Expression of the ARPC4 subunit of human Arp2/3 severely affects mycobacterium tuberculosis growth and suppresses immunogenic response in murine macrophages

Background: The search for molecules against Mycobacterium tuberculosis is urgent. The mechanisms facilitating the intra-macrophage survival of Mycobacterium tuberculosis are as yet not entirely understood. However, there is evidence showing the involvement of host cell cytoskeleton in every step of establishment and persistence of mycobacterial infection. Methodology/Principal Findings: Here we show that expression of ARPC4, a subunit of the Actin related protein 2/3 (Arp2/3) protein complex, severely affects the pathogen’s growth. TEM studies display shedding of the mycobacterial outer-coat. Furthermore, in infected macrophages, mycobacteria expressing ARPC4 were cleared off at a much faster rate, and were unable to mount a pro-inflammatory cytokine response. The translocation of ARPC4-expressing mycobacteria to the lysosome of the infected macrophage was also impaired. Additionally, the ARPC4 subunit was shown to interact with Rv1626, an essential secretory mycobacterial protein. Real-time PCR analysis showed that upon expression of ARPC4 in mycobacteria, Rv1626 expression is downregulated as much as six-fold. Rv1626 was found to also interact with mammalian cytoskeleton protein, Arp2/3, and enhance the rate of actin polymerization. Conclusions/Significance: With crystal structures for Rv1626 and ARPC4 subunit already known, our finding lays out the effect of a novel molecule on mycobacteria, and represents a viable starting point for developing potent peptidomimetics

Implementing and sustaining a mobile medical clinic for prenatal care and sexually transmitted infection prevention in rural Mysore, India

Background In rural India, mobile medical clinics are useful models for delivering health promotion, education, and care. Mobile medical clinics use fewer providers for larger catchment areas compared to traditional clinic models in resource limited settings, which is especially useful in areas with shortages of healthcare providers and a wide geographical distribution of patients. Methods From 2008 to 2011, we built infrastructure to implement a mobile clinic system to educate rural communities about maternal child health, train community health workers in common safe birthing procedures, and provide comprehensive antenatal care, prevention of mother-to-child transmission (PMTCT) of human immunodeficiency virus (HIV), and testing for specific infections in a large rural catchment area of pregnant women in rural Mysore. This was done using two mobile clinics and one walk-in clinic. Women were tested for HIV, hepatitis B, syphilis, and bacterial vaginosis along with random blood sugar, urine albumin, and anemia. Sociodemographic information, medical, and obstetric history were collected using interviewer-administered questionnaires in the local language, Kannada. Data were entered in Microsoft Excel and analyzed using Stata SE 14.1. Results During the program period, nearly 700 community workers and 100 health care providers were trained; educational sessions were delivered to over 15,000 men and women and integrated antenatal care and HIV/sexually transmitted infection testing was offered to 3545 pregnant women. There were 22 (0.6%) cases of HIV, 19 (0.5%) cases of hepatitis B, 2 (0.1%) cases of syphilis, and 250 (7.1%) cases of BV, which were identified and treated. Additionally, 1755 (49.5%) cases of moderate to severe anemia and 154 (4.3%) cases of hypertension were identified and treated among the pregnant women tested. Conclusions Patient-centered mobile medical clinics are feasible, successful, and acceptable models that can be used to provide quality healthcare to pregnant women in rural and hard-to-reach settings. The high numbers of pregnant women attending mobile medical clinics show that integrated antenatal care with PMTCT services were acceptable and utilized. The program also developed and trained health professionals who continue to remain in those communities

