Colistin Resistance and Management of Drug Resistant Infections.

Colistin resistance is a globalized sensible issue because it has been considered a drug of the last-line resort to treat drug-resistant bacterial infections. The product of the mobilized colistin resistance (mcr) gene and its variants are the significant causes of colistin resistance, which is emerging due to the frequent colistin use in veterinary, and these genes circulate among the bacterial community. Apart from mcr genes, some other intrinsic genes and proteins are also involved in colistin resistance. Researchers focus on the most advanced genomics (whole genome sequencing), proteomics, and bioinformatics approaches to explore the question of colistin resistance. To combat colistin resistance, researchers developed various strategies such as the development of newer drugs, the repurposing of existing drugs, combinatorial treatment by colistin with other drugs, a nano-based approach, photodynamic therapy, a CRISPRi-based strategy, and a phage-based strategy. In this timeline review, we have discussed the development of colistin resistance and its management in developing countries.

Prevalence and risk factors of tuberculosis in developing countries through health care workers.

In the last two decades, tuberculosis (TB) have threatened the public across the globe and continuing new TB cases and their transmission pooled with the global emergence of drug-resistant strains present an enduring occupational risk for health care workers (HCWs). Since last decade, government and funding agencies has given a significant amount of funds to tackle the problem of TB infection among medical staff or HCW in hospitals of developing countries, but the effects of these efforts have not yet been reported. Working environments are the major risk factors for TB infections among the HCW in hospital settings. Twenty-two high burden countries endorsed to the preponderance of worldwide tuberculosis cases in 2015. Urgent preventive strategies and mediations are needed to ensure the safety and sustained availability of these exquisite healthcare resources. This timeline review will provide the theoretical basis of high TB burden among the HCW which can be used for further improvement in strategies for the prevention of TB infections in hospital settings and provide a reliable basis for improving the personal health of HCW or medical staff.

Assessment of phagosomes infected with Mycobacterium tuberculosis as a vaccine candidate against tuberculosis.

The present study describes a novel and simple vaccination strategy that involve culturing of M. tuberculosis in the macrophage cells. Isolation of phagosome from macrophage (cell line J774) infected with M. tuberculosis (H37) and M. bovis (BCG) at early and late phase of infection was done ensuing the identification and characterization of these phagosome. In vitro study of apoptosis induced by phagosome infected with (H37) and (BCG) was performed. The vaccine candidate with H1137 MOI- 1:10 at 3 h, MOI- 1:20 at 1, 1.5, 2.5 and 3 h and BCG MOI- 1:20 at 3.5 h showed percentage apoptosis as 38.64, 39.93, 34.66, 22.56,34.59 and 37.81% respectively. The results designates that macrophages provide cellular niche during infection and illustrate considerable immunogenic property. Novel antigens expressed or secreted by H37 in infected macrophages can provide evidence to be a successful vaccine candidate as it endures enhanced immune response than BCG.

Psychological Distress in Low-Income and Economically Marginalized Populations in India: Protective and Risk Factors.

Studies at the juncture of development economics and public health take on considerable responsibility in addressing inequality and related mental health distress. Mental healthcare in economically marginalized populations requires depicting the linkages between socioeconomic status and psychological distress. In the present work, a sequential mixed-methods design was used to study 190 people in such communities in India. Gender-dependent psychological distress was found according to the Kessler Psychological Distress Scale (K-10) with moderate distress in women (M = 26.30, SD = 9.15) and mild distress in men (M = 21.04, SD = 8.35). Regression analysis indicated that gender significantly predicted psychological distress, followed by age, marital status, and the level of education of the head of the family. The Interpretative Phenomenological Analysis of semi-structured interviews of the six women who scored the highest on the distress scale unveiled three master themes: (1) manifestation of psychological distress, (2) contextual challenges, and (3) sources of strength and resilience. Overall, participants reported a lack of resources, community violence, gender discrimination, and widespread substance use as major contributors to the ongoing distress. These findings can pave the way for future studies to expand beyond independent economic indicators and curate clinical interventions for culturally competent mental healthcare.

