideration of previously underestimated variables. Two hundred patients with impacted third molars were enrolled, and a preoperative clinical and radiographic assessment of difficulty was made by an oral surgeon using the new index. Five oral surgeons with similar degrees of experience then evaluated the surgical difficulty during operation. The kappa test and weighted kappa were used to evaluate the level of agreement between the preoperative and postoperative evaluations.

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Cognition and Cancer: Conceptual and Methodological Issues and Future Directions

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Understanding acceptability of and engagement with web-based interventions aiming to improve quality of life in cancer survivors- a synthesis of current research

Abstract

Purpose

This review sought to summarize existing knowledge in order to inform the development of an online intervention that aims to improve quality of life after cancer treatment.

Methods

To inform our intervention, we searched for studies relating to web-based interventions designed to improve QoL in adults who have completed primary treatment for breast, prostate and colorectal cancer (as these are three of the most common cancers and impact a large number of cancer survivors). We included a variety of study designs (qualitative research, feasibility/pilot trials, randomised trials, and process evaluations) and extracted all available information regarding intervention characteristics, experiences, and outcomes. Data were synthesised as textual (qualitative) data and analysed using thematic analysis.

Results

Fifty-seven full text articles were assessed for eligibility and 16 papers describing nine interventions were analysed. Our findings suggest that cancer survivors value interventions that offer content specific to their changing needs and are delivered at the right stage of the cancer trajectory. Social networking features do not always provide added benefit, and behaviour change techniques need to be implemented carefully to avoid potential negative consequences for some users.

Conclusions

Future work should aim to identify appropriate strategies for promoting health behaviour change, as well as the optimal stage of cancer survivorship to facilitate intervention delivery.

Clinical Implications

The development of web-based interventions for cancer survivors requires further exploration to better understand how interventions can be carefully designed to match this group's unique needs and capabilities. User involvement during development may help to ensure that interventions are accessible, perceived as useful, and appropriate for challenges faced at different stages of the cancer survivorship trajectory.

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Trastuzumab Use, on Its Own, Should Not Delay Post-surgical Breast Reconstruction

Breast reconstruction after cancer surgery doesn't need to be delayed if the patient is taking trastuzumab, new research suggests.
Reuters Health Information

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Pediatric Glial Heterotopia in the Medial Canthus.

Glial heterotopias are rare, benign, congenital, midline, and nonteratomatous extracranial glial tissue. They may be confused as encephalocele or dermoid cysts and are mostly present in the nose. An 8-month-old African female child presented with a slow growing paranasal mass. The mass had been present at the left upper medial canthus since birth and had slowly and progressively enlarged. There was no communication between the mass and the cranial cavity during the operational procedure. The mass was immunohistochemically positive for S-100 protein as well as for glial fibrillary acidic protein, but negative for proliferating cell nuclear antigen. This suggested that the mass was composed of benign glial tissues with many astrocytes. The purpose of this report is to demonstrate the first patient with pediatric glial heterotopic tissue in the medial canthus and to report the clinical importance of its immunohistochemical findings. (C) 2017 by Mutaz B. Habal, MD.

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Postoperative Respiratory Complications After Cleft Palate Closure in Patients With Pierre Robin Sequence: Operative Considerations.

Background: In cleft palate surgery, there is currently no consensus on the management of patients with Pierre Robin Sequence (PRS). The authors aimed to evaluate the treatment strategy of cleft palate in our centers, with emphasis on patients with PRS, as the authors noted some patients with severe respiratory distress. Moreover, the authors aimed to investigate the prevalence of postoperative respiratory complications, using a modified-Furlow palatoplasty in combination with intravelar veloplasty in both patients with PRS and patients with non-PRS. Methods: The authors retrospectively identified all consecutive patients, both PRS and non-PRS, who underwent palate repair between January 1, 2012 and December 15, 2014 at 2 cooperating cleft centers (Bruges, Belgium; Budapest, Hungary). The treatment modality was uniform and performed by the same 2 surgeons. Results: In 92 consecutive patients, 4 patients experienced respiratory distress after palate repair. The female-to-male ratio was 1:1. The mean age at surgery in these 4 patients was 15 months (range 13-19 months). Fifteen percent (2/13) of patients with PRS experienced respiratory distress in comparison to 3% (2/79) of non-PRS ([chi]2 = 4.43; P = 0.035). Conclusions: This is the first report of postoperative respiratory difficulties, while using a modified-Furlow palatoplasty in combination with intravelar veloplasty. In the present author's experience, the authors suggest to perform a 2-stage closure of the cleft palate in patients with PRS and to do so at a later age, when the palatal tissues and airway structures are more mature. Moreover, patients with PRS should be monitored closely, as they can present with different degrees of respiratory distress after palatoplasty. (C) 2017 by Mutaz B. Habal, MD.

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Statistical Analysis of Influences on the Psychosocial Status of Children With Hemangiomas and Their Families.

The psychologic stress on the child and family, which arise from hemangiomas, the most common neoplasm of childhood, cannot be overestimated. This study determined the preoperative and postoperative psychosocial status and variation among Oriental children with hemangiomas and their families by questionnaire. Thirty patients who underwent surgery for hemangiomas were assessed for preoperative and postoperative psychosocial status by questionnaire. The distribution of the total mean score and variation between the preoperative and postoperative status was estimated. Based on these results, the significance was statistically analyzed according to variable determinants. This study showed that hemangiomas have harmful effects on psychosocial status of patients and families. After corrective surgery, an improvement in psychosocial status was noted with respect to the self-esteem category or categories related to social activity, and in the following variables, women, face, and dissatisfaction with appearance. When the authors care for patients with hemangiomas and their families, the psychosocial health must be presumed to be at particular risk. Earlier surgical interventions with esthetic concerns have permitted the patient and family the opportunity to reduce the psychologic impact that the hemangioma may otherwise have. (C) 2017 by Mutaz B. Habal, MD.

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Mandibular Condyle Reconstruction With Fibula Free-Tissue Transfer: The Role of the Masseter Muscle.

Background: Free fibula flap is an option for primary restoration after disarticulation mandibular resection, though literature on technique refinements is scarce. The authors hypothesized that inset of the masseter, the key mandibular elevator muscle, at the reconstructed mandible may optimize functional recovery. Methods: All patients undergoing reconstruction of mandibulectomy-condylectomy defect (January 2009 to January 2014) by means of a fibular flap were prospectively studied. The neocondyle was formed by the distal portion of the fibula and placed directly into the glenoid fossa with preservation of the temporomandibular disc. The deep portion of the masseter was inset at the angle of the reconstructed mandible. Condylar position was postoperatively evaluated by panoramic radiographs. Patients self-evaluated speech, chewing, swallowing, and facial appearance. Results: Two patients had immediate and 3 delayed reconstruction involving condyle ramus body, in the study period. During a mean follow-up of 32 months, 4 patients had satisfactory occlusion, 1 patient had an open-bite deformity, but was able to masticate solid food and maintain an oral diet. Although no significant condyle dislocation was recorded, 2 patients had slight ipsilateral deviation on mouth opening. Nevertheless, cosmesis was satisfactory and all patients maintained intelligible speech. Functional score was 13.6 +/- 1.14 and facial appearance score was 4 +/- 0.7. Conclusion: The free fibula transfers with direct seating of the fibula into the condylar fossa followed by masseter muscle reinsertion provides acceptable functional reconstruction of the mandibulectomy-condylectomy defect. (C) 2017 by Mutaz B. Habal, MD.

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The Morphological Grading and Comparison of Sutural Patency Among Cranial Sutures in Dry Human Skulls.