The Mysuru stUdies of Determinants of Health in Rural Adults (MUDHRA), India

Between 2006 and 2010, in 16 randomly selected villages in rural areas of Mysore district, in south India, 8,457 subjects aged 30 and above were screened for symptoms of chronic respiratory disease. Of the 8,457 subjects, 1,692 were randomly invited for further evaluation of lung function and chronic obstructive pulmonary disease (COPD) by spirometry, and 1,085 of these subjects underwent lung function assessments for prevalent COPD and its risk factors. These 1,085 subjects, who were then aged between 35 and 80 years, constituted the Mysuru stUdies of Determinants of Health in Rural Adults (MUDHRA) cohort. Among other findings, threshold of biomass fuel smoke exposure suitable for use as a dichotomous risk factor for the diagnosis of chronic bronchitis was established, with a minimum biomass smoke exposure index of 60 found to be significantly associated with an elevated risk of developing chronic bronchitis. Five years later (between 2014 and 2016), 869 of the 1,085 participants were followed up with repeat lung function assessments for incident COPD and all-cause mortality. A subset of these participants (n=200) underwent blood tests for vitamin D levels, antioxidant activity, an assessment for anxiety and depression, and another subset (n=98) underwent a bioplex assay for 40 serum cytokines

Leveraging human capital to reduce maternal mortality in India: enhanced public health system or public-private partnership?

Developing countries are currently struggling to achieve the Millennium Development Goal Five of reducing maternal mortality by three quarters between 1990 and 2015. Many health systems are facing acute shortages of health workers needed to provide improved prenatal care, skilled birth attendance and emergency obstetric services – interventions crucial to reducing maternal death. The World Health Organization estimates a current deficit of almost 2.4 million doctors, nurses and midwives. Complicating matters further, health workforces are typically concentrated in large cities, while maternal mortality is generally higher in rural areas. Additionally, health care systems are faced with shortages of specialists such as anaesthesiologists, surgeons and obstetricians; a maldistribution of health care infrastructure; and imbalances between the public and private health care sectors. Increasingly, policy-makers have been turning to human resource strategies to cope with staff shortages. These include enhancement of existing work roles; substitution of one type of worker for another; delegation of functions up or down the traditional role ladder; innovation in designing new jobs;transfer or relocation of particular roles or services from one health care sector to another. Innovations have been funded through state investment, public-private partnerships and collaborations with nongovernmental organizations and quasi-governmental organizations such as the World Bank. This paper focuses on how two large health systems in India – Gujarat and Tamil Nadu – have successfully applied human resources strategies in uniquely different contexts to the challenges of achieving Millennium Development Goal Five

Vitamin D deficiency is associated with chronic obstructive pulmonary disease and exacerbation of COPD

Introduction Low Vitamin D levels have been associated with Chronic Obstructive Pulmonary Disease (COPD) and acute exacerbations. Objectives There is a paucity of data on Vitamin D and COPD, its severity and exacerbations in populations that are exposed to sunlight regularly with high levels of physical activity most of their lives. Methods Serum levels of 25-OH-Vitamin-D were assessed in 100 COPD subjects and 100 age- and gender-matched controls from the rural community-based MUDHRA cohort in South India. Levels of <20 ng/mL were defined as Vitamin D deficiency. Smoking habits, occupation, Charlson co-morbidity index, Standard of living index(SLI), body mass index(BMI), 6-minute walking distance were examined for associations with logistic regression between controls and COPD subjects. Unconditional logistic regression was used to examine the association with exacerbation of COPD. Results Vitamin D deficiency was observed in 64.5% (95%CI 57.7-70.8) of the subjects in spite of regular exposure to sunlight. Subjects with COPD had higher risk of Vitamin D deficiency (Adjusted OR: 5.05; 95%CI 1.4-17.8) as compared to controls. Amongst subjects with COPD, Vitamin D deficient subjects were three times more likely to have exacerbations in the previous year (Adjusted OR:3.51; 95%CI 1.27-9.67) as compared to COPD subjects without Vitamin D deficiency. Levels of Vitamin D <20.81 ng/mL and <18.45 ng/mL had the highest levels of combined sensitivity and specificity for COPD and acute exacerbation of COPD (AECOPD) respectively. Conclusion In a rural population exposed to sunlight many hours a day throughout their lives, low Vitamin D levels were associated with COPD and exacerbations of COPD

