Notes

Mechanisms as well as Management of Late-Life Depression.
The disorders of sexual development (DSD) represent an array of phenotypes with ambiguous genitalia. The present case had microphallus with fused and bifid scrotum and was initially assigned androgen insensitivity syndrome; however, sequencing of the complete coding region of the androgen receptor gene failed to identify a causative mutation. We undertook whole exome sequencing for identification of the pathogenic mutation. The most promising pathogenic variants were genotyped using Sanger sequencing to confirm the genotypes. We found compound heterozygous mutations, c.169G>T and c.586G>A in the SRD5A2 gene in this case, resulting in a nonsense (p.Glu57Ter) and a nonsynonymous substitution (p.Gly196Ser), respectively. While the nonsense mutation would result in a truncated protein, p.Gly196Ser substitution has been previously reported to be pathogenic. The mutations were confirmed by Sanger sequencing. Sequencing of 96 normal male individuals did not show the above mutations, suggesting their pathogenic nature. In conclusion, we identified compound heterozygous pathogenic mutations, c.169G>T (p.Glu57Ter) and c.586G>A (p.Gly196Ser), in the SRD5A2 gene in a case of ambiguous genitalia. p.Glu57Ter is a novel mutation, which in compound heterozygote combination with Gly196Ser causes 5a reductase deficiency.A sedentary lifestyle combined with the intake of high-calorie diet has been the paramount cause of metabolic syndrome (MS) which is now a serious concern of public health worldwide as it involves the coexistence of hypertension, hyperlipidemia, glucose intolerance, and obesity. Hence, identifying a suitable strategy to overcome the worldwide menace of MS is imperative. Macrotyloma uniflorum a lesser known legume is highly nutritious and notable for its ethano-medicinal potential. Herein, the influence of M. uniflorum in high-fat dietinduced metabolic changes in a rodent model of metabolic syndrome was evaluated. Serum levels of glucose, total cholesterol, triglycerides, VLDL-c, and bodyweight were decreased, whereas HDL-c was increased in M. uniflorum-treated MS rats. The protein expression (AMPK-α, PPAR-α, and PPAR-γ) and gene expression (leptin, adiponectin, resistin, UCP2, NF-κB, and IL-6) results are impressive to highlight that M. uniflorum modulates the pathological conditions of MS and proves to be caumes could bring a revolution in public health and nutraceutical industries. This study scientifically validated the phytochemicals in M. uniflorum for its functional potential in the management of Metabolic Syndrome (MS). This study would help the nutraceutical industries to develop functional foods using M. uniflorum seeds to make porridges and soups or nutraceutical supplements with the bioflavonoids isolated from M. uniflorum for the management of metabolic disorders by mitigating hyperlipidemia, oxidative stress, and inflammation.
This cross-sectional study assessed differences in oral health and related behaviours and risk indicators by rurality in a north-central Appalachian population using the Andersen behavioural model as a conceptual framework.

Participants were residents aged 18-59years (n=1311) from the Center for Oral Health Research in Appalachia, selected according to a household-based sampling strategy. Rural-Urban Continuum codes (RUC) corresponding to the participants' residences were used to classify participants as rural or urban. Mixed models were used to test rural-urban differences in measures of oral health, related behaviours, and need, enabling, and predisposing risk indicators. Models were adjusted for sociodemographic variables age, sex, race, income, perceived socioeconomic status, educational attainment and dental insurance.

Rural residents had poorer oral health overall, with fewer sound teeth (β=-1.79), more dental caries (β=0.27) and higher rates of edentulism (5.2% vs 2.8%). Differences also were observed fordental care utilization and perceived barriers to care. Rural residents were less likely to attend dental visits as often as needed (26.9% vs 42.8%) and were more prone to seek care only after experiencing a dental problem (64.3% vs 43.9%). Rural residents also were more likely to report high costs (89% vs 62.6%) as a major reason for not having dental visits. Rural-urban differences for some oral health characteristics and behaviours could be explained by sociodemographic characteristics, whereas others could not.