Objective: To investigate the degree of fusion (patency) among cranial sutures in human dry skulls in the Anatolia. Methods: One-hundred fifty-eight human dry skulls that were accepted as adults according to the teeth eruption were macroscopically examined and photographed with Canon 400B (55 mm objective). The grades of fusion of coronal, sagittal, and lambdoid were quantitatively analyzed by using the modified grading scale. According to the extent of patency, the sutures were graded as grade-0 (open), grade-1 (fused but not obliterated), grade-2 (50% obliterated), and grade-4 (100% obliterated). The authors determined and compared the rate for each grade of sutural patency on coronal, sagittal, and lambdoid sutures. Results: The cranial sutures of 4 cranii (4/158; 2.53%) had grade-4 fusion, whereas there were no any cranii with sutures of grade-0 fusion. The number of each grade of fusion among cranial sutures of 158 skulls, in descending order, was as follows: 171 (grade-3), 145 (grade-1), 133 (grade-2), and 25 (grade-4). The grade-4 fusion was significantly less observed than the others. The grade-1 and grade-4 fusion of lambdoid sutures were established as the most (66/41.8%) and least (5/3.2%) common fusions among cranial sutures, respectively. The frequencies of each grade of fusion for each cranial suture were determined in a descending order: coronal (grade-3 > 2 > 1 > 4), sagittal (grade-3 > 2 > 1 > 4), and lambdoid sutures (grade-1 > 3 > 2 > 4). The frequency of grade-1 fusion of lambdoid suture (66/41.8%) was significantly different when compared with coronal (39/24.7%) and sagittal sutures (40/25.3%), respectively. Conclusion: The grades of fusion (or sutural patency) vary among cranial sutures. (C) 2017 by Mutaz B. Habal, MD.

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Confidence in masked orientation judgments is informed by both evidence and visibility

Abstract

How do human observers determine their degree of belief that they are correct in a decision about a visual stimulus—that is, their confidence? According to prominent theories of confidence, the quality of stimulation should be positively related to confidence in correct decisions, and negatively to confidence in incorrect decisions. However, in a backward-masked orientation task with a varying stimulus onset asynchrony (SOA), we observed that confidence in incorrect decisions also increased with stimulus quality. Model fitting to our decision and confidence data revealed that the best explanation for the present data was the new weighted evidence-and-visibility model, according to which confidence is determined by evidence about the orientation as well as by the general visibility of the stimulus. Signal detection models, postdecisional accumulation models, two-channel models, and decision-time-based models were all unable to explain the pattern of confidence as a function of SOA and decision correctness. We suggest that the metacognitive system combines several cues related to the correctness of a decision about a visual stimulus in order to calculate decision confidence.

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From eyes to hands: Transfer of learning in the Simon task across motor effectors

Abstract

Inhibition of irrelevant and conflicting information and responses is crucial for goal-directed behaviour and adaptive functioning. In the Simon task, for example, responses are slowed if their mappings are spatially incongruent with stimuli that must be discriminated on a nonspatial dimension. Previous work has shown that practice with incongruent spatial mappings can reduce or even reverse the Simon effect. We asked whether such practice transfers between the manual and oculomotor systems and if so to what extent this occurs across a range of behavioural tasks. In two experiments, one cohort of participants underwent anti-saccade training, during which they repeatedly inhibited the reflexive impulse to look toward a briefly presented target. Additionally, two active-control training groups were included, in which participants either trained on Pro-saccade or Fixation training regimens. In Experiment 1, we probed whether the Simon effect and another inhibitory paradigm, the Stroop task, showed differential effects after training. In Experiment 2, we included a larger battery of inhibitory tasks (Simon, Stroop, flanker and stop-signal) and noninhibitory control measures (multitasking and visual search) to assess the limits of transfer. All three training regimens led to behavioural improvements in the trained-upon task, but only the anti-saccade training group displayed benefits that transferred to the manual response modality. This transfer of training benefit replicated across the two experiments but was restricted to the Simon effect. Evidence for transfer of inhibition training across motor systems offers important insights into the nature of stimulus-response representations and their malleability.

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Above , on , or shang (上)? Language and spatial representations among English–Mandarin bilinguals

Abstract

This study investigated if exposure to spatial language could affect spatial cognition in English-Mandarin bilinguals by focusing on contact/noncontact distinctions, an area that has been a source of contention in the language-and-thought literature. Sixty-three participants were first primed with sentences containing spatial terms (e.g., above, on) before performing a spatial decision task. Approximately half of the participants (n = 33) were primed in English; for the remaining participants (n = 30), primes comprising Mandarin spatial terms―which mark spatial distinctions differently than in English (e.g., shang in Mandarin signifies both above and on in English)―were employed instead. Our findings revealed that participants' performance was influenced by spatial primes in the English experiment, thereby proffering evidence for thinking-for-speaking effects. However, these findings were not mirrored for the Mandarin experiment, confirming that the contact/noncontact specificity of spatial terms may have been instrumental in engendering the thinking-for-speaking effects observed in English.

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Secular trends in height, weight and body mass index of primary school children in Turkey between 1993 and 2016

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Issue: Ahead of print


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Effects of 1-year growth hormone replacement therapy on thyroid volume and function of the children and adolescents with idiopathic growth hormone deficiency

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Issue: Ahead of print


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Early-onset severe obesity due to complete deletion of the leptin gene in a boy

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Issue: Ahead of print


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Proposal of a Budget-Friendly Camera Holder for Endoscopic Ear Surgery.

Endoscopic ear surgery (EES) is increasingly a preferred technique in otologic society. It offers excellent visualization of the anatomical structures directly and behind the corners with variable angled telescopes. It also provides reduced operative morbidity due to being able to perform surgical interventions with less invasive approaches. Operative preparation and setup time and cost of endoscopy system are less expensive compared with surgical microscopes. On the other hand, the main disadvantage of EES is that the surgery has to be performed with 1 single hand. It is certainly restrictive for an ear surgeon who has been operating with 2 hands under otologic microscopic views for years and certainly requires a learning period and perseverance. Holding the endoscope by a second surgeon is not executable because of insufficient surgical space. Endoscope/camera holders have been developed for those who need the comfort and convenience afforded by double-handed microscopic ear surgery. An ideal endoscope holder should be easy-to-set up, easily controlled, providing a variety of angled views, allowing the surgeon to operate with 2 hands and, budget-friendly. In this article, a commercially available 11-inch magic arm camera holder is proposed by the authors to be used in EES due to its versatile, convenient, and budget-friendly features. It allows 2-handed EES through existing technology and is affordable for surgeons looking for a low-cost and practical solution. (C) 2017 by Mutaz B. Habal, MD.

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Surgical Treatment of Dentofacial Deformities Caused by Juvenile Idiopathic Arthritis.

The purpose of our retrospective study was to evaluate the results of orthognathic treatment, distraction osteogenesis, and/or prosthetic reconstruction of the temporomandibular joints in patients with juvenile idiopathic arthritis (JIA). Twelve patients with severely affected temporomandibular joints (TMJs) and reduced ramus height were treated with mandibular advancement with orthognathic surgery (11) and additional bilateral or unilateral mandibular ramus distraction (3) or additional bilateral or unilateral prosthetic reconstruction of the TMJ (3). One patient was treated surgically with bilateral TMJ prosthetic reconstruction only. The patients were followed up clinically and radiologically with emphasis on healing, TMJ function, stability of the occlusion, skeletal stability, and facial appearance for an average of 2.3 years after the final surgery. The mean mandibular advancement was 10.1 mm. The mean relapse at pogonion was 2.1 mm, which represents 20.8% of the surgical advancement. The occlusion was stable in 11/12 patients. The TMJ function was good and the facial esthetics improved in all patients. Orthognathic treatment and mandibular ramus distraction osteogenesis provide beneficial lengthening of the mandibular body in JIA patients with asymptomatic and stabile condyles. In adult patients with relapse of the disease or postoperative condylar relapse prosthetic total joint replacement is a reliable and safe alternative. (C) 2017 by Mutaz B. Habal, MD.

