Evaluation of risk factors, clinico-radiographic presentations of COVID-associated mucormycosis in the maxillofacial region reporting to a tertiary care dental facility.

Purpose: To evaluate the prevalence of risk factors associated with COVID-associated mucormycosis (CAM) in the maxillofacial region with emphasis on clinical and radiological characteristics of the disease reporting to the dentists. Methods: Archival records of the patients diagnosed with rhino-cerebral mucormycosis through histopathology or culture, were screened and 266 records were included. These records were divided into three groups-previously diabetic (PD, n = 122), recently diagnosed diabetic (RD, n = 105) and non-diabetic (ND, n = 39). All the records were evaluated and compared among the three groups for the duration of presentation, history of co-existing medical conditions, the association of treatment given during COVID-19, and the clinical and radiographic presentations of the disease. Results: The results confirmed uncontrolled diabetes mellitus as the major risk factor for the disease. The prevalence of steroid administration was lower in our study in contrast to previous literature. The risk factors and treatment rendered during COVID-19 did not differ significantly among the three groups (p > 0.05). The findings indicate that the disease was milder and progressed more slowly in the ND group, both clinically and radiographically, and it had close resemblance to odontogenic infection. Conclusion: Patients with early CAM mimicked the odontogenic infection and were more likely to report in a dental setup. Hence, a multidisciplinary and holistic management approach is necessary.

Mucor infection associated with global COVID-19 pandemic - an institutional histopathological study

Background: Coronavirus disease 2019 (COVID-19) in the recent times have instilled signs of immunosuppression globally which has further precipitated increasing range of opportunistic infections. Mucormycosis is a distressing opportunistic fungal infection with a high incidence and is the third commonest acute invasive infection following candidiasis and aspergillosis. The aim of the present observational study is to delineate the enigmatic histopathological profile between mucormycosis cases seen prior to pandemic (PPM) and pandemic associated mucormycosis (PAM). Material and methods: Tissue archives of 105 histopathologically diagnosed cases of mucormycosis were included and analysed for demographical details and histopathological parameters like fungal load and localization, granuloma formation, necrosis, inflammatory infiltrate and tissue invasion. Results: 0ut of 105 included cases, 11/105 (10.48%) were reported PPM and 94/105 (89.52%) PAM. Among 94 cases of PAM, 51/94 (54%) cases also showed COVID-19 positivity, while 43/94 (46%) did not. Of all the histological variables, increased fungal load and necrosis were observed in PAM relative to PPM cases. Conclusions: The histopathological variables like fungal load, necrosis, granuloma formation and tissue invasion, could help the clinician in assessing the clinical status at the time of tissue diagnosis and improve the treatment accordingly. (AU)

Comparative Efficacy of Platelet-Rich Plasma and Dry Needling for Management of Trigger Points in Masseter Muscle in Myofascial Pain Syndrome Patients: A Randomized Controlled Trial.

AIMS: To compare the efficacy of platelet-rich plasma (PRP) injection vs dry needling (DN) for management of trigger points in the masseter muscle in myofascial pain syndrome (MPS) patients. METHODS: This randomized controlled trial included 30 clinically confirmed cases of myofascial trigger points (MTrPs) in the masseter muscle who were randomly and equally (1:1) assigned to the test (PRP) and control (DN) groups. Both groups were evaluated for pain (visual analog scale [VAS]), range of functional movements, need for pain medication, patient satisfaction (Likert scale), and sleep (VAS) at baseline and 2-week, 1-month, and 3-month follow-ups. VAS pain and Likert score were also obtained at 6-month intervals. RESULTS: The use of PRP solution in MTrPs in MPS patients had a better effect on pain and patient satisfaction compared to DN. CONCLUSION: PRP appears to be a more effective treatment modality compared to DN in the management of MTrPs in MPS patients.

Adiponectin to Leptin Ratio and its Association with Insulin Resistance in Women with Polycystic Ovarian Syndrome.

Background: Adiponectin and leptin play a major role in metabolic homeostasis. Adiponectin to Leptin ratio can be used as an indicator of insulin resistance and a marker of polycystic ovarian syndrome (PCOS). The study was planned to compare serum adiponectin, leptin, and adiponectin to leptin ratio in age and BMI matched women with and without PCOS and to find out the association of adiponectin to leptin ratio with Insulin resistance in these women. Methods: It was a cross-sectional study done in the Gynecology outpatient clinic in a tertiary care center. A total of 120 women, 60 with PCOS and 60 age and BMI matched women without PCOS, who presented in the clinic after the index cases were enrolled and tested for serum adiponectin, leptin, and insulin sensitivity. The main outcome measures were serum levels of adiponectin, leptin, adiponectin to leptin ratio, oral glucose tolerance test, serum insulin and HOMA-IR. Results: PCOS women had lower serum Adiponectin, higher serum Leptin level and lower Adiponectin to Leptin ratio compared to non PCOS women, 2.15 ± 3.07 ng/ml vs 10.7 ± 27.91 ng/ml, P < 0.0001; 24.25 ± 16.5 ng/ml vs 13.89 ± 11.19 ng/ml, P = 0.0003 and 0.15 ± 0.24 vs 3.03 ± 15.04, P < 0.0001, respectively. Plasma glucose 2 hours after 75 gm glucose and serum Insulin was significantly increased in PCOS women (108.78 ± 10.22 mg/dl vs 100.18 ± 4.89 mg/dl, P = 0.001 and 5.7 ± 9.53 mU/ml vs 3.02 ± 5.34 mU/ml, P = 0.02, respectively). The mean values of fasting plasma glucose and HOMA-IR were comparable in both groups, P = 0.145, P = 0.719, respectively. There was no significant association of A/L Ratio with BMI, plasma glucose 2 hours after 75 gm glucose, serum Insulin and HOMA-IR, in these women, r = -0.074, P = 0.5754; r = -0.203, P = 0.12; r = -0.018, P = 0.8915; and r = -0.041, P = 0.757, respectively. Conclusion: Adiponectin to leptin ratio is significantly reduced in women with PCOS but has no association with insulin resistance.

