Optimisation of vitamin D status in global populations.

Vitamin D is important for musculoskeletal health. Concentrations of 25-hydroxyvitamin D, the most commonly measured metabolite, vary markedly around the world and are influenced by many factors including sun exposure, skin pigmentation, covering, season and supplement use. Whilst overt vitamin D deficiency with biochemical consequences presents an increased risk of severe sequelae such as rickets, osteomalacia or cardiomyopathy and usually warrants prompt replacement treatment, the role of vitamin D supplementation in the population presents a different set of considerations. Here the issue is to keep, on average, the population at a level whereby the risk of adverse health outcomes in the population is minimised. This position paper, which complements recently published work from the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases, addresses key considerations regarding vitamin D assessment and intervention from the population perspective. This position paper, on behalf of the International Osteoporosis Foundation Vitamin D Working Group, summarises the burden and possible amelioration of vitamin D deficiency in global populations. It addresses key issues including screening, supplementation and food fortification.

Rising hospital admissions for alcohol-related cirrhosis and the impact of sex and comorbidity - a data linkage study.

OBJECTIVES: International studies have shown shifting demographic data and rising hospitalizations for alcohol-related cirrhosis (ARC), with a paucity of data from Australia. We examined hospitalizations, mortality and demographic data for people admitted with ARC over the last decade in Queensland, Australia. STUDY DESIGN: Data linkage study. METHODS: A retrospective analysis of adults hospitalized with ARC during 2008-2019 was performed using state-wide admissions data. International Classification of Diseases, 10th revision, codes identified admissions with the principal diagnosis of ARC based on validated algorithms. Comorbidity was assessed using the Charlson Comorbidity Index. RESULTS: A total of 7152 individuals had 24,342 hospital admissions with ARC (16,388 were for ARC). There was a predominance of males (72.6%) and age ≥50 years (80.4%) at index admission. Females were admitted at a significantly younger age than men (59% of women and 43% of men were aged <60 years, P < 0.001). Comorbidities were common, with 45.1% of people having at least one comorbidity. More than half (54.6%) of the patients died over the study period (median follow-up time was 5.1 years; interquartile range 2.4-8.6). Women had significantly lower mortality, with 47.6% (95% confidence interval [CI] 45.0-50.2) probability of 5-year survival, compared with 40.1% (95% CI 38.5-41.6) in men. In multivariable analysis, this was attributable to significantly lower age and comorbidity burden in women. Significantly lower survival was seen in people with higher comorbidity burden. Overall, the number of admissions for ARC increased 2.2-fold from 869 admissions in 2008 to 1932 in 2019. CONCLUSIONS: Hospital admissions for ARC have risen substantially in the last decade. Females were admitted at a younger age, with fewer comorbidities and had lower mortality compared with males. The association between greater comorbidity burden and higher mortality has important clinical implications, as comorbidity-directed interventions may reduce mortality.

A kilonova as the electromagnetic counterpart to a gravitational-wave source.

Gravitational waves were discovered with the detection of binary black-hole mergers and they should also be detectable from lower-mass neutron-star mergers. These are predicted to eject material rich in heavy radioactive isotopes that can power an electromagnetic signal. This signal is luminous at optical and infrared wavelengths and is called a kilonova. The gravitational-wave source GW170817 arose from a binary neutron-star merger in the nearby Universe with a relatively well confined sky position and distance estimate. Here we report observations and physical modelling of a rapidly fading electromagnetic transient in the galaxy NGC 4993, which is spatially coincident with GW170817 and with a weak, short γ-ray burst. The transient has physical parameters that broadly match the theoretical predictions of blue kilonovae from neutron-star mergers. The emitted electromagnetic radiation can be explained with an ejected mass of 0.04 ± 0.01 solar masses, with an opacity of less than 0.5 square centimetres per gram, at a velocity of 0.2 ± 0.1 times light speed. The power source is constrained to have a power-law slope of -1.2 ± 0.3, consistent with radioactive powering from r-process nuclides. (The r-process is a series of neutron capture reactions that synthesise many of the elements heavier than iron.) We identify line features in the spectra that are consistent with light r-process elements (atomic masses of 90-140). As it fades, the transient rapidly becomes red, and a higher-opacity, lanthanide-rich ejecta component may contribute to the emission. This indicates that neutron-star mergers produce gravitational waves and radioactively powered kilonovae, and are a nucleosynthetic source of the r-process elements.