This study revealed rural-urban differences in risk indicators and oral health outcomes in north-central Appalachia. Many of these differences were explained, completely or partly, by sociodemographic factors.
This study revealed rural-urban differences in risk indicators and oral health outcomes in north-central Appalachia. Many of these differences were explained, completely or partly, by sociodemographic factors.Diesel vehicles are significant contributors to air pollution in Mexico City. We estimate the costs and mortality benefits of retrofitting heavy-duty vehicles with particulate filters and oxidation catalysts. The feasibility and cost-effectiveness of controls differ by vehicle model-year and type. MT-802 nmr We evaluate 1985 to 2014 model-year vehicles from 10 vehicle classes and five model-year groups. Our analysis shows that retrofitting all vehicles with the control that maximizes expected net benefits for that vehicle type and model-year group has the potential to reduce emissions of primary fine particles (PM2.5 ) by 950 metric tons/year; cut the population-weighted annual mean concentration of PM2.5 in Mexico City by 0.90 µg/m3 ; reduce the annual number of deaths attributable to air pollution by over 80; and generate expected annual health benefits of close to 250 million US$. These benefits outweigh expected costs of 92 million US$ per year. Diesel retrofits are but one step that should viewed in the context of other efforts--such as development of an integrated public transportation system, promotion of the rational use of cars, reduction of emissions from industrial sources and fires, and redesign of the Mexico City Metropolitan Area to reduce urban sprawl--that must be analyzed and implemented to substantially control air pollution and protect public health. Even if considering other potential public health interventions, which would offer greater benefits at the same or lower costs, only by conducting, promoting, and publishing this sort of analyses, we can make strides to improve public health cost-effectively.Venetoclax (Ven) is a selective small-molecule inhibitor of BCL-2 that exhibits antitumoral activity against MM cells with t(11;14) translocation. We evaluated the safety and efficacy of Ven and dexamethasone (VenDex) combination in patients with t(11;14) positive relapsed/refractory (R/R) multiple myeloma (MM). This open-label, multicenter study had two distinct phases (phase one [P1], phase two [P2]). Patients in both phases received VenDex (oral Ven 800 mg/day + oral Dex 40 mg [20 mg for patients ≥75 years] on days 1, 8, and 15, per 21-day cycle). The primary objective of the P1 VenDex cohort was to assess safety and pharmacokinetics. Phase two further evaluated efficacy with objective response rate (ORR) and very good partial response or better. Correlative studies explored baseline BCL2 (BCL-2) and BCL2L1 (BCL-XL ) gene expression, cytogenetics, and recurrent somatic mutations in MM. Twenty and 31 patients in P1 and P2 with t(11;14) positive translocation received VenDex. P1/P2 patients had received a median of 3/5 lines of prior therapy, and 20%/87% were refractory to daratumumab. Predominant grade 3/4 hematological adverse events (AEs) with ≥10% occurrence included lymphopenia (20%/19%), neutropenia (15%/7%), thrombocytopenia (10%/10%), and anemia (5%/16%). At a median follow-up of 12.3/9.2 months, ORR was 60%/48%. The duration of response estimate at 12 months was 50%/61%, and the median time to progression was 12.4/10.8 months. In biomarker evaluable patients, response to VenDex was independent of concurrent del(17p) or gain(1q) and mutations in key oncogenic signaling pathways, including MAPK and NF-kB. VenDex demonstrated efficacy and manageable safety in heavily-pre-treated patients with t(11;14) R/R MM.This case study highlights that how a disorder of sexual development when goes unnoticed at birth and unreported during childhood or adolescence can present with major problems and even complications in adulthood. Since our patient was young and in a childbearing age, he presented with bilateral undescended testes and orgasmic anejaculation when he first came to the hospital. Subsequently, having a normal 46XY karyotype but remnants of persistent Mullerian duct made him little confused about his identity. After giving him the confidence, that he was still a male and could lead the life he did previously, the explanation about future risk of malignancy in the intra-abdominal testes was another difficult task. Early detection and management of male pseudohermaphroditism with persistent Mullerian duct requires a co-ordinated approach of a team of endocrinologist, physician, surgeon and radiologist. Integrated imaging in the form of ultrasound, genitography and MRI is important in demonstrating the anatomy, classification, possible effects or congenital malformations in other organs, warning patients of any risk of neoplasia and guiding the clinician to plan other investigations, hormonal replacement or reconstruction surgery if required. Such a systemic approach that allays anxiety and gives psychological relief to the patient should be taken as it can deeply change the life of a person and their family.Internet of things (IoT) business partnership are formed by technological partners and traditional manufacturers. IoT sensors and devices capture data from manufacturers' products. Data enforce product/service innovation thanks to data sharing among companies. However, data sharing among firms increases the risk of data breaches. The latter is due to two phenomena information linkage and privacy interdependency. Data Protection Authorities (DPA) protect data users' rights and fine firms if there is an infringement of privacy laws. DPA sanction the responsible for the infringement of privacy laws. We present two different business scenarios the first occurs when each firm is a data owner; the second occurs when only the manufacturer is the data owner. For both scenarios, we present two fair penalty schemes that suggest the following total amount of the fine; and how to share the fine among participants. Penalties critically vary at how innovation networks are structured in IoT industries. Our penalties provide incentives to data sharing since they redistribute firms' responsibility against data breaches. Our penalties may mitigate the risk on the manufacturer if is the unique responsible for data handling.The intraflagellar transport (IFT) machinery consists of the anterograde motor kinesin-II, the retrograde motor IFT dynein, and the IFT-A and -B complexes. However, the interaction among IFT motors and IFT complexes during IFT remains elusive. Here, we show that the IFT-B protein IFT54 interacts with both kinesin-II and IFT dynein and regulates anterograde IFT. Deletion of residues 342-356 of Chlamydomonas IFT54 resulted in diminished anterograde traffic of IFT and accumulation of IFT motors and complexes in the proximal region of cilia. IFT54 directly interacted with kinesin-II and this interaction was strengthened for the IFT54Δ342-356 mutant in vitro and in vivo. The deletion of residues 261-275 of IFT54 reduced ciliary entry and anterograde traffic of IFT dynein with accumulation of IFT complexes near the ciliary tip. IFT54 directly interacted with IFT dynein subunit D1bLIC, and deletion of residues 261-275 reduced this interaction. The interactions between IFT54 and the IFT motors were also observed in mammalian cells.
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