Discovery of low-molecular-weight phenylalanine derivatives as novel HIV capsid modulators with improved antiretroviral activity and metabolic stability.

The HIV capsid (CA) protein is a promising target for anti-AIDS treatment due to its critical involvement in viral replication. Herein, we utilized the well-documented CA inhibitor PF74 as our lead compound and designed a series of low-molecular-weight phenylalanine derivatives. Among them, compound 7t exhibited remarkable antiviral activity with a high selection index (EC50 = 0.040 µM, SI = 2815), surpassing that of PF74 (EC50 = 0.50 µM, SI = 258). Furthermore, when evaluated against the HIV-2 strain, 7t (EC50 = 0.13 µM) demonstrated approximately 14-fold higher potency than that of PF74 (EC50 = 1.76 µM). Insights obtained from surface plasmon resonance (SPR) revealed that 7t exhibited stronger target affinity to the CA hexamer and monomer in comparison to PF74. The potential interactions between 7t and the HIV-1 CA were further elucidated using molecular docking and molecular dynamics simulations, providing a plausible explanation for the enhanced target affinity with 7t over PF74. Moreover, the metabolic stability assay demonstrated that 7t (T1/2 = 77.0 min) significantly outperforms PF74 (T1/2 = 0.7 min) in human liver microsome, exhibiting an improvement factor of 110-fold. In conclusion, 7t emerges as a promising drug candidate warranting further investigation.

Mapping of adult plant recessive resistance to anthracnose in Indian common bean landrace Baspa/KRC 8.

BACKGROUND: The common bean (Phaseolus vulgaris) has become the food of choice owing to its wealthy nutritional profile, leading to a considerable increase in its cultivation worldwide. However, anthracnose has been a major impediment to production and productivity, as elite bean cultivars are vulnerable to this disease. To overcome barriers in crop production, scientists worldwide are working towards enhancing the genetic diversity of crops. One way to achieve this is by introducing novel genes from related crops, including landraces like KRC 8. This particular landrace, found in the North Western Himalayan region, has shown adult plant resistance against anthracnose and also possesses a recessive resistance gene. METHODS AND RESULTS: In this study, a population of 179 F2:9 RIL individuals (Jawala × KRC 8) was evaluated at both phenotypic and genotypic levels using over 830 diverse molecular markers to map the resistance gene present in KRC 8. We have successfully mapped a resistance gene to chromosome Pv01 using four SSR markers, namely IAC 238, IAC 235, IAC 259, and BM 146. The marker IAC 238 is closely linked to the gene with a distance of 0.29 cM, while the other markers flank the recessive resistance gene at 10.87 cM (IAC 259), 17.80 cM (BM 146), and 25.22 cM (IAC 235). Previously, a single recessive anthracnose resistance gene (co-8) has been reported in the common bean accession AB 136. However, when we performed PCR amplification with our tightly linked marker IAC 238, we got different amplicons in AB 136 and KRC 8. Interestingly, the susceptible cultivar Jawala produced the same amplicon as AB 136. This observation indicated that the recessive gene present in KRC 8 is different from co-8. As the gene is located far away from the Co-1 locus, we suggest naming the recessive gene co-Indb/co-19. Fine mapping of co-Indb in KRC 8 may provide new insights into the cloning and characterization of this recessive gene so that it can be incorporated into future bean improvement programs. Further, the tightly linked marker IAC 238 can be utilized in marker assisted introgression in future bean breeding programs. CONCLUSION: The novel co-Indb gene present in Himalayan landrace KRC 8, showing adult plant resistance against common bean anthracnose, is independent from all the resistance genes previously located on chromosome Pv01.

Increased taxes and regulation of Indian cigarillos (bidi) industry: Effects on revenue and years of life lost.

