Bacterial and fungal co-infection is a major barrier in COVID-19 patients: A specific management and therapeutic strategy is required

Microbial co-infections are another primary concern in patients with coronavirus disease 2019 (COVID-19), yet it is an untouched area among researchers. Preliminary data and systematic reviews only show the type of pathogens responsible for that, but its pathophysiology is still unknown. Studies show that these microbial co-infections are hospital-acquired/nosocomial infections, and patients admitted to intensive care units with invasive mechanical ventilation are highly susceptible to it. Patients with COVID-19 had elevated inflammatory cytokines and a weakened cell-mediated immune response, with lower CD4⁺ T and CD8⁺ T cell counts, indicating vulnerability to various co-infections. Despite this, there are only a few studies that recommend the management of co-infections.     

The Impact of “COVID-19” and “Webinar Pandemic” on Plastic Surgery Practice in Teaching Institutes and Resident Training—A Multicentric Perspective

Introduction  The study was carried out to quantify the changes induced by the pandemic in plastic surgery practice and training and to study the impact of the webinars on plastic surgery education from a residents’ perspective. Methods  In this multicentric study, the number and type of surgeries, cause of injuries, and their regional variation during the coronavirus disease 2019 (COVID-19) period (February–September 2020) were compared with pre–COVID-19 time. An online survey on the impact of webinars was conducted for plastic surgery trainees across the country. Results  There was a significant reduction in total number of surgeries ( p = 0.003). The procedures for hand ( p = 0.156), faciomaxillary injuries ( p = 0.25), and replantations ( p = 0.46) were comparable; there was a significant reduction in combined orthopedic-plastic-surgical procedures ( p = 0.009) during the pandemic. There was a significant reduction in road accidents ( p = 0.007) and suicidal injuries ( p = 0.002) and increase in assault ( p = 0.03) and domestic accidents ( p = 0.01) during the COVID-19 period. A usefulness score of >8 was given for the webinars by 68.7% residents. There was no significant difference in perception of utility when correlated with the academic program at their institutes ( p = 0.109); 92% opined webinars should continue in post-COVID times. Conclusion  There was a drastic reduction in number of elective and emergency procedures during the COVID-19 time, negatively affecting resident training program. Majority of residents felt that webinars could prove a useful adjunct to training in formal training program in post-COVID-19 scenario.     

Isolation of hypoglycemic phytoconstituent from Swietenia macrophylla seeds

The present study was undertaken to isolate a novel antidiabetic molecule from Swietenia macrophylla seeds. The hydroalcohol extract of Swietenia macrophylla seeds was subjected for bioassay guided isolation employing glucose utilization assay by the isolated rat hemi‐diaphragm method in vitro. One tetranortriterpenoid, swietenine, isolated from the chloroform fraction exhibited significant (p < 0.01) activity and the effect was comparable to that of human insulin (p < 0.01). Copyright © 2009 John Wiley & Sons, Ltd.     

In vivo effects of anti-leprosy drugs on the rat peritoneal macrophages and lymphocyte subpopulations.

The present study describes the in vivo effects of anti-leprosy drugs on rat peritoneal macrophages and T-cell homeostasis. It was observed that BCG-elicited rat peritoneal macrophages produced more H2O2 and expressed more Ia antigen on their cell surfaces compared with resident peritoneal macrophages. Furthermore, elicited macrophages isolated from rats administered multidrug therapy (MDT), consisting of dapsone, clofazimine and rifampicin in high dose (10 x MDT) released more O2-. On the contrary, there was a significant decrease in the Ia antigen expression on these macrophages. Anti-leprosy drug treatment in high dose (10 x MDT) decreased the total number of blood T-helper (W3/25+) cells and increased the total number of blood T-suppressor (OX-8+) cells which resulted in a significant decrease in a W3/25: OX-8 ratio. Electron microscopy of elicited macrophages isolated from 10 x MDT treated rats showed development of many filipodia compared with control macrophages. These data show that 10 x MDT treatment in rats for 1 month alters the homeostasis of blood T-cell subpopulations which perhaps decreases the Ia expression on macrophages. However, the increase in O2- production and the appearance of filipodia on the macrophages is due to a direct effect of drugs on the macrophages. MDT treatment for 1 month in a therapeutic dose has no effect on the above-mentioned parameters.     

