Covid-19-Associated Mucormycosis: Histopathology of the Deadly Fungal Infection.

Introduction Many patients suffered from rhino-orbital-cerebral mucormycosis during the coronavirus disease 2019 (COVID-19) pandemic in India. Diabetes is a known risk factor of COVID-19 infection and mucormycosis. Objective The present study was done to describe the clinical spectrum and histopathological findings of mucormycosis in COVID-19 patients and their outcomes. Methods A cross-sectional study was done over a period of two and half months. The biopsy samples or scrapings from sinonasal or periorbital tissue of 38 patients were analyzed. Hematoxylin & Eosin (H&E stain) slides were evaluated along with Grocott-Gomori methenamine-silver and Periodic acid-Schiff stains to highlight the fungal elements. Results The male to female ratio was 2.5:1, and the mean age of the subjects was 53 years old. A total of 68.4% ( n = 26/38) of the patients had diabetes as a comorbidity, 84.2% ( n = 32/38) had a history of steroid intake, and 55.3% ( n = 21/38) were given supplemental oxygen during their treatment. The common presentations were nasal blockage, discharge, eye pain, headache, and altered mentation. The sites of biopsy were: nasal cavity 76.3% ( n = 29/38), periorbital fat/orbit 21.1% ( n = 8/38), maxillary sinus 15.8% ( n = 6/38) and ethmoid sinus 13.2% ( n = 5/38). In 76.3% ( n = 29/38) cases, broad, irregular, nonseptate, and right-angle branching hyphae were seen on H&E-stained tissue sections. Conclusion COVID-19 led to various complications in individuals affected by it. Mucormycosis was one such lethal complication. An early diagnosis and prompt treatment is crucial to control the progression of the disease and improve outcomes.

Hepatitis C virus core antigen: A diagnostic and treatment monitoring marker of hepatitis C virus in Indian population.

BACKGROUND: The diagnosis and treatment monitoring of hepatitis C is quite challenging. The screening test, i.e. antibody assay, is unable to detect acute cases, while the gold standard hepatitis C virus (HCV) reverse transcriptase polymerase chain reaction (RTPCR) assay is not feasible in resource-limited countries such as India due to high cost and infrastructure requirement. European Association for the Study of the Liver and World Health Organization have approved a new marker, i.e. HCV core antigen (HCVcAg) assay, as an alternative to molecular assay. In this study, we have evaluated HCVcAg assay for diagnosis and treatment monitoring follow-up in Indian population infected with hepatitis C. METHODS: Blood specimen of 90 clinically suspected cases of acute hepatitis C were tested simultaneously for anti-HCV antibody assay via ELISA (enzyme-linked immunoassay), HCVcAg assay by chemiluminescence immune assay (CLIA) and HCV RTPCR VL (viral load) assay. Thirty-four HCV RTPCR positive patients were further enrolled in treatment monitoring group whose blood samples were tested at the beginning of treatment, two weeks, four weeks and 12 weeks via HCV core Ag assay and HCV RTPCR Viral Load assay. RESULTS: Considering HCV RTPCR as gold standard, diagnostic performance of HCV core Ag assay and anti-HCV antibody assay was evaluated. The sensitivity and specificity of HCV core Ag assay were higher than that of anti-HCV Antibody assay, i.e. 88.3% and 100% vs. 23.3% and 83.3%, respectively. The overall diagnostic accuracy of HCV core Ag assay was 92.20%. Among treatment follow-up group, HCV core Ag levels correlated well with HCV viral load levels, at the beginning of treatment (baseline) till 12 weeks showing highly significant Spearman rank correlation coefficient of > 0.9 with HCV viral load levels. CONCLUSIONS: HCV core Ag assay is a cost-effective, practically feasible substitute of HCV RTPCR viral load assay for diagnosis as well as long duration treatment monitoring of hepatitis C infection in resource-limited settings.

Can Radiological Tumour Thickness Predict Pathological Prognostic Factors in Clinicoradiologically Node-Negative Oral Squamous Carcinoma? A Prospective Study.