INTRODUCTION: Indian cigarillos (bidi) are low-cost alternatives to cigarettes with only 22% imposed taxes, and turnover of upto INR 4 million per annum exempted from taxation. This paper estimates revenue implications and potential loss of life years (YLLs) averted, if bidi industry is subjected to increased regulations and taxation. METHODS: Revenue estimated at 10% increased regulation and 100% regulation were calculated, followed by estimates at taxes equivalent to cigarettes and World Health Organization - Framework Convention on Tobacco Control (WHO-FCTC) recommendation. Price elasticity was considered to assess demand. Price change in separate fractions (previously regulated and unregulated) were calculated to obtain potential YLLs averted. RESULTS: Current revenue of USD 59.25 million is projected to increase to USD 179.25 million with 695,159 averted YLLs at cigarette equivalent taxes and 10% increased regulation; USD 639.38 million with 4,527,597 averted YLLs with 100% regulation; USD 54.75 million, at WHO recommended taxes with 2,233,740 YLLs averted at 10% increased regulation, and 10,486,192 YLLs at 100% regulation. CONCLUSION: Proposed estimates are inline with WHO recommendations as they consider price elasticity and suggest substantial increase in revenue, while averting YLLs. A national action is needed to drive the policy decisions towards increased regulation and taxation and revision of India's tobacco control legislation. IMPLICATIONS: Our study presented empirical evidence of how the currently underutilized tool of taxation, as proposed in the WHO-FCTC, can be utilized to decrease bidi smoking prevalence and save measurable life years while generating government revenue simultaneously. While the revenue statistics counter the misleading tobacco industry narratives, the projected reduction in mortality will be seen as an irrefutable driving force for policy reforms, targeted at strategic increase in regulation and taxation of the traditional Indian cigarillos industry.

Quality Assessment of Interactive Mobile Application - Maternal and Infant Care for Tribal Birth Attendants.

Digital health interventions can overcome geographical barriers and prepare health-care providers for better health outcomes in rural and remote tribal areas, however, it has not been explored among traditional birth attendants (TBAs). A mobile application, "maternal and infant care" (MAI) for capacity building of tribal birth attendants was developed and its quality was evaluated using the Mobile Application Rating Scale for user's interest in and satisfaction with the esthetics, information, and functionality. Thirteen Android user TBAs with the MAI application were piloted with the MARS checklist. Engagement, functionality, esthetics, and information quality; and one subjective quality scale having 29 items were used. The application was found to be entertaining excellent rating (mean score ± standard deviation) (4.00 ± 0.58), and scored high on performance (3.77 ± 0.93); layout design (3.85 ± 0.90); subjective quality (4.23 ± 0.93), however, scored minimum on interest; gestural design; visual appeal, etc. MAI is a user-friendly, culturally acceptable Android app that can be used for the capacity building of frontline workers.

Gum acacia based hydrogels and their composite for waste water treatment: A review.

The non-toxic nature of natural polysaccharides and their biodegradability makes them the first choice of researchers. Various natural polysaccharides are available nowadays, like cellulose, starch, chitosan, gum acacia, guar gum etc. Among these, gum acacia is a common natural polysaccharide presently used in research and technology. It is highly biodegradable, pH stable and shows appropriate water solubility. It is used in research to synthesize hydrogels and hydrogel nanocomposites for various applications because of its antimicrobial, anti-inflammatory and excellent absorption properties. The major fields of applications include the stabilization of metal nanoparticles in the form of nanocomposites, wound dressing materials, delivery systems of various drugs and pharmaceutical agents, bioengineering, tissue engineering, purification of water, synthesis of antibacterial and antifungal composites for agricultural improvements, and many others. Due to the increasing problem of water pollution, the major focus is on research helping to reduce this problem. Gum acacia-based hydrogel and hydrogel composites were synthesized and tested for pollutant removal efficiency from wastewater by different researchers. The research on gum acacia hydrogel and their hydrogel composite applications for water purification, as well as their synthesis processes and properties, are summarized in this review article.

Going the extra mile: Developing an interactive mobile application for maternal and infant care for tribal birth attendants.

Background: Mobile health applications are an established tool for healthcare management, patient education, and even capacity building for healthcare providers. However, its use among traditional birth attendants (TBAs) is limited. The aim of this study is to explore the needs and bottlenecks of developing an interactive mobile application for maternal and infant care (MAI) of TBAs. Materials and Methods: It is a qualitative study having in-depth interviews (face-to-face approach) conducted among the seekers of MAI services. Setting: This study is conducted in tribal and rural locations in the district Sirohi, Rajasthan. Participants: TBAs and tribal females of reproductive age in tribal-dominated areas have participated. The development of an interactive mobile application MAI has three phases: (1) a need-based approach to identify the needs on the ground; (2) identifying intervention bottlenecks and possible solutions; (3) design and development of the mobile application. Results: Ninety-six tribal females of reproductive age participated in the needs assessment. Eighty percent of them were ≤ 30 years of age and 40% of them were uneducated. Most participants informed that lack of information (culturally/locally appropriate content), peer advocacy, affordability, lack of transportation, and the influence of TBAs are the significant factors for less uptake of maternity and child health services in the tribal and rural areas. Conclusion: The MAI app has culturally/locally appropriate content and is prepared by the local TBAs and Accredited Social Health Activists, with full local character and clothing. MAI app has videos and audio in the local language (Marwari) with pictorial quizzes. Using the MAI app, TBAs may self-educate and guide tribal pregnant women about maternal hygiene and infant healthcare as needed at various stages of pregnancy and childbirth.

