E. coli Group 1 Capsular Polysaccharide Exportation Nanomachinary as a Plausible Antivirulence Targetin the Perspective of Emerging Antimicrobial Resistance

Bacteria evolving resistance against the action of multiple drugs and its ability to disseminate the multidrug resistance trait(s) across various strains of the same bacteria or different bacterial species impose serious threat to public health. Evolution of such multidrug resistance is due to the fact that, most of the antibiotics target bacterial survival mechanisms which exert selective pressure on the bacteria and aids them to escape from the action of antibiotics. Nonetheless, targeting bacterial virulence strategies such as bacterial surface associated polysaccharides biosynthesis and their surface accumulation mechanisms may be an attractive strategy, as they impose less selective pressure on the bacteria. Capsular polysaccharide (CPS) or K-antigen that is located on the bacterial surface armors bacteria from host immune response. Thus, unencapsulating bacteria would be a good strategy for drug design, besides CPS itself being a good vaccine target, by interfering with CPS biosynthesis and surface assembly pathway. Gram-negative Escherichia coli uses Wzy-polymerase dependent (Groups 1 and 4) and ATP dependent (Groups 1 and 3) pathways for CPS production. Considering E. coli as a case in point, this review explains the structure and functional roles of proteins involved in Group 1 Wzy dependent CPS biosynthesis, surface expression and anchorage in relevance to drug and vaccine developments

The role of immunohistochemistry in medullomyoblastoma – a case series highlighting divergent differentiation

<p>Abstract</p> <p>Aims</p> <p>To analyse the histo-morphology of cases of medullomyoblastoma and identifying its divergent differentiation.</p> <p>Methods</p> <p>A retrospective review of all cases reported as medulloblastoma between the period of Jan 2000 to Dec 2006 was carried out on Hematoxylin and eosin (H & E) stained slides. The cases were screened on light microscopy for primitive neuroectodermal component of a medulloblastoma accompanied by areas of "myoid" differentiation, identified on the basis of presence of strap cells (indicating a clear skeletal muscle differentiation) and/or large anaplastic cells with vescicular nuclei and moderate to abundant amount of eosinophilic cytoplasm. All these cases were subjected to a panel of immunohistochemical stains, including Desmin, GFAP, NFP, HMB45, SMA, S100, CK and EMA. Ultrastructral analysis was done on tissue obtained from paraffin blocks in 2 cases.</p> <p>Results</p> <p>Male predominance (M:F = 5:1) was noted with an incidence of five percent of all cases of medulloblastoma (6 out of 120 cases) over a period of 6 years. Primitive neuroectodermal areas were accompanied with areas of "myoid" differentiation, 5 cases showing strap cells. Two cases with epithelial and cartilaginous differentiation were seen. Three cases showed focal melanocytic differentiation, identified only on HMB45 immunostaining. Four cases showed glial differentiation. Neuronal differentiation again was very focally seen in two cases, of which one was identified only by NFP immunostain. Seventh case is included in the study, however it is not considered to calculate incidence as it occurred beyond the period of 6 years of records search.</p> <p>Conclusion</p> <p>Medullomyoblastoma is a rare childhood tumor of cerebellum. Majority of cases reveal divergent differentiation, which are identified with the help of panel of immunostains indicating multi-potential nature of primitive neuroectodermal cells.</p

Klotho and the treatment of human malignancies

Klotho was first discovered as an anti-ageing protein linked to a number of age-related disease processes, including cardiovascular, renal, musculoskeletal, and neurodegenerative conditions. Emerging research has also demonstrated a potential therapeutic role for Klotho in cancer biology, which is perhaps unsurprising given that cancer and ageing share similar molecular hallmarks. In addition to functioning as a tumour suppressor in numerous solid tumours and haematological malignancies, Klotho represents a candidate therapeutic target for patients with these diseases, the majority of whom have limited treatment options. Here, we examine contemporary evidence evaluating the anti-neoplastic effects of Klotho and describe the modulation of downstream oncogenic signalling pathways, including Wnt/β-catenin, FGF, IGF1, PIK3K/AKT, TGFβ, and the Unfolded Protein Response. We also discuss possible approaches to developing therapeutic Klotho and consider technological advances that may facilitate the delivery of Klotho through gene therapy

Tuberculosis treatment in the private healthcare sector in India: An analysis of recent trends and volumes using drug sales data

