Association between Regulator of G Protein Signaling 9–2 and Body Weight

Regulator of G protein signaling 9–2 (RGS9–2) is a protein that is highly enriched in the striatum, a brain region that mediates motivation, movement and reward responses. We identified a naturally occurring 5 nucleotide deletion polymorphism in the human RGS9 gene and found that the mean body mass index (BMI) of individuals with the deletion was significantly higher than those without. A splicing reporter minigene assay demonstrated that the deletion had the potential to significantly decrease the levels of correctly spliced RGS9 gene product. We measured the weights of rats after virally transduced overexpression of RGS9–2 or the structurally related RGS proteins, RGS7, or RGS11, in the nucleus accumbens (NAc) and observed a reduction in body weight after overexpression of RGS9–2 but not RGS7 or 11. Conversely, we found that the RGS9 knockout mice were heavier than their wild-type littermates and had significantly higher percentages of abdominal fat. The constituent adipocytes were found to have a mean cross-sectional area that was more than double that of corresponding cells from wild-type mice. However, food intake and locomotion were not significantly different between the two strains. These studies with humans, rats and mice implicate RGS9–2 as a factor in regulating body weight.National Institute of Mental Health (U.S.) (R41MH78570 award)National Center for Research Resources (U.S.) (Rhode Island IDeA Network of Biomedical Research Excellence (RI-INBRE) Award P20RR016457-10

Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990–2017: A systematic analysis for the Global Burden of Disease Study 2017

Background: The Global Burden of Diseases, Injuries, and Risk Factors Study 2017 (GBD 2017) includes a comprehensive assessment of incidence, prevalence, and years lived with disability (YLDs) for 354 causes in 195 countries and territories from 1990 to 2017. Previous GBD studies have shown how the decline of mortality rates from 1990 to 2016 has led to an increase in life expectancy, an ageing global population, and an expansion of the non-fatal burden of disease and injury. These studies have also shown how a substantial portion of the world's population experiences non-fatal health loss with considerable heterogeneity among different causes, locations, ages, and sexes. Ongoing objectives of the GBD study include increasing the level of estimation detail, improving analytical strategies, and increasing the amount of high-quality data. Methods: We estimated incidence and prevalence for 354 diseases and injuries and 3484 sequelae. We used an updated and extensive body of literature studies, survey data, surveillance data, inpatient admission records, outpatient visit records, and health insurance claims, and additionally used results from cause of death models to inform estimates using a total of 68 781 data sources. Newly available clinical data from India, Iran, Japan, Jordan, Nepal, China, Brazil, Norway, and Italy were incorporated, as well as updated claims data from the USA and new claims data from Taiwan (province of China) and Singapore. We used DisMod-MR 2.1, a Bayesian meta-regression tool, as the main method of estimation, ensuring consistency between rates of incidence, prevalence, remission, and cause of death for each condition. YLDs were estimated as the product of a prevalence estimate and a disability weight for health states of each mutually exclusive sequela, adjusted for comorbidity. We updated the Socio-demographic Index (SDI), a summary development indicator of income per capita, years of schooling, and total fertility rate. Additionally, we calculated differences between male and female YLDs to identify divergent trends across sexes. GBD 2017 complies with the Guidelines for Accurate and Transparent Health Estimates Reporting. Findings: Globally, for females, the causes with the greatest age-standardised prevalence were oral disorders, headache disorders, and haemoglobinopathies and haemolytic anaemias in both 1990 and 2017. For males, the causes with the greatest age-standardised prevalence were oral disorders, headache disorders, and tuberculosis including latent tuberculosis infection in both 1990 and 2017. In terms of YLDs, low back pain, headache disorders, and dietary iron deficiency were the leading Level 3 causes of YLD counts in 1990, whereas low back pain, headache disorders, and depressive disorders were the leading causes in 2017 for both sexes combined. All-cause age-standardised YLD rates decreased by 3·9% (95% uncertainty interval [UI] 3·1-4·6) from 1990 to 2017; however, the all-age YLD rate increased by 7·2% (6·0-8·4) while the total sum of global YLDs increased from 562 million (421-723) to 853 million (642-1100). The increases for males and females were similar, with increases in all-age YLD rates of 7·9% (6·6-9·2) for males and 6·5% (5·4-7·7) for females. We found significant differences between males and females in terms of age-standardised prevalence estimates for multiple causes. The causes with the greatest relative differences between sexes in 2017 included substance use disorders (3018 cases [95% UI 2782-3252] per 100 000 in males vs 1400 [1279-1524] per 100 000 in females), transport injuries (3322 [3082-3583] vs 2336 [2154-2535]), and self-harm and interpersonal violence (3265 [2943-3630] vs 5643 [5057-6302]). Interpretation: Global all-cause age-standardised YLD rates have improved only slightly over a period spanning nearly three decades. However, the magnitude of the non-fatal disease burden has expanded globally, with increasing numbers of people who have a wide spectrum of conditions. A subset of conditions has remained globally pervasive since 1990, whereas other conditions have displayed more dynamic trends, with different ages, sexes, and geographies across the globe experiencing varying burdens and trends of health loss. This study emphasises how global improvements in premature mortality for select conditions have led to older populations with complex and potentially expensive diseases, yet also highlights global achievements in certain domains of disease and injury