Provider's satisfaction with telemedicine services for tribals of Western Rajasthan: A qualitative analysis.

Background: There are significant barriers to healthcare access in tribal areas, even though for every 834 people, there is one public physician (registered allopathic and AYUSH doctors). More than 86% of hospital visits occur in rural areas. Furthermore, the bulk of them travel long distances to reach hospitals. A telemedicine center was established in the aspirational tribal district of Sirohi, Rajasthan, to provide accessible quality health care. Objective: To understand providers' attitudes and satisfaction with telemedicine services for tribal populations. Materials and Methods: This cross-sectional, mixed-method study enrolled consultants from various clinical departments of AIIMS Jodhpur (n = 23) who provide teleconsultations to the tribal population. Result: The mean score of the satisfactory index was 54.7 ± 22.04. The higher score is 87.4 regarding the ability to use the technology platform during teleconsultation. The lower score was 34.7 for video quality during teleconsultation at STHR. 91.3% found this a beneficial model for the tribal population. Consultants providing teleconsultations expressed that this model is a boon for tribal patients as a screening tool and will save time and money for improved accessibility. Conclusion: Positive indications of teleconsultation with a provider's utility, acceptability, and satisfaction. Most marginalized people can efficiently access all levels of (primary, secondary, or tertiary) health care from experts through telemedicine, which will broaden outreach in hard-to-reach or inaccessible tribal or rural areas.

The genomic history and global migration of a windborne pest.

Many insect pests, including the brown planthopper (BPH), undergo windborne migration that is challenging to observe and track. It remains controversial about their migration patterns and largely unknown regarding the underlying genetic basis. By analyzing 360 whole genomes from around the globe, we clarify the genetic sources of worldwide BPHs and illuminate a landscape of BPH migration showing that East Asian populations perform closed-circuit journeys between Indochina and the Far East, while populations of Malay Archipelago and South Asia undergo one-way migration to Indochina. We further find round-trip migration accelerates population differentiation, with highly diverged regions enriching in a gene desert chromosome that is simultaneously the speciation hotspot between BPH and related species. This study not only shows the power of applying genomic approaches to demystify the migration in windborne migrants but also enhances our understanding of how seasonal movements affect speciation and evolution in insects.

A new species of Bactrocera Macquart reared from Solanum khasianum Clarke in northern India and a new synonym.

A new species of genus Bactrocera Macquart, Bactrocera (Bactrocera) prabhakari Maneesh, Gupta & Hancock, sp. n., is described from Himachal Pradesh, Northern India, reared from Solanum khasianum Clarke commonly known as medicinal solanum or Dutch eggplant. This species resembles Bactrocera latifrons (Hendel) and an updated key to Indian fruit flies of subgenus Bactrocera Macquart is provided. Bactrocera yoshimotoi (Hardy) (= B. luteicinctuta Ito, syn. nov.) in newly recorded from Himachal Pradesh in northern India and variability in B. scutellaris (Bezzi) is discussed together with illustrations.

Gap identification for improvement in maternal and early infant health care practices among tribal pregnant women in an aspirational tribal district Sirohi, Rajasthan.

Background: Sirohi is one of the aspirational districts of Rajasthan which is also tribal-dominated. The maternal and early infant health indicators are worrisome compared to regional or national statistics. First-trimester registration of pregnant women is 54% in district Sirohi, which is much less as compared to registration in the state of Rajasthan (63%) and India (59%). Four antenatal care (ANC) visits of pregnant women are 32% in district Sirohi, which is also much less as compared to ANC visits in the state of Rajasthan (39%) and India (51%). However, there was no tribal-specific data regarding maternal and early infant health. Objective: The study aims to identify gaps for improvement in maternal and early infant health care practices among tribal pregnant women in an aspirational tribal district of Sirohi, Rajasthan. Materials and Methods: It was a cross-sectional study conducted among 560 tribal pregnant women to assess the existing maternal, and early infant health care knowledge and practices through a pre-validated questionnaire in the tribal population of district Sirohi Rajasthan. Result: Nineteen per cent (19.5%, n = 109) of tribal pregnant women got married between the age of 10 and 17 (less than the legal age of marriage of 18 years). There is a significant relationship between early age at marriage and low educational status P < 0.001, r = 0.241 among participants. Measurement of weight, blood pressure and urine examination was done in 32.5% (n = 181), 19.5% (n = 109) and 7.1% (n = 39), respectively, among tribal pregnant women. The majority (94.6%) of the pregnant tribal women (385/407) were anaemic. Approximately 60% (n = 337) of mothers were unaware of thermal protection (skin-to-skin care). Sixty per cent (n = 334) of tribal pregnant women preferred to seek consultation regarding antenatal and infant health care from doctors, while 40.1% (n = 224) were more comfortable seeking advice from traditional birth attendants (TBAs). Conclusion: The study finds inadequate knowledge and practice towards maternal and early infant care among tribal pregnant women. As TBAs influence tribal pregnant women, systematic training and involvement of TBAs in maternal and child health are indispensable.

