Ubiquitination of hnRNPA1 by TRAF6 links chronic innate immune signaling with myelodysplasia.

Toll-like receptor (TLR) activation contributes to premalignant hematologic conditions, such as myelodysplastic syndromes (MDS). TRAF6, a TLR effector with ubiquitin (Ub) ligase activity, is overexpressed in MDS hematopoietic stem/progenitor cells (HSPCs). We found that TRAF6 overexpression in mouse HSPC results in impaired hematopoiesis and bone marrow failure. Using a global Ub screen, we identified hnRNPA1, an RNA-binding protein and auxiliary splicing factor, as a substrate of TRAF6. TRAF6 ubiquitination of hnRNPA1 regulated alternative splicing of Arhgap1, which resulted in activation of the GTP-binding Rho family protein Cdc42 and accounted for hematopoietic defects in TRAF6-expressing HSPCs. These results implicate Ub signaling in coordinating RNA processing by TLR pathways during an immune response and in premalignant hematologic diseases, such as MDS.

Does India need a new pharmaceutical policy? Examining the implications of the drug price control order.

OBJECTIVES: This article aims to analyse the impact of the pharmaceutical policy on the availability, accessibility and affordability of medicines to the Indian populace. The article delves into the shortcomings of the Drug Price Control Order 2013 and highlights its real-world implications. METHODS: Published literature in the form of scientific articles on the proposed reforms that took place in the pharmaceutical policy was reviewed. The study used the memorandums, laws and government decisions published by the Department of Pharmaceuticals, Ministry of Health and Family Welfare and National Pharmaceutical Pricing Authority|National Pharmaceutical Pricing Authorities. RESULTS: The pharmaceutical policy in India underwent several changes during 2013-2020 to enhance the affordability and accessibility of drugs. The stringent policy hampered innovation due to the lack of profitability to the Multinational Companies. Moreover, it was found that the impact of the price control order on the low-cost local generic manufacturers affected much of the country's price-sensitive population. CONCLUSION: The pharmaceutical policy of India needs to be amended to extend its benefit to its stakeholders. The government should shift its attention to improving the quality of drugs, increasing competition amongst manufacturers and enhancing the accessibility of medicines through state/centre sponsored initiatives.

Best-Practice Recommendations for Chiropractic Care for Pregnant and Postpartum Patients: Results of a Consensus Process.

OBJECTIVE: The purpose of this project was to develop a best-practices document on chiropractic care for pregnant and postpartum patients with low back pain (LBP), pelvic girdle pain (PGP), or a combination. METHODS: A modified Delphi consensus process was conducted. A multidisciplinary steering committee of 11 health care professionals developed 71 seed statements based on their clinical experience and relevant literature. A total of 78 panelists from 7 countries were asked to rate the recommendations (70 chiropractors and representatives from 4 other health professions). Consensus was reached when at least 80% of the panelists deemed the statement to be appropriate along with a median response of at least 7 on a 9-point scale. RESULTS: Consensus was reached on 71 statements after 3 rounds of distribution. Statements included informed consent and risks, multidisciplinary care, key components regarding LBP during pregnancy, PGP during pregnancy and combined pain during pregnancy, as well as key components regarding postpartum LBP, PGP, and combined pain. Examination, diagnostic imaging, interventions, and lifestyle factors statements are included. CONCLUSION: An expert panel convened to develop the first best-practice consensus document on chiropractic care for pregnant and postpartum patients with LBP or PGP. The document consists of 71 statements on chiropractic care for pregnant and postpartum patients with LBP and PGP.

Characterization of telerehabilitation visits and patient satisfaction in outpatient physical medicine and rehabilitation clinics from March 2020 to November 2021.

OBJECTIVE: To explore the usability of and satisfaction with telerehabilitation services provided to rehabilitation patients with various diagnoses at two large urban medical facilities during the Covid-19 pandemic. DESIGN: This was a usability study and all patients that received telerehabilitation services from March 2020 to November 2021 were included. Of the 4,070 surveys sent via mail or email links to RedCap, 405 were completed (10% Response Rate). Participants completed demographic surveys, surveys on the telerehabilitation visit characteristics, telerehabilitation usability, and overall satisfaction with the visit. RESULTS: Patients were mostly women (64.4%), White, non-hispanic (74.3%) and English speaking (99%). Most patients were seen via telerehabilitation due to Covid-19 restrictions (37.1%). Patients were generally satisfied with their telerehabilitation visit (3.64 out of 4). Additionally, patients generally found telerehab to be useful (6.4 out of 7), easy to use (6.3 out of 7), effective (6.2 out of 7), satisfactory (6.3 out of 7) and comparable to in-person visits (6.5 out of 7). CONCLUSION: Patients generally reported feeling satisfied and comfortable with telerehabilitation visits, and felt they were comparable to in-person visits. Future research should examine the impact of socioeconomic factors on telerehabilitation use, with a focus on education level and non-English speakers.

Suicide and suicidal ideation in the times of the Covid-19 pandemic: A scientometric analysis.

Objectives: The article aims to explore the studies performed on suicide because of coronavirus disease 19 through a bibliometric analysis. A quantitative analysis of the topic furnishes data on the publication pattern, influential research journals, highly cited articles, productive countries and organizations, the authorship pattern, and the collaborative pattern between authors. Methods: Data regarding the type of documents, most cited articles, influential research journals, contributions per country, and so on were extracted for the study from the Scopus database. Data analysis and visualization were performed through R-Studio and the VOSviewer application. Results: A bibliometric analysis encompassing scientific contributions based on suicide or suicide-related ideation because of the coronavirus pandemic showed a total of 494 documents published in 230 journals/books. The articles published by proficient authors in reputed journals highlighted the key areas of research in the field. USA dominated the list of scientific production of countries contributing to 340 documents. Conclusion: The results provided by this analysis could act as a steppingstone for experts to design a roadmap for mental health research during the pandemic. Studies can be designed to gather information on mental health conditions across specific age groups. Research collaborations that facilitate the publication of pooled protocols and data are encouraged.