Background: This research investigates potential connections between radiological tumour thickness determined by CT scans and various pathological prognostic factors. These factors include pathological tumour thickness (pTT), pathological depth of invasion (DOI), and positive cervical nodal metastasis. This analysis focuses on cases of clinicoradiologically node-negative squamous cell carcinoma of the buccal mucosa. Method: Sixty-one previously untreated clinicoradiologically node-negative squamous cell carcinoma of buccal mucosa were included in the study. The radiological tumour thickness in the preoperative CT scans is correlated with other prognostic factors like pathological tumour thickness, DOI and presence or absence of neck node. Result: Sixty-one patients were included in the study with a median age of 54 years (Range 27-84). Forty-two patients (68.9%) were male, and 19 were females (31.1%). There was no statistically significant difference in mean values of rTT among patients with positive or negative post-operative nodal metastases. However, a significant correlation could be established with rTT to other potential prognostic factors. Conclusion: Tumor thickness in preoperative CT scans can be used to predict post-operative prognostic factors in oral squamous cell carcinoma.

An assessment of the impact of traditional rice cooking practice and eating habits on arsenic and iron transfer into the food chain of smallholders of Indo-Gangetic plain of South-Asia: Using AMMI and Monte-Carlo simulation model.

The current study was designed to investigate the consequences of rice cooking and soaking of cooked rice (CR) with or without arsenic (As) contaminated water on As and Fe (iron) transfer to the human body along with associated health risk assessment using additive main-effects and multiplicative interaction (AMMI) and Monte Carlo Simulation model. In comparison to raw rice, As content in cooked rice (CR) and soaked cooked rice (SCR) enhanced significantly (at p < 0.05 level), regardless of rice cultivars and locations (at p < 0.05 level) due to the use of As-rich water for cooking and soaking purposes. Whereas As content in CR and SCR was reduced significantly due to the use of As-free water for cooking and soaking purposes. The use of As-free water (AFW) also enhanced the Fe content in CR. The overnight soaking of rice invariably enhanced the Fe content despite the use of As-contaminated water in SCR however, comparatively in lesser amount than As-free rice. In the studied area, due to consumption of As-rich CR and SCR children are more vulnerable to health hazards than adults. Consumption of SCR (prepared with AFW) could be an effective method to minimize As transmission and Fe enrichment among consumers.

Poly(acrylamide)-co-poly(hydroxyethyl)methacrylate-co-poly(cyclohexyl methacrylate) hydrogel platform for stability, storage and biocatalytic applications of urease.

In our present work, an explicit crosslinked thermo-responsive hydrogel platform has been developed, by using polyacrylamide (PAAm), poly(2-hydroxyethyl methacrylate) (PHEMA) and poly(cyclohexyl methacrylate) (PCHMA), and then coupled with urease to yield bioconjugates (BCs). Synergic effect of these polymer units provides thermoresponsive nature, optimum crosslinking with desired swelling behaviour, and stability and improved catalytic to Urease in the resultant BCs. Synthesis of the terpolymer has been achieved by employing HEMA (monomer as well as crosslinker), instead of using the conventional crosslinkers, through free radical solution polymerization technique. Various grades of TRPUBs have been fabricated by varying HEMA and CHMA contents while keeping fixed amounts of AAm. Further, the structural analysis of BCs has been done by fourier transform infra-red spectroscopic study and their thermal stabilities have been studied by thermogravimetric analysis. Urea present in TRPUBs has beenanalysed for its hydrolysis atdifferent temperatures viz., 25 °C, 45 °C and 70 °C. Further, the effect of crosslinking, temperature and reaction time on catalytic activities of TRPUBs has been studied. TRPUBs grades have showna maximum swelling capacity up to 5200 %; excellent catalytic activity even at 70 °C; and 85 % activity retention after 18 days storage in buffer medium.

Generation and Application of Aryl Radicals Under Photoinduced Conditions.

Photoinduced aryl radical generation is a powerful strategy in organic synthesis that facilitates the formation of diverse carbon-carbon and carbon-heteroatom bonds.  The synthetic applications of photoinduced aryl radical formation in the synthesis of complex organic compounds, including natural products, physiologically significant molecules, and functional materials, have received immense attention. An overview of current developments in photoinduced aryl radical production methods and their uses in organic synthesis is given in this article. A generalized idea of how to choose the reagents and approach for the generation of aryl radicals is described, along with photoinduced techniques and associated mechanistic insights. Overall, this article offers a critical assessment of the mechanistic results as well as the selection of reaction parameters for specific reagents in the context of radical cascades, cross-coupling reactions, aryl radical functionalization, and selective C-H functionalization of aryl substrates.

