MC3R links nutritional state to childhood growth and the timing of puberty.

The state of somatic energy stores in metazoans is communicated to the brain, which regulates key aspects of behaviour, growth, nutrient partitioning and development1. The central melanocortin system acts through melanocortin 4 receptor (MC4R) to control appetite, food intake and energy expenditure2. Here we present evidence that MC3R regulates the timing of sexual maturation, the rate of linear growth and the accrual of lean mass, which are all energy-sensitive processes. We found that humans who carry loss-of-function mutations in MC3R, including a rare homozygote individual, have a later onset of puberty. Consistent with previous findings in mice, they also had reduced linear growth, lean mass and circulating levels of IGF1. Mice lacking Mc3r had delayed sexual maturation and an insensitivity of reproductive cycle length to nutritional perturbation. The expression of Mc3r is enriched in hypothalamic neurons that control reproduction and growth, and expression increases during postnatal development in a manner that is consistent with a role in the regulation of sexual maturation. These findings suggest a bifurcating model of nutrient sensing by the central melanocortin pathway with signalling through MC4R controlling the acquisition and retention of calories, whereas signalling through MC3R primarily regulates the disposition of calories into growth, lean mass and the timing of sexual maturation.

Public Health Response to Multistate Salmonella Typhimurium Outbreak Associated with Prepackaged Chicken Salad, United States, 2018.

Quantifying the effect of public health actions on population health is essential when justifying sustained public health investment. Using modeling, we conservatively estimated that rapid response to a multistate foodborne outbreak of Salmonella Typhimurium in the United States in 2018 potentially averted 94 reported cases and $633,181 in medical costs and productivity losses.

How annulus defects can act as initiation sites for herniation.

PURPOSE: Both posture and loading rate are key factors in the herniation process and can determine the mechanism of disc failure. The aim of this study was to test the hypothesis that disruption visible with HR-MRI post-testing corresponds with microstructural features and further elucidate the mechanism by which this disruption weakens the disc. This will enable us to gain new insights into the herniation process. METHODS: Thirty ovine lumbar spinal segments were subjected to combinations of four loading conditions (0-12° flexion, 0-9° lateral bending, 0-4° axial rotation, 0-1500 N axial compression) for 1000 loading cycles at 2 Hz in a dynamic disc loading simulator. The discs were scanned in an ultra-high field MRI (11.7 T) then examined using brightfield microscopy to examine their microstructure. RESULTS: Four discs herniated and seven discs suffered nucleus displacement. These discs contained pre-existing defects in the central posterior annulus. Generally, following testing discs contained more posterior annulus disruption, Microstructural investigation revealed there was clear correspondence between HR-MRI and microstructural observations, and that the mid-outer annular-endplate junction had failed in all discs examined in this study. CONCLUSIONS: While all discs suffered outer annulus damage, only the discs containing pre-existing defects herniated. These pre-existing defects weakened the inner and mid annulus, allowing herniation to occur once the mid and outer annular wall was compromised. We propose this can occur during the degenerative cascade.

Disc wall structural abnormalities can act as initiation sites for herniation.

Both posture and loading rate are key factors in the herniation process and can determine the failure mechanism of the disc. The influence of disc structure on the herniation process has yet to be directly observed, thus the aim of this study was to test the hypothesis that discs containing greater levels of pre-existing disruption would be more vulnerable to herniation when subjected to severe levels of posture and loading. 30 ovine lumbar motion segments were subjected to combinations of 4 loading conditions (0 - 12° flexion,0 - 9° lateral bending, 0 - 4° axial rotation, 0-1500 N axial compression) for 1000 loading cycles at 2 Hz in a dynamic disc loading simulator. The discs were scanned in an ultra-high field MRI (magnetic resonance imaging, 11.7 T) prior to and following testing. 4 discs herniated and 7 discs suffered nucleus displacement. These discs contained pre-existing defects in the central dorsal annulus. Generally, following testing, discs contained more dorsal annulus disruption, including 7 discs which developed similar characteristic defects although these did not herniate. Overall, more severe complex postures produced more disruption. While more severe postures such as twisting and bending increased disc damage, these results are probably the first directly showing that naturally occurring defects in the disc can act as initiation sites for herniation. The clinical significance of these findings is that, in principle at least, MRI based techniques could be capable of identifying vulnerable discs, with the obvious caveat that further correlation with clinical techniques is required.

