Transition to Medicare Does Not Contribute to Rise in Outpatient Visits for Nonmelanoma Skin Cancer, Actinic Keratosis, or Actinic Cheilitis in the US Population.

BACKGROUND: Outpatient visits for nonmelanoma skin cancer (NMSC) and actinic keratoses (AK) have risen steadily in the United States, notably among Medicare beneficiaries. Individuals may delay seeking care for minimally symptomatic conditions until they qualify for Medicare coverage, indicating potential delay of nonurgent screening interventions for uninsured or underinsured patients younger than 65 years. OBJECTIVE: This study investigates whether an atypical increase in outpatient visits for NMSC, AK, or actinic cheilitis (AC) occurs at the age of Medicare transition by utilizing the National Ambulatory Care Survey from 1993 to 2019. MATERIALS AND METHODS: The National Ambulatory Care Survey data were analyzed for patients aged within 5 years of 65 years. Diagnoses were identified using International Classification of Diseases codes. Linear regression and outlier detection were used to identify a relationship between Medicare eligibility and outpatient visits for NMSC and AK/AC. RESULTS: Predicted visits for AK/AC and NMSC increased with age. However, there was no evidence of a disproportionate increase in outpatient visits for NMSC and AK/AC at the age of Medicare eligibility. CONCLUSION: Outside evidence indicates health care utilization increases after Medicare transition. This study's data do not support a corresponding rise in outpatient visits for NMSC and AK/AC at the age of Medicare eligibility.

Sex Does Not Affect Changes in Body Composition and Insulin-Like Growth Factor-I During US Army Basic Combat Training.

ABSTRACT: Roberts, BM, Staab, JS, Caldwell, AR, Sczuroski, CE, Staab, JE, Lutz, LJ, Reynoso, M, Geddis, AV, Taylor, KM, Guerriere, KI, Walker, LA, Hughes, JM, and Foulis, SA. Sex does not affect changes in body composition and insulin-like growth factor-I during US Army basic combat training. J Strength Cond Res 38(6): e304-e309, 2024-Insulin-like growth factor 1 (IGF-I) has been implicated as a biomarker of health and body composition. However, whether changes in body composition are associated with changes in IGF-I is unclear. Therefore, we examined the relationship between body composition changes (i.e., fat mass and lean mass) and total serum IGF-I levels in a large cohort of young men ( n = 809) and women ( n = 397) attending US Army basic combat training (BCT). We measured body composition using dual energy x-ray absorptiometry and total serum IGF-I levels during week 1 and week 9 of BCT. We found that pre-BCT lean mass ( r = 0.0504, p = 0.082) and fat mass ( r = 0.0458, p = 0.082) were not associated with pre-BCT IGF-I. Body mass, body mass index, body fat percentage, and fat mass decreased, and lean mass increased during BCT (all p < 0.001). Mean (± SD ) IGF-I increased from pre-BCT (176 ± 50 ng·ml -1 ) to post-BCT (200 ± 50 ng·ml -1 , p < 0.001). Inspection of the partial correlations indicated that even when considering the unique contributions of other variables, increases in IGF-I during BCT were associated with both increased lean mass ( r = 0.0769, p = 0.023) and increased fat mass ( r = 0.1055, p < 0.001) with no sex differences. Taken together, our data suggest that although changes in IGF-I weakly correlated with changes in body composition, IGF-I, in isolation, is not an adequate biomarker for predicting changes in body composition during BCT in US Army trainees.

Body mass index, but not sex, influences exertional heat stroke risk in young healthy men and women.

Exertional heat stroke (EHS) remains a persistent threat for individuals working or playing in the heat, including athletes and military and emergency service personnel. However, influence of biological sex and/or body mass index (BMI) on the risk of EHS remain poorly understood. The purpose of this study was to retrospectively assess the influence of sex and BMI on risk of EHS in the active-duty US Army. We analyzed data from 2016 to 2021, using a matched case-control approach, where each individual with a diagnosis of EHS was matched to five controls based on calendar time, unit ID, and job category, to capture control individuals who were matched to EHS events by location, time, and activity. We used a multivariate logistic regression model mutually adjusted for sex, BMI, and age to compare 745 (n = 61 F) individuals (26 ± 7 yr) with a diagnosed EHS to 4,290 (n = 384 F) case controls (25 ± 5 yr). Group average BMI were similar: 26.6 ± 3.1 (EHS) and 26.5 ± 3.6 kg/m2 (CON). BMI was significantly (P < 0.0001) associated with higher risk of EHS with a 3% increase in risk of EHS for every unit increase in BMI. Notably, sex was not associated with any difference in risk for EHS (P = 0.54). These data suggest that young healthy people with higher BMI have significantly higher risk of EHS, but, contrary to what some have proposed, this risk was not higher in young women.