Peeping Beyond TNM Stage: Prognostic Factors Affecting Oncological Outcomes in Surgically Treated Early Oral Cancer.

Surgery is the primary modality for the treatment of early oral cancer. The present study aims to evaluate the oncological outcomes, patterns of failure, and prognostic predictors of recurrence in patients of early oral cancer (Stage I and II) treated by surgery alone. It is a single institutional, observational retrospective cohort study conducted from 2012 to 2017.The study was approved by institutional ethics committee. All consecutive patients who underwent upfront curative surgery alone (wide excision of tumour + neck dissection) for pathologically proven early oral cavity SCC(Squamous Cell Carcinoma) pT1-2N0 were included in the study. 113 patients were included in the study after a median follow-up of 58.2 months. The median age was 58.5 years. 25 patients were stage I, and 88 patients were stage II. The most common subsite was buccal mucosa. There were 31 recurrences and 24 deaths. Using Kaplan Meier method, 3 and 5 year overall survival was 92% and 71.8%, respectively, while 3 year and 5 year recurrence-free survival was 77.9% and 69.4%, respectively. Perineural invasion and poor differentiation affected recurrence-free survival significantly (p value < 0.05). More than one-fourth of surgically treated early oral SCC patients developed recurrence. Presence of poorly differentiated histology and the perineural invasion were the high risk factors which hampered the recurrence free survival. High consumption of betel quid consumption in this part of the world leads to differences in the involved subsite from the Western literature. Adding adjuvant treatment in the presence of these adverse histopathological features may improve prognosis. Randomised studies are warranted to answer this dilemma. Level of Evidence IV.

Intelligent deep learning-based disease monitoring system in 5G network using multi-disease big data.

Recently, real-world disease monitoring techniques designed based on wearable medical equipment efficiently minimize the mortality rate. Initially, the data are manually collected from the patients to predict five diseases using 5 G frameworks. Then, the collected data are pre-processed to obtain high-quality data using the techniques like contrast enhancement, median filtering, fill empty space, remove repeated value and stemming. The pre-processed data are taken for extracting the features using a One-Dimensional Convolutional Neural Network (1D-CNN) to obtain the deep features. The parameters like hidden neuron count and epoch are tuned by the proposed Modified Predator Presence Probability-based Squirrel Search-Glowworm Swarm Optimization (MPPP-SSGSO) algorithm to enhance the variance. Then, the extracted features acquired using the 1D-CNN are given to the ensemble boosting-based models for predicting the score, which is combined by comprising approaches like Adaptive Boosting (AdaBoost), eXtreme Gradient Boosting (XGBoost) and Category Boosting (CatBoost). Further, the predicted scores obtained from such models are concatenated and passed to the Ensemble Boosting Scores-based Fuzzy Classifier (EBS-FC) for classifying the five different diseases. Here, the membership function of the fuzzy is optimized by the same developed MPPP-SSGSO algorithm for enhancing accuracy. Experiments are conducted, and validation is performed, which showcased that the recommended framework achieved a better outcome rate than the conventional techniques. Finally, the suggested strategy outperforms the current state-of-the-art methods with an accuracy rate of 91.34%.Communicated by Ramaswamy H. Sarma.

Extending the theory of planned behavior to envisage social distancing behavior in containing the COVID-19 outbreak.

The study investigates the antecedents that influence social distancing behavior during the COVID-19 outbreak and develops a hypothetical model integrating additional pertinent variables into the classic theory of planned behavior (TPB) to grasp the social distancing behavior accurately. The extended model was investigated employing structural equation modeling using the data collected through Snowball Technology from 331 respondents. The results unearth significant influences of all the predictor variables on their outcome variables. Surprisingly, the supportive government strategy has no crucial impact on perceived behavioral control toward social distancing. Furthermore, the study reports no trivial difference between young and old and high-low income groups on the intention-actual social distancing. The study outlines policy interventions to prevent mass transmission of the COVID-19 catastrophe. Lastly, limitations are specified to open up novel insights for future researchers.

