North Carolina is developing a unique and innovative infrastructure to support integrated physical, behavioral, and social health care. Efforts by the North Carolina Department of Health and Human Services, the Foundation for Health Leadership & Innovation, Cone Health, Atrium Health, and the One Charlotte Health Alliance advance our understanding of how to best operationalize the design and payment of integrated services. Best practices such as the collaborative care and primary care behavioral health models reduce inefficiencies and disparities by bringing together teams of primary care and behavioral health care providers.

Repeated alcohol experiences can produce long-lasting memories for sensory cues associated with intoxication. These memories can problematically trigger relapse in individuals recovering from alcohol use disorder (AUD). The molecular mechanisms by which ethanol changes memories to become long-lasting and inflexible remain unclear. New methods to analyze gene expression within precise neuronal cell types can provide further insight toward AUD prevention and treatment. Here, we used genetic tools in Drosophila melanogaster to investigate the lasting consequences of ethanol on transcription in memory-encoding neurons. Drosophila rely on mushroom body (MB) neurons to make associative memories, including memories of ethanol-associated sensory cues. Differential expression analyses revealed that distinct transcripts, but not genes, in the MB were associated with experiencing ethanol alone compared to forming a memory of an odor cue associated with ethanol. Adult MB-specific knockdown of spliceosome-associated proteins demonstrated the necessity of RNA-processing in ethanol memory formation. These findings highlight the dynamic, context-specific regulation of transcription in cue-encoding neurons, and the lasting effect of ethanol on transcript usage during memory formation.

Tree structures, showing hierarchical relationships and the latent structures between samples, are ubiquitous in genomic and biomedical sciences. A common question in many studies is whether there is an association between a response variable measured on each sample and the latent group structure represented by some given tree. Currently, this...

Noemie Liesch and Friedrich Ladich

In vocal fish species, males possess larger sound-generating organs and signal acoustically with pronounced sex-specific differences. Sound production is known in two out of three species of croaking gouramis (Trichopsis vittata and T. schalleri). The present study investigates sex-specific differences in sonic organs, vocalizing behaviour and sounds emitted in the third species, the pygmy gourami T. pumila, in order to test the hypothesis that females are able to vocalize despite their less-developed sonic organs, and despite contradictory reports. Croaking gouramis stretch and pluck two enhanced (sonic) pectoral fin tendons during alternate fin beating, resulting in a series of double-pulsed bursts termed croaking sound. We measured the diameter of the first and second sonic tendon and showed that male tendons were twice as large as in same-sized females. We also determined the duration of dyadic contests, visual displays, number of sounds and buttings. Sexes differ in all sound characteristics but in no behavioural variable. Male sounds consisted of twice as many bursts, a higher percentage of double-pulsed bursts and a higher burst period. Additionally, male sounds had a lower dominant frequency and a higher sound level. In summary, female pygmy gouramis possessed sonic organs and vocalized in most dyadic contests. The sexual dimorphism in sonic tendons is clearly reflected in sex-specific differences in sound characteristics, but not in agonistic behaviour, supporting the hypothesis that females are vocal.

Dual amylin and calcitonin receptor agonists (DACRAs) are novel candidates for treatment of type 2 diabetes and obesity because of their beneficial effects on body weight, blood glucose, insulin sensitivity, and food preference, at least short-term. DACRAs activate the receptors for a prolonged time period, resulting in metabolic effects superior to those of amylin. Because of the prolonged receptor activation, different dosing intervals and, hence, less frequent receptor activation might change the efficacy of DACRA treatment in terms of weight loss and food preference. In this study, we compared daily dosing to dosing every other day with the aim of understanding the optimal balance between efficacy and tolerability. Obese and lean male Sprague-Dawley rats were treated with the DACRA KBP-088, applying two different dosing intervals (1.5 nmol/kg once daily and 3 nmol/kg every other day) to assess the effect on body weight, food intake, glucose tolerance, and food preference when given the choice between chow (13% fat) and a high-fat diet (60% fat). Treatment with KBP-088 induced significant weight loss, reduction in adiposity, improvement in glucose control, and altered food preference toward food that is less calorie-dense. KBP-088 dosed every other day (3 nmol/kg) was superior to KBP-088 once daily (1.5 nmol/kg) in terms of weight loss and improvement of food preference. The beneficial effects were evident in both lean and obese rats. Hence, dosing KBP-088 every other day positively affects overall efficacy on metabolic parameters regardless of the lean/obese state, suggesting that less-frequent dosing with KBP-088 could be feasible.