Estrogens as regulator of hematopoietic stem cell, immune cells and bone biology.

Hematopoietic stem cells provide continuous supply of all the immune cells, through proliferation and differentiation decisions. These decisions are controlled by local bone marrow environment as well as by long-range signals for example endocrine system. Sex dependent differential immunological responses have been described under homeostasis and disease conditions. Females show higher longevity than male counterpart that seems to depend on major female sex hormone, estrogen. There are four estrogens - Estrone (E1), estradiol (E2), Estriol (E3) and Estetrol (E4) that spatially and temporarily present during different female reproductive phases. In this review, we discussed recent updates describing the effects of estrogen on HSC, immune cells and in bone biology. Estradiol (E2) being a major/abundant estrogen is extensively investigated, while effects of other estrogens E1, E3 and E4 are started to unravel recently. Furthermore, clinical effect of estrogen as hormone therapy is discussed in HSC and immune cells perspectives. The data presented in this review is compiled by searches of PubMed, database of American Cancer Society (ACS). We have included article from September 1994 to March 2020 as covering all article in chronological order is not fissile so we included relevant article with substantial information in this specific area of research by using the search term (alone or in combination) estrogen, hematopoietic stem cell, immune cells, gender difference, estrone, estriol, estetrol, therapeutic application, pregnancy, effect on bone.

Canonical Wnt Signaling Ameliorates Aging of Intestinal Stem Cells.

Although intestinal homeostasis is maintained by intestinal stem cells (ISCs), regeneration is impaired upon aging. Here, we first uncover changes in intestinal architecture, cell number, and cell composition upon aging. Second, we identify a decline in the regenerative capacity of ISCs upon aging because of a decline in canonical Wnt signaling in ISCs. Changes in expression of Wnts are found in stem cells themselves and in their niche, including Paneth cells and mesenchyme. Third, reactivating canonical Wnt signaling enhances the function of both murine and human ISCs and, thus, ameliorates aging-associated phenotypes of ISCs in an organoid assay. Our data demonstrate a role for impaired Wnt signaling in physiological aging of ISCs and further identify potential therapeutic avenues to improve ISC regenerative potential upon aging.

The small GTPase Rap1b negatively regulates neutrophil chemotaxis and transcellular diapedesis by inhibiting Akt activation.

Neutrophils are the first line of cellular defense in response to infections and inflammatory injuries. However, neutrophil activation and accumulation into tissues trigger tissue damage due to release of a plethora of toxic oxidants and proteases, a cause of acute lung injury (ALI). Despite its clinical importance, the molecular regulation of neutrophil migration is poorly understood. The small GTPase Rap1b is generally viewed as a positive regulator of immune cell functions by controlling bidirectional integrin signaling. However, we found that Rap1b-deficient mice exhibited enhanced neutrophil recruitment to inflamed lungs and enhanced susceptibility to endotoxin shock. Unexpectedly, Rap1b deficiency promoted the transcellular route of diapedesis through endothelial cell. Increased transcellular migration of Rap1b-deficient neutrophils in vitro was selectively mediated by enhanced PI3K-Akt activation and invadopodia-like protrusions. Akt inhibition in vivo suppressed excessive Rap1b-deficient neutrophil migration and associated endotoxin shock. The inhibitory action of Rap1b on PI3K signaling may be mediated by activation of phosphatase SHP-1. Thus, this study reveals an unexpected role for Rap1b as a key suppressor of neutrophil migration and lung inflammation.

Social network and risk-taking behavior most associated with rapid HIV testing, circumcision, and preexposure prophylaxis acceptability among high-risk Indian men.

Indian truck drivers and their younger apprentice drivers are at increased risk of HIV infection. We determine network and risk practices associated with willingness to adopt HIV prevention interventions currently not being used in India: rapid HIV testing, circumcision, and preexposure prophylaxis (PrEP) in order to inform the National AIDS Control Program (NACP). Truck drivers and truck cleaners were systematically recruited to participate in a social network and risk survey in Hyderabad, Southern India. Three separate composite measures of acceptability of rapid HIV testing, circumcision, and PrEP acceptability were utilized to independently assess the relationship of these prevention interventions with risk-practices and social network characteristics. An 89% participation rate yielded 1602 truck drivers and truck cleaners with 54.2% younger than 30 years of age and 2.8% HIV infected. Twenty-five percent of respondents reported sex with female sex workers (FSW) and 5% with men (MSM). Rapid testing, circumcision, and PrEP acceptability were 97.4%, 9.1%, and 85.9%, respectively. Participants reporting prosocial network characteristics were more accepting of rapid testing (adjusted odds ratio [AORs] 3.07-6.71; p<0.05) and demonstrated variable PrEP acceptability (AORs 0.08-2.22; p<0.001). Sex with FSWs was associated with PrEP acceptability (AOR 4.27; p<0.001); sex with MSM was associated with circumcision acceptability only (AOR 2.66; p<0.01). Social network factors and risk-practices were associated with novel prevention acceptability, but not consistently across intervention type and with variable directionality. The NACP will need to consider that intervention uptake may likely be most successful when efforts are targeted to individuals with specific behavior and social network characteristics.