Global, regional, and national age-sex-specific mortality and life expectancy, 1950-2017: a systematic analysis for the Global Burden of Disease Study 2017

Background: Assessments of age-specific mortality and life expectancy have been done by the UN Population Division, Department of Economics and Social Affairs (UNPOP), the United States Census Bureau, WHO, and as part of previous iterations of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD). Previous iterations of the GBD used population estimates from UNPOP, which were not derived in a way that was internally consistent with the estimates of the numbers of deaths in the GBD. The present iteration of the GBD, GBD 2017, improves on previous assessments and provides timely estimates of the mortality experience of populations globally. Methods: The GBD uses all available data to produce estimates of mortality rates between 1950 and 2017 for 23 age groups, both sexes, and 918 locations, including 195 countries and territories and subnational locations for 16 countries. Data used include vital registration systems, sample registration systems, household surveys (complete birth histories, summary birth histories, sibling histories), censuses (summary birth histories, household deaths), and Demographic Surveillance Sites. In total, this analysis used 8259 data sources. Estimates of the probability of death between birth and the age of 5 years and between ages 15 and 60 years are generated and then input into a model life table system to produce complete life tables for all locations and years. Fatal discontinuities and mortality due to HIV/AIDS are analysed separately and then incorporated into the estimation. We analyse the relationship between age-specific mortality and development status using the Socio-demographic Index, a composite measure based on fertility under the age of 25 years, education, and income. There are four main methodological improvements in GBD 2017 compared with GBD 2016: 622 additional data sources have been incorporated; new estimates of population, generated by the GBD study, are used; statistical methods used in different components of the analysis have been further standardised and improved; and the analysis has been extended backwards in time by two decades to start in 1950. Findings: Globally, 18·7% (95% uncertainty interval 18·4–19·0) of deaths were registered in 1950 and that proportion has been steadily increasing since, with 58·8% (58·2–59·3) of all deaths being registered in 2015. At the global level, between 1950 and 2017, life expectancy increased from 48·1 years (46·5–49·6) to 70·5 years (70·1–70·8) for men and from 52·9 years (51·7–54·0) to 75·6 years (75·3–75·9) for women. Despite this overall progress, there remains substantial variation in life expectancy at birth in 2017, which ranges from 49·1 years (46·5–51·7) for men in the Central African Republic to 87·6 years (86·9–88·1) among women in Singapore. The greatest progress across age groups was for children younger than 5 years; under-5 mortality dropped from 216·0 deaths (196·3–238·1) per 1000 livebirths in 1950 to 38·9 deaths (35·6–42·83) per 1000 livebirths in 2017, with huge reductions across countries. Nevertheless, there were still 5·4 million (5·2–5·6) deaths among children younger than 5 years in the world in 2017. Progress has been less pronounced and more variable for adults, especially for adult males, who had stagnant or increasing mortality rates in several countries. The gap between male and female life expectancy between 1950 and 2017, while relatively stable at the global level, shows distinctive patterns across super-regions and has consistently been the largest in central Europe, eastern Europe, and central Asia, and smallest in south Asia. Performance was also variable across countries and time in observed mortality rates compared with those expected on the basis of development. Interpretation: This analysis of age-sex-specific mortality shows that there are remarkably complex patterns in population mortality across countries. The findings of this study highlight global successes, such as the large decline in under-5 mortality, which reflects significant local, national, and global commitment and investment over several decades. However, they also bring attention to mortality patterns that are a cause for concern, particularly among adult men and, to a lesser extent, women, whose mortality rates have stagnated in many countries over the time period of this study, and in some cases are increasing

Cleistanthin A, a diphyllin glycoside from Cleistanthus collinus, is cytotoxic to PHA-stimulated (proliferating) human lymphocytes

An ideal anticancer drug would be one that preferentially kills tumor cells with the least toxicity to normal cells. Cleistanthin A, a diphyllin glycoside of the tropical plant Cleistanthus collinus, was found to possess cytotoxic and tumor regressing properties. To find out whether this compound acts selectively on proliferating cells it was tested against quiescent and proliferating human lymphocytes. Mitogen-stimulated and unstimulated human lymphocytes were treated with cleistanthin A. A cytotoxicity assay using MTT was used to assess the viability of the cells. Percentage viability of the unstimulated and treated cells were normalized to that of the untreated and unstimulated cells and percentage viability of stimulated and treated cells were normalized to that of stimulated and untreated cells. Quiescent lymphocytes were refractory to the action of cleistanthin A. Only proliferating cells were killed. Cell death was proportional to the percentage of cells in the proliferating stage and was also dose-dependent. Quiescent lymphocytes pretreated with cleistanthin A had the ability to proliferate upon subsequent stimulation with PHA. These results indicate that cleistanthin A does not affect the viability of quiescent cells. Also, it did not affect the proliferating potential of quiescent cells. However, this compound drastically affected proliferating cells by reducing their viability to 10-20%. Our results therefore indicate that the antiproliferative property of cleistanthin A could be used in regimens for treating tumors with extensive proliferative potencies

