Acute and Sub-acute Oral Toxicity Assessment of Ferrum phosphoricum in Rats.

BACKGROUND: Ferrum phosphoricum (FP) has been used by traditional medicine practitioners for various ailments since ancient times. However, scientific evidence on the safety of FP is still unavailable. Thus, the current study aimed to investigate the acute and sub-acute oral toxicity of homeopathic FP in experimental rats. METHODS: In an acute toxicity investigation, a single dose of 2,000 µL/kg of FP 6c, 30c and 200c was administered to female Wistar rats, which were monitored for up to 14 days according to the Organization for Economic Cooperation and Development (OECD) guideline 423. For a sub-acute toxicity study, FP 6c, 30c and 200c (200 µL/kg) were administered to male and female rats for 28 days as per the OECD guideline 407. All the animals were observed for mortality, clinical signs and body weight during the study. At the end of the experiment, hematological, biochemical and histopathological assessments were performed. RESULTS: During the acute toxicity study, no mortality was observed in rats administered with FP, and thus the median lethal dose (LD50) was identified as >2,000 µL/kg. In the sub-acute study, no mortality or adverse clinical signs were noticed with FP treatment. Moreover, weekly body weight gain was normal. Hematological and biochemical investigations revealed no abnormalities. Furthermore, histological analysis of FP-treated rats' vital organs revealed no pathological changes. CONCLUSION: Overall, our findings imply that FP 6c, 30c and 200c potencies are safe and do not cause toxicity when given orally to Wistar albino rats for an extended period at a dose of 200 µL/kg.

Interventions to improve linkage along the HIV-tuberculosis care cascades in low- and middle-income countries: A systematic review and meta-analysis.

INTRODUCTION: In support of global targets to end HIV/AIDS and tuberculosis (TB) by 2030, we reviewed interventions aiming to improve TB case-detection and anti-TB treatment among people living with HIV (PLHIV) and HIV testing and antiretroviral treatment initiation among people with TB disease in low- and middle-income countries (LMICs). METHODS: We conducted a systematic review of comparative (quasi-)experimental interventional studies published in Medline or EMBASE between January 2003-July 2021. We performed random-effects effect meta-analyses (DerSimonian and Laird method) for interventions that were homogenous (based on intervention descriptions); for others we narratively synthesized the intervention effect. Studies were assessed using ROBINS-I, Cochrane Risk-of-Bias, and GRADE. (PROSPERO #CRD42018109629). RESULTS: Of 21,516 retrieved studies, 23 were included, contributing 53 arms and 84,884 participants from 4 continents. Five interventions were analyzed: co-location of test and/or treatment services; patient education and counselling; dedicated personnel; peer support; and financial support. A majority were implemented in primary health facilities (n = 22) and reported on HIV outcomes in people with TB (n = 18). Service co-location had the most consistent positive effect on HIV testing and treatment initiation among people with TB, and TB case-detection among PLHIV. Other interventions were heterogenous, implemented concurrent with standard-of-care strategies and/or diverse facility-level improvements, and produced mixed effects. Operational system, human resource, and/or laboratory strengthening were common within successful interventions. Most studies had a moderate to serious risk of bias. CONCLUSIONS: This review provides operational clarity on intervention models that can support early linkages between the TB and HIV care cascades. The findings have supported the World Health Organization 2020 HIV Service Delivery Guidelines update. Further research is needed to evaluate the distinct effect of education and counselling, financial support, and dedicated personnel interventions, and to explore the role of community-based, virtual, and differentiated service delivery models in addressing TB-HIV co-morbidity.

Tuberculosis screening among ambulatory people living with HIV: a systematic review and individual participant data meta-analysis.