Comparative analysis of the large fragment of the 5′ untranslated region (LF-5′ UTR) of serotype A foot-and-mouth disease virus field isolates from India

India is endemic for foot-and-mouth disease (FMD) and in recent years a unique group within serotype A, carrying a codon deletion at an antigenically critical site in capsid protein VP3 has emerged (VP3⁵⁹-deletion group). This tempted us to analyze the noncoding region, which is an under represented area, though critically associated with virus biology and pathogenesis. Analysis of the large fragment of 5′ untranslated region (LF-5′ UTR) of type A FMD virus revealed discrepancy in the overall tree topology between LF-5′ UTR and 1D region possibly due to independent evolution of coding and noncoding regions. The VP3⁵⁹-deletion group maintained its phylogenetic distinctness even at the LF-5′ UTR. Eighteen lineage specific signatures detected here support independent evolutionary paths for the lineages. Extensive deletions of 45 and 89 nucleotides corresponding to the pseudoknot region were noticed. Conservation pattern in the ‘A₂₅₃AACA’ motif in the cre/bus stem-loop indicates the importance of first three ‘A’ residues in VPg uridylylation. Of the three polypyrimidine tract binding protein (PTB) binding sites mapped on the internal ribosome entry site (IRES), the pyrimidine tract (Py tract) in the loop of domain 2 was found to be maximally conserved and it might be the major PTB binding site. Strikingly, a deletion group lineage specific transversion was noticed in the Py tract at the 3′ end of IRES without significantly affecting its in vitro infectious titer. Hence, we presume that for efficient cap-independent viral translation, either a minimum number of pyrimidine residues rather than a complete Py tract or a Py tract tolerating transversions only at specific locations and a core motif ‘CUUU’ within the Py tract is essential.     

Primary mucormycosis of abdominal wall: A rare fungal infection in a immunocompetent patient

Mucormycosis of the anterior abdominal wall is an uncommon disease and it is very rare to find this disease in immunocompetent, non-diabetic patients which usually affects patients with trauma, with contaminated wounds, patients with underlying malignancies or patients with immunocompromised state, e.g., diabetics. We herein report a case of primary cutaneous mucormycosis in an immunocompetent and non-diabetic patient. Our patient was a 48-year-old female, executive by profession. She was diagnosed to have cutaneous mucormycosis of the anterior abdominal wall, and was managed with multiple debridements of the wound and intravenous amphotericin B therapy. She was administered a total of 1500 mg of liposomal amphotericin B and when fully healed, split skin grafting was done. We would like to emphasize the importance of high index of suspicion and early start of therapy in a condition with high rate of mortality.     

Changes in hypothalamic gene expression associated with the arrest of pulsatile gonadotropin-releasing hormone release during infancy in the agonadal male rhesus monkey (Macaca mulatta)

This study examined whether changes in the levels of the messenger RNAs (mRNAs) encoding the gamma-aminobutyric acid (GABA) synthesizing enzymes, glutamate decarboxylase (GAD)65 and GAD67 and transforming growth factor-alpha (TGFalpha) in the hypothalamus are correlated with the arrest of pulsatile GnRH release during infancy in the agonadal male monkey. This experiment also provided the opportunity to examine changes in hypothalamic GnRH gene expression during this critical phase of primate development. Male rhesus monkeys were castrated at 1 week of age: four were killed 4-7 weeks after orchidectomy while pulsatile GnRH release was robust as reflected by high circulating LH levels, and four were killed at 12-15 months of age after establishing that pulsatile GnRH release had been arrested. GAD65, GAD67, TGFalpha, and GnRH mRNA levels were estimated using RNase protection assays employing homologous probes and the results were expressed relative to cyclophilin mRNA levels. GnRH peptide was measured by RIA. GAD65 and GAD67 mRNA levels in the hypothalamus of juveniles were significantly greater than those in neonatal monkeys. On the other hand, hypothalamic TGFalpha and GnRH mRNA (and peptide) levels in agonadal neonate and juvenile monkeys were indistinguishable. These results indicate that the molecular concomitants associated with bringing the hypothalamic GnRH pulse generator into check in agonadal neonatal males are not a mirror image of those previously reported at the time this neuronal network is reactivated at puberty when TGFalpha and GnRH gene expression increase and GAD65 and GAD67 mRNA levels remain unchanged. Thus, the neurobiological mechanism that reactivates pulsatile GnRH release at puberty is likely to involve more than a simple reversal of that underlying inhibition of the same network in late infancy.     