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Long-Term Effects of Bone Morphogenetic Protein-2-Loaded Calcium Phosphate on Maxillary Sinus Lift Surgery for Delayed and Simultaneous Dental Implantation.

Maxillary sinus lift surgery (MSLS) is considered to be a useful treatment method for patients with atrophic alveolar bone. Choosing a suitable surgical procedure to simultaneously decrease graft absorption and obtain long-term survival of dental implants is still a challenge. In this study, 20 patients received MSLS with graft of bone morphogenetic protein 2 (BMP2)-loaded calcium phosphate. Dental implants were placed simultaneously in 10 patients receiving MSLS (1-stage group), and in 10 patients receiving dental implants with a 3 to 6 months delay (2-stage group). The effects were evaluated based on clinical and radiographic examination during a 4 to 5 years follow-up. The results showed that only 1 perforation of the maxillary sinus mucosa was observed in 1-stage group, and was patched with a collagen membrane. An average bone gain of 6.8 mm was observed, and all implants exhibited no looseness, peri-implantitis, or fracture, all of which were stable during the follow-up and exhibited nice dental function during a 4 to 5 years follow-up. The loss of peri-implant bone height was 1.12 +/- 0.47 and 1.10 +/- 0.39 mm, the probing depth of periodontal pocket was 1.79 +/- 0.62 and 1.81 +/- 0.71 mm, the sulcular bleeding index was 1.63 +/- 0.47 and 1.72 +/- 0.54 in 1-stage group and 2-stage group, respectively, and no significant differences existed between these 2 groups. These findings implied that BMP2-loaded calcium phosphate may be a suitable material for MSLS, especially for patients with minimal bone height. Clinicians can use the 1- or 2-stage technique based on clinical condition, patients' choice and clinicians' experience. In patients where implants cannot be stabilized for patients with minimal bone height, 2-stage surgery may be more suitable. (C) 2017 by Mutaz B. Habal, MD.

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The Pantheon Variant of the Classic Cathedral Dome Procedure for Parieto-Occipital Skull Deformities.

Objective: To describe a new technique for the reconstruction of parieto-occipital skull deformities. Methods and Results: The technique is a variant of the previously described "cathedral dome procedure" used for frontal skull deformities. The authors apply the same principle of remodeling by making meridional slat craniotomies surrounding the depressed dome of the posterior skull deformity, followed by "green-stick fracture-reshaping" of the meridional slats to elevate and support the excised depressed dome. The authors present an illustrative patient with a follow-up of 2 years and an excellent cosmetic result. Conclusion: The authors introduce a new operative technique for the reconstruction of parieto-occipital skull deformities with excellent long-term results. The freshly reconstructed occiput resembles the dome of the pantheon in Rome, Italy, whose unique features inspired us to name this procedure the "Pantheon" variant of the cathedral dome operation. (C) 2017 by Mutaz B. Habal, MD.

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Clinical Evaluation of Standardized Fronto-Orbital Advancement for Correction of Isolated Trigonocephaly.

Corrective surgery of trigonocephaly is a major challenge, owing to the complex development of the craniofacial skull. Although reports on the clinical success of standardized fronto-orbital advancement have been promising, there is a lack of studies, assessing this method. Hence, the aim of our study was to evaluate the clinical outcome of a standardized fronto-orbital advancement procedure for correction of isolated nonsyndromic trigonocephaly, in our patient cohort. The retrospective study included 30 patients from 2008 to 2015. Inclusion criteria were treatment-naive children with isolated nonsyndromic trigonocephaly, being treated with standardized frontoorbital advancement in our department. We considered postoperative complications and the Whitaker Score to evaluate the success of the clinical outcome. Surgery was performed at a mean age of 9.3 months. The mean operation time was 153 minutes. All patients were assigned I according to the Whitaker score. One patient suffered from a small inconsequential subdural hematoma. Another patient suffered from dural tears, which were identified and treated intraoperatively. No major complications occurred within our patient cohort. The standardized fronto-orbital advancement is a safe and successful method, as it is associated with a high morphological outcome and low complication rate. (C) 2017 by Mutaz B. Habal, MD.

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Proof of Concept Study for the Design, Manufacturing, and Testing of a Patient-Specific Shape Memory Device for Treatment of Unicoronal Craniosynostosis.

Treatment of unicoronal craniosynostosis is a surgically challenging problem, due to the involvement of coronal suture and cranial base, with complex asymmetries of the calvarium and orbit. Several techniques for correction have been described, including surgical bony remodeling, early strip craniotomy with orthotic helmet remodeling and distraction. Current distraction devices provide unidirectional forces and have had very limited success. Nitinol is a shape memory alloy that can be programmed to the shape of a patient-specific anatomy by means of thermal treatment. In this work, a methodology to produce a nitinol patient-specific distractor is presented: computer tomography images of a 16-month-old patient with unicoronal craniosynostosis were processed to create a 3-dimensional model of his skull and define the ideal shape postsurgery. A mesh was produced from a nitinol sheet, formed to the ideal skull shape and heat treated to be malleable at room temperature. The mesh was afterward deformed to be attached to a rapid prototyped plastic skull, replica of the patient initial anatomy. The mesh/skull construct was placed in hot water to activate the mesh shape memory property: the deformed plastic skull was computed tomography scanned for comparison of its shape with the initial anatomy and with the desired shape, showing that the nitinol mesh had been able to distract the plastic skull to a shape close to the desired one. The shape-memory properties of nitinol allow for the design and production of patient-specific devices able to deliver complex, preprogrammable shape changes. (C) 2017 by Mutaz B. Habal, MD.

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Circadian Clocks: Role in Health and Disease

No abstract available

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Age Modulates Physiological Responses during Fan Use under Extreme Heat and Humidity

Purpose: We examined the effect of electric fan use on cardiovascular and thermoregulatory responses of nine young (26 ± 3 yr) and nine aged (68 ± 4 yr) adults exposed to extreme heat and humidity. Methods: While resting at a temperature of 42°C, relative humidity increased from 30% to 70% in 2% increments every 5 min. On randomized days, the protocol was repeated without or with fan use. HR, core (Tcore) and mean skin (Tsk) temperatures were measured continuously. Whole-body sweat loss was measured from changes in nude body weight. Other measures of cardiovascular (cardiac output), thermoregulatory (local cutaneous and forearm vascular conductance, local sweat rate), and perceptual (thermal and thirst sensations) responses were also examined. Results: When averaged over the entire protocol, fan use resulted in a small reduction of HR (−2 bpm, 95% confidence interval [CI], −8 to 3), and slightly greater Tcore (+0.05°C; 95% CI, −0.13 to 0.23) and Tsk (+0.03°C; 95% CI, −0.36 to 0.42) in young adults. In contrast, fan use resulted in greater HR (+5 bpm; 95% CI, 0–10), Tcore (+0.20°C; 95% CI, 0.00–0.41), and Tsk (+0.47°C; 95% CI, 0.18–0.76) in aged adults. A greater whole-body sweat loss during fan use was observed in young (+0.2 kg; 95% CI, −0.2 to 0.6) but not aged (0.0 kg; 95% CI, −0.2 to 0.2) adults. Greater local sweat rate and cutaneous vascular conductance were observed with fan use in aged adults. Other measures of cardiovascular, thermoregulatory, and perceptual responses were unaffected by fan use in both groups. Conclusions: During extreme heat and humidity, fan use elevates physiological strain in aged, but not young, adults.