The LIV-1 Subfamily of Zinc Transporters: From Origins to Present Day Discoveries.

This review explains the origin of the LIV-1 family of zinc transporters, paying attention to how this family of nine human proteins was originally discovered. Structural and functional differences between these nine human LIV-1 family members and the five other ZIP transporters are examined. These differences are both related to aspects of the protein sequence, the conservation of important motifs and to the effect this may have on their overall function. The LIV-1 family are dependent on various post-translational modifications, such as phosphorylation and cleavage, which play an important role in their ability to transport zinc. These modifications and their implications are discussed in detail. Some of these proteins have been implicated in cancer which is examined. Furthermore, some additional areas of potential fruitful discovery are discussed and suggested as worthy of examination in the future.

Psychosis Early Intervention Across the Life Span: A Service Perspective.

Previously youth-orientated, UK early intervention in psychosis (EI) services expanded care in 2016 to adults of any age. To compare EI care offering, clinical characteristics, and potential benefits for under-35s and over-35s, an observational study considering anonymised data for users of London-based EI services between April 2016 and December 2019 was conducted. Descriptive statistics and between groups comparisons are reported. The analysis considered 692 service users (32.5% over-35). Over-35s were more likely to be female, of poorer physical health, with severer problems at intake (Health of the Nation Outcome Scale, HoNOS). Under-35s had poorer appointment attendance, required increased use of inpatient facilities, and demonstrated greater risks to themselves and others. At discharge, HoNOS ratings indicated improvements for both groups. Over-35s constitute a considerable proportion of EI service-users, their care may involve less crisis management, more recovery-oriented intervention and physical health needs consideration. Care offering should reflect these needs.

Zinc transporters and their functional integration in mammalian cells.

Zinc is a ubiquitous biological metal in all living organisms. The spatiotemporal zinc dynamics in cells provide crucial cellular signaling opportunities, but also challenges for intracellular zinc homeostasis with broad disease implications. Zinc transporters play a central role in regulating cellular zinc balance and subcellular zinc distributions. The discoveries of two complementary families of mammalian zinc transporters (ZnTs and ZIPs) in the mid-1990s spurred much speculation on their metal selectivity and cellular functions. After two decades of research, we have arrived at a biochemical description of zinc transport. However, in vitro functions are fundamentally different from those in living cells, where mammalian zinc transporters are directed to specific subcellular locations, engaged in dedicated macromolecular machineries, and connected with diverse cellular processes. Hence, the molecular functions of individual zinc transporters are reshaped and deeply integrated in cells to promote the utilization of zinc chemistry to perform enzymatic reactions, tune cellular responsiveness to pathophysiologic signals, and safeguard cellular homeostasis. At present, the underlying mechanisms driving the functional integration of mammalian zinc transporters are largely unknown. This knowledge gap has motivated a shift of the research focus from in vitro studies of purified zinc transporters to in cell studies of mammalian zinc transporters in the context of their subcellular locations and protein interactions. In this review, we will outline how knowledge of zinc transporters has been accumulated from in-test-tube to in-cell studies, highlighting new insights and paradigm shifts in our understanding of the molecular and cellular basis of mammalian zinc transporter functions.

The ZIP6/ZIP10 heteromer is essential for the zinc-mediated trigger of mitosis.

Zinc has been known to be essential for cell division for over 40 years but the molecular pathways involved remain elusive. Cellular zinc import across biological membranes necessitates the help of zinc transporters such as the SLC39A family of ZIP transporters. We have discovered a molecular process that explains why zinc is required for cell division, involving two highly regulated zinc transporters, as a heteromer of ZIP6 and ZIP10, providing the means of cellular zinc entry at a specific time of the cell cycle that initiates a pathway resulting in the onset of mitosis. Crucially, when the zinc influx across this heteromer is blocked by ZIP6 or ZIP10 specific antibodies, there is no evidence of mitosis, confirming the requirement for zinc influx as a trigger of mitosis. The zinc that influxes into cells to trigger mitosis additionally changes the phosphorylation state of STAT3 converting it from a transcription factor to a protein that complexes with this heteromer and pS38Stathmin, the form allowing microtubule rearrangement as required in mitosis. This discovery now explains the specific cellular role of ZIP6 and ZIP10 and how they have special importance in the mitosis process compared to other ZIP transporter family members. This finding offers new therapeutic opportunities for inhibition of cell division in the many proliferative diseases that exist, such as cancer.