Macular serpiginous choroiditis

PURPOSE: To report a variant form of serpiginous choroiditis, that initially or predominantly involved the macular area. METHODS: Nine eyes of 6 patients with the macular form of serpiginous choroiditis were evaluated clinically and angiographically in a longitudinal fashion for a period of 12-36 months. The active stage and the recurrences were treated by oral and periocular cortico steroids; and two patients were supplemented with oral azathioprine. Most of these patients were referred to our center with varied diagnoses. RESULTS: In this group, 4 were male and 2 were female with an average age of 30.5 years. Three patients had bilateral macular lesions, two had typical serpiginous choroiditis in the fellow eye and the remaining one had unilateral macular involvement alone. The initial visual acuity was 6/60 or less in 60% eyes whereas the final visual acuity was 6/18 or better in 66% eyes. Angiographic findings were typical of serpiginous choroiditis characterised by early hypofluorescence followed by leakage and staining of the borders and the lesion itself without any evidence of choroidal ischaemia or retinal vascular abnormalities. CONCLUSION: The macular variant of serpiginous choroiditis can mimic many other macular pathologic lesions, thus posing a diagnostic dilemma. Because of its relentless destructive course, early diagnosis and prompt treatment is required to prevent sight-threatening complications.     

Leptin signaling in the hypothalamus: emphasis on energy homeostasis and leptin resistance

Leptin, the long-sought satiety factor of adipocytes origin, has emerged as one of the major signals that relay the status of fat stores to the hypothalamus and plays a significant role in energy homeostasis. Understanding the mechanisms of leptin signaling in the hypothalamus during normal and pathological conditions, such as obesity, has been the subject of intensive research during the last decade. It is now established that leptin action in the hypothalamus in regulation of food intake and body weight is mediated by a neural circuitry comprising of orexigenic and anorectic signals, including NPY, MCH, galanin, orexin, GALP, alpha-MSH, NT, and CRH. In addition to the conventional JAK2-STAT3 pathway, it has become evident that PI3K-PDE3B-cAMP pathway plays a critical role in leptin signaling in the hypothalamus. It is now established that central leptin resistance contributes to the development of diet-induced obesity and ageing associated obesity. Central leptin resistance also occurs due to hyperleptinimia produced by exogenous leptin infusion. A defective nutritional regulation of leptin receptor gene expression and reduced STAT3 signaling may be involved in the development of leptin resistance in DIO. However, leptin resistance in the hypothalamic neurons may occur despite an intact JAK2-STAT3 pathway of leptin signaling. Thus, in addition to defective JAK2-STAT3 pathway, defects in other leptin signaling pathways may be involved in leptin resistance. We hypothesize that defective regulation of PI3K-PDE3B-cAMP pathway may be one of the mechanisms behind the development of central leptin resistance seen in obesity.     

Silica induced early fibrogenic reaction in lung of mice ameliorated by Nyctanthes arbortristis extract

Objective To investigate the pharmacological effect of Nyctanthes arbortristis (NAT) leaf extract in the prevention of lung injury induced by silica particles. Method Lung injury was induced in Swiss mice through inhalation exposure to silica particles (<5μ) using a Flow Past Nose Only Inhalation Chamber at the rate of -10 mg/m3 respirable mass for 5 h. Lung bronchoalveolar lavage (BAL) fluid collected between 48 and 72 h was subjected to protein profiling by electrophoresis and cytokine evaluation by solid phase sandwich ELISA. Lung histopathology was performed to evaluate lung injury. Results Inhalation of silica increased the level of tumor necrosis factor-α(TNF-α), and of the 66 and 63 kDa peptides in the BAL fluid in comparison to sham-treated control. Pre-treatment of silica exposed mice with NAT leaf extract significantly prevented the accumulation of TNF-α in the BAL fluid, but the 66 and 63 kDa peptides remained unchanged. The extract was also effective in the prevention of silica-induced early fibrogenic reactions like congestion, edema and infiltration of nucleated cells in the interstitial alveolar spaces, and thickening of alveolar septa in mouse lung. Conclusion NAT leaf extract helps in bypassing silica induced initial lung injury in mice.