BACKGROUND: The WHO-recommended tuberculosis screening and diagnostic algorithm in ambulatory people living with HIV is a four-symptom screen (known as the WHO-recommended four symptom screen [W4SS]) followed by a WHO-recommended molecular rapid diagnostic test (eg Xpert MTB/RIF [hereafter referred to as Xpert]) if W4SS is positive. To inform updated WHO guidelines, we aimed to assess the diagnostic accuracy of alternative screening tests and strategies for tuberculosis in this population. METHODS: In this systematic review and individual participant data meta-analysis, we updated a search of PubMed (MEDLINE), Embase, the Cochrane Library, and conference abstracts for publications from Jan 1, 2011, to March 12, 2018, done in a previous systematic review to include the period up to Aug 2, 2019. We screened the reference lists of identified pieces and contacted experts in the field. We included prospective cross-sectional, observational studies and randomised trials among adult and adolescent (age ≥10 years) ambulatory people living with HIV, irrespective of signs and symptoms of tuberculosis. We extracted study-level data using a standardised data extraction form, and we requested individual participant data from study authors. We aimed to compare the W4SS with alternative screening tests and strategies and the WHO-recommended algorithm (ie, W4SS followed by Xpert) with Xpert for all in terms of diagnostic accuracy (sensitivity and specificity), overall and in key subgroups (eg, by antiretroviral therapy [ART] status). The reference standard was culture. This study is registered with PROSPERO, CRD42020155895. FINDINGS: We identified 25 studies, and obtained data from 22 studies (including 15 666 participants; 4347 [27·7%] of 15 663 participants with data were on ART). W4SS sensitivity was 82% (95% CI 72-89) and specificity was 42% (29-57). C-reactive protein (≥10 mg/L) had similar sensitivity to (77% [61-88]), but higher specificity (74% [61-83]; n=3571) than, W4SS. Cough (lasting ≥2 weeks), haemoglobin (<10 g/dL), body-mass index (<18·5 kg/m2), and lymphadenopathy had high specificities (80-90%) but low sensitivities (29-43%). The WHO-recommended algorithm had a sensitivity of 58% (50-66) and a specificity of 99% (98-100); Xpert for all had a sensitivity of 68% (57-76) and a specificity of 99% (98-99). In the one study that assessed both, the sensitivity of sputum Xpert Ultra was higher than sputum Xpert (73% [62-81] vs 57% [47-67]) and specificities were similar (98% [96-98] vs 99% [98-100]). Among outpatients on ART (4309 [99·1%] of 4347 people on ART), W4SS sensitivity was 53% (35-71) and specificity was 71% (51-85). In this population, a parallel strategy (two tests done at the same time) of W4SS with any chest x-ray abnormality had higher sensitivity (89% [70-97]) and lower specificity (33% [17-54]; n=2670) than W4SS alone; at a tuberculosis prevalence of 5%, this strategy would require 379 more rapid diagnostic tests per 1000 people living with HIV than W4SS but detect 18 more tuberculosis cases. Among outpatients not on ART (11 160 [71·8%] of 15 541 outpatients), W4SS sensitivity was 85% (76-91) and specificity was 37% (25-51). C-reactive protein (≥10 mg/L) alone had a similar sensitivity to (83% [79-86]), but higher specificity (67% [60-73]; n=3187) than, W4SS and a sequential strategy (both test positive) of W4SS then C-reactive protein (≥5 mg/L) had a similar sensitivity to (84% [75-90]), but higher specificity than (64% [57-71]; n=3187), W4SS alone; at 10% tuberculosis prevalence, these strategies would require 272 and 244 fewer rapid diagnostic tests per 1000 people living with HIV than W4SS but miss two and one more tuberculosis cases, respectively. INTERPRETATION: C-reactive protein reduces the need for further rapid diagnostic tests without compromising sensitivity and has been included in the updated WHO tuberculosis screening guidelines. However, C-reactive protein data were scarce for outpatients on ART, necessitating future research regarding the utility of C-reactive protein in this group. Chest x-ray can be useful in outpatients on ART when combined with W4SS. The WHO-recommended algorithm has suboptimal sensitivity; Xpert for all offers slight sensitivity gains and would have major resource implications. FUNDING: World Health Organization.

Turning threats into opportunities: how to implement and advance quality TB services for people with HIV during the COVID-19 pandemic and beyond.