Behavioral couples therapy for brain injury: single case methodology with bi-phasic design.

OBJECTIVES: To explore the outcomes of Behavioral Couples Therapy (BCT) for couples with brain injury. BACKGROUND: Brain injury can result in communication, emotional and behavioral disturbances, leading to higher levels of depression, anxiety and relationship distress. Currently, no study has explored the outcomes of BCT in couples impacted by brain injury. METHOD: Four heterosexual couples living with brain injury were seen at a specialist outpatient service, and attended an average of 13 (range 8-25) BCT sessions. Participants with brain injury and their partners completed weekly measures of depression, anxiety, and couple satisfaction throughout baseline, assessment, intervention, and follow-up phases. Data were visually analyzed, and effects examined using reliable change analysis, and between-phase comparison conducted using Tau-U. RESULTS: Tau-U analysis demonstrated that both the patient and partner groups experienced significant overall improvement in relationship satisfaction and anxiety. Partners also reported significant reduction in depression scores overall. Reliable change analysis indicated improvement for some individual patients and partners, with effects maintained at follow-up in some cases. CONCLUSIONS: The results offer promising results regarding the use of BCT for brain injury in increasing relationship satisfaction and reducing psychological distress. Further investigation is warranted.

Detailed analyses of the crucial functions of Zn transporter proteins in alkaline phosphatase activation.

Numerous zinc ectoenzymes are metalated by zinc and activated in the compartments of the early secretory pathway before reaching their destination. Zn transporter (ZNT) proteins located in these compartments are essential for ectoenzyme activation. We have previously reported that ZNT proteins, specifically ZNT5-ZNT6 heterodimers and ZNT7 homodimers, play critical roles in the activation of zinc ectoenzymes, such as alkaline phosphatases (ALPs), by mobilizing cytosolic zinc into these compartments. However, this process remains incompletely understood. Here, using genetically-engineered chicken DT40 cells, we first determined that Zrt/Irt-like protein (ZIP) transporters that are localized to the compartments of the early secretory pathway play only a minor role in the ALP activation process. These transporters included ZIP7, ZIP9, and ZIP13, performing pivotal functions in maintaining cellular homeostasis by effluxing zinc out of the compartments. Next, using purified ALP proteins, we showed that zinc metalation on ALP produced in DT40 cells lacking ZNT5-ZNT6 heterodimers and ZNT7 homodimers is impaired. Finally, by genetically disrupting both ZNT5 and ZNT7 in human HAP1 cells, we directly demonstrated that the tissue-nonspecific ALP-activating functions of both ZNT complexes are conserved in human cells. Furthermore, using mutant HAP1 cells, we uncovered a previously-unrecognized and unique spatial regulation of ZNT5-ZNT6 heterodimer formation, wherein ZNT5 recruits ZNT6 to the Golgi apparatus to form the heterodimeric complex. These findings fill in major gaps in our understanding of the molecular mechanisms underlying zinc ectoenzyme activation in the compartments of the early secretory pathway.

Body mass does not reflect the body composition changes in response to similar physical training in young women and men.

INTRODUCTION: U.S. Army Basic Combat Training (BCT) prepares new recruits to meet soldier physical demands. It also serves as a model of physical changes in healthy young nonobese women and men during an intensive 10-week training program without diet restriction. In this prospective observational study, we quantified the changes in lean mass and body fat induced by BCT in a large sample of men and women undergoing the same physical training program. METHODS: Young women (n = 573) and men (n = 1071) meeting Army health and fitness recruitment standards volunteered to provide DXA-derived body composition data at the beginning and end of BCT. RESULTS: During BCT, there was no change in body mass in women and a 1.7-kg loss in men. Relative body fat (%BF) declined by an average of 4.0 ± 2.4 and 3.4 ± 2.8 percentage points (±SD) for women and men, respectively. The greatest predictor of change in %BF during BCT for both sexes was %BF at the beginning of training. Women and men gained an average 2.7 ± 1.6 kg and 1.7 ± 2.0 kg of lean mass during BCT. CONCLUSIONS: Army BCT produced significant effects on body composition despite minimal changes in total body mass. These findings demonstrate the ability of a 10-week sex-integrated physical training program to positively alter body composition profiles of young adults.