Corannulene Amino Acid-Derived Water-Soluble Amphiphilic Buckybowls as Broad-Spectrum Membrane Targeting Antibacterial Agents.

To date, the use of corannulene has been restricted in the area of material science, but its application in biomedical research has yet to be established due to its nonsolubility in an aqueous environment and synthetic infeasibility. Herein, we detail the development of a new family of highly curved π-conjugated corannulene-containing unnatural α-amino acid (CAA) derivatives to overcome this challenge. These CAAs have been extended as novel constituents for the synthesis of corannulene-containing water-soluble cationic peptides (CCPs), which display inhibitory activity against broad-spectrum pathogenic bacteria along with drug-resistant bacteria via a membrane-damaging mechanism. Importantly, several of the synthesized peptides were found to be appreciably nonhemolytic against hRBCs and noncytotoxic against mammalian 3T3 cells. In vivo efficacy studies of the potent and least cytotoxic peptide 6a demonstrated clearance of bacteria from the spleen, liver, lung, and blood of mice infected with S. aureus ATCC 25923.

Understanding the effectiveness of school-based interventions to prevent suicide: a realist review.

BACKGROUND: Schools appear an obvious place to deliver suicide prevention interventions for children and adolescents. The complexity of suicide interventions lead to a paucity of good quality evidence. An alternate approach of information gathering is needed to identify and collate evidence from existing interventions. SCOPE: We completed a realist review of school-based suicide interventions. This is a novel method of understanding complex interventions that uses an iterative approach. In this review, we attempt to clarify and lay out what type of suicide intervention programme might be useful in schools, based on the local needs and context. CONCLUSION: It is possible to develop and implement an evidence-based suicide intervention in schools by understanding the different processes that can contribute to success or failure of these interventions in a real-world setting.

Engineering of Saccharomyces cerevisiae as a consolidated bioprocessing host to produce cellulosic ethanol: Recent advancements and current challenges.

Lignocellulosic biomass, a rich and inexpensive source of fermentable and renewable carbon, is the most abundant material on earth. Microbial bioprocessing of lignocellulosic biomass to produce biofuels (bioethanol, biobutanol, biodiesel) is a sustainable blueprint to reduce our depleting energy reserves and carbon footprint. Saccharomyces cerevisiae, being an excellent industrial ethanologenic organism, is an ideal candidate to engineer as a consolidated bio-processing (CBP) host, a concept that integrates the different steps of cellulosic ethanol production, from hydrolysis of cellulose to glucose and fermentation of glucose to ethanol in one step. Owing to the developments in the field of genetic engineering and sequencing technologies, research in the past two decades have made pivotal achievements to realize CBP enabling yeast suited for industrial applications. However, overcoming major limitations such as incomplete substrate catabolism, low titres of heterologous protein expression, sub-optimal operational conditions and impediment due to toxic inhibitors/by-products accumulation is still challenging. This review focuses on the progress achieved in constructing S. cerevisiae to produce bioethanol in a CBP framework. The different techniques of developing cellulolytic yeast strains are initially explained followed by relevant strategies to tackle the key bottlenecks associated with the process. Additionally, engineering efforts towards designing hemicellulose-derived sugar utilizing yeast strains are discussed.

Enhanced biodiesel and ß-carotene production in Rhodotorula pacifica INDKK using sugarcane bagasse and molasses by an integrated biorefinery framework.

Dependency on fossil fuels raises an economic and ecological concern that has urged to look for alternative sources of energy. Bio-refinery concept is one of the alternate frameworks for the biomass conversion into biofuel and other value-added by-products. The present work illustrates importance of an oleaginous yeast Rhodotorula pacifica INDKK in an integrated bio-refinery field by utilizing renewable sugars generated from lignocellulosic biomass. The maximum 11.8 g/L lipid titer, 210.4 mg/L ß-carotene and 7.1 g animal feed were produced by R. pacifica INDKK in bioreactor containing 5% (v/v) molasses supplemented with enzymatically hydrolyzed and alkali-pretreated sugarcane bagasse hydrolysate (35% v/v). Furthermore, xylooligosaccharides (20.6 g/L), a beneficial prebiotics were also produced from the hemicellulosic fraction separated after alkali pretreatment of bagasse. This novel concept of integrated yeast bio-refinery for concomitant production of biodiesel and multiple value-added products with minimum waste generation is proposed as a sustainable and profitable process.