Non-medical cannabis in North America: an overview of regulatory approaches.

OBJECTIVES: The objective of this study was to describe existing regulations of non-medical cannabis legalization in North America to inform recommendations for future health policy. These regulations are among the first in the world and will set a precedent for other jurisdictions globally who legalize cannabis. STUDY DESIGN: This was a review of online grey literature on regulatory approaches to non-medical cannabis legalization in North American jurisdictions. METHODS: We conducted an internet search in June 2019 to identify government and public health resources published after January 1, 2012. We were able to achieve data saturation using a limited number of resources. Data extraction was conducted by two independent reviewers, with disagreements resolved by consensus. RESULTS: Eleven US states, the District of Columbia, and Canada have enacted legal recreational cannabis regulations. The legal age of cannabis possession matches the legal drinking age in all jurisdictions except one. Most consumption is in private residences only, with some provinces/territories permitting public consumption where tobacco is permitted. Most jurisdictions allow for home growing of up to 6 (US) or 4 (Canada) plants and a maximum possession of 1 oz. (US) or 1.06 oz. (Canada). Cannabis is available for purchase only in private retail stores in US states, while Canada has also legalized online sales. Impaired driving assessment is not cannabis-specific in most US states, while Canada has federal driving limits. CONCLUSIONS: Although North American approaches to regulating recreational cannabis use are consistent in many aspects, some exceptions exist (e.g., home growing, personal possession). More research is needed to assess the impact of variations in regulatory policies on potential harms from legalization to inform future policy decisions in North America and abroad. Complementary public health interventions will be crucial in ensuring public health and safety.

Measurements of adiposity as prognostic biomarkers for survival with anti-angiogenic treatment in epithelial ovarian cancer: An NRG Oncology/Gynecologic Oncology Group ancillary data analysis of GOG 218.

OBJECTIVE: Adiposity has been hypothesized to interfere with the activity of bevacizumab (BEV), an anti-angiogenic agent. Measurements of adiposity, BMI, surface fat area (SFA), and visceral fat area (VFA) were investigated as prognostic of oncologic outcomes among patients treated with chemotherapy, with or without BEV, on GOG 218, a prospective phase III trial. METHOD: Pretreatment computed tomography (CT) for 1538 GOG 218 participants were analyzed. Proportional hazards models assessed association between adiposity and overall survival (OS) adjusted for other prognostic factors. The predictive value of adiposity as a function of BEV treatment was assessed in 1019 patients randomized to either chemotherapy (CT) + placebo (P) → P or CT + BEV → BEV. RESULTS: After adjusting for prognostic factors, SFA was not associated with the overall hazard of death (p = 0.981). There was a non-significant 0.1% (p = 0.062) increase in hazard of death associated with a unit increase in VFA. When comparing the treatment HRs for patients who did and did not receive BEV, there was no association with SFA (p = 0.890) or VFA (p = 0.106). A non-significant 0.8% increase in the hazard of death with unit increase in BMI (p = 0.086) was observed. BMI values were not predictive of a longer survival for patients with BEV vs placebo (p = 0.606). CONCLUSION: Measures of adiposity strongly correlated to one another but were not predictive of efficacy for BEV. VFA is a weak prognostic factor.

Effect of feeding system and grain source on lactation characteristics and milk components in dairy cattle.