INTRODUCTION: Until COVID-19, tuberculosis (TB) was the leading infectious disease killer globally, disproportionally affecting people with HIV. The COVID-19 pandemic is threatening the gains made in the fight against both diseases. DISCUSSION: Although crucial guidance has been released on how to maintain TB and HIV services during the pandemic, it is acknowledged that what was considered normal service pre-pandemic needs to improve to ensure that we rebuild person-centred, inclusive and quality healthcare services. The threat that the pandemic may reverse gains in the response to TB and HIV may be turned into an opportunity by pivoting to using proven differentiated service delivery approaches and innovative technologies that can be used to maintain care during the pandemic and accelerate improved service delivery in the long term. Models of care should be convenient, supportive and sufficiently differentiated to avoid burdensome clinic visits for medication pick-ups or directly observed treatments. Additionally, the pandemic has highlighted the chronic and short-sighted lack of investment in health systems and the need to prioritize research and development to close the gaps in TB diagnosis, treatment and prevention, especially for children and people with HIV. Most importantly, TB-affected communities and civil society must be supported to lead the planning, implementation and monitoring of TB and HIV services, especially in the time of COVID-19 where services have been disrupted, and to report on legal, policy and gender-related barriers to access experienced by affected people. This will help to ensure that TB services are held accountable by affected communities for delivering equitable access to quality, affordable and non-discriminatory services during and beyond the pandemic. CONCLUSIONS: Successfully reaching the related targets of ending TB and AIDS as public health threats by 2030 requires rebuilding of stronger, more inclusive health systems by advancing equitable access to quality TB services, including for people with HIV, both during and after the COVID-19 pandemic. Moreover, services must be rights-based, community-led and community-based, to ensure that no one is left behind.

New opportunities in tuberculosis prevention: implications for people living with HIV.

INTRODUCTION: Tuberculosis (TB) is a leading cause of mortality among people living with HIV (PLHIV). An invigorated global END TB Strategy seeks to increase efforts in scaling up TB preventive therapy (TPT) as a central intervention for HIV programmes in an effort to contribute to a 90% reduction in TB incidence and 95% reduction in mortality by 2035. TPT in PLHIV should be part of a comprehensive approach to reduce TB transmission, illness and death that also includes TB active case-finding and prompt, effective and timely initiation of anti-TB therapy among PLHIV. However, the use and implementation of preventive strategies has remained deplorably inadequate and today TB prevention among PLHIV has become an urgent priority globally. DISCUSSION: We present a summary of the current and novel TPT regimens, including current evidence of use with antiretroviral regimens (ART). We review challenges and opportunities to scale-up TB prevention within HIV programmes, including the use of differentiated care approaches and demand creation for effective TB/HIV services delivery. TB preventive vaccines and diagnostics, including optimal algorithms, while important topics, are outside of the focus of this commentary. CONCLUSIONS: A number of new tools and strategies to make TPT a standard of care in HIV programmes have become available. The new TPT regimens are safe and effective and can be used with current ART, with attention being paid to potential drug-drug interactions between rifamycins and some classes of antiretrovirals. More research and development is needed to optimize TPT for small children, pregnant women and drug-resistant TB (DR-TB). Effective programmatic scale-up can be supported through context-adapted demand creation strategies and the inclusion of TPT in client-centred services, such as differentiated service delivery (DSD) models. Robust collaboration between the HIV and TB programmes represents a unique opportunity to ensure that TB, a preventable and curable condition, is no longer the number one cause of death in PLHIV.

Quality of TB care among people living with HIV: Gaps and solutions.

Tuberculosis (TB) is the leading infectious cause of death among people living with HIV, causing one third of AIDS-related deaths globally. The concerning number of missing TB cases, ongoing high TB mortality, slow reduction in TB incidence, and limited uptake of TB preventive treatment among people living with HIV, all indicate the urgent need to improve quality of TB services within HIV programs. In this mini-review we discuss major gaps in quality of TB care that impede achieving prevention and treatment targets within the TB-HIV care cascades, show approaches of assessing gaps in TB service provision, and describe outcomes from innovative quality improvement projects among HIV and TB programs. We also offer recommendations for measuring quality of TB care.

Do Quality Improvement Initiatives Improve Outcomes for Patients in Antiretroviral Programs in Low- and Middle-Income Countries? A Systematic Review.