Aromatase-Inhibitor-Induced Musculoskeletal Inflammation Is Observed Independent of Oophorectomy in a Novel Mouse Model.

Aromatase Inhibitors (AIs) block estrogen production and improve survival in patients with hormone-receptor-positive breast cancer. However, half of patients develop aromatase-inhibitor-induced arthralgia (AIIA), which is characterized by inflammation of the joints and the surrounding musculoskeletal tissue. To create a platform for future interventional strategies, our objective was to characterize a novel animal model of AIIA. Female BALB/C-Tg(NFκB-RE-luc)-Xen mice, which have a firefly luciferase NFκB reporter gene, were oophorectomized and treated with an AI (letrozole). Bioluminescent imaging showed significantly enhanced NFκB activation with AI treatment in the hind limbs. Moreover, an analysis of the knee joints and legs via MRI showed enhanced signal detection in the joint space and the surrounding tissue. Surprisingly, the responses observed with AI treatment were independent of oophorectomy, indicating that inflammation is not mediated by physiological estrogen levels. Histopathological and pro-inflammatory cytokine analyses further demonstrated the same trend, as tenosynovitis and musculoskeletal infiltrates were detected in all mice receiving AI, and serum cytokines were significantly upregulated. Human PBMCs treated with letrozole/estrogen combinations did not demonstrate an AI-specific gene expression pattern, suggesting AIIA-mediated pathogenesis through other cell types. Collectively, these data identify an AI-induced stimulation of disease pathology and suggest that AIIA pathogenesis may not be mediated by estrogen deficiency, as previously hypothesized.

Prevalence of anemia in pre-school tribal children with reference to parasitic infections and nutritional impact.

Objectives: Anemia is a global health problem and has very high prevalence in developing as well as developed countries, particularly in children and women. The present study evaluates hematological predictors, nutrition deficiency, parasitic infections and their association with the prevalence of anemia. This analysis will help to identify the anemic status of tribal preschool children. Methods: This was a cross-sectional study conducted in 300 children (age: 6 months to 5 years) in Santrampur village, Gujarat. Blood was collected and used to determine complete blood count (CBC); we also performed ELISA (enzyme-linked immunoassay) for the estimation of ferritin, transferrin, sTfR (soluble transferrin receptor), vitamin B12 and vitamin B9 (folate). Stool samples were also collected and assessed by ELISA for Entamoeba histolytica, Giardia lamblia and Cryptosporidium parvum. Microscopy was used to screen samples for malaria. Results: Of the 300 children analyzed, 87.7% were anemic, 239 children were mildly anemic, 20 were moderately anemic and 4 were severely anemic. Mean Hb level was 9.49 ± 1.47 g/dL; males and females had an Hb level of 9.39 ± 1.59 g/dL and 9.58 ± 1.34 g/dL, respectively. Twenty-six children had sickle cell anemia and five had thalassemia. Over 50% of the children had vitamin B12 and B9 deficiency and 16% had abnormalities in CRP (C-reactive protein) levels. Parasitic infection by C. parvum was positively associated the anemia followed by the prevalence of G. lamblia and E. histolytica. Conclusion: An increased awareness of parents in the improvement of sanitary facilities and nutritional counselling with regards to iron-rich food consumption is recommended to if we are to prevent anemia among pre-school children. To reduce parasitic infestation, effective periodic deworming measures are also recommended.

Exploring the Mystery of Angiotensin-Converting Enzyme II (ACE2) in the Battle against SARS-CoV-2.