Background

The increasing incidence of life-threatening Pneumocystis pneumonia (PCP) in non-HIV immunocompromised patients is a global concern. Yet, no reports have examined the prognostic significance of pre-existing interstitial lung disease (ILD) in non-HIV PCP.

The bioprocessing industry uses recombinant mammalian cell lines to generate therapeutic biologic drugs. To ensure consistent product quality of the therapeutic proteins, it is imperative to have a controlled production process. Regulatory agencies and the biotechnology industry consider cell line "clonal origin" an important aspect of maintaining process control. Demonstration of clonal origin of the cell substrate, or production cell line, has received considerable attention in the past few years, and the industry has improved methods and devised standards to increase the probability and/or assurance of clonal derivation. However, older production cell lines developed before the implementation of these methods, herein referred to as "legacy cell lines," may not meet current regulatory expectations for demonstration of clonal derivation. In this article, the members of the IQ Consortium Working Group on Clonality present our position that the demonstration of process consistency and product comparability of critical quality attributes throughout the development life cycle should be sufficient to approve a license application without additional genetic analysis to support clonal origin, even for legacy cell lines that may not meet current day clonal derivation standards. With this commentary, we discuss advantages and limitations of genetic testing methods to support clonal derivation of legacy cell lines and wish to promote a mutual understanding with the regulatory authorities regarding their optional use during early drug development, subsequent to Investigational New Drug (IND) application and before demonstration of product and process consistency at Biologics License Applications (BLA) submission.

ABSTRACTBackground:A significant number of girls are married as children, which negatively impacts their health, education, and development. Given the sheer numbers of girls at risk of child marriage globally, the challenge to eliminate the practice is daunting. Programs to prevent child marriage are typically small-scale and overlook the costs and scalability of the intervention.Implementation:This study tested and costed different approaches to preventing child marriage in rural Burkina Faso and Tanzania. The approaches tested were community dialogue, provision of school supplies, provision of a livestock asset, a model including all components, and a control arm. A quasi-experimental design was employed with surveys undertaken at baseline and after 2 years of intervention. We examined the prevalence of child marriage and school attendance controlling for background characteristics and stratified by age group. Programmatic costs were collected prospectively.Results:Among those in the community dialogue arm in Burkina Faso, girls aged 15 to 17 years had two-thirds less risk (risk ratio [RR]=0.33; 95% confidence interval [CI]=0.19, 0.60) of being married and girls aged 12 to 14 years had a greater chance of being in school (RR=1.18; 95% CI=1.07,1.29) compared to the control site. In Tanzania, girls aged 12 to 14 years residing in the multicomponent arm had two-thirds less risk of being married (RR=0.33; 95% CI=0.11, 0.99), and girls 15 to 17 in the conditional asset location had half the risk (RR=0.52; 95% CI=0.30, 0.91). All the interventions tested in Tanzania were associated with increased risk of girls 12 to 14 years old being in school, and the educational promotion arm was also associated with a 30% increased risk of girls aged 15 to 17 years attending school (RR=1.3; 95% CI=1.01, 1.67). Costs per beneficiary ranged from US$9 to US$117.Conclusion:The study demonstrates that minimal, low-cost approaches can be effective in delaying child marriage and increasing school attendance. However, community dialogues need to be designed to ensure sufficient quality and intensity of messaging. Program managers should pay attention to the cost, quality, and coverage of interventions, especially considering that child marriage persists in the most hard-to-reach rural areas of many countries.

OBJECTIVE

Nonalbuminuric diabetic kidney disease (DKD) has become the prevailing phenotype in patients with type 2 diabetes. However, it remains unclear whether its prognosis is poorer than that of other DKD phenotypes.

Glucagon is classically described as a counterregulatory hormone that plays an essential role in the protection against hypoglycemia. In addition to its role in the regulation of glucose metabolism, glucagon has been described to promote ketosis in the fasted state. Sodium–glucose cotransporter 2 inhibitors (SGLT2i) are a new class of glucose-lowering drugs that act primarily in the kidney, but some reports have described direct effects of SGLT2i on α-cells to stimulate glucagon secretion. Interestingly, SGLT2 inhibition also results in increased endogenous glucose production and ketone production, features common to glucagon action. Here, we directly test the ketogenic role of glucagon in mice, demonstrating that neither fasting- nor SGLT2i-induced ketosis is altered by interruption of glucagon signaling. Moreover, any effect of glucagon to stimulate ketogenesis is severely limited by its insulinotropic actions. Collectively, our data suggest that fasting-associated ketosis and the ketogenic effects of SGLT2 inhibitors occur almost entirely independent of glucagon.