Greening Family Medicine clinic operations and clinical care, where do we start? A scoping review of toolkits and aids.

BACKGROUND: There is a pressing need for healthcare to respond to the climate crisis. Family physicians, given their central role in community healthcare provision, are strategically placed to lead, support, and promote sustainable healthcare, yet guidance on how to do this is fragmented. OBJECTIVE: To identify and evaluate toolkits and aids on sustainable healthcare to act as a curated resource for family physicians and their care teams interested in delivering evidence-based sustainable healthcare in their clinical practices. METHODS: A scoping review was completed of the published and grey literature across 4 databases and 2 search engines to identify articles and aids/toolkits from 1990 to present. Toolkits were subsequently evaluated for purpose, evidence-base, implementation process, adaptability to family medicine, and outcome measures. RESULTS: The search identified 17,751 articles. Screening resulted in 20 published articles and 11 toolkits. Most articles presented simple checklists to support greening clinic initiatives, 3 studies focussed on partial carbon footprint analyses, and 4 on educational initiatives. Toolkits ranged in sustainability topics and degree of depth covered, and adaptability and outcome measures. None of the resources identified have been formally evaluated for effectiveness. CONCLUSIONS: A range of aids exist to support greening of clinic operations; however, there is a significant gap in the literature for greening clinical care. Two toolkits were found to be comprehensive, one requiring tracking and reporting of sustainability initiatives. This scoping review provides a starting point for motivated family doctors and community clinics to initiate change and support more sustainable healthcare.

Subclinical to catastrophic: a range of outcomes in cerebral air embolism.

Cerebral air embolism (CAE) is a rare, yet potentially devastating condition characterized by entrance of air into cerebral vasculature, that is nearly always iatrogenic. While many findings of CAE are subclinical and incidental at computed tomography (CT), there remain cases of catastrophic and fatal embolisms. Increasing physician awareness of prevention, presentation, and treatment for CAE is crucial for reducing morbidity and mortality. In this case series, we highlight this preventable entity by comparing three cases of CAE that showcase a diverse array of presentations, radiologic findings, and clinical outcomes. We will also explore predisposing factors, prognostic predictors, diagnostic considerations, and available treatments.

Core principles for fracture prevention: North American Consensus from the National Osteoporosis Foundation, Osteoporosis Canada, and Academia Nacional de Medicina de Mexico.

Core principles for fracture prevention address fundamental concepts for the evaluation and management of patients at risk for fracture. These are intended to form the foundation of clinical practice guidelines and represent a first step toward guideline harmonization. INTRODUCTION: The large number of clinical practice guidelines for osteoporosis and discordance of recommendations has led to confusion among clinicians and patients, and likely contributes to the large osteoporosis treatment gap. We propose that stakeholder organizations reach agreement on fundamental principles in the management of osteoporosis and prevention of fracture as a first step toward a goal of guideline harmonization. METHODS: The best available evidence, as interpreted by an ad hoc working group of expert representatives from major osteoporosis societies in North America, was considered in the development of core principles for skeletal healthcare. These principles were subsequently endorsed by the USA National Osteoporosis Foundation, Osteoporosis Canada, and Academia Nacional de Medicina de Mexico (National Academy of Medicine of Mexico). RESULTS: Core principles are summarized here in bullet format. Categories include evaluation, lifestyle and nutrition, pharmacological therapy, and monitoring. A pathway forward to achieve guideline harmonization, at least in part, is proposed. CONCLUSION: Greater concordance of recommendations for the care of patients at risk for fracture are expected to lead to improved patient care across jurisdictions, with a narrowing of the osteoporosis treatment gap and reduced burden of fractures.

Millennial-scale variability in Antarctic ice-sheet discharge during the last deglaciation.