Relationship between biochemical parameters of mineral bone disease and static bone histomorphometry in chronic kidney disease patients on hemodialysis: An Indian cross-section study.

AIM: We estimated the relationship between routine biochemical laboratory parameters with static bone histomorphometric parameters and their high and low bone turnover capacity predictability in hemodialysis patients. METHOD: It was a single-center cross-sectional study, included 28 hemodialysis patients. The routine biochemical parameters measured including calcium, phosphorous, alkaline phosphatase, intact PTH, and 25-hydroxycholecalciferol. The histomorphometric parameters assessed were osteoblasts perimeter, osteoclast perimeter, eroded perimeter, osteoid perimeter, bone fibrosis and bone volume. RESULT: Total 28 hemodialysis patients underwent bone biopsy. Seventy percent were male, with a mean age was 33.07±10.42 yrs; serum alkaline phosphatase was 219.10±311.3IU/ml; vitamin D was 18.18±9.56ng/ml, and intact PTH was 650.7±466.0pg/ml. Intact PTH had a significant positive association with osteoblast, osteoclast, eroded surface, and osteoid perimeter. Serum alkaline phosphatase had a significant relationship with bone fibrosis (r=0.525, p-value=0.004). Intact PTH was significantly higher in females than males (1078.75±533.04 vs. 479.6±309.83; p-value=0.004). The osteoid surface was significantly high in females compared to males (p=0.038). Age had a significant impact on osteoblast and eroded surface (p=0.008 and p=0.031, respectively). Intact PTH is a reliable biomarkers for bone turnover compare to ALP (p<0.001 and p=0.554, respectively). CONCLUSION: Intact PTH strongly associated with bone formation, bone resorption parameters. Gender and age had significant impact on static histomorphometric parameters in our study.

Impact of brief exposure to antifungal agents on the post-antifungal effect and hemolysin activity of oral Candida albicans

AbstractPost-antifungal effect (PAFE) of Candida and its production of hemolysin are determinants of candidal pathogenicity. Candida albicans is the foremost aetiological agent of oral candidosis, which can be treated with polyene, azole, and echinocandin antifungals. However, once administered, the intraoral concentrations of these drugs tend to be subtherapeutic and transient due to the diluent effect of saliva and cleansing effect of the oral musculature. Hence, intra-orally, Candidamay undergo a brief exposure to antifungal drugs.Objective Therefore, the PAFE and hemolysin production of oral C. albicans isolates following brief exposure to sublethal concentrations of the foregoing antifungals were evaluated.Material and Methods A total of 50 C. albicans oral isolates obtained from smokers, diabetics, asthmatics using steroid inhalers, partial denture wearers and healthy individuals were exposed to sublethal concentrations of nystatin, amphotericin B, caspofungin, ketoconazole and fluconazole for 60 min. Thereafter, the drugs were removed and the PAFE and hemolysin production were determined by previously described turbidometric and plate assays, respectively.Results Nystatin, amphotericin B, caspofungin and ketoconazole induced mean PAFE (hours) of 2.2, 2.18, 2.2 and 0.62, respectively. Fluconazole failed to produce a PAFE. Hemolysin production of these isolates was suppressed with a percentage reduction of 12.27, 13.47, 13.33, 8.53 and 4.93 following exposure to nystatin, amphotericin B, caspofungin, ketoconazole and fluconazole, respectively.Conclusions Brief exposure to sublethal concentrations of antifungal drugs appears to exert an antifungal effect by interfering with the growth as well as hemolysin production of C. albicans.