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Greater Oxidative Capacity in Primary Myotubes from Endurance-trained Women

Purpose: Exercise training promotes skeletal muscle mitochondrial biogenesis and an increase in maximal oxygen consumption. Primary myotubes retain some metabolic properties observed in vivo but it is unknown whether this includes exercise-induced mitochondrial adaptations. The goal of this study was to test if primary myotubes from exercise-trained women have higher mitochondrial content and maximal oxygen consumption compared with untrained women. Methods: Six trained and nine untrained white women participated in this study. Muscle biopsies from the vastus lateralis muscle of the right leg were obtained and primary muscle cells were isolated. Maximal respiration rates, mitochondrial mRNA and protein content, and succinate dehydrogenase activity were measured in skeletal muscle and primary myotubes from trained and untrained women. Results: Trained women, compared with untrained women, had higher maximal whole-body oxygen consumption (+18%, P = 0.03), in vivo maximal skeletal muscle oxidative capacity measured with near infrared spectroscopy (+48%, P

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Increased Protein Requirements in Female Athletes after Variable-Intensity Exercise

Purpose: Protein requirements are primarily studied in the context of resistance or endurance exercise with little research devoted to variable-intensity intermittent exercise characteristic of many team sports. Further, female populations are underrepresented in dietary sports science studies. We aimed to determine a dietary protein requirement in active females performing variable-intensity intermittent exercise using the indicator amino acid oxidation (IAAO) method. We hypothesized that these requirements would be greater than current IAAO-derived estimates in nonactive adult males. Methods: Six females (21.2 ± 0.8 yr, 68.8 ± 4.1 kg, 47.1 ± 1.2 mL O2·kg−1·min−1; mean ± SE) completed five to seven metabolic trials during the luteal phase of the menstrual cycle. Participants performed a modified Loughborough Intermittent Shuttle Test before consuming eight hourly mixed meals providing the test protein intake (0.2–2.66 g·kg−1·d−1), 6 g·kg−1·d−1 CHO and sufficient energy for resting and exercise-induced energy expenditure. Protein was provided as crystalline amino acid modeling egg protein with [13C]phenylalanine as the indicator amino acid. Phenylalanine turnover (Q) was determined from urinary [13C]phenylalanine enrichment. Breath 13CO2 excretion (F13CO2) was analyzed using mixed effects biphase linear regression with the breakpoint and upper 95% confidence interval approximating the estimated average requirement and recommended dietary allowance, respectively. Results: Protein intake had no effect on Q (68.7 ± 7.3 μmol·kg−1·h−1; mean ± SE). F13CO2 displayed a robust biphase response (R2 = 0.66) with an estimated average requirement of 1.41 g·kg−1·d−1 and recommended dietary allowance of 1.71 g·kg−1·d−1. Conclusions: The protein requirement estimate of 1.41 and 1.71 g·kg−1·d−1 for females performing variable-intensity intermittent exercise is greater than the IAAO-derived estimates of adult males (0.93 and 1.2 g·kg−1·d−1) and at the upper range of the American College of Sports Medicine athlete recommendations (1.2–2.0 g·kg−1·d−1).

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Longitudinal Associations between Physical Activity and Educational Outcomes

Purpose: This longitudinal study examined the role of leisure-time physical activity in academic achievement at the end of compulsory basic education and educational attainment in adulthood. Methods: The data were drawn from the ongoing longitudinal Cardiovascular Risk in Young Finns Study, which was combined with register-based data from Statistics Finland. The study consisted of children who were 12 yr (n = 1723, 49% boys) and 15 yr (n = 2445, 48% boys) of age at the time when physical activity was measured. The children were followed up until 2010, when their mean age was 40 yr. Physical activity was self-reported and included several measurements: overall leisure-time physical activity outside school hours, participation in sports club training sessions, and participation in sports competitions. Individuals' educational outcomes were measured with the self-reported grade point average at age 15 yr and register-based information on the years of completed postcompulsory education in adulthood. Ordinary least squares models and the instrumental variable approach were used to analyze the relationship between physical activity and educational outcomes. Results: Physical activity in adolescence was positively associated with educational outcomes. Both the physical activity level at age 15 yr and an increase in the physical activity level between the ages of 12 and 15 yr were positively related to the grade point average at age 15 yr and the years of postcompulsory education in adulthood. The results were robust to the inclusion of several individual and family background factors, including health endowments, family income, and parents' education. Conclusion: The results provide evidence that physical activity in adolescence may not only predict academic success during compulsory basic education but also boost educational outcomes later in life.

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Response

No abstract available

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Effects of a Long-Term Physical Activity Program on Activity Patterns in Older Adults

Purpose: To examine the effect of a long-term structured physical activity (PA) intervention on accelerometer-derived metrics of activity pattern changes in mobility-impaired older adults. Methods: Participants were randomized to either a PA or health education (HE) program. The PA intervention included a walking regimen with strength, flexibility, and balance training. The HE program featured health-related discussions and a brief upper body stretching routine. Participants (n = 1341) wore a hip-worn accelerometer for ≥10 h·d−1 for ≥3 d at baseline and again at 6, 12, and 24 months postrandomization. Total PA (TPA)—defined as movements registering 100+ counts per minute—was segmented into the following intensities: low-light PA (LLPA; 100–759 counts per minute), high light PA (HLPA; 760–1040 counts per minute), low moderate PA (LMPA; 1041–2019 counts per minute), and high moderate and greater PA (HMPA; 2020+ counts per minute). Patterns of activity were characterized as bouts (defined as the consecutive minutes within an intensity). Results: Across groups, TPA decreased an average of 74 min·wk−1 annually. The PA intervention attenuated this effect (PA = −68 vs HE: −112 min·wk−1, P = 0.002). This attenuation shifted TPA composition by increasing time in LLPA (10+ bouts increased 6 min·wk−1), HLPA (1+, 2+, 5+, and 10+ bouts increased 6, 3, 2, and 1 min·wk−1, respectively), LMPA (1+, 2+, 5+, and 10+ bouts increased: 19, 17,16, and 8 min·wk−1, respectively), and HMPA (1+, 2+, 5+, and 10+ bouts increased 23, 21, 17, and 14 min·wk−1, respectively). Conclusions: The PA intervention increased PA by shifting the composition of activity toward higher-intensity activity in longer-duration bouts. However, a long-term structured PA intervention did not completely eliminate overall declines in total daily activity experienced by mobility-impaired older adults.

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Cognitive Resilience and Psychological Responses across a Collegiate Rowing Season

Introduction: Student-athletes face numerous challenges across their competitive season. Although mood states have been previously studied, little is known about adaptations in other psychological responses, specifically cognition. The purpose of this study was to characterize cognitive function, mood, sleep, and stress responses at select time points of a season in collegiate rowers. It was hypothesized that during baseline, typical training, and recovery, athletes would show positive mental health profiles, in contrast to decreases in cognition with increases in negative mood and measurements of stress during peak training. Methods: Male and female Division I rowers (N = 43) and healthy controls (N = 23) were enrolled and assessed at baseline, typical training, peak training, and recovery. At each time point, measures of cognitive performance (Stroop color-naming task), academic and exercise load, perceived cognitive deficits, mood states, sleep, and stress (via self-report and salivary cortisol) were recorded. Results: Repeated-measures ANOVA revealed significant group–time interactions for perceived exercise load, cognitive deficits, mood states, and perceived stress (P

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Physical Activity Dimensions Associated with Impaired Glucose Metabolism