Our understanding of the deglacial evolution of the Antarctic Ice Sheet (AIS) following the Last Glacial Maximum (26,000-19,000 years ago) is based largely on a few well-dated but temporally and geographically restricted terrestrial and shallow-marine sequences. This sparseness limits our understanding of the dominant feedbacks between the AIS, Southern Hemisphere climate and global sea level. Marine records of iceberg-rafted debris (IBRD) provide a nearly continuous signal of ice-sheet dynamics and variability. IBRD records from the North Atlantic Ocean have been widely used to reconstruct variability in Northern Hemisphere ice sheets, but comparable records from the Southern Ocean of the AIS are lacking because of the low resolution and large dating uncertainties in existing sediment cores. Here we present two well-dated, high-resolution IBRD records that capture a spatially integrated signal of AIS variability during the last deglaciation. We document eight events of increased iceberg flux from various parts of the AIS between 20,000 and 9,000 years ago, in marked contrast to previous scenarios which identified the main AIS retreat as occurring after meltwater pulse 1A and continuing into the late Holocene epoch. The highest IBRD flux occurred 14,600 years ago, providing the first direct evidence for an Antarctic contribution to meltwater pulse 1A. Climate model simulations with AIS freshwater forcing identify a positive feedback between poleward transport of Circumpolar Deep Water, subsurface warming and AIS melt, suggesting that small perturbations to the ice sheet can be substantially enhanced, providing a possible mechanism for rapid sea-level rise.

Novel Nicotine Delivery Systems.

Electronic nicotine delivery systems (ENDS) are devices that contain a power source, a heating element, and a tank or cartridge containing an "e-liquid," which is a mixture of nicotine and flavoring in a glycerol-propylene glycol vehicle. Their increasing popularity among adolescents might be attributed to aggressive marketing in physical venues, social media outlets, as well as irreversible changes caused by nicotine in the developing brains of youth and young adults, predisposing them to addictive behaviors. Adolescent ENDS users were 4 times more likely to initiate cigarette smoking, and the odds of quitting smoking were lower and, in many instances, delayed for those using ENDS. ENDS also renormalize cigarette-like behaviors, such as inhaling/exhaling smoke. The oral cavity is the initial point of contact of ENDS and the first affected system in humans. Oral health depends on an intricate balance in the interactions between oral bacteria and the human immune system, and dysbiosis of oral microbial communities underlies the etiology of periodontitis, caries, and oral cancer. Emerging evidence from subjects with periodontitis as well as periodontally healthy subjects demonstrates that e-cigarette use is associated with a compositional and functional shift in the oral microbiome, with an increase in opportunistic pathogens and virulence traits.

The burden of musculoskeletal disorders in Mexico at national and state level, 1990-2016: estimates from the global burden of disease study 2016.

Worldwide, musculoskeletal (MSK) disorders are the second cause of living with disability. According to our data, in Mexico, MSK conditions are an important cause of disability, at national and state level. Preventive actions promoted by health systems to reduce the burden of MSK disorders are essential. INTRODUCTION: We describe premature mortality and disability due to musculoskeletal (MSK) disorders in Mexico at national and state level from 1990 to 2016. METHODS: Using data from the global burden of disease study 2016 (GBD 2016), we present rates and trends in years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life years (DALYs) caused by MSK disorders in Mexico by state from 1990 to 2016. The burden of MSK disorders was computed using standard GBD methodology. To compare the burden of MSK disorders across the country, states were grouped by sociodemographic index (SDI). RESULTS: In Mexico, MSK disorders were the 3rd and 17th greatest cause of YLDs and YLLs in 2016, respectively, accounting for 1.95 million (95% UI 1.4-2.5) DALYs. Among all MSK disorders, low back and neck pain had the highest all-ages DALYs rate and represented 3.6% of total DALYs. All-ages YLLs and YLDs rates of MSK disorders were 234 and 37% higher in females (YLLs 102.2, 95% UI 79.9-110.7; YLDs 1677.9, 95% UI 1213.5-2209.4) than in males (YLLs 30.6, 95% UI 28.3-34.0; YLDs 1224.7, 95% UI 887.2-1608.3), respectively. Northern and high SDI states had higher rates of MSK disorders in comparison with southern and low SDI states. Only 16% of YLDs caused by all MSK disorders could be attributed to risk factors currently assessed in GBD. CONCLUSION: MSK conditions are an important cause of premature mortality and disability. Researcher engagement and cross-sectorial actions to address the burden of MSK disorders are essential.