Suicidal ideation and behaviour in patients with persecutory delusions: Prevalence, symptom associations, and psychological correlates.

BACKGROUND: To determine the prevalence of suicidal ideation and behaviour - and their correlates - in patients with persecutory delusions. METHODS: 110 patients with persecutory delusions in the context of non-affective psychosis were assessed for suicidal thoughts and behaviours over the past month. Symptom and psychological assessments were also completed. RESULTS: The severity of suicidal ideation was: no suicidal ideation (n = 26, 23.6%); wish to be dead (n = 21, 19.1%); nonspecific active suicidal thoughts (n = 14, 12.7%); suicidal thoughts with methods but no intent (n = 29, 26.4%); suicidal thoughts with intent but no specific plan (n = 13, 11.8%); and suicidal intent with plan (n = 7, 6.4%). In the past month, five patients (4.5%) had made an actual, interrupted, or aborted suicide attempt. The severity of suicidal ideation was associated with higher levels of depression, paranoia, hallucinations, anger, insomnia, negative beliefs about the self and others, pessimism, worry, and delusion safety-seeking behaviours and lower levels of psychological well-being and reward responsiveness. Severity of ideation was not associated with cannabis or alcohol use, working memory, pain, or meaningful activity levels. CONCLUSIONS: Patients with persecutory delusions are typically in a severe state of psychological stress, and at risk of suicide, as indicated by very high levels of suicidal ideation. This exploratory study also identifies correlates of suicidal ideation that could be investigated in causal research designs.

Cognitive Behavioural Therapy for Nightmares for Patients with Persecutory Delusions (Nites): An Assessor-Blind, Pilot Randomized Controlled Trial.

OBJECTIVE: Nightmares are relatively common in patients experiencing psychosis but rarely assessed or treated. Nightmares may maintain persecutory delusions by portraying fears in sensory-rich detail. We tested the potential benefits of imagery-focused cognitive behavioural therapy (CBT) for nightmares on nightmare severity and persecutory delusions. METHOD: This assessor-blind parallel-group pilot trial randomized 24 participants with nightmares and persecutory delusions to receive CBT for nightmares delivered over 4 weeks in addition to treatment as usual (TAU) or TAU alone. Assessments were at 0, 4 (end of treatment), and 8 weeks (follow-up). Feasibility outcomes assessed therapy uptake, techniques used, satisfaction, and attrition. The primary efficacy outcome assessed nightmare severity at week 4. Analyses were intention to treat, estimating treatment effect with 95% confidence intervals (CIs). RESULTS: All participants offered CBT completed therapy (mean [SD], 4.8 [0.6] sessions) with high satisfaction, and 20 (83%) participants completed all assessments. Compared with TAU, CBT led to large improvements in nightmares (adjusted mean difference = -7.0; 95% CI, -12.6 to -1.3; d = -1.1) and insomnia (6.3; 95% CI, 2.6 to 10.0; d = 1.4) at week 4. Gains were maintained at follow-up. Suicidal ideation was not exacerbated by CBT but remained stable to follow-up, compared with TAU, which reduced at follow-up (6.8; 95% CI, 0.3 to 3.3; d = 0.7). CBT led to reductions in paranoia (-20.8; 95% CI, -43.2 to 1.7; d = -0.6), although CIs were wide. Three serious adverse events were deemed unrelated to participation (CBT = 2, TAU = 1). CONCLUSIONS: CBT for nightmares is feasible and may be efficacious for treating nightmares and comorbid insomnia for patients with persecutory delusions. It shows promise on paranoia but potentially not on suicidal ideation.

A mixed methods randomised control trial to evaluate the effectiveness of the journey to social inclusion - phase 2 intervention for chronically homeless adults: study protocol.