Purpose: Physical activity (PA) is important in the prevention of Type 2 diabetes, yet little is known about the role of specific dimensions of PA, including sedentary time in subgroups at risk for impaired glucose metabolism (IGM). We applied a data-driven decision tool to identify dimensions of PA associated with IGM across age, sex, and body mass index (BMI) groups. Methods: This cross-sectional study included 1501 individuals (mean (SD) age, 65.6 (6.8) yr) at high risk for Type 2 diabetes from the ADDITION-PRO study. PA was measured by an individually calibrated combined accelerometer and heart rate monitor worn for 7 d. PA energy expenditure, time spent in different activity intensities, bout duration, and sedentary time were considered determinants of IGM together with age, sex, and BMI. Decision tree analysis was applied to identify subgroup-specific dimensions of PA associated with IGM. IGM was based on oral glucose tolerance test results and defined as a fasting plasma glucose level of ≥6.1 mmol·L−1 and/or a 2-h plasma glucose level of ≥7.8 mmol·L−1. Results: Among overweight (BMI ≥25 kg·m−2) men, accumulating less than 30 min·d−1 of moderate-to-vigorous PA was associated with IGM, whereas among overweight women, sedentary time was associated with IGM. Among individuals older than 53 yr with normal weight (BMI

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The Effects of Acute Interval Exercise and Strawberry Intake on Postprandial Lipemia

Purpose: Raised postprandial triglycerides (TAG) and related oxidative stresses are strongly associated with increased cardiovascular disease risk. Acute exercise and strawberry ingestion independently ameliorate postprandial lipid excursions and oxidative stress. However, the combined effects of these lifestyle interventions are unknown. We investigated whether acute exercise and strawberry consumption improved postprandial responses to an oral fat tolerance test (OFTT) in overweight/obese males. Methods: Overweight/obese adult males underwent four separate OFTT (73 g fat, 33 g carbohydrate) with blood sampled at baseline and hourly for 4 h after OFTT. Two OFTT contained 25 g freeze-dried strawberries and two contained strawberry flavoring (placebo). Participants performed 40 min of submaximal high-intensity interval cycling exercise 16 h before one strawberry and one placebo OFTT and rested before the remaining two OFTT. Serum TAG was analyzed, and TAG area under the curve (AUC) and incremental AUC (iAUC) were calculated. Oxidative stress markers were measured at baseline and 4 h. Differences between conditions (strawberry/placebo and exercise/rest) were assessed using repeated-measures ANOVA. Results: Ten males (age = 31.5, interquartile range = 17.8 yr, body mass index = 29.9 ± 1.8 kg·m−2) completed the study. TAG AUC was 1.5 mmol per 4 h−1·L−1 lower for the exercise conditions compared with the rest conditions (95% confidence interval [CI] = −2.3 to −0.8 mmol per 4 h−1·L−1, P = 0.001). TAG AUC was not different between strawberry and placebo conditions (95% CI = −1.3 to 0.6 mmol per 4 h−1·L−1, P = 0.475). TAG iAUC was 0.5 mmol per 4 h−1·L−1 greater for the strawberry compared with the placebo conditions (95% CI = 0.1 to 1.0 mmol per 4 h−1·L−1, P = 0.021). There were no changes in markers of lipid related oxidative stress (P > 0.05). Conclusion: Acute submaximal high-intensity interval cycling exercise appears effective in reducing postprandial lipemia in overweight/obese adult males. However, strawberry ingestion did not improve postprandial TAG.

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Individualized Estimation of Physical Activity in Older Adults with Type 2 Diabetes

Purpose: Compare physical activity intensity in older adults with type 2 diabetes mellitus (T2DM) using individualized, relative cutpoints with standard, absolute cutpoints. Methods: One hundred older adults with T2DM (68.9 ± 5.1 yr, 65% male, 32.7 ± 6.3 kg·m−2, 7.2% ± 1.1% glycosylated hemoglobin) completed a two-speed walking protocol (varying, walking between 1 and 2.5 mph), followed by a modified Bruce peak exercise test. Participants wore an accelerometer-based physical activity monitor at their waist, and oxygen consumption was measured. Afterward, participants wore the activity monitor for seven consecutive days. Linear equations for each individual were derived from the activity counts and energy expenditure measured during the walking protocol. Relative intensity cutpoints were calculated by using standard classifications of 44% oxygen consumption (V˙O2)peak to determine moderate and 59% V˙O2peak to determine vigorous intensity. Average time spent in intensity categories per day were calculated using relative and absolute (moderate, 2020 counts per minute; vigorous, 5999 counts per minute) cutpoints. t-Tests were run to compare estimated time spent in intensity category by cutpoint. Results: Mean V˙O2peak was 17.9 ± 4.5 mL·kg−1·min−1 and relative cutpoints were, on average, 1033.5 counts per minute (SD, 741.2 counts per minute) for moderate and 2211.7 counts per minute (SD, 1512.4) for vigorous activity. Using the relative cutpoints, participants accumulated an average of 157.2 min (SD, 73.7 min) of light, 33.3 min (SD, 35.6 min) of moderate, and 15.6 min (SD, 26.7 min) of vigorous activity per day. Use of the absolute cutpoint resulted in significantly different estimations based on intensity category: light, 200.7 min (SD, 74.7 min; P

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Generating ActiGraph Counts from Raw Acceleration Recorded by an Alternative Monitor

Purpose: This study aimed to implement an aggregation method in Matlab for generating ActiGraph counts from raw acceleration recorded with an alternative accelerometer device and to investigate the validity of the method. Methods: The aggregation method, including the frequency band-pass filter, was implemented and optimized based on standardized sinusoidal acceleration signals generated in Matlab and processed in the ActiLife software. Evaluating the validity of the aggregation method was approached using a mechanical setup and with a 24-h free-living recording using a convenient sample of nine subjects. Counts generated with the aggregation method applied to Axivity AX3 raw acceleration data were compared with counts generated with ActiLife from ActiGraph GT3X+ data. Results: An optimal band-pass filter was fitted resulting in a root-mean-square error of 25.7 counts per 10 s and mean absolute error of 15.0 counts per second across the full frequency range. The mechanical evaluation of the proposed aggregation method resulted in an absolute mean ± SD difference of −0.11 ± 0.97 counts per 10 s across all rotational frequencies compared with the original ActiGraph method. Applying the aggregation method to the 24-h free-living recordings resulted in an epoch level bias ranging from −16.2 to 0.9 counts per 10 s, a relative difference in the averaged physical activity (counts per minute) ranging from −0.5% to 4.7% with a group mean ± SD of 2.2% ± 1.7%, and a Cohen's kappa of 0.945, indicating almost a perfect agreement in the intensity classification. Conclusion: The proposed band-pass filter and aggregation method is highly valid for generating ActiGraph counts from raw acceleration data recorded with alternative devices. It would facilitate comparability between studies using different devices collecting raw acceleration data.

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Meta-analysis of Cigarette Smoking and Musculoskeletal Injuries in Military Training

Purpose: Tobacco use is common among military personnel, as is musculoskeletal injury during training. In a review of the literature on musculoskeletal injuries, there was mixed evidence on the role of smoking as a risk factor. The purpose of this study is to review and analyze the literature on the impact of cigarette smoking on lower-extremity overuse injuries in military training. Methods: We performed a literature search on articles published through October 2016. Search terms focused on lower-extremity overuse musculoskeletal injuries and cigarette smoking in military populations. We conducted a meta-analysis overall and by sex, including smoking intensity. Results: We identified 129 potential studies and selected 18 based on quality. The overall rate ratio for smoking was 1.31, 1.31 for men, and 1.23 for women. Overall and for each sex, rate ratios were significantly greater than 1.0 for each intensity level of smoking. Conclusions: Smoking is a moderate risk factor for musculoskeletal injury and may account for a meaningful proportion of injuries among men and women due to the high prevalence of smoking and injury in this population. Although enlistees are not allowed to smoke during basic training, their risk of injury remains high, indicating that smokers may remain at increased risk for medium- to long-term duration.