Health-related quality of life during the first year after a hip fracture: results of the Mexican arm of the International Cost and Utility Related to Osteoporotic Fractures Study (MexICUROS).

We investigated changes in health-related quality of life (HRQoL) due to hip fracture in Mexican adults aged ≥ 50 years during the first year post-fracture. Mean accumulated loss was 0.27 quality-adjusted life years (QALYs). HRQoL before fracture was the main contributor to explain the loss of QALYs. INTRODUCTION: We aimed to estimate the health-related quality of life (HRQoL) loss over 1 year in patients sustaining a hip fracture in Mexico. METHODS: Individuals aged ≥ 50 years old with diagnosis of a low-energy-induced hip fracture enrolled in the International Costs and Utilities Related to Osteoporotic Fractures Study (ICUROS) composed the study population. After a recall of their own pre-fracture status, HRQoL was prospectively collected in three phases over 12 months of follow-up using EQ-5D-3L. The UK preference weight set was applied to calculate the utility values. The accumulated quality-adjusted life years (QALYs) loss in the first year post-fracture was estimated using the trapezoid method. Multivariate regression analysis allowed identifying determinants of QALYs loss. RESULTS: One hundred ninety-three patients (mean ± SD age 77.2 ± 9.9 years; 80% women; 15.5% with prior fracture in the last 5 years; 78% in low-income category) were evaluated. Mean (95% CI) utility value before fracture was 0.64 (0.59-0.68). It dropped to 0.01 (0.01-0.02) immediately after fracture and then improved to 0.46 (0.42-0.51) and 0.60 (0.55-0.64) at 4 and 12 months post-fracture, respectively. Disregarding fracture-related mortality, accumulated QALYs loss over the first year was 0.27 (0.24-0.30) QALYs. Mobility, self-care, and usual activities were the most affected domains throughout the whole year. HRQoL before fracture was the main contributor to explain the loss of QALYs. CONCLUSIONS: Hip fractures reduce dramatically the HRQoL, with the loss sustained at least over the first year post-fracture in Mexico. The utility values derived from this study can be used in future economic evaluations.

FRAX-based intervention and assessment thresholds in seven Latin American countries.

Age-specific intervention and assessment thresholds were developed for seven Latin American countries. The intervention threshold ranged from 1.2% (Ecuador) to 27.5% (Argentina) at the age of 50 and 90 years, respectively. In the Latin American countries, FRAX offers a substantial advance for the detection of subjects at high fracture risk. INTRODUCTION: Intervention thresholds are proposed using the Fracture Risk Assessment (FRAX) tool. We recommended their use to calculate the ten-year probability of fragility fracture (FF) in both, men and women with or without the inclusion of bone mineral density (BMD). The purpose of this study is to compute FRAX-based intervention and BMD assessment thresholds for seven Latin American countries in men and women ≥ 40 years. METHODS: The intervention threshold (IT) was set at a 10-year probability of a major osteoporotic fracture (MOF) equivalent to a woman with a prior FF and a body mass index (BMI) equal to 25.0 kg/m2 without BMD or other clinical risk factors. The lower assessment threshold was set at a 10-year probability of a MOF in women with BMI equal to 25.0 kg/m2, no previous fracture and no clinical risk factors. The upper assessment threshold was set at 1.2 times the IT. RESULTS: For the seven LA countries, the age-specific IT varied from 1.5 to 27.5% in Argentina, 3.8 to 25.2% in Brazil, 1.6 up to 20.0% in Chile, 0.6 to 10.2% in Colombia, 0.9 up to 13.6% in Ecuador, 2.6 to 20.0% in Mexico, and 0.7 up to 22.0% in Venezuela at the age of 40 and 90 years, respectively. CONCLUSIONS: In the LA countries, FRAX-based IT offers a substantial advance for the detection of men and women at high fracture risk, particularly in the elderly. The heterogeneity of IT between the LA countries indicates that country-specific FRAX models are appropriate rather than a global LA model.

Correction to: Global dietary calcium intake among adults: a systematic review.