COVID-19 is the newly born pandemic caused by the SARS-CoV-2 virus, which is the recently emerged betacoronavirus that crosses the species barrier. It predominantly infects pneumocytes of the respiratory tract, but due to the presence of angiotensin-converting enzyme II (ACE2) on other cells like surface enterocytes of the upper esophagus and colon, these are also considered as the primary sites of infection. ACE2 receptor served as a cellular entry point for SARS-CoV-2. The expression of the ACE2 receptors is regulated by several factors such as age, tobacco smoking, inflammatory signaling, ACE inhibitors, angiotensin receptor blockers, and comorbidities (chronic obstructive pulmonary disease (COPD), tuberculosis, cerebrovascular disease, coronary heart disease, hypertension, and diabetes). Therefore, scientists are trying to explore the in-depth knowledge of ACE2 and considered it as a potential indirect target for COVID-19 therapeutics. In this focused review, we discussed in detail ACE2 expressions and regulation by different factors in the primary or vulnerable sites of SARS-CoV-2 infections. Clinical trials of rhACE2 in COVID-19 patients are ongoing, and if the outcome of the trials proves positive, it will be a breakthrough for the management of COVID-19. Finally, we suggest that targeting the ACE2 (a master regulator) in a balanced way could serve as a potential option against the management of COVID-19.

The Challenges and Successes of Dealing with the COVID-19 Pandemic in India.

As the infectivity of the SARS-CoV-2 virus is higher compared with other coronaviruses reported so far, so effective therapeutics and vaccines are the best way to control the proliferation of this infection The COVID-19 mortality rate is lower compared with other similar viral diseases such as severe acute respiratory Ssndrome (SARS) and Middle East respiratory syndrome (MERS). However, due to the evolution of SARS-CoV-2 mutants that are responsible for the subsequent waves, mortality due to COVID-19 has increased across the globe. Currently, the magnitude of SARS-CoV-2 infection is highly severe and is leading to a tremendously increased number of deaths globally. Scientists expect that SARS-CoV-2 has the potential to become a seasonal disease like influenza and may persist with humanity in the future. Currently, preventive strategies such as sanitation, social distancing, use of masks, potential chemotherapies (pathogen-centric and host-centric), and vaccines are the only option to fight against COVID-19. Many groups of Indian government-public private consortia had set up different strategies (development of multiple vaccines) for combat of this unique threat through stepssuch as an increase in vaccinations and sample testing per day. In this focused review, we have discussed the challenges faced and success stories employed to manage COVID-19.

Potential strategies for the management of drug-resistant tuberculosis.

In the current scenario, the emergence of drug resistance in Mycobacterium tuberculosis is the consequence of the failure of conventional diagnostic and treatment approaches. To combat this global emergence of drug resistance, alternative approaches such as pathogen-centric (use of repurposed drugs, novel analogues of existing anti-TB drugs and novel compounds with a different mechanism of action), host-centric (immunomodulatory agents, therapeutic vaccines, immune and cellular therapies) and nano-based drug/vaccine delivery should be used singly or in combination. Diverse types of nano-carriers have assessed as auspicious diagnostic and drug delivery systems. In this focused review, we have suggested a long-term solution for combating antimicrobial resistance and also an attractive means to increase patient compliance and reduce treatment duration.

Legume lectins: Potential use as a diagnostics and therapeutics against the cancer.

Legume lectins are carbohydrate-binding protein and widely distributed in a variety of species of leguminous plants and have drawn increased attention toward cancer. Nowadays, the lectins have been studied for the screening of potential biomarkers which increased its importance in cancer research. Few plant lectins have been shown to destroy cancer cells, suggesting that lectins may have biological potential in cancer treatments. In this review, we present a focused outline of legume lectins in descriptive their complex anti-cancer mechanisms on the bases of their properties of recognition and interacting specifically with carbohydrates binding sites. Existing reports suggested the binding of lectins to cancerous cells with their cell surface markers speculated by histochemistry in vitro and in vivo. In this review, we illuminate the use of legume lectins as a natural source for diagnostics and therapeutics purpose against cancer.