Identification of primary metabolites in fungal species of Trichophyton mentagrophyte and Trichophyton rubrum by NMR spectroscopy.

BACKGROUND: Superficial mycoses are fungal infections limited to the outermost layers of the skin and its appendages. The chief causative agents of these mycoses are dermatophytes and yeasts. The diagnosis of dermatophytosis can be made by direct mycological examination with potassium hydroxide (10%-30%) of biological material obtained from patients with suspected mycosis, providing results more rapid than fungal cultures, which may take days or weeks. This information, together with clinical history and laboratory diagnosis, ensures that the appropriate treatment is initiated promptly. However, false negative results are obtained in 5%-15%, by conventional methods of diagnosis of dermatophytosis. OBJECTIVES: To study the metabolic profiles of the commonly occurring dermatophytes by NMR spectroscopy. PATIENTS/MATERIALS: We have used 1D and 2D Nuclear Magnetic Resonance (NMR) experiments along with Human Metabolome Database (HMDB) and Chenomx database search for identification of primary metabolites in the methanol extract of two fungal species: Trichophyton mentagrophyte (T. mentagrophyte) and Trichophyton rubrum (T. rubrum). Both standard strains and representative number of clinical isolates of these two species were investigated. Further, metabolic profiles obtained were analysed using multivariate analysis. RESULTS: We have identified 23 metabolites in the T. mentagrophyte and another 23 metabolites in T. rubrum. Many important metabolites like trehalose, proline, mannitol, acetate, GABA and several other amino acids were detected, which provide the necessary components for fungal growth and metabolism. Altered metabolites were defined between Trichophyton mentagrophyte and T. rubrum strains. CONCLUSION: We have detected many metabolites in the two fungal species T. mentagrophyte and T. rubrum by using NMR spectroscopy. NMR spectroscopy provides a holistic snapshot of the metabolome of an organism. Key metabolic differences were identified between the two fungal strains. We need to perform more studies on metabolite profiling of the samples from these species for their rapid diagnosis and prompt treatment.

IADVL SIG Recalcitrant Dermatophytosis Position Statement on Super Bioavailable Itraconazole.

Itraconazole (ITZ) has been the mainstay of oral antifungal treatment for the current epidemic of recalcitrant dermatophytosis (RD) in India. Recently, a newer formulation of ITZ, super bioavailable itraconazole (SUBA-ITZ), is made available in the market by many pharmaceutical companies. It is important for dermatologists to understand the pharmacokinetic properties of SUBA-ITZ vis-a-vis conventional pellet formulation to use it effectively and safely. Indian Association of Dermatologists, Venereologists and Leprologists (IADVL) has established a special interest group for recalcitrant dermatophytosis (SIG-RD) to strengthen research, continuing medical education, and industry collaboration on the subject. This position statement on SUBA-ITZ by SIG-RD is an attempt to address current pieces of evidence and the position of this new formulation in the management of RD.

Selenium - An environmentally friendly micronutrient in agroecosystem in the modern era: An overview of 50-year findings.

Agricultural productivity is constantly being forced to maintain yield stability to feed the enormously growing world population. However, shrinking arable and nutrient-deprived soil and abiotic and biotic stressor (s) in different magnitudes put additional challenges to achieving global food security. Though well-defined, the concept of macro, micronutrients, and beneficial elements is from a plant nutritional perspective. Among various micronutrients, selenium (Se) is essential in small amounts for the life cycle of organisms, including crops. Selenium has the potential to improve soil health, leading to the improvement of productivity and crop quality. However, Se possesses an immense encouraging phenomenon when supplied within the threshold limit, also having wide variations. The supplementation of Se has exhibited promising outcomes in lessening biotic and abiotic stress in various crops. Besides, bulk form, nano-Se, and biogenic-Se also revealed some merits and limitations. Literature suggests that the possibilities of biogenic-Se in stress alleviation and fortifying foods are encouraging. In this article, apart from adopting a combination of a conventional extensive review of the literature and bibliometric analysis, the authors have assessed the journey of Se in the "soil to spoon" perspective in a diverse agroecosystem to highlight the research gap area. There is no doubt that the time has come to seriously consider the tag of beneficial elements associated with Se, especially in the drastic global climate change era.