The original Electronic Supplementary Material file 3 contained an erroneous reference for Mali. A link to the corrected file is provided here.

Quality of life for up to 18 months after low-energy hip, vertebral, and distal forearm fractures-results from the ICUROS.

This study used data from the International Costs and Utilities Related to Osteoporotic fractures Study (ICUROS) to estimate the quality of life (QoL) impact of fracture. Hip, vertebral, and distal forearm fractures incur substantial QoL losses. Hip and vertebral fracture results in markedly impaired QoL for at least 18 months. INTRODUCTION: The International Costs and Utilities Related to Osteoporotic fractures Study (ICUROS) is a multinational observational study that aims to describe costs and quality of life (QoL) consequences of osteoporotic fractures. To date, 11 countries have participated in the study: Australia, Austria, Estonia, France, Italy, Lithuania, Mexico, Russia, Spain, the UK, and the USA. The objective of this paper is to describe the QoL impact of hip, vertebral, and distal forearm fracture. METHODS: Data were collected at four time-points for five QoL point estimates: within 2 weeks after fracture (including pre-fracture recall) and at 4, 12, and 18 months after fracture. Quality of life was measured as health state utility values (HSUVs) derived from the EQ-5D-3L. Complete case analysis was conducted as the base case with available case and multiple imputation performed as sensitivity analyses. Multivariate analysis was performed to explore predictors of QoL impact of fracture. RESULTS: Among 5456 patients enrolled using convenience sampling, 3021 patients were eligible for the base case analysis (1415 hip, 1047 distal forearm, and 559 vertebral fractures). The mean (SD) difference between HSUV before and after fracture for hip, vertebral, and distal forearm fracture was estimated at 0.89 (0.40), 0.67 (0.45), and 0.48 (0.34), respectively (p < 0.001 for all fracture types). Eighteen months after fracture, mean HSUVs were lower than before the fracture in patients with hip fracture (0.66 vs. 0.77 p < 0.001) and vertebral fracture (0.70 vs. 0.83 p < 0.001). Hospitalization and higher recalled pre-fracture QoL were associated with increased QoL impact for all fracture types. CONCLUSIONS: Hip, vertebral, and distal forearm fractures incur substantial loss in QoL and for patients with hip or vertebral fracture, QoL is markedly impaired for at least 18 months.

A survey on awareness, knowledge, and attitudes toward epilepsy in an urban community in Turkey.

BACKGROUND AND AIM: Epilepsy is one of the most common chronic neurological disorders with a high prevalence. Epileptic people and their family members suffer more from social stigma than the disorder itself. Among various complex reasons knowledge and awareness about epilepsy are the two important factors underlying discriminatory attitudes towards epileptic people. Community pharmacists play a major role in the care of these patients. In this study we mainly aimed to gain insights into the knowledge and awareness of and attitudes (AKA) towards epilepsy both in epileptic and healthy individuals in an urban community. To this end we also aimed at developing a reliable and valid measurement tool to assess AKA levels. MATERIALS AND METHODS: This study was conducted in 13 community pharmacies with 219 respondents. Factor analysis yielded three clear subscales. RESULTS: It was found that a vast majority of the participants were familiar with epilepsy; yet only 18 of them had detailed information. The community pharmacists were indicated as a main source of information about epilepsy at the same rate to that of physicians. Although most of the respondents knew that epilepsy was not a form of mental illness only about one forth of them knew the real cause. More than half of the respondents supported the epileptics' socialization in the community. CONCLUSION: We believe that the questionnaire developed in the study is a promising instrument for determining educational needs and offering guidance to healthcare professionals in developing standardized educational tools and programs.

Unmethylated Insulin DNA Is Elevated After Total Pancreatectomy With Islet Autotransplantation: Assessment of a Novel Beta Cell Marker.