The objective of this study was to examine the effect of feeding systems [component and total mixed rations (TMR)] and dietary grain sources (barley, commercial concentrate, corn grain, and high-moisture corn) on lactation characteristics and milk composition. A total of 852,242 test-day records, information on animal characteristics, feed composition, and feeding systems from 104,129 Holstein cows in 4,319 herds covering a period of 5 yr were obtained from Quebec's Dairy Herd Improvement Association (Valacta). We performed descriptive statistics and graphical representations of the data for each type of feeding system and grain source by parity (1 to 3). The milk records were binned in 15-d in milk blocks. Mixed models using a combination of forward and backward stepwise selections were developed to predict milk and milk component yields. The TMR-fed cows had greater yield of milk, fat, protein, and lactose and lower milk urea N (MUN) concentration than component-fed cows at all parities. Cows fed a TMR had higher peak milk yields and greater persistency after peak lactation compared with component-fed cows. In addition, greater yields of milk fat and protein from peak to mid-lactation were found in TMR- versus component-fed cows. In general, greater milk fat and protein yields as well as lower MUN concentration were observed in cows fed corn grain or high-moisture corn compared with barley or commercial concentrate, but parity influenced these relationships. The feeding system by day in milk blocks interaction was significant in models of milk and components yields for all parities, but only for second-lactation cows for MUN concentration. This means that effect of TMR and component feeding differs with stage of lactation. In conclusion, feeding TMR and corn-based diets are associated with greater yield of milk and milk components under commercial conditions.

Persistence of self-injury, aggression and property destruction in children and adults with tuberous sclerosis complex.

BACKGROUND: Individuals with tuberous sclerosis complex (TSC) are at increased risk of developing self-injurious behaviour. The persistence of this deleterious behaviour over years is reported in aetiologically heterogeneous samples to be between 60% and 80% but is unknown for TSC. METHOD: In this study, we determined the 3-year persistence of self-injury in a sample (n = 52) of children (with and without ID) and adults (with ID) with TSC and examined characteristics associated with persistence. RESULTS: Findings for self-injury were contrasted to those for aggression and property destruction to examine the specificity of results to this behaviour. Self-injury was persistent in 84.6% of those with TSC who showed this behaviour, in contrast to 66.7% both for aggression and destruction. Persistent self-injury was associated with poor self-help skills, greater overactivity/impulsivity and more behavioural indicators of pain. These latter two characteristics were also associated with persistent aggression. No characteristics were associated with persistence of property destruction. CONCLUSION: These findings suggest that self-injurious behaviours in individuals with TSC, together with aggressive and destructive behaviours, are highly persistent and would benefit from targeted intervention. Poor adaptive skills, overactivity/impulsivity and painful health conditions may differentiate those at most risk for persistent self-injury or aggression.

The impact of posture and basking orientation on thermoregulation in the Sungazer (Smaug giganteus).

Body temperature (Tb) is one of the most influential factors affecting physiological processes in ectothermic animals. Reptiles use behaviours such as shuttling, and postural and orientation adjustments to ensure that Tb remains close to a target. It is thought that target body temperature (Ttarget) is aligned to the physiological and behavioural thermal optima of the animal. The Sungazer (Smaug giganteus), a Threatened lizard species, is unique amongst the Cordylidae in that lizards inhabit self-excavated burrows in open grasslands, a habitat in which there are few exposed rock basking sites. In this situation, Tbs are likely to be greatly influenced by postural and orientation adjustments during basking. We measured Tbs using modified iButtons, and calculated Ttarget of free-ranging Sungazers in order to assess the impact of body posture and orientation in the thermoregulation of the species. We used camera traps to record lizard behaviour at burrow entrances and aligned these measures to measures of Tb. Ttarget was 30 ±â€¯1.4 °C, and Tbs remained within this range for 371 ±â€¯162 min per day. The anterior body-up postures resulted in faster heating and higher Tbs. Lizards heated faster when facing away from the sun and spent proportionally more time in this orientation in the morning when Tbs were lower than Ttarget. Our findings suggest that their wide behavioural repertoire allows Sungazers to thermoregulate effectively over a broad range of environmental conditions and may thus be able to effectively respond to changing climatic conditions.

'What vision?': experiences of Team members in a community service for adults with intellectual disabilities.