Topical and Systemic Therapies in Melasma: A Systematic Review.

Introduction: Melasma is an acquired disorder, which presents with well-demarcated, brown-colored hyperpigmented macules, commonly involving the sun-exposed areas such as the face. It is a chronic and distressing condition, affecting the patients' quality of life, and has been conventionally treated with "first-line" agents including hydroquinone (HQ) alone or as a part of a triple combination cream (TCC), while "second-line" options include chemical peels, and third line options include laser therapy. Materials and Methods: A systematic search was performed for all topical and systemic treatments for melasma up till May 4, 2021, using the PubMed and EMBASE databases, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol. The search terms "melasma" and "treatment" were used to search for the relevant articles on both these databases, and a total of 4020 articles were identified. After removing the duplicate entries and screening the titles, abstracts, and full-text articles, we identified 174 randomized controlled trials (RCTs) or controlled clinical trials. Results: Based on our review, HQ, TCCs, sunscreens, kojic acid (KA), and azelaic acid receive grade A recommendation. Further large-scale studies are required to clearly establish the efficacy of topical vitamin C, resorcinol, and topical tranexamic acid (TXA). Several newer topical agents may play a role only as an add-on or second-line drugs or as maintenance therapy. Oral TXA has a strong recommendation, provided there are no contraindications. Procyanidins, Polypodium leucotomos (PL), and even synbiotics may be taken as adjuncts. Discussion: Several newer topical and systemic agents with multimodal mechanisms of action have now become available, and the balance seems to be tipping in favor of these innovative modalities. However, it is worth mentioning that the choice of agent should be individualized and subject to availability in a particular country.

Comparative Efficacy and Safety of Super-Bioavailable Itraconazole-130 mg Once Daily in Obese and Non-Obese Patients of Glabrous Tinea.

Background: Obesity is considered one of the risk factors for dermatophytosis and warrants systemic therapy. Itraconazole is the most commonly used antifungal, but owing to pharmacokinetic challenges, super-bioavailable itraconazole (SITZ) was approved globally, recently. For the management of dermatophytosis in obese patients, there are mixed opinions regarding the dosing of systemic antifungals. Materials and Methods: This study was conducted to compare the efficacy and safety of SITZ-130 mg once daily in glabrous tinea or dermatophytosis in obese and non-obese patients for a total duration of 10 weeks on 87 eligible patients. Efficacy and safety assessments were done at weeks 3 and 6 with follow-up at week 10 for relapse. The primary objective was to assess the proportion of patients achieving complete cure at week 6 with the assessment of safety, clinical, and mycological cure rates as secondary objectives. Results: Out of 87 patients, 80 were considered for analysis. At week 6, 22/35 (63%) and 33/45 (73%) patients in obese and non-obese groups were completely cured (P = 0.47). Similarly, there was no statistically significant difference for mycological and clinical cure in both the groups (P = 0.17 and P = 0.61, respectively). Four patients in the obese group (18% of completely cured), while one patient in the non-obese group (3% of completely cured), relapsed within 4 weeks of completion of treatment (P = 0.14). The therapy was well tolerated by both groups, with only one patient in the non-obese group experiencing pruritus. Conclusion: SITZ-130 mg once daily achieved desired and similar clinical response in obese patients as of non-obese patients suffering from dermatophytosis, and hence, a higher dose may not require in obesity.

Red Flaging Unscientific Prescriptions in Dermatophytosis: An Overview.

Dermatophytosis has acquired an epidemic-like proportion, fuelling a wide gamut of irrational, unethical and unscientific prescriptions. The menace can be attributed to poorly regulated legislative laws controlling the approval of molecules, unscientific marketing gimmicks by the pharmaceutical industry, over-the-counter availability of drugs and lack of awareness and knowledge among the prescribing physicians. In this review, we have attempted to enlist the irrational and unethical prescription patterns for dermatophytosis.

Newer Therapies in Dermatophytosis.

With the advent of newer drugs and formulations, the armamentarium to combat dermatophytosis is ever-expanding. However, we must be rational and scientific when choosing the drugs. This review is an attempt to summarise the recently approved and upcoming therapeutic options for dermatophytosis.