BACKGROUND: Chronic homelessness is a problem characterised by longstanding inability to attain or maintain secure accommodation. Longitudinal research with homeless populations is challenging, and randomised controlled trials that evaluate the effectiveness of intensive, case management interventions aimed at improving housing and health-related outcomes for chronically homelessness people are scant. More research is needed to inform programmatic design and policy frameworks in this area. This study protocol details an evaluation of the Journey to Social Inclusion - Phase 2 program, an intervention designed to reduce homelessness and improve outcomes in chronically homeless adults. METHODS/DESIGN: J2SI Phase 2 is a three-year, mixed methods, multi-site, RCT that enrolled 186 participants aged 25 to 50 years between 07 January 2016 and 30 September 2016 in Melbourne. The intervention group (n = 90 recruited) receives the J2SI Phase 2 program, a trauma-informed intervention that integrates intensive case management and service coordination; transition to housing and support to sustain tenancy; and support to build social connections, obtain employment and foster independence. The comparison group (n = 96 recruited) receives standard service provision. Prior to randomisation, participants completed a baseline survey. Follow-up surveys will be completed every six months for three years (six in total). In addition to self-report data on history of homelessness and housing, physical and mental health, substance use, quality of life, social connectedness and public service utilisation, linked administrative data on participants' public services utilisation (e.g., hospitalisation, justice system) will be obtained for the three-year period pre- and post-randomisation. Semi-structured, qualitative interviews will be conducted with a randomly selected subset of participants and service providers at three time-points to explore changes in key outcome variables and to examine individual experiences with the intervention and standard service provision. An economic evaluation of the intervention and associated costs will also be undertaken. DISCUSSION: Results of this trial will provide robust evidence on the effectiveness of J2SI Phase 2 compared to standard service provision. If the intervention demonstrates effectiveness in improving housing, health, quality-of-life, and other social outcomes, it may be considered for broader national and international dissemination to improve outcomes among chronically homeless adults. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12616000162415 (retrospectively registered 10-February-2016).

A prospective field study of U.S. Army trainees to identify the physiological bases and key factors influencing musculoskeletal injuries: a study protocol.

BACKGROUND: Musculoskeletal injuries (MSKIs) are common in military trainees and present a considerable threat to occupational fitness, deployability, and overall military readiness. Despite the negative effects of MSKIs on military readiness, comprehensive evaluations of the key known and possible risk factors for MSKIs are lacking. The U.S. Army Research Institute of Environmental Medicine (ARIEM) is initiating a large-scale research effort, the ARIEM Reduction in Musculoskeletal Injury (ARMI) Study, to better understand the interrelationships among a wide range of potential MSKI risk factors in U.S. Army trainees in order to identify those risk factors that most contribute to MSKI and may be best targeted for effective mitigation strategies. METHODS: This prospective study aims to enroll approximately 4000 (2000 male and 2000 female) U.S. Army trainees undergoing Basic Combat Training (BCT). Comprehensive in-person assessments will be completed at both the beginning and end of BCT. Participants will be asked to complete surveys of personal background information, medical history, physical activity, sleep behaviors, and personality traits. Physical measurements will be performed to assess anthropometrics, tibial microarchitecture and whole body bone mineral density, muscle cross-sectional area, body composition, and muscle function. Blood sampling will be also be conducted to assess musculoskeletal, genetic, and nutritional biomarkers of risk. In addition, participants will complete weekly surveys during BCT that examine MSKI events, lost training time, and discrete risk factors for injury. Participants' medical records will be tracked for the 2 years following graduation from training to identify MSKI events and related information. Research hypotheses focus on the development of a multivariate prediction model for MSKI. DISCUSSION: Results from this study are expected to inform current understanding of known and potential risk factors for MSKIs that can be incorporated into solutions that optimize Soldier health and enhance military readiness.

Zinc transporter ZIP10 forms a heteromer with ZIP6 which regulates embryonic development and cell migration.

There is growing evidence that zinc and its transporters are involved in cell migration during development and in cancer. In the present study, we show that zinc transporter ZIP10 (SLC39A10) stimulates cell motility and proliferation, both in mammalian cells and in the zebrafish embryo. This is associated with inactivation of GSK (glycogen synthase kinase)-3α and -3ß and down-regulation of E-cadherin (CDH1). Morpholino-mediated knockdown of zip10 causes delayed epiboly and deformities of the head, eye, heart and tail. Furthermore, zip10 deficiency results in overexpression of cdh1, zip6 and stat3, the latter gene product driving transcription of both zip6 and zip10 The non-redundant requirement of Zip6 and Zip10 for epithelial to mesenchymal transition (EMT) is consistent with our finding that they exist as a heteromer. We postulate that a subset of ZIPs carrying prion protein (PrP)-like ectodomains, including ZIP6 and ZIP10, are integral to cellular pathways and plasticity programmes, such as EMT.