BACKGROUND: In the UK, the closure of 'long-stay' hospitals was accompanied by the development of community teams (CTs) to support people with intellectual disabilities (IDs) to live in community settings. The self-reported experiences of staff working in such teams have been neglected. METHODS: Focusing on a single county-wide service, comprising five multi-disciplinary and inter-agency CTs, we measured perceptions among the health care and care management Team members of (1) their personal well-being; (2) the functioning of their team; and (3) the organisation's commitment to quality, and culture. RESULTS: Almost three-quarters of the questionnaires were returned (73/101; 72%). The scores of health care practitioners and care managers were very similar: (1) the MBI scores of more than half the respondents were 'of concern'; (2) similarly, almost four in ten respondents' scores on the Vision scale of the TCI were 'of concern'; (3) the perceived commitment to quality (QIIS-II Part 2) was uncertain; and (4) the organisational culture (QIIS-II, Part 1) was viewed as primarily hierarchical. DISCUSSION: The perceived absence of a vision for the service, combined with a dominant culture viewed by its members as strongly focussed on bureaucracy and process, potentially compromises the ability of these CTs to respond proactively to the needs of people with IDs. Given the changes in legislation, policy and practice that have taken place since CTs were established, it would be timely to revisit their role and purpose.

The impact of medical tourism on colorectal screening among Korean Americans: A community-based cross-sectional study.

BACKGROUND: Colorectal cancer (CRC) remains the most commonly diagnosed cancer among Korean Americans (KAs) in part due to low screening rates. Recent studies suggest that some KA patients engage in medical tourism and receive medical care in their home country. The impact of medical tourism on CRC screening is unknown. The purpose of this paper was to 1) investigate the frequency of medical tourism, 2) examine the association between medical tourism and CRC screening, and 3) characterize KA patients who engage in medical tourism. METHODS: This is a community-based, cross-sectional study involving self-administered questionnaires conducted from August 2013 to October 2013. Data was collected on 193 KA patients, ages 50-75, residing in the Seattle metropolitan area. The outcome variable is up-to-date with CRC screening, defined as having had a stool test (Fecal Occult Blood Test or Fecal Immunochemical Test) within the past year or a colonoscopy within 10 years. Predictor variables are socio-demographics, health factors, acculturation, knowledge, financial concerns for medical care costs, and medical tourism. RESULTS: In multi-variate modeling, medical tourism was significantly related to being up-to-date with CRC screening. Participants who engaged in medical tourism had 8.91 (95% CI: 3.89-23.89) greater odds of being up-to-date with CRC screening compared to those who did not travel for healthcare. Factors associated with engaging in medical tourism were lack of insurance coverage (P = 0.008), higher levels of education (P = 0.003), not having a usual place of care (P = 0.002), older age at immigration (P = 0.009), shorter years-of-stay in the US (P = 0.003), and being less likely to speak English well (P = 0.03). CONCLUSIONS: This study identifies the impact of medical tourism on CRC screening and characteristics of KA patients who report engaging in medical tourism. Healthcare providers in the US should be aware of the customary nature of medical tourism among KAs and consider assessing medical tests done abroad when providing cancer care. TRIAL REGISTRATION: Not applicable.

An emerging role for the gut microbiome in tauopathy.

Tauopathies constitute a group of neurodegenerative diseases characterized by abnormal aggregation of the protein tau, progressive neuronal and synaptic loss, and eventual cognitive and motor impairment. In this review, we will highlight the latest efforts investigating the intricate interplay between the gut microbiome and tauopathies. We discuss the physiological interactions between the microbiome and the brain as well as clinical and experimental evidence that suggests that the presence of tauopathy alters the composition of gut microbiota. We explore both animal and human studies that define causative relationships between the gut microbiome and tauopathy by directly manipulating or transferring gut microbiota. This review highlights future directions into identifying and mechanistically elucidating microbial species causally linked to tauopathies, with an ultimate goal of devising therapeutic targets towards the gut microbiome to treat tauopathies.

mcaGUI: microbial community analysis R-Graphical User Interface (GUI).