Background There is a pressing need for systematic approaches for monitoring how much TB treatment is ongoing in the private sector in India: both to cast light on the true scale of the problem, and to help monitor the progress of interventions currently being planned to address this problem. Methods We used commercially available data on the sales of rifampicin-containing drugs in the private sector, adjusted for data coverage and indication of use. We examined temporal, statewise trends in volumes (patient-months) of TB treatment from 2013 to 2016. We additionally analysed the proportion of drugs that were sold in combination packaging (designed to simplify TB treatment), or as loose pills. Results Drug sales suggest a steady trend of TB treatment dispensed by the private sector, from 18.4 million patient-months (95% CI 17.3–20.5) in 2013 to 16.8 patient-months (95% CI 15.5–19.0) in 2016. Overall, seven of 29 states in India accounted for more than 70% of national-level TB treatment volumes, including Uttar Pradesh, Maharashtra and Bihar. The overwhelming majority of TB treatment was dispensed not as loose pills, but in combination packaging with other TB drugs, accounting for over 96% of private sector TB treatment in 2017. Conclusions Our findings suggest consistent levels of TB treatment in the private sector over the past 4 years, while highlighting specific states that should be prioritized for intervention. Drug sales data can be helpful for monitoring a system as large, disorganised and opaque as India’s private sector

Symptomatic hypercalcemia in a patient with chronic tophaceous gout: a case report

Hypercalcemia has been widely associated with granulomatous processes. This is due to enhanced extra-renal conversion of calcidiol to calcitriol by activated macrophages within the granuloma. Symptomatic hypercalcemia due to granulomatous disorders is not common, with the incidence in sarcoidosis ranging from 10–20%. Large aggregates of monosodium urate crystals in patients with longstanding chronic tophaceous gout can serve as the inciting antigen for the development of granuloma, but hypercalcemia has not been described in this context. We report a case of symptomatic hypercalcemia due to gouty tophi induced granulomatous inflammation. Long term treatment with immunosuppressants, in addition to bisphosphonates and uric acid lowering therapy, has led to stabilization of serum calcium levels and other lab parameters indicative of granulomatous burden

Studies on feasibility of sett planting through single eye bud technique for rapid multiplication of existing and new varieties in Saraswati sugar mills command area, Haryana, India

The conventional system of sugarcane (Saccharum sp.) planting is inefficient for rapidly multiplying the seed cane of newly released varieties due to a higher seed rate (7.5-8.0 t ha-1) and low germination rate (40-50%). The present study was conducted at 8 sites in Saraswati Sugar Mill zone area of Haryana, India area during planting season 2017-18 and its subsequent ratoon 2018-19. The effect of planting methods on the multiplication rate of seed cane, yield potential and economics of sugarcane was calculated. Forty day old plantlets grown in polythene bags/trays/seedbed nursery using 19000 single-bud cane setts per ha area were transplanted at row to row and plant to plant distance of 120 x 45 cm. The results were compared with those obtained by the conventional practice of planting the three and two budded cane setts at the rate of 33600 and 50250 setts per ha, respectively. It was found that seedlings raised through bed nursery method recorded 46.39% higher cane yield (102.50 t ha-1) than farmers’ practice of conventional 3-budded method. The same also produced higher millable cane/ha (97620). The improved practices also recorded the higher gross return of Rs. 3, 48,500 ha-1, B:C ratio (2.17) with additional net return of Rs.1,30,215 ha-1 over local check of conventional three eye budded method which can effectively be replaced in the existing farming situation for higher productivity. The results further indicated that the rate of seed cane multiplication was about 51.37 times by the bed nursery method and 7.99 times by the conventional planting method. The results of study showed that farmers could increase the sugarcane productivity significantly by switching over to improved technology

Outcomes of patients with end-stage kidney disease hospitalized with COVID-19.

Given the high risk of infection-related mortality, patients with end-stage kidney disease (ESKD) may be at increased risk with COVID-19. To assess this, we compared outcomes of patients with and without ESKD, hospitalized with COVID-19. This was a retrospective study of patients admitted with COVID-19 from 13 New York. hospitals from March 1, 2020, to April 27, 2020, and followed through May 27, 2020. We measured primary outcome (in-hospital death), and secondary outcomes (mechanical ventilation and length of stay), Of 10,482 patients with COVID-19, 419 had ESKD. Patients with ESKD were older, had a greater percentage self-identified as Black, and more comorbid conditions. Patients with ESKD had a higher rate of in-hospital death than those without (31.7% vs 25.4%, odds ratio 1.38, 95% confidence interval 1.12 - 1.70). This increase rate remained after adjusting for demographic and comorbid conditions (adjusted odds ratio 1.37, 1.09 - 1.73). The odds of length of stay of seven or more days was higher in the group with compared to the group without ESKD in both the crude and adjusted analysis (1.62, 1.27 - 2.06; vs 1.57, 1.22 - 2.02, respectively). There was no difference in the odds of mechanical ventilation between the groups. Independent risk factors for in-hospital death for patients with ESKD were increased age, being on a ventilator, lymphopenia, blood urea nitrogen and serum ferritin. Black race was associated with a lower risk of death. Thus, among patients hospitalized with COVID-19, those with ESKD had a higher rate of in-hospital death compared to those without ESKD