Optical Damage Limit of Efficient Spintronic THz Emitters

Summary: THz pulses are generated from femtosecond pulse-excited ferromagnetic/nonmagnetic spintronic heterostructures via inverse spin Hall effect. The highest possible THz signal strength from spintronic THz emitters is limited by the optical damage threshold of the corresponding heterostructures at the excitation wavelength. For the thickness-optimized spintronic heterostructure, the THz generation efficiency does not saturate with the excitation fluence even up till the damage threshold. Bilayer (Fe, CoFeB)/(Pt, Ta)-based ferromagnetic/nonmagnetic (FM/NM) spintronic heterostructures have been studied for an optimized performance for THz generation when pumped by sub-50 fs amplified laser pulses at 800 nm. Among them, CoFeB/Pt is the best combination for an efficient THz source. The optimized FM/NM spintronic heterostructure having α-phase Ta as the nonmagnetic layer shows the highest damage threshold as compared to those with Pt, irrespective of their generation efficiency. The damage threshold of the Fe/Ta heterostructure on a quartz substrate is ∼85 GW/cm2

A Comprehensive Review of Microbial Contamination in the Indoor Environment: Sources, Sampling, Health Risks, and Mitigation Strategies

The quality of the indoor environment significantly impacts human health and productivity, especially given the amount of time individuals spend indoors globally. While chemical pollutants have been a focus of indoor air quality research, microbial contaminants also have a significant bearing on indoor air quality. This review provides a comprehensive overview of microbial contamination in built environments, covering sources, sampling strategies, and analysis methods. Microbial contamination has various origins, including human occupants, pets, and the outdoor environment. Sampling strategies for indoor microbial contamination include air, surface, and dust sampling, and various analysis methods are used to assess microbial diversity and complexity in indoor environments. The review also discusses the health risks associated with microbial contaminants, including bacteria, fungi, and viruses, and their products in indoor air, highlighting the need for evidence-based studies that can relate to specific health conditions. The importance of indoor air quality is emphasized from the perspective of the COVID-19 pandemic. A section of the review highlights the knowledge gap related to microbiological burden in indoor environments in developing countries, using India as a representative example. Finally, potential mitigation strategies to improve microbiological indoor air quality are briefly reviewed

Antiurolithiatic and antioxidant activity of Mimusops elengi on ethylene glycol-induced urolithiasis in rats

Objective: To evaluate the potential of Mimusops elengi in the treatment of renal calculi. Materials and Methods: Petroleum ether, chloroform, and alcohol extracts of Mimusops elengi bark were evaluated for antiurolithiatic and antioxidant activity in male albino Wistar rats. Ethylene glycol (0.75%) in drinking water was fed to all the groups (Groups II-IX) except normal control (Group I) for 28 days to induce urolithiasis for curative (CR) and preventive (PR) regimen. Groups IV, V, and VI served as CR, and groups VII, VIII, and IX as PR were treated with different extracts of M. elengi bark. Groups I, II, and III served as normal control, positive control (hyperurolithiatic), and standard (cystone 750 mg/kg), respectively. Oxalate, calcium, and phosphate were monitored in the urine and kidney. Serum BUN, creatinine, and uric acid were also recorded. In vivo antioxidant parameters such as lipid peroxidation (MDA), glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) were also monitored. Results: All the extracts of M. elengi were safe orally and exhibited no gross behavioral changes in the rats. In hypercalculi animals, the oxalate, calcium, and phosphate excretion grossly increased. However, the increased deposition of stone forming constituents in the kidneys of calculogenic rats were significantly (P < 0.001) lowered by curative and preventive treatment with alcohol extract (AlE) of M. elengi. It was also observed that alcoholic extract of M. elengi produced significant (P < 0.001) decrease in MDA, and increased GSH, SOD, and CAT. These results confirm that AlE of M. elengi possess potent antiurolithiatic activity. Conclusion: The results obtained suggest potential usefulness of the AlE of M. elengi bark as an antiurolithiatic agent