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Response

No abstract available

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Power Training–induced Increases in Muscle Activation during Gait in Old Adults

Introduction/Purpose: Aging modifies neuromuscular activation of agonist and antagonist muscles during walking. Power training can evoke adaptations in neuromuscular activation that underlie gains in muscle strength and power but it is unknown if these adaptations transfer to dynamic tasks such as walking. We examined the effects of lower-extremity power training on neuromuscular activation during level gait in old adults. Methods: Twelve community-dwelling old adults (age ≥ 65 yr) completed a 10-wk lower-extremity power training program and 13 old adults completed a 10-wk control period. Before and after the interventions, we measured maximal isometric muscle strength and electromyographic (EMG) activation of the right knee flexor, knee extensor, and plantarflexor muscles on a dynamometer and we measured EMG amplitudes, activation onsets and offsets, and activation duration of the knee flexors, knee extensors, and plantarflexors during gait at habitual, fast, and standardized (1.25 ± 0.6 m·s−1) speeds. Results: Power training-induced increases in EMG amplitude (~41%; 0.47 ≤ d ≤ 1.47; P ≤ 0.05) explained 33% (P = 0.049) of increases in isometric muscle strength (~43%; 0.34 ≤ d ≤ 0.80; P ≤ 0.05). Power training-induced gains in plantarflexor activation during push-off (+11%; d = 0.38; P = 0.045) explained 57% (P = 0.004) of the gains in fast gait velocity (+4%; d = 0.31; P = 0.059). Furthermore, power training increased knee extensor activation (~18%; 0.26 ≤ d ≤ 0.29; P ≤ 0.05) and knee extensor coactivation during the main knee flexor burst (~24%, 0.26 ≤ d ≤ 0.44; P ≤ 0.05) at habitual and fast speed but these adaptations did not correlate with changes in gait velocity. Conclusions: Power training increased neuromuscular activation during isometric contractions and level gait in old adults. The power training–induced neuromuscular adaptations were associated with increases in isometric muscle strength and partly with increases in fast gait velocity.

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Impact of HSCT Conditioning and Glucocorticoid Dose on Exercise Adherence and Response

Purpose: Evidence from randomized controlled trials (RCT) that exercise interventions have beneficial effects in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) is growing. However, intensive chemotherapy conditioning and glucocorticoid (GC) treatment is always part of an allo-HSCT and possibly affect exercise adherence and training response. Therefore, we aimed to examine whether various conditioning protocols or different doses of GC treatment affect exercise adherence and/or training response during the inpatient period. Methods: We analyzed inpatient data from intervention groups of two large RCT in allo-HSCT patients (n = 113). The intervention incorporated partly supervised endurance and resistance exercise three to five times per week. According to the potentially interfering factors, the patients were divided into groups depending on intensity of conditioning (myeloablative conditioning (MAC), reduced-intensity conditioning (RIC), and nonmyeloablative conditioning (NMC)) and cumulative dose of GC treatment (GC low ≤9 mg·kg−1 prednisone or GC high >9 mg·kg−1 prednisone) and were compared. Results: Median exercise adherence (target value, five sessions weekly) during the inpatient period was 64% in MAC, 54% in RIC, and 63% in NMC. The proportion of prematurely terminated training sessions ranged from 11% to 15%. Tiredness was the most frequent cause of exercise termination in all groups. Exercise adherence, duration (min·wk1) and type of training was significantly associated with GC dose. With regard to training response, results suggest that GC-low patients tend to respond better in knee extensor muscle strength. Conclusions: Exercise adherence during inpatient period is significantly affected by dose of GC treatment but not by condition regimen. However, given the reasonable adherence rates also in the GC-high group, data support the feasibility and importance of exercising for all allo-HSCT patients during the inpatient period.

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Cardiorespiratory Reference Data in Older Adults: The Generation 100 Study

Purpose: Cardiorespiratory fitness (CRF) is regarded a clinical vital sign, and accurate reference values for all age groups are essential. Little data exist on CRF and cardiorespiratory function in older adults. The aim of this study was to provide normative values for CRF and cardiorespiratory function in older adults, including people with history of cardiovascular diseases (CVD). Methods: In total, 1537 (769 women) participants age 70 to 77 yr underwent clinical examinations and cardiopulmonary exercise tests. Peak oxygen uptake (V˙O2peak), ventilation (V˙Epeak), expiration of carbon dioxide (VV˙CO2peak), breathing frequency (BFpeak), tidal volume (VTpeak), oxygen pulse (O2 pulsepeak), ventilatory efficiency (EqV˙O2peak and EqV˙CO2peak), and 1-min HR recovery were assessed. Results: Men compared with women had higher V˙O2peak (31.3 ± 6.7 vs 26.2 ± 5.0 mL·min−1·kg−1), BFpeak (41.8 ± 8.0 vs 39.7 ± 7.1 breaths per minute), VTpeak (2.3 ± 0.5 vs 1.6 ± 0.3), O2 pulsepeak (16.4 ± 3.2 vs 11.3 ± 2.0), V˙CO2peak (2.9 ± 0.2 and 1.9 ± 0.1 L·min−1), V˙Epeak (96.2 ± 21.7 vs 61.1 ± 21.6 L·min−1), EqV˙O2peak (38.0 ± 6.9 vs 35.1 ± 5.6), and EqV˙CO2peak (33.5 ± 5.7 vs 31.9 ± 4.5). Women and men with CVD had lower V˙O2peak (14% and 19%), peak HR (5% and 6%), V˙Epeak (8% and 10%), VTpeak (7% and 4%), and lower EqV˙CO2peak (4% and 6%) compared with their healthy counterparts, respectively. Compared with healthy women and men, 1-min HR recovery was 12% and 16% lower for women and men with CVD. Conclusions: This study represents the largest reference material on directly measured CRF and cardiorespiratory function in older men and women, with and without CVD. This novel information will help researchers and clinicians to interpret data form cardiopulmonary testing in older adults.

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Effects of Four Weeks of Strength Training on the Corticomotoneuronal Pathway

Purpose: Neural adaptations to strength training have long been recognized, but knowledge of mechanisms remains incomplete. Using novel techniques and a design which limited experimental bias, this study examined if 4 wk of strength training alters voluntary activation and corticospinal transmission. Methods: Twenty-one subjects were randomized into strength training (n = 10; 7 females, 3 males; 23.5 ± 7.5 yr; mean ± SD) and control groups (n = 11; 2 females, 9 males; 23.0 ± 4.2 yr). Strength training involved 12 sessions of high-force isometric contractions of the elbow flexors. Before and after training, voluntary activation of the elbow flexors was assessed via transcranial magnetic stimulation. Also, for the first time, magnetic stimulation of corticospinal axons was used to examine spinal-level adaptations to training. The evoked responses, termed cervicomedullary motor-evoked potentials (CMEPs), were acquired in resting biceps brachii in three arm postures. Muscle adaptations were assessed via electrical stimulation of biceps. Results: Compared with the control group, the strength training group exhibited greater increases in maximal strength (12.8% ± 6.8% vs 0.0% ± 2.7%; P

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Fitness Moderates Glycemic Responses to Sitting and Light Activity Breaks