UNLABELLED: Microbial communities have an important role in natural ecosystems and have an impact on animal and human health. Intuitive graphic and analytical tools that can facilitate the study of these communities are in short supply. This article introduces Microbial Community Analysis GUI, a graphical user interface (GUI) for the R-programming language (R Development Core Team, 2010). With this application, researchers can input aligned and clustered sequence data to create custom abundance tables and perform analyses specific to their needs. This GUI provides a flexible modular platform, expandable to include other statistical tools for microbial community analysis in the future. AVAILABILITY: The mcaGUI package and source are freely available as part of Bionconductor at http://www.bioconductor.org/packages/release/bioc/html/mcaGUI.html

Exercise intervention for a musculoskeletal disorder in an oral health student: a case report.

OBJECTIVES: to describe and evaluate the effect of an exercise self-management programme for an oral health student who was suffering from a musculoskeletal disorder which had developed in the clinical environment during the course of training. DESIGN: Single participant case report. SETTING: The University of Otago Faculty of Dentistry and School of Physiotherapy. METHODS: The participant was a 21-year-old female student, enrolled in the University of Otago Bachelor of Oral Health (BOH) course, who was suffering back and neck pain which had developed during her training. A series of chairside stretches, regular home-based stretches, aerobic conditioning and postural strengthening exercises was prescribed. Pain and function was assessed using standardised questionnaires at the commencement of the exercise programme, and again at 6 weeks and 13 weeks. RESULTS: The participant demonstrated an improvement in her outcome questionnaires exceeding the MCID scores after 13 weeks. CONCLUSIONS: This case report provides a basis for highlighting the importance of measuring and monitoring MSD in a student learning oral health skills; it supports the findings of previous studies showing that an exercise intervention has some benefit for MSD in oral health students.

Emerging diagnostics and therapeutics for Alzheimer disease.

Alzheimer disease (AD) is the most common contributor to dementia in the world, but strategies that slow or prevent its clinical progression have largely remained elusive, until recently. This Review highlights the latest advances in biomarker technologies and therapeutic development to improve AD diagnosis and treatment. We review recent results that enable pathological staging of AD with neuroimaging and fluid-based biomarkers, with a particular emphasis on the role of amyloid, tau and neuroinflammation in disease pathogenesis. We discuss the lessons learned from randomized controlled trials, including some supporting the proposal that certain anti-amyloid antibodies slow cognitive decline during the mildly symptomatic phase of AD. In addition, we highlight evidence for newly identified therapeutic targets that may be able to modify AD pathogenesis and progression. Collectively, these recent discoveries-and the research directions that they open-have the potential to move AD clinical care toward disease-modifying treatment strategies with maximal benefits for patients.

Protein kinetics of superoxide dismutase-1 in familial and sporadic amyotrophic lateral sclerosis.

OBJECTIVE: Accumulation of misfolded superoxide dismutase-1 (SOD1) is a pathological hallmark of SOD1-related amyotrophic lateral sclerosis (ALS) and is observed in sporadic ALS where its role in pathogenesis is controversial. Understanding in vivo protein kinetics may clarify how SOD1 influences neurodegeneration and inform optimal dosing for therapies that lower SOD1 transcripts. METHODS: We employed stable isotope labeling paired with mass spectrometry to evaluate in vivo protein kinetics and concentration of soluble SOD1 in cerebrospinal fluid (CSF) of SOD1 mutation carriers, sporadic ALS participants and controls. A deaminated SOD1 peptide, SDGPVKV, that correlates with protein stability was also measured. RESULTS: In participants with heterozygous SOD1A5V mutations, known to cause rapidly progressive ALS, mutant SOD1 protein exhibited ~twofold faster turnover and ~ 16-fold lower concentration compared to wild-type SOD1 protein. SDGPVKV levels were increased in SOD1A5V carriers relative to controls. Thus, SOD1 mutations impact protein kinetics and stability. We applied this approach to sporadic ALS participants and found that SOD1 turnover, concentration, and SDGPVKV levels are not significantly different compared to controls. INTERPRETATION: These results highlight the ability of stable isotope labeling approaches and peptide deamidation to discern the influence of disease mutations on protein kinetics and stability and support implementation of this method to optimize clinical trial design of gene and molecular therapies for neurological disorders. TRIAL REGISTRATION: Clinicaltrials.gov: NCT03449212.

Effect of cationic polyacrylamides on the interactions between cellulose fibers.