PURPOSE

We aimed to evaluate the efficacy and safety of use of the Fasting Algorithm for Singaporeans with Type 2 Diabetes (FAST) during Ramadan.

Although not as ubiquitous as antibacterial susceptibility testing, antifungal susceptibility testing (AFST) is a tool of increasing importance in clinical microbiology laboratories. The goal of AFST is to reliably produce MIC values that may be used to guide patient therapy, inform epidemiological studies, and track rates of antifungal drug resistance. There are three methods that have been standardized by standards development organizations: broth dilution, disk diffusion, and azole agar screening for Aspergillus. Other commonly used methods include gradient diffusion and the use of rapid automated instruments. Novel methodologies for susceptibility testing are in development. It is important for laboratories to consider not only the method of testing but also the interpretation (or lack thereof) of in vitro data.

Skeletal muscle wasting is a devastating consequence of cancer that contributes to increased complications and poor survival, but is not well understood at the molecular level. Herein, we investigated the role of Myocilin (Myoc), a skeletal muscle hypertrophy-promoting protein that we showed is downregulated in multiple mouse models of cancer cachexia. Loss of Myoc alone was sufficient to induce phenotypes identified in mouse models of cancer cachexia, including muscle fiber atrophy, sarcolemmal fragility, and impaired muscle regeneration. By 18 months of age, mice deficient in Myoc showed significant skeletal muscle remodeling, characterized by increased fat and collagen deposition compared with wild-type mice, thus also supporting Myoc as a regulator of muscle quality. In cancer cachexia models, maintaining skeletal muscle expression of Myoc significantly attenuated muscle loss, while mice lacking Myoc showed enhanced muscle wasting. Furthermore, we identified the myocyte enhancer factor 2 C (MEF2C) transcription factor as a key upstream activator of Myoc whose gain of function significantly deterred cancer-induced muscle wasting and dysfunction in a preclinical model of pancreatic ductal adenocarcinoma (PDAC). Finally, compared with noncancer control patients, MYOC was significantly reduced in skeletal muscle of patients with PDAC defined as cachectic and correlated with MEF2c. These data therefore identify disruptions in MEF2c-dependent transcription of Myoc as a novel mechanism of cancer-associated muscle wasting that is similarly disrupted in muscle of patients with cachectic cancer.Significance:This work identifies a novel transcriptional mechanism that mediates skeletal muscle wasting in murine models of cancer cachexia that is disrupted in skeletal muscle of patients with cancer exhibiting cachexia.

Preimplantation genetic testing (PGT) is a reproductive technology that, in the course of in vitro fertilization (IVF), allows prospective parents to select their future offspring based on genetic characteristics. PGT could be seen as an exercise of reproductive liberty, thus potentially raising significant socioethical and legal controversy. In this review, we examine—from a comparative perspective—variations in policy approaches to the regulation of PGT. We draw on a sample of 19 countries (Australia, Austria, Belgium, Brazil, Canada, China, France, Germany, India, Israel, Italy, Japan, Mexico, Netherlands, Singapore, South Korea, Switzerland, United Kingdom, and the United States) to provide a global landscape of the spectrum of policy and legislative approaches (e.g., restrictive to permissive, public vs. private models). We also explore central socioethical and policy issues and contentious applications, including permissibility criteria (e.g., medical necessity), nonmedical sex selection, and reproductive tourism. Finally, we further outline genetic counseling requirements across policy approaches.

Consistently, the field of genetic counseling has advocated that parents be advised to defer elective genetic testing of minors until adulthood to prevent a range of potential harms, including stigma, discrimination, and the loss of the child's ability to decide for him- or herself as an adult. However, consensus around the policy of "defer-when-possible" obscures the extent to which this norm is currently under siege. Increasingly, routine use of full or partial genome sequencing challenges our ability to control what is discovered in childhood or, when applied in a prenatal context, even before birth. The expansion of consumer-initiated genetic testing services challenges our ability to restrict what is available to minors. As the barriers to access crumble, medical professionals should proceed with caution, bearing in mind potential risks and continuing to assess the impact of genetic testing on this vulnerable population.

The decision to list your home for resale is a big one. No doubt it came about after much thought, weighing pros and cons, and series of long discussions. However, once you decide to put your home on the market, get ready for the next big discussion: interior design.

According to a study done by Professor Paul Anglin from the University of Guelph in Ontario, there are certain words used in home listings that have a magical effect on a home for sale. These are the most powerful words in a home for sale listing that help the owner sell quickly and/or get a higher asking price.

Writing a home for sale listing is not an easy task, especially for those who are doing it for the first time, but if you can manage to avoid the worst words in a home for sale listing, rest assured that you will be one step closer to selling your home in a timely manner.