Purpose: This study aimed to experimentally determine whether cardiorespiratory fitness (CRF) modifies postprandial glycemia during prolonged sitting and investigated the potentially blunting influence this may have on the benefits of interrupting postprandial sitting time with light activity breaks. Methods: Thirty-four adults (18 women; 16 men; mean ± SD age, 40 ± 9 yr, body mass index, 24.5 ± 3 kg·m−2) undertook two 7.5-h experimental conditions in a randomized order: 1) Prolonged sitting; 2) Sitting interspersed with 5 min light walking bouts every 30 min. Blood samples were obtained while fasting and postprandially after ingestion of two identical meals. Incremental area under the curve (iAUC) was calculated for glucose and insulin throughout experimental conditions. Maximal exercise testing quantified peak oxygen consumption (V˙O2 peak) as a measure of CRF. A repeated-measures ANOVA investigated whether V˙O2 peak modified glucose and insulin iAUC between conditions. Results: Breaking sedentary time with light walking breaks reduced blood glucose iAUC from 3.89 ± 0.7 to 2.51 ± 0.7 mmol·L−1·h−1 (P = 0.015) and insulin iAUC from 241 ± 46 to 156 ± 24 mU·L−1·h−1 (P = 0.013) after adjustment for V˙O2 peak and sex. A significant interaction between treatment response and V˙O2 peak was observed for glucose (P = 0.035), but not insulin (P = 0.062), whereby the treatment effect reduced with higher CRF. Average blood glucose iAUC responses for a man at the 25th centile of CRF within our cohort (42.5 mL·kg−1·min−1) went from 5.80 to 2.98 mmol·L−1·h−1 during the prolonged sitting and light walking break conditions respectively, whereas average responses for a man at the 75th centile of CRF (60.5 mL·kg−1·min−1) went from 1.99 to 1.78 mmol·L−1·h−1. Similar trends were observed for women. Conclusions: Individuals with low CRF gained the most metabolic benefit from breaking prolonged sitting with regular bouts of light walking.

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Intermittent Standing but not a Moderate Exercise Bout Reduces Postprandial Glycemia

Purpose: This study aimed to determine whether minimum recommended moderate-to-vigorous physical activity (MVPA; 30-min bout of continuous moderate-intensity walking) is sufficient to counteract the detrimental effects of prolonged sitting on postprandial metabolism and if there are any effects of breaking up sitting with intermittent standing when achieving minimum recommended MVPA. Methods: Fourteen (n = 14) physically inactive healthy adult males underwent four intrahospital 27-h interventions: 9-h continuous sitting (SIT), 15-min standing bouts every 30 min during the 9-h sitting (STAND), 30-min moderate-intensity walking bout followed by 8.5 h of sitting (MVPA), and 30-min moderate-intensity walking bout followed by 15-min standing bouts every 30 min during 8.5 h of sitting (MVPA + STAND). Three standardized meals on intervention day (day 1) and breakfast the following day (day 2) were served. Results: Cumulative postprandial glucose response (incremental area under the curve) was lower in STAND versus SIT (↓27%, P = 0.04, effect size [ES] = −0.7) because of decreases in postprandial glucose after breakfast on day 1 (STAND vs SIT: ↓40%, P = 0.01, ES = −0.7) and day 2 (STAND vs SIT: ↓33%, P = 0.06, ES = −0.6). STAND did not affect postprandial insulin responses. Cumulative postprandial insulin response was lower in MVPA versus SIT (↓18%, P = 0.03, ES = −0.3) and MVPA + STAND versus SIT (↓26%, P = 0.02, ES = −0.4) because of expected exercise-induced decreases in postprandial insulin after breakfast on day 1 only (MVPA vs SIT: ↓36%, P = 0.003, ES = −0.7; MVPA + STAND vs SIT: ↓43%, P = 0.0001, ES = −0.8). Conclusion: Breaking up prolonged sitting with nonambulatory standing across 9 h acutely reduced postprandial glycemic response during and the day after the intervention independent of insulin levels, whereas a 30-min MVPA bout did not.

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Neurovascular Response during Exercise and Mental Stress in Anabolic Steroid Users.

Purpose: Increased resting muscle sympathetic nerve activity (MSNA) and lower forearm blood flow (FBF) were observed in young men who use anabolic androgenic steroids (AAS). However, the response of MSNA and FBF in AAS users triggered by muscle mechanoreflex and central command has never been tested. Additionally, we evaluated the blood pressure (BP) and heart rate (HR) responses during these maneuvers. Methods: Nineteen AAS users (AASU) aged 31+/-6 yr and 18 AAS nonusers (AASNU) aged 29+/-4 yr were recruited. All participants were involved in strength training. AAS use was determined with a urine test (liquid chromatography with tandem mass spectrometry). MSNA was measured with the microneurography technique. FBF was measured by venous occlusion plethysmography. BP was measured with an automatic oscillometric device. HR was recorded continuously through ECG. Isometric handgrip exercise was performed at 30% of the maximum voluntary contraction for 3 minutes; and mental stress was elicited by the Stroop color-word test for 4 minutes. Results: The MSNA and FBF responses during exercise were similar between AASU and AASNU, with a trend toward higher MSNA (bursts/min; P=0.084) and lower forearm vascular conductance (FVC, units; P=0.084) in AASU than AASNU. During mental stress, AASU showed a significantly higher MSNA (P

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Effect of Losartan on the Acute Response of Human Elderly Skeletal Muscle to Exercise.

Purpose: To investigate the effect of blocking the angiotensin II type I receptor (AT1R) upon the response to acute heavy resistance exercise in elderly human skeletal muscle. The hypothesis was that AT1R blocking would result in a superior myogenic response accompanied by downregulation of TGF-[beta] and upregulation of IGF-1 signalling. Methods: 28 healthy elderly men (+64 years) were randomized into two groups, consuming either AT1R blocker (Losartan, 100mg/day) or Placebo for 18 days prior to exercise. Participants performed one bout of heavy unilateral resistance exercise. Six muscle biopsies were obtained from the vastus lateralis muscles of each subject: two before exercise, and four after exercise (4.5 hours and 1, 4 and 7 days). Blood pressure and blood samples were collected at the same time points. Biopsies were sectioned for immunohistochemistry to determine the number of satellite cells associated with type I and type II fibres. Gene expression levels of Notch, connective tissue and myogenic signalling pathways were determined by real time RT-PCR. Results: Changes over time were detected for circulating creatine kinase, the number of satellite cells per type I fibre and most of the gene targets, with no specific effect of losartan on these. However, when compared with placebo, Losartan intake resulted in a greater suppression of myostatin mRNA. Conclusion: In general, there does not appear to be any effect of AT1R blocking upon satellite cell number or myogenic pathways in elderly men in the days after one bout of heavy resistance exercise. However, the greater suppression of myostatin may prove to be beneficial over a long term intervention designed to induce hypertrophy. (C) 2017 American College of Sports Medicine

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Validation of a Novel Device to Measure and Provide Feedback on Sedentary Behavior.

Purpose: Pedometers, which enable self-monitoring of step counts, are effective in facilitating increases in physical activity. Similar devices which provide real-time feedback on sedentary (sitting) behavior are limited. This study aimed to develop and validate a novel device - the SitFIT - which could accurately measure and provide feedback on sedentary behavior and physical activity. Methods: The SitFIT is a tri-axial accelerometer, developed by PAL Technologies, which is worn in the front trouser pocket. This enables tracking of thigh inclination and therefore differentiation between sitting and upright postures, as well as tracking of step count. It has a display to provide user feedback. To determine the validity of the SitFIT for measuring sedentary behavior and step counts, 21 men, aged 30-65 years, with body mass index 26.6+/-3.9 kg.m-2 wore a SitFIT in a front trouser pocket and an activPAL accelerometer attached to their thigh for up to seven days. Outputs from the SitFIT were compared with the activPAL, which was assumed to provide gold-standard measurements of sitting and step counts. Results: Mean step counts were ~4% lower with the SitFIT than activPAL, with correlation between the two methods being very high (r=0.98) and no obvious bias from the line of equality (regression line: y=1.0035x+418.35). Mean sedentary time was ~5% higher with the SitFIT than activPAL, correlation between methods was high (r=0.84) and the equation of the regression line was close to the line of equality (y=0.8728x+38.445). Conclusions: The SitFIT has excellent validity for measurement of free-living step counts and sedentary time and therefore addresses a clear need for a device that can be used as a tool to provide feedback on sedentary behavior to facilitate behavior change. (C) 2017 American College of Sports Medicine

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Propranolol and Oxandrolone Therapy Accelerated Muscle Recovery in Burned Children.