Characterization of Zinc Influx Transporters (ZIPs) in Pancreatic ß Cells: ROLES IN REGULATING CYTOSOLIC ZINC HOMEOSTASIS AND INSULIN SECRETION.

Zinc plays an essential role in the regulation of pancreatic ß cell function, affecting important processes including insulin biosynthesis, glucose-stimulated insulin secretion, and cell viability. Mutations in the zinc efflux transport protein ZnT8 have been linked with both type 1 and type 2 diabetes, further supporting an important role for zinc in glucose homeostasis. However, very little is known about how cytosolic zinc is controlled by zinc influx transporters (ZIPs). In this study, we examined the ß cell and islet ZIP transcriptome and show consistent high expression of ZIP6 (Slc39a6) and ZIP7 (Slc39a7) genes across human and mouse islets and MIN6 ß cells. Modulation of ZIP6 and ZIP7 expression significantly altered cytosolic zinc influx in pancreatic ß cells, indicating an important role for ZIP6 and ZIP7 in regulating cellular zinc homeostasis. Functionally, this dysregulated cytosolic zinc homeostasis led to impaired insulin secretion. In parallel studies, we identified both ZIP6 and ZIP7 as potential interacting proteins with GLP-1R by a membrane yeast two-hybrid assay. Knock-down of ZIP6 but not ZIP7 in MIN6 ß cells impaired the protective effects of GLP-1 on fatty acid-induced cell apoptosis, possibly via reduced activation of the p-ERK pathway. Therefore, our data suggest that ZIP6 and ZIP7 function as two important zinc influx transporters to regulate cytosolic zinc concentrations and insulin secretion in ß cells. In particular, ZIP6 is also capable of directly interacting with GLP-1R to facilitate the protective effect of GLP-1 on ß cell survival.

Human exposure to nitro musks and the evaluation of their potential toxicity: an overview.

Synthetic nitro musks are fragrant chemicals found in household and personal care products. The use of these products leads to direct exposures via dermal absorption, as well as inhalation of contaminated dust and volatilized fragrances. Evidence also suggests that humans are exposed to low doses of these chemicals through oral absorption of contaminated liquids and foods. As these compounds are lipophilic, they and their metabolites, have been found not only in blood, but also breast milk and adipose tissue. After personal use, these environmentally persistent pollutants then pass through sewage treatment plants through their effluent into the environment.Little is known about the biological effects in humans after such a prolonged low dose exposure to these chemicals. While epidemiologic studies evaluating the effects of nitro musk exposures are lacking, there is limited evidence that suggest blood levels of nitro musks are inversely related to luteal hormone levels. This is supported by animal models and laboratory studies that have shown that nitro musks are weakly estrogenic. Nitro musks exposure has been associated with an increased risk of tumor formation in mice. The evidence suggests that while nitro musks by themselves are not genotoxic, they may increase the genotoxicity of other chemicals. However, animal models for nitro musk exposure have proven to be problematic since certain outcomes are species specific. This may explain why evidence for developmental effects in animals is conflicting and inconclusive. Given that animal models and cell-line experiments are suggestive of adverse outcomes, further epidemiologic studies are warranted.

A mechanism for epithelial-mesenchymal transition and anoikis resistance in breast cancer triggered by zinc channel ZIP6 and STAT3 (signal transducer and activator of transcription 3).