Beta cell death may occur both after islet isolation and during infusion back into recipients undergoing total pancreatectomy with islet autotransplantation (TPIAT) for chronic pancreatitis. We measured the novel beta cell death marker unmethylated insulin (INS) DNA in TPIAT recipients before and immediately after islet infusion (n = 21) and again 90 days after TPIAT, concurrent with metabolic functional assessments (n = 25). As expected, INS DNA decreased after pancreatectomy (p = 0.0002). All TPIAT recipients had an elevated unmethylated INS DNA ratio in the first hours following islet infusion. In four samples (three patients), INS DNA was also assessed immediately after islet isolation and again before islet infusion to assess the impact of the isolation process: Unmethylated and methylated INS DNA fractions both increased over this interval, suggesting death of beta cells and exocrine tissue before islet infusion. Higher glucose excursion with mixed-meal tolerance testing was associated with persistently elevated INS DNA at day 90. In conclusion, we observed universal early elevations in the beta cell death marker INS DNA after TPIAT, with pronounced elevations in the islet supernatant before infusion, likely reflecting beta cell death induced by islet isolation. Persistent posttransplant elevation of INS DNA predicted greater hyperglycemia at 90 days.

Global dietary calcium intake among adults: a systematic review.

Low calcium intake may adversely affect bone health in adults. Recognizing the presence of low calcium intake is necessary to develop national strategies to optimize intake. To highlight regions where calcium intake should be improved, we systematically searched for the most representative national dietary calcium intake data in adults from the general population in all countries. We searched 13 electronic databases and requested data from domain experts. Studies were double-screened for eligibility. Data were extracted into a standard form. We developed an interactive global map, categorizing countries based on average calcium intake and summarized differences in intake based on sex, age, and socioeconomic status. Searches yielded 9780 abstracts. Across the 74 countries with data, average national dietary calcium intake ranges from 175 to 1233 mg/day. Many countries in Asia have average dietary calcium intake less than 500 mg/day. Countries in Africa and South America mostly have low calcium intake between about 400 and 700 mg/day. Only Northern European countries have national calcium intake greater than 1000 mg/day. Survey data for three quarters of available countries were not nationally representative. Average calcium intake is generally lower in women than men, but there are no clear patterns across countries regarding relative calcium intake by age, sex, or socioeconomic status. The global calcium map reveals that many countries have low average calcium intake. But recent, nationally representative data are mostly lacking. This review draws attention to regions where measures to increase calcium intake are likely to have skeletal benefits.

Biologic therapies and bone loss in rheumatoid arthritis.

INTRODUCTION: Rheumatoid arthritis (RA) is a common systemic autoimmune disease of unknown cause, characterized by a chronic, symmetric, and progressive inflammatory polyarthritis. One of the most deleterious effects induced by the chronic inflammation of RA is bone loss. During the last 15 years, the better knowledge of the cytokine network involved in RA allowed the development of potent inhibitors of the inflammatory process classified as biological DMARDs. These new drugs are very effective in the inhibition of inflammation, but there are only few studies regarding their role in bone protection. The principal aim of this review was to show the evidence of the principal biologic therapies and bone loss in RA, focusing on their effects on bone mineral density, bone turnover markers, and fragility fractures. METHODS: Using the PICOST methodology, two coauthors (PC, LM-S) conducted the search using the following MESH terms: rheumatoid arthritis, osteoporosis, clinical trials, TNF- antagonists, infliximab, adalimumab, etanercept, certolizumab, golimumab, IL-6 antagonists, IL-1 antagonists, abatacept, tocilizumab, rituximab, bone mineral density, bone markers, and fractures. The search was conducted electronically and manually from the following databases: Medline and Science Direct. The search period included articles from 2003 to 2015. The selection included only original adult human research written in English. Titles were retrieved and the same two authors independently selected the relevant studies for a full text. The retrieved selected studies were also reviewed completing the search for relevant articles. The first search included 904 titles from which 253 titles were selected. The agreement on the selection among researchers resulted in a Kappa statistic of 0.95 (p < 0.000). Only 248 abstracts evaluated were included in the acronym PICOST. The final selection included only 28 studies, derived from the systematic search. Additionally, a manual search in the bibliography of the selected articles was made and included into the text and into the section of "small molecules of new agents." CONCLUSION: Treatment with biologic drugs is associated with the decrease in bone loss. Studies with anti-TNF blocking agents show preservation or increase in spine and hip BMD and also a better profile of bone markers. Most of these studies were performed with infliximab. Only three epidemiological studies analyzed the effect on fractures after anti-TNF blocking agent's treatment. IL-6 blocking agents also showed improvement in localized bone loss not seen with anti-TNF agents. There are a few studies with rituximab and abatacept. Although several studies reported favorable actions of biologic therapies on bone protection, there are still unmet needs for studies regarding their actions on the risk of bone fractures.