Power Quality Improvement in a Cascaded Multilevel Inverter Interfaced Grid Connected System Using a Modified Inductive–Capacitive–Inductive Filter with Reduced Power Loss and Improved Harmonic Attenuation

Recently, multilevel inverters are more researched due to the advantages they offer over conventional voltage source inverters in grid connected applications. Passive filters are connected at the output of these inverters to produce sinusoidal waveforms with reduced harmonics and to satisfy grid interconnection standard requirements. This work proposes a new passive filter topology for a pulse width modulated five-level cascaded inverter interfaced grid connected system. The proposed passive filter inserts an additional resistance-capacitance branch in parallel to the filter capacitor of the traditional inductive–capacitive–inductive filter in addition to a resistance in series with it to reduce damping power loss. It can attenuate the switching frequency harmonic current components much better than the traditional filter while maintaining the same overall inductance, reduced capacitance and resistance values. The basic parameter design procedure and an approach to discover the parameters of the proposed filter is introduced. Further, a novel methodology using Particle Swarm Optimization (PSO) is recommended to guarantee minimum damping loss while ensuring reduced peak during resonance. In addition, PSO algorithm is newly employed in this work to maximize harmonic attenuation in and around the switching frequency on the premise of allowable values of filter inductance and capacitance. A comparative discussion considering traditional passive filters and the proposed filter is presented and evaluated through experiments conducted on a 110 V, 1 kW five-level grid connected inverter. The modulation algorithm for the multilevel inverter is implemented using a SPARTAN 6-XC6SLX25 Field Programmable Gate Array (FPGA) processor. The analysis shows that the proposed filter not only provides decreased damping power loss but also is capable of providing considerable harmonic ripple reduction in the high frequency band, improved output waveforms and lesser Total Harmonic Distortion (THD) with improved power quality for the multilevel inverter based grid connected system

Inhibition of matrix metalloproteinase-9 (MMP-9) activity by cleistanthin A, a diphyllin glycoside from Cleistanthus collinus

Matrix metalloproteinases (MMPs) are responsible for the remodeling of the extracellular matrix throughout the body. Inhibitors of these enzymes have been suggested as potential therapeutic agents for use in treatment of cancer. Our observations showed that cleistanthin A, a diphyllin glycoside from the leaves of the plant Cleistanthus collinus inhibited MMP-9, a 92 kDa matrix metalloproteinase. Further evaluation of this compound might reveal many such novel properties that might help in the evolution of this compound as an anticancer drug

Prevalence of immune mediated vesiculobullous lesions among patients visiting a private dental hospital with special emphasis on gingival manifestation

Background and Aim: Vesiculobullous lesions are a group of mucocutaneous lesions that are predominantly immune-mediated but may also have a genetic or viral origin. The most common site of occurrence is buccal mucosa, whereas the number of cases involving gingiva is comparatively low. Based on the literature, although numerous studies have reported the prevalence of vesiculobullous lesions in the nonkeratinized epithelium, there is a dearth of knowledge about its occurrence in keratinized oral mucosa, especially gingiva. The objective of the study was to assess the prevalence of immune-mediated oral vesiculobullous lesions emphasizing the occurrence in keratinized mucosa, especially the gingiva, among patients visiting a private dental hospital. Materials and Methods: The study was conducted in a private teaching dental institute and hospital setting. Out of 615 incisional biopsies received in the department of oral pathology, between June 2019 and April 2021, n = 22 samples were immune-mediated vesiculobullous lesions confirmed by clinical and histopathological diagnosis after eliminating lesions of viral origin. Patient details including age, gender, site, duration, and systemic illness were collected from the digital information archiving software and analyzed by appropriate statistics using SPSS software. Results: Based on the results, 95.5% of the patients had histopathological features of intraepithelial clefting and only 4.5% of them showed subepithelial clefting. Female predilection was 6.3:1. The most common site of involvement was nonkeratinized mucosa (36.36%) and 59.09% of the patients presented with systemic illness. Conclusion: The study shows most of the features of pemphigus is consistent in gingiva and other parts of oral mucosa. The dental practitioners should be aware of the various oral manifestations of such lesions to ensure accurate diagnosis and adequate treatment

Visual function assessment, ocular examination, and intervention in children with developmental delay: A systematic approach. Part 1

Children with special needs form a unique subset with regards to visual function and examination techniques needed to assess them. With more awareness among the general public, neurologists, and pediatricians, these children are referred for assessment to the ophthalmologist or optometrist and sometimes even to the rehabilitation professional at an early age. This clinical practice guideline and review gives a systematic approach for examining the visual functions of a child with special needs. It outlines the procedures to be followed with equipment needed in clinical practice. Functional vision assessment guidelines are also included. This is the first part in a two-part series, with the first part presenting clinical examination guidelines and the second presenting intervention and vision enhancement techniques