Introduction: Severe burns result in prolonged hypermetabolism and skeletal muscle catabolism. Rehabilitative exercise training (RET) programs improved muscle mass and strength in severely burned children. The combination of RET with [beta]-blockade or testosterone analogues showed improved exercise-induced benefits on body composition and muscle function. However, the effect of RET combined with multiple drug therapy on muscle mass, strength, cardiorespiratory fitness and protein turnover are unknown. In this placebo-controlled randomized trial, we hypothesize that RET combined with oxandrolone and propranolol (Oxprop) will improve muscle mass and function and protein turnover in severely burned children compared to burned children undergoing the same RET with a placebo. Methods: We studied 42 severely burned children (7 - 17 years) with severe burns over 30% of the total body surface area. Patients were randomized to placebo (22 control) or to Oxprop (20) and began drug administration within 96 hours of admission. All patients began RET at hospital discharge as part of their standardized care. Muscle strength (N[middle dot]m), power (W), VO2peak, body composition, and protein fractional synthetic (FSR) and breakdown (FBR) rates were measured pre- (PRE) and post-RET (POST). Results: Muscle strength and power, lean body mass and VO2peak increased with RET in both groups (p

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Thermoeffector Responses at a Fixed Rate of Heat Production in Heart Failure Patients.

Purpose: Heart failure (HF) patients appear to exhibit altered thermoregulatory responses during exercise in the heat. However, the extent to which these responses are altered due to physiological impairments independently of biophysical factors associated with differences in metabolic heat production (Hprod), evaporative heat balance requirements (Ereq) and/or body size, is presently unclear. Therefore, we examined thermoregulatory responses in 10 HF and 10 age-matched controls (CON) similar in body size during exercise at a fixed rate of Hprod, and therefore Ereq in a 30[degrees]C environment. Methods: Rectal temperature (Trec), local sweat rate (LSR), and cutaneous vascular conductance (CVC) were measured throughout 60-min of cycle ergometry. Whole-body sweat rate (WBSR) was estimated from pre-post nude body weight corrected for fluid intake. Results: Despite exercising at the same rate of Hprod (HF: 338+/-43; CON: 323+/-31W, p=0.25), the rise in Trec was greater (p

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Altered Macular Microvasculature in Mild Cognitive Impairment and Alzheimer Disease.

Background: The goal of the present study was to analyze the macular microvacular network in mild cognitive impirment (MCI) and Alzheimer disease (AD). Methods: Twelve patients with AD and 19 patients with MCI were recruited together with 21 cognitively normal controls with a similar range of ages. Optical coherence tomography angiography was used to image the retinal microvascular network at the macular region, including retinal vascular network (RVN), superficial vascular plexus (SVP), and deep vascular plexus (DVP). Fractal analysis (box counting, Dbox) representing the microvascular density was performed in different annular zones and quadrantal sectors. The macular ganglion cell-inner plexiform layer (GC-IPL) thickness was measured using Zeiss OCT. The relationship between the retinal microvasculature and clinical manifestations was analyzed. Results: Patients with AD had lower densities of RVN, SVP, and DVP in the annulus, from 0.6 to 2.5 mm in diameter ( 0.05). There was a trend of vascular density loss from control to MCI then AD (

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Clinical profile of silent growth hormone pituitary adenomas; higher recurrence rate compared to silent gonadotroph pituitary tumors, a large single center experience

Abstract

Purpose

Study and comparison of characteristics of silent growth hormone adenomas (SGHA), silent corticotroph adenomas (SCA), and silent gonadotroph adenomas (SGA) in a single institution cohort of surgically treated pituitary adenomas.

Methods

Retrospective analysis of SGHA surgically resected over 10 years: SGHA was defined as no clinical or biochemical evidence of acromegaly and positive GH immunostaining.

Results

Of 814 pituitary surgeries; 2.1% (n = 17) were SGHA, 4.5% (n = 37) SCA, and 18.9% (n = 70/371; 2011–2016) SGA. Mean age at SGHA diagnosis was 43 years, with a large female predominance (82%). Mean tumor size and cavernous/sphenoid sinus invasiveness for SGHA, SCA, and SGA were 1.5 ± 1.0 cm and 25%, 2.5 ± 1.2 cm and 43%, 2.9 ± 2.0 cm and 41%, respectively (tumor size p = 0.009, SGHA vs. SGA, and invasion p; not-significant). During mean follow-up of 3.9 years, two patients (11%) developed elevated insulin-like growth factor-1 and five patients (29%) required a second surgery for tumor recurrence. Rate of surgical reintervention was similar to SCA (31%), but higher than SGA (10%) (p = 0.035, SGHA vs. SGA), and 18% underwent radiation therapy, similar to SCA (19%, p; not-significant) but higher than SGA (2.9%, p = 0.018).

Conclusion

This is the largest single center study characterizing SGHA behavior with SGA and SCA control groups in a cohort of surgically resected pituitary adenomas. SGHA present mostly in young females, and should be closely followed due to their higher likelihood of recurrence and potential of progression to clinical acromegaly. We propose that a complete hormonal staining panel be routinely performed for all pituitary adenomas.

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Inherited and acquired clinical phenotypes associated with neuroendocrine tumors.

Purpose of review: Overview of neuroendocrine neoplasms in the context of their associations with primary and secondary immunodeficiency states. Recent findings: Malignancies of neuroendocrine origin are well known to be associated with hereditary syndromes, including multiple endocrine neoplasia type 1, von Hippel-Lindau syndrome, neurofibromatosis type 1, and tuberous sclerosis. This review includes the X-linked form of hyper-IgM syndrome (XHIGM), due to mutations in the CD40Ligand gene (CD40LG), as an additional inherited disorder with susceptibility to such malignancies, and discusses neuroendocrine tumors (NETs) arising in other immunocompromised states. Of all primary immune deficiency diseases, NETs appear to be unique to XHIGM patients. Outcomes for XHIGM patients with NETs is poor, and the mechanism behind this association remains unclear. In secondary immune deficiency states, NET occurrences were primarily in patients with HIV or AIDS, the autoimmune disease systemic lupus erythematosus and solid organ transplant recipients. Gastroenteropancreatic NETs were most frequent in XHIGM patients, whereas nongastroenteropancreatic-NETs, like Merkel cell carcinoma and small-cell lung carcinoma, affected HIV/AIDS patients. Possible mechanisms as to the nature of these associations are discussed, including chronic infections and inflammation, and CD40-CD40L interactions. Many questions remain, and further studies are needed to clarify the predisposition of patients with XHIGM to the development of NETs. Given that many of these patients present late in their disease state and have poor outcomes, it is imperative to keep a high index of suspicion at the advent of early signs and symptoms. Regular monitoring with laboratory or imaging studies, including tumor markers, may be warranted, for which further studies are needed. Summary: Of all primary immunodeficiency diseases, NETs appear to be unique to XHIGM, and the mechanism behind this association remains unclear. Outcome for XHIGM patients with NETs is poor, and it is imperative to keep a high index of suspicion at the advent of early signs and symptoms. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2gq1pSD