BACKGROUND: There have been a range of quality improvement (QI) and quality assurance initiatives in low- and middle-income countries to improve antiretroviral therapy (ART) treatment outcomes for people living with HIV. To date, these initiatives have not been systematically assessed and little is known about how effective, cost-effective, or sustainable these strategies are in improving clinical outcomes. METHODS: We conducted a systematic review adhering to PRISMA guidelines (PROSPERO ID: CRD42017071848), searching PubMed, MEDLINE, Embase, Web of Science, and the Cochrane database of controlled trials for articles reporting on the effectiveness of QI and quality assurance initiatives in HIV programs in low- and middle-income countries in relation to ART uptake, retention in care, adherence, viral load suppression, mortality, and other outcomes including cost-effectiveness and long-term sustainability. RESULTS: One thousand eight hundred sixty articles were found, of which 29 were included. QI approaches were categorized as follows: (1) health system approaches using QI methods; (2) QI learning networks including collaboratives; (3) standard-based methods that use QI tools to improve performance gaps; and (4) campaigns using QI methods. The greatest improvements were seen in ART uptake [median increase of 14.0%; interquartile range (IQR) -9.0 to 29.3], adherence [median increase of 22.0% (IQR -7.0 to 25.0)], and viral load suppression [median increase 26.0% (IQR -8.0 to 26.0)]. CONCLUSIONS: QI interventions can be effective in improving clinical outcomes; however, there was significant variability, making it challenging to identify which aspects of interventions lead to clinical improvements. Standardizing reporting and assessment of QI initiatives is needed, supported by national quality policies and directorates, and robust research.

Identifying priorities for HIV-associated tuberculosis research through the WHO guidelines process.

PURPOSE OF REVIEW: Guidelines developed by the WHO aim to provide recommendations to support best practice in health delivery, with a focus on low-income and middle-income countries. As part of the guideline development process, critical knowledge gaps are identified and one of the core functions of WHO guidelines is to set forth priorities for future research. A review of research priorities identified through the WHO guideline development has recently been promoted as one approach to building an overarching priority research agenda in a given area. This paper outlines priorities for HIV-associated TB research identified in WHO HIV and TB guidelines published since 2015. RECENT FINDINGS: Nine guidelines were reviewed and 29 priority research questions were identified. Research priorities were identified for prevention of HIV-associated TB (11 questions), screening of latent and active TB in people living with HIV (six questions), treatment of drug sensitive (four questions), and drug-resistant (two questions) TB, and treatment of HIV in people coinfected with TB (three questions). SUMMARY: Multiple approaches to defining priority research questions for health research exist. Research priorities that arise from the WHO guideline development process are limited to those areas for which guidelines are developed. One strength of this approach is that it takes as a starting point a desire to make actionable recommendations for policy makers. WHO is working to further refine the formulation of research questions within the guideline development process.

Assessment of Salivary Catalase, a-Amylase, and Cotinine Levels in Chronic Smokers: A Comparative Study.

INTRODUCTION: One of the common practices observed in many parts of the world is smoking, of which tobacco forms an important constituent which is burned and inhaled. Smoking is known to have potential effect on body's immune system, antioxidants level, and salivary cotinine levels. Hence, we planned the present study to evaluate the impact of cigarette smoke on salivary anti-oxidant levels and cotinine levels in smokers and nonsmokers. MATERIALS AND METHODS: The present study included assessment of salivary parameters of smokers and nonsmokers. A total of 400 subjects were analyzed, of which 200 were active smokers and 200 were nonsmokers. Unstimulated salivary samples were taken and assessment of a-amylase levels was done using biochemical kit and spectrophotometer. Assessment of salivary catalase (CAT) activity was done using Luck method. For the determination of cotinine levels, Bioassay Technology Laboratory kit was used using enzyme-linked immunosorbent assay (ELISA) technique. After the assessment of levels of all the salivary parameters, all the data were recorded, compiled, and analyzed. RESULTS: a-Amylase in smokers and nonsmokers group was found to be 206.25 and 169.85 U/mL respectively. Nonsignificant results were obtained while comparing the salivary a-amylase levels among the two study groups. Nonsignificant results were obtained while comparing the salivary CAT levels among the smokers and nonsmokers group. We observed statistically significant results while comparing mean cotinine levels among smokers group and nonsmokers group. CONCLUSION: Alteration in cotinine levels occurs in smokers in comparison to nonsmokers. CLINICAL SIGNIFICANCE: Smoking can cause harmful effect on the oral mucous membrane by altering salivary defense components.