Genes involved in normal developmental processes attract attention as mediators of tumour progression as they facilitate migration of tumour cells. EMT (epithelial-mesenchymal transition), an essential part of embryonic development, tissue remodelling and wound repair, is crucial for tumour metastasis. Previously, zinc transporter ZIP6 [SLC39A6; solute carrier family 39 (zinc transporter), member 6; also known as LIV-1) was linked to EMT in zebrafish gastrulation through a STAT3 (signal transducer and activator of transcription 3) mechanism, resulting in nuclear localization of transcription factor Snail. In the present study, we show that zinc transporter ZIP6 is transcriptionally induced by STAT3 and unprecedented among zinc transporters, and is activated by N-terminal cleavage which triggers ZIP6 plasma membrane location and zinc influx. This zinc influx inactivates GSK-3ß (glycogen synthase kinase 3ß), either indirectly or directly via Akt or GSK-3ß respectively, resulting in activation of Snail, which remains in the nucleus and acts as a transcriptional repressor of E-cadherin (epithelial cadherin), CDH1, causing cell rounding and detachment. This was mirrored by ZIP6-transfected cells which underwent EMT, detached from monolayers and exhibited resistance to anoikis by their ability to continue proliferating even after detachment. Our results indicate a causative role for ZIP6 in cell motility and migration, providing ZIP6 as a new target for prediction of clinical cancer spread and also suggesting a ZIP6-dependent mechanism of tumour metastasis.

Relation of body surface area-to-mass ratio to risk of exertional heat stroke in healthy men and women.

Risk of exertional heat stroke (EHS) is an ongoing challenge for United States military personnel, for athletes and for individuals with occupational stressors that involve prolonged activity in hot environments. Higher body mass index (BMI) is significantly associated with increased risk for EHS in activity duty U.S. Soldiers. During exercise, heat is generated primarily by contracting skeletal muscle (and other metabolically active body mass) and dissipated based on body surface area (BSA). Thus, in compensable environments, a higher BSA·mass-1 may be a benefit to heat dissipation and decrease the risk of EHS. The purpose of the present analysis was to test the hypothesis that BSA·mass-1 ratio is an important biophysical characteristic contributing to the risk of EHS. We employed a matched case-control approach, where each individual with a diagnosis of EHS was matched to five controls who were never diagnosed with EHS but were in the same unit and had the same job title. We used a multivariate conditional logistic regression model including variables of BSA·mass-1, sex, age, military rank, and race. BSA·mass-1 significantly predicted EHS risk (P = 0.006), such that people with higher BSA·mass-1 were at lower risk of developing EHS when controlling for other potential factors such as age and race. This relationship persisted after adjustment for other anthropometric measures of body size including weight, BMI, and BSA. These data suggest that biophysical factors play an important role in EHS risk, particularly in a healthy military-aged cohort of men and women.NEW & NOTEWORTHY With the impacts of climate change yielding higher average ambient temperatures over time, the incidence of EHS for individuals participating in outdoor activities may consequently increase. With the larger sample size in this study compared with prior research in this field, we were able to use various methods that had not been applied before. For example, we were able to mutually adjust for different measurements of body size to understand which metric had the highest association with EHS risk. Understanding factors that may be modifiable may be important for developing interventions to counteract the increased risk of EHS associated with climate change.

Development and cross-validation of a circumference-based predictive equation to estimate body fat in an active population.

Objective: The U.S. Army uses sex-specific circumference-based prediction equations to estimate percent body fat (%BF) to evaluate adherence to body composition standards. The equations are periodically evaluated to ensure that they continue to accurately assess %BF in a diverse population. The objective of this study was to develop and validate alternative field expedient equations that may improve upon the current Army Regulation (AR) body fat (%BF) equations. Methods: Body size and composition were evaluated in a representatively sampled cohort of 1904 active-duty Soldiers (1261 Males, 643 Females), using dual-energy X-ray absorptiometry (%BFDXA), and circumferences obtained with 3D imaging and manual measurements. Sex stratified linear prediction equations for %BF were constructed using internal cross validation with %BFDXA as the criterion measure. Prediction equations were evaluated for accuracy and precision using root mean squared error, bias, and intraclass correlations. Equations were externally validated in a convenient sample of 1073 Soldiers. Results: Three new equations were developed using one to three circumference sites. The predictive values of waist, abdomen, hip circumference, weight and height were evaluated. Changing from a 3-site model to a 1-site model had minimal impact on measurements of model accuracy and performance. Male-specific equations demonstrated larger gains in accuracy, whereas female-specific equations resulted in minor improvements in accuracy compared to existing AR equations. Equations performed similarly in the second external validation cohort. Conclusions: The equations developed improved upon the current AR equation while demonstrating robust and consistent results within an external population. The 1-site waist circumference-based equation utilized the abdominal measurement, which aligns with associated obesity related health outcomes. This could be used to identify individuals at risk for negative health outcomes for earlier intervention.