A 3D imaging and visualization workflow, using confocal microscopy and advanced image processing for brachyuran crab larvae.

Confocal laser scanning microscopy is an excellent tool for nondestructive imaging of arthropods and can provide detailed information on morphology including fine surface detail. A methodology is presented here for the visualization by confocal microscopy of arthropods, using brachyuran crab zoeal stages as examples and postprocessing techniques derived from micro-CT protocols to improve the final images. This protocol is divided into description of the preprocessing steps (cleaning, staining, digesting and mounting), confocal laser scanning microscopy and data visualization using open-source, freeware programs ImageJ and Drishti. The advantages of using ImageJ to standardize stack data and Drishti for surface rendering are discussed. The methodology has been comprehensively tested using data acquired from all four brands of confocal microscope (Leica, Nikon, Olympus and Zeiss).

Complement C5 Inhibition Reduces T Cell-Mediated Allograft Vasculopathy Caused by Both Alloantibody and Ischemia Reperfusion Injury in Humanized Mice.

Allograft vasculopathy (AV) is characterized by diffuse stenoses in the vasculature of solid organ transplants. Previously, we developed two humanized models showing that alloantibody and ischemia reperfusion injury (IRI) exacerbated T cell-mediated AV in human arterial xenografts in vivo. Herein we examined a causal role for terminal complement activation in both settings. IRI, in contrast to alloantibody, elicited widespread membrane attack complex (MAC) assembly throughout the vessel wall. Both alloantibody and IRI caused early (24 h) and robust endothelial cell (EC) activation localized to regions of intimal MAC deposition, indicated by increases in nuclear factor kappa B (NF-κB)-inducing kinase, an MAC-dependent activator of noncanonical NF-kB, VCAM-1 expression and Gr-1+ neutrophil infiltration. Endothelial cell activation by alloantibody was inhibited by antimouse C5 mAb, but not by anti-C5a mAb or by control mAb, implicating MAC as the primary target of anti-C5 mAb. Antimouse C5 mAb significantly reduced alloantibody- and IRI-enhanced T cell infiltration and AV-like changes, including neointimal hyperplasia as well as intraluminal thrombosis in a subset of IRI-treated arterial grafts. These results indicate that increased AV lesion formation in response to either alloantibody or IRI is dependent on complement C5 activation and, accordingly, inhibition of this pathway may attenuate AV.

Dietary patterns are associated with bone mineral density in an urban Mexican adult population.

UNLABELLED: Several types of nutrients and foods affect bone mineral density (BMD). However, these nutrients occur together in food groups and dietary patterns, and the overall effects of dietary patterns are not yet well known. INTRODUCTION: We evaluated the associations between dietary patterns and BMD among adults participating in the Health Workers Cohort Study. METHODS: In a cross-sectional analysis, we examined 6915 Mexican adults aged 20-80 years. All participants completed a validated self-administered food frequency questionnaire (FFQ) and had total, hip, and spine BMD measurements assessed by dual-energy X-ray absorptiometry (DXA). The FFQ included 116 foods, which were grouped into 22 categories and entered into a factor analysis to derive dietary patterns. RESULTS: Three dietary patterns emerged-a Prudent, a Refined foods, and a Dairy and fish pattern. After adjustment for potential confounders, those in the highest quintile of the Prudent pattern had lower odds (OR) of low spine BMD (OR = 0.80; 95 % CI 0.68, 0.94; P for trend = 0.031) compared to those in the lowest quintile. In contrast, participants in the highest quintile of the Refined foods pattern had greater odds of low total BMD (OR = 1.74; 95 % CI 1.10, 2.76; P for trend = 0.016) than those in the lowest quintile. Finally, participants in the highest quintile of the Dairy and fish dietary pattern had significantly lower likelihood of having low BMD. CONCLUSION: This study identified specific dietary patterns associated with BMD among a Mexican adult population and highlights the importance of promoting food-based prevention strategies for maintaining bone health.