Comparative evaluation of anti-obesity effect of Aloe vera and Gymnema sylvestre supplementation in high-fat diet fed C57BL/6J mice.

BACKGROUND: The aim of the present study was to investigate, anti-obesity effect of Aloe vera (AV), and Gymnema sylvestre (GS) whole extract powders administration to high-fat diet (HFD) fed C57BL/6J mice for 12 weeks. MATERIALS AND METHODS: At the end of experiment, different parameters such as body weight, feed intake, organ weights, fasting blood glucose, oral glucose tolerance test, plasma lipid levels, and expression analysis of adipocytokines were evaluated. RESULTS: At the end of experimental period, oral administration of both herbs showed a significant (P < 0.05 and P < 0.001) decrease in the plasma glucose and lipid levels in HFD fed mice. In addition, increased in the epididymal fat (E. fat) weight in the HFD group was significantly (P < 0.05) reduced on GS administration alone. Finally, quantitative mRNA expression analysis of adiponectin gene was significantly up-regulated in AV supplementation. Further, no effect was observed with the both herbs on pro-inflammatory cytokines (interleukin 6 and tumor necrosis factor-a) in the E. fat tissue of HFD fed group. CONCLUSIONS: The anti-obesity and other metabolic studies depend on the type of diet, different parts of herbal extractions, and animal models used. Further studies are required in this area to strengthen the anti-obesity effects of herbs with active component, and it can be used a pro-drug instead of whole extract.

Hypoglycemic and Hypolipidemic Effects of Aloe vera Extract Preparations: A Review.

Obesity is considered to be an epidemic disease, and it is associated with several metabolic disorders. Pharmacological treatments currently available are not effective for prolonged treatment duration. So, people are looking toward new therapeutic approach such as herbal ingredients. Since ancient periods, different herbs have been used for remedy purposes such as anti-obesity, antidiabetes, and antiinflammatory. Among the several herbal ingredients, Aloe vera (Aloe barbadensis Miller) is widely used to curb the metabolic complications. Till date, reports are not available for the side effects of A. vera. Several researchers are used to different solvents such as aqueous solution, alcohol, ethanol, and chloroform for the A. vera extract preparations and studied their hypoglycemic and hypolipidemic effects in animal and human studies. Furthermore, little information was recorded with the active compounds extracted from the A. vera and their anti-obesity and antidiabetic effects in clinical studies. In this review, we made an attempt to compile all the available literature by using different search engines (PubMed, Scopus, and Google Scholar) on the A. vera extract preparations and the possible mechanism of action involved in carbohydrate and lipid metabolism.

Understanding the adsorption behavior of surface active molecules on ZnO nanostructures by experimental and first-principles calculations.

Zinc oxide (ZnO) nanostructures with different morphologies are prepared in the presence of surface active molecules such as sodium dodecyl sulphate (SDS), Tween 80 and Triton X-100 by a chemical method. The experimental and first principles methods are employed to understand the microscopic origin of the asymmetric growth mechanism of ZnO in the presence of various surface active molecules. Effect of increase in the amount of surface active molecules and temperature is studied on the growth morphology of ZnO. An innovative method is developed to synthesize ZnO nanowires (NWs) in the presence of SDS. Spherical nanoparticles (NPs) to spherical clusters are obtained in the presence of Triton X-100 and Tween 80. These results are then supported by first principles calculations. The adsorption of the -OH functional group on both polar and nonpolar surfaces of ZnO is modelled by using density functional theory (DFT). The calculated binding energy (BE) is almost equivalent on both the surfaces with no preference on any particular surface. The calculated value of BE shows that the -OH group is physio-adsorbed on both the surfaces. This results in the spherical morphology of nanoparticles prepared in the presence of Tween 80. Bader charge analysis shows that the charge transfer mainly takes place on top two layers of the ZnO(101[combining macron]0) surface. The absence of high values of electron localization function (ELF) reflects the lack of covalent bonding between the -OH group and the ZnO(101[combining macron]0) surface.