Chondroblastic Osteosarcoma of the Maxilla with Poor Response to Neoadjuvant Chemotherapy: A Rare Case Report and Updated Review of Literature.

Craniofacial osteosarcoma is a relatively rare disease entity. In the craniofacial region, mandible is the commonest site followed by maxilla and skull bone. Due to its rare occurrence standard treatment guidelines are not formulated as in long bone or extremity sarcoma. Here we have reported a locally advanced case of a maxillary osteosarcoma of chondroblastic variant who was initially considered for neoadjuvant chemotherapy. However there was radiological evience of disease progression. Then the patient was considered for surgery followed by adjuvant radiotherapy. A literature review of the published cases of maxillary chondroblastic osteosarcoma has also been done here.

Orbital Exenteration: Tumour Diversity and Survival-Report from a Cancer Centre of Northeast India.

Orbital exenteration is a mutilating surgery which involves the removal of the entire contents of the bony orbit, including the globe, extraocular muscles and periorbital fat, and many times includes the eyelids. Since it leads to severe disfigurement, it is an infrequent procedure largely indicated in malignant conditions. The current study aims to report the clinicodemographic profile and treatment outcome of orbital exenteration patients done in a cancer care center in Northeast India. This is a hospital-based retrospective study between January 2017 and December 2021, including patients undergoing orbital exenteration. All patient and treatment-related data were retrieved from the record of hospital files. A total of 18 patients were included in the study. The mean age of the patients was 51 ± 18 years and male: female ratio was 1:1. Most patients had primary in orbit (55.6%). The most common histology was squamous cell carcinoma, (8/18, 44.4%), followed by basal cell carcinoma (two patients, 11.1%). After a median follow-up was 25 months (range 3-92), the median DFS of the study population was 31.4 months. The five-year overall survival of the patients was 54%. Orbital exenteration is an infrequent surgery due to the associated disfigurement and hence reserved for conditions where eye preservation is impossible. We tried to report the experience of orbital exenteration from a single cancer center for five years.

Efficacy of Super-Bioavailable Itraconazole and Conventional Itraconazole at Different Dosing Regimens in Glabrous Tinea Infection - A Randomized Clinical Trial.

Introduction: Itraconazole follows non-linear pharmacokinetics and hence is recommended once daily, but in real-world practice, is commonly prescribed as twice daily. Hence, this study aimed to evaluate the efficacy and safety of super-bioavailable-itraconazole-130 mg (SB-130) and conventional-itraconazole-200 mg (CITZ-200) once daily compared with conventional-itraconazole-100 mg (CITZ-100) twice daily in glabrous tinea. Methods: A total of 261 eligible patients were enrolled in this prospective, randomized, clinical study from December-2021 to August-2022 at seven centers in India. Efficacy and safety assessments were done at week-3 and 6, with follow-up at week-10 for relapse. The primary objective was to assess the proportion of patients who achieved complete cure at week-6 following treatment in all itraconazole groups. The secondary outcomes were safety and clinical and mycological cure rates. Results: Of 261 patients, 240 were included in the analysis. At week-6, 140 patients were completely cured; thus, overall cure rate was 58.33%. Fifty-five patients (69%) in SB-130 while 47/77 (61%) and 38/83 (46%) patients were completely cured in CITZ-200 and CITZ-100 groups respectively (p<0.05; SB-130: CITZ-100, p=0.32; SB-130: CITZ-200, p=0.058; CITZ-200: CITZ-100). There was no statistical difference in the mycological cure rate and area clearance rate between any of the groups (p=0.14); however, a statistically significant difference was noted for OD dosing over BD dosing in achieving clinical cure rates (p<0.05). A total of 13/140 patients (9%) relapsed following complete cure, with no statistically significant difference between any of the groups (p=0.50). All treatments were safe and well-tolerated, with no discontinuation. Conclusion: In this clinical study, moderate efficacy with all doses of ITZ was reported but was better with OD dosing. Although there was no statistical difference between SB-130 and CITZ-200, SB-130 may be preferred over CITZ-200 owing to the advantage of SB over the conventional ITZ.