The interaction between cellulose fibers in the presence of cationic polyacrylamide (CPAM) was analyzed by rheology as a function of polyelectrolyte concentration, charge density, and molecular weight. CPAM was found to strongly influence the yield stress of cellulose suspensions; low doses of CPAM increased the yield stress, but at higher concentrations the yield stress declined. The charge density of the CPAM was the most significant factor in how yield stress responded to CPAM concentration; this effect was able to be normalized to a master curve by considering only the charged fraction of the polymer. The molecular weight of CPAM samples had some effect at high concentrations, but for lower CPAM doses the yield stress was independent of molecular weight over the range studied. The data suggest that CPAM modifies the interaction between cellulose surfaces via several mechanisms, with electrostatic interactions in the form of charge neutralization and charged patch formation dominating; polymer bridging and steric repulsion also influence the overall balance of forces between interacting cellulose fibers.

Keeping profitable cows in the herd: A lifetime cost-benefit assessment to support culling decisions.

Increasing the productive lifespan of dairy cows is important to achieve a sustainable dairy industry, but making strategic culling decisions based on cow profitability is challenging for farmers. The objective of this study was to carry out a lifetime cost-benefit analysis based on production and health records and to explore different culling decisions among farmers. The cost-benefit analysis was conducted for 22 747 dairy cows across 114 herds in Quebec, Canada for which feed costs and the occurrence of diseases were reported. Costs and revenues related to productive lifespan were compared among cohorts of cows that left their respective herd at the end of their last completed lactation or stayed for a complete additional lactation. Hierarchical clustering analysis was carried out based on costs and revenues to explore different culling decisions among farmers. Our results showed that the knowledge of lifetime cumulative costs and revenues was of great importance to identify low-profitable cows at an earlier lactation, while only focusing on current lactation costs and revenues can lead to an erroneous assessment of profitability. While culling decisions were mostly based on current lactation costs and revenues and disregarded the occurrence of costly events on previous lactations, there was variation among farmers as we identified three different culling decision clusters. Monitoring cumulative costs and revenues would help farmers to identify low-profitable cows at an earlier lactation and make the decision to increase herd productive lifespan and farm profitability by keeping the most profitable cows.

Prevalence of methicillin-resistant staphylococcus aureus in a combat support hospital in Iraq.

Methicillin-resistant Staphylococcus aureus (MRSA) in health-care settings results in life-threatening infections. We examined the incidence of MRSA at the combat support hospital located at the Ibn Sina Hospital in Baghdad, Iraq. We compiled isolate data from 2005 to 2009 characterizing antibiotic susceptibilities, annual trends, patient populations, infection sites, and hospital locations. Approximately 46.1% of S. aureus were MRSA, with increase in numbers of yearly isolates. MRSA was isolated in higher numbers from U.S. military personnel. Non-U.S. patient isolates displayed higher antibiotic susceptibility compared to U.S. military personnel isolates. Outpatient clinic, forward operating bases, and intermediate care ward 1 isolated the most MRSA. Common isolation sites were wound and skin cultures. Community-acquired MRSA was likely present in 291 out of 303 isolates based on antibiotic susceptibility. Our data suggests that most MRSA were community-acquired with limited nosocomial spread. We recommend increases in combat support hospital molecular lab capability to rapidly identify both MRSA categories.

Rates of gonorrhea and Chlamydia in U.S. military personnel deployed to Iraq and Afghanistan (2004-2009).

The increased incidence of sexually transmitted infections has historically been associated with military personnel at war. The incidence of gonorrhea and Chlamydia in personnel deployed in the current wars in Iraq and Afghanistan has not been reported. An electronic records' review of testing done from January 2004 to September 2009 revealed higher rates of Chlamydia than gonorrhea, especially among females who deploy to Iraq. Additionally, increasing Chlamydia rates were noted over the study. Overall, the rates of gonorrhea and Chlamydia were the same or lower than age- and year-matched U.S. rates reported by the Center for Disease Control and Prevention. Ongoing education with emphasis on prevention and treatment are needed, as are development of specific projects to define the risk factors and timing of acquisition of sexually transmitted infections in combat zones.