Impact of Makowal type water system on crop productivity in Shivalik foothills of India.

The availability of water through community based water harvesting structure has intensified agriculture and improved livelihood of the surveyed beneficiary households in the Shivalik foothills of India. Before the introduction of Makowal Type Water Harvesting System (before MTWHS), only 83.8% farmers in kharif and 79.7% during rabi season were growing crops but after its introduction (after MTWHS) the corresponding values improved to 100% and 97.3%, respectively, thus increasing cropping intensity from 145% to 189%. Introduction of MTWHS enabled farmers to take paddy and agro-forestry during Kharif, and vegetables and fodder during Rabi season. The increase in cultivated area due to MTWHS was to the tune of 46.1% in Kharif and 36.3% during Rabi, while increase in crop productivity ranged from 55.1% to 111.3% in kharif and 8.6 to 132.0% in Rabiseason. Better availability of irrigation changed varietal spectrum in favour of hybrids and high yielding varieties and farmers started adopting improved agronomic practices targeting better input-use efficiency. The MTWHS produced positive impact on the on-farm (crops, dairy and agro-forestry) sources of income and reduced the relative dependence on off-farm activities (labour, community forest area, etc.) for earnings. This system has brought drinking water very close to hutments of rural women thus reducing their drudgery and saving time. In general, rainwater harvesting from forest watersheds has resulted in quantum jumps in crop and milk production and acted as a catalyst to tie up the economic interest of communities, along with forest protection.

Probiotics: Interaction with gut microbiome and antiobesity potential.

Obesity is a metabolic disorder afflicting people globally. There has been a pivotal advancement in the understanding of the intestinal microbiota composition and its implication in extraintestinal (metabolic) diseases. Therefore, any agent modulating gut microbiota may produce an influential effect in preventing the pathogenesis of disease. Probiotics are live microbes that, when administered in adequate amounts, have been shown to confer health benefits to the host. Over the years, probiotics have been a part of the human diet in the form of different fermented foods consumed around the world. Their influence on different physiologic functions in the host is increasingly being documented. The antiobesity potential of probiotics is also gaining wide attention because of increasing evidence of the role of gut microbiota in energy homeostasis and fat accumulation. Probiotics have also been shown to interact with the resident bacterial members already present in the gut by altering their properties, which may also affect the metabolic pathways involved in the regulation of fat metabolism. The underlying pathways governing the antiobesity effects of probiotics remain unclear. However, it is hoped that the evidence presented and discussed in this review will encourage and thus drive more extensive research in this field.

Virological response and HIV drug resistance 12 months after antiretroviral therapy initiation at 2 clinics in Nigeria.

This report describes a pilot study, conducted in Nigeria, of the World Health Organization protocol for monitoring human immunodeficiency virus (HIV) drug resistance (HIVDR) and associated program factors among patients receiving first-line antiretroviral therapy (ART). In 2008, 283 HIV-infected patients starting ART were consecutively enrolled at 2 ART clinics in Abuja. Twelve months after ART initiation, 62% were alive and on first-line ART, 3% had died, 1% had transferred out of the program, and 34% were lost to follow-up. Among patients on first-line ART at 12 months, 90% had viral suppression. However, in view of the high loss to follow-up rate (34%), strategies for patient retention and tracking are critical to minimize possible HIVDR and optimize treatment outcomes.

Targeted cancer therapies: the future of cancer treatment.

For decades, the hallmark of medical treatment for cancer has been intravenous cytotoxic chemotherapy, where these drugs target rapidly dividing cells, including cancer cells and certain normal tissues. As a result, many patients experience the classic toxicities of alopecia, gastrointestinal symptoms, and myelosuppression. In the past decade, however, a dramatic shift has been witnesses in the cancer therapy. Although traditional cytotoxic chemotherapy still remains the treatment of choice for many malignancies, targeted therapies are now a component of treatment for many types of cancer, including breast, colorectal, lung, and pancreatic cancers, as well as lymphoma, leukemia, and multiple myeloma.