Every home seller wants to sell it fast and reach as many buyers as possible. Here are some tips to make your listing stand out to potential buyers from the crowd.

If you make a mistake during the listing process, you might end up getting less than your home is worth or find that it takes significantly longer to sell your home than it should.

With a budget of 1 billion VND, the best way for investors to get high-return and low-risk investment in Ho Chi Minh property market in 2015 is choosing one of three segments below: project land, apartment or townhouse in suburbs.

If you don’t have a big budget to invest in largest cities, think about buying properties in regional towns with many advantages. However, it’s important to look for the right location to pour your money.

Choosing good location, prestigious investor, reasonable price; considering legal issues and focusing on infrastructure are the secrets for investors to gain high profit from investing in land.

Choosing good location, prestigious investor, reasonable price; considering legal issues and focusing on infrastructure are the secrets for investors to gain high profit from investing in land.

Thị trường bất động sản Canberra, Australia gần đây sôi động hơn trước do sự có mặt của các nhà đầu tư và người mua nhà theo đuổi chiến lược rentvesting – vừa thuê nhà ở, vừa đầu tư khi nhận thấy khả năng sinh lời ở hai thị trường trọng điểm truyền thống là Sydney và Melbourne đang giảm sút.

Artificial intelligence is helping optimise the recharging batteries in electric vehicles, balancing speed while maximising lifespan

Artificial intelligence can tell whether a human or a bot is posting on Twitter based on how regularly they post and how much they reply to others, which could help identify fake accounts

Telling Lies is a game where you sift through video calls to solve a mystery. Half the time you don't know what you should be doing, but that's part of the fun, says Jacob Aron

Being at home this long, or really, just in one place for this long, has led me to see how much waste I produce. Spoiler alert: it’s a lot more than I thought. But I’m not here to shame anyone, in fact, quite the opposite. I think there are plenty of small ways we can cut down our carbon footprint, from driving less (check), to not using a washing machine or dryer (also, sadly, check), but gardening is what I’ve been doing, and is something that I’d recommend everyone give a shot now that we all have a little more times on our hands.

GETTING STARTED

Composting is a natural way to recycle all of the organic materials in your house through decomposition. Compost can improve your soil’s water retention, which saves you money on your water bills, and helps keep excess garbage out of landfills, too. To get started you need two things. The first is a compost bin for your kitchen. This is great whether you want to start a compost at home or if you have a compost center you can bring them to. You want something sleek, designy, yet simple because after all, it’s really just a trash can. This is an excellent one.

Read more at The Daily Beast.

A huge black hole from when the universe was less than a billion years old is shooting a powerful jet at Earth, and studying it could help us understand the young cosmos

Codemasters next racing game, DIRT 5 has been announced.

THE SCOTTISH Government is reviewing its Covid-19 testing strategy after the Deputy First Minster has been left “frustrated” by reports home care workers have been told to travel to the other side of Scotland for tests.

Efforts to scale up testing for the covid-19 coronavirus have been slow in some countries, and some tests are more accurate than others, which could make it harder to slow the spread

The infection is being eliminated as a public health threat by countries that introduce widespread testing and treatment for those at risk

We need to be very cautious about preliminary studies estimating how many people have already been infected by the coronavirus

Many countries are focusing coronavirus testing on people who have covid-19 symptoms. But regularly testing all essential workers would have more of an impact

The BCG tuberculosis vaccine boosts the production of immune cells and this may explain how it protects newborns from dying of sepsis

A COVID-19 mass testing effort within San Francisco's Mission District  — which aimed to broadly test individuals regardless of symptoms  — found stark inequalities in how the virus is affecting different groups. About 95% of the people who tested positive were Latino, and the vast majority could not work from home. Not a single white person tested positive, despite making up about a third of the people who were tested. 

According to The Verge, popular music app Spotify is testing...

The post Spotify Is Testing Video Podcasts With YouTube Stars appeared first on Man's World India.

The UFC comeback event on Saturday will feature one less match up after middleweight fighter Jacaré Souza tested positive for coronavirus. 

The UFC comeback event on Saturday will feature one less match up after middleweight fighter Jacaré Souza tested positive for coronavirus. 

A new title from Smithsonian Books highlights the diversity of Earth's 10 to 100 million insect species

Repurposing existing medicines focused on known drug targets is likely to offer a more rapid hope of tackling COVID-19 than developing and manufacturing a vaccine, argue an international team of scientists.

Read our live coronavirus updates HERE Coronavirus: The symptoms

Follow our live coronavirus updates HERE Coronavirus: the symptoms