Identification of End-User Economical Relationship Graph Using Lightweight Blockchain-Based BERT Model.

Current methods for extracting information from user resumes do not work well with unstructured user resumes in economic announcements, and they do not work well with documents that have the same users in them. Unstructured user information is turned into structured user information templates in this study. It also proposes a way to build person relationship graphs in the field of economics. First, the lightweight blockchain-based BERT model (B-BERT) is trained. The learned B-BERT pretraining model is then utilized to get the event instance vector, categorize it appropriately, and populate the hierarchical user information templates with accurate user characteristics. The aim of this research is that it has investigated the approach of creating character connection graphs in the Chinese financial system and suggests a framework for doing so in the economic sector. Furthermore, the relationship between users is found through the filled-in user information template, and a graph of user relationships is made. This is how it works: finally, the experiment is checked by filling in a manually annotated dataset. In tests, the method can be used to get text information from unstructured economic user resumes and build a relationship map of people in the financial field. The experimental results show that the proposed approach is capable of efficiently retrieving information from unstructured financial personnel resume text and generating a character relationship graph in the economic sphere.

Are Low Serum Vitamin D Levels a Risk Factor for Advent of COVID-19 Associated Rhinocerebral Mucormycosis: A Preliminary Case Control Study.

To determine whether low serum vitamin D level is a risk factor for development of Rhinocerebral mucormycosis in COVID-19 afflicted patients. A case control study was conducted in a tertiary care hospital utilizing the archived records of COVID-19 afflicted Rhinocerebral mucormycosis cases and age and gender matched controls. The mean value (± standard deviation) of vitamin D level in patients with Mucormycosis was 19.65 ± 13.07 ng/ml and in control subjects it was 27.88 ± 18.04 ng/ml.There was a significant difference between groups (p = 0.02). Thus, low Vitamin D level may be implicated as a risk factor for the advent of mucormycosis in a COVID-19 afflicted patient and therefore Vitamin D supplements may be provided to such patients to achieve normal serum levels.

Association of COVID-19 with Rhino-Cerebral Mucormycosis: An Observational Study.

Mucormycosis is becoming more common in patients infected with or recovering from COVID-19 under the current situation. However, there is a scarcity of research on a specific group of COVID-19 individuals who are predisposed to mucormycosis. As a result, a retrospective observational study was undertaken to assess the possible connection of mucormycosis with COVID-19. The goal was also to investigate the link between diabetes mellitus, mucormycosis and COVID-19. The occurrence and severity of the disease among the case records were assessed using signs and symptoms, investigations conducted during COVID-19, and serological test results. Patients were classified as previously known diabetics, recently diagnosed diabetics, or non-diabetics based on their history of pre-existing DM and HBA1c levels at the time of reporting for mucormycosis. The findings show that mild COVID-19-infected patients and non-diabetic patients have a high incidence of COVID-19-associated mucormycosis (CAM). As a result, all clinicians participating in the care of COVID-infected patients must be aware of the significant risk of secondary mucormycosis in the post-recovery phase, even in those with mild or moderate symptoms.

Cytochrome P4504f, a potential therapeutic target limiting neuroinflammation.

Inflammatory processes are involved in the pathogenesis and/or progression of acute central nervous system (CNS) infection, traumatic brain injury and neurodegenerative disorders among others indicating the need for novel strategies to limit neuroinflammation. Eicosanoids including leukotrienes, particularly leukotriene B(4) (LTB(4)) are principle mediator(s) of inflammatory response, initiating and amplifying the generation of cytokines and chemokines. Cytochrome P450 (Cyp), a family of heme proteins mediate metabolism of xenobiotics and endogenous compounds, such as eicosanoids and leukotrienes. Cytochrome P4504F (Cyp4f) subfamily includes five functional enzymes in mouse. We cloned and expressed the mouse Cyp4f enzymes, assayed their relative expression in brain and examined their ability to hydroxylate the inflammatory cascade prompt LTB(4) to its inactive 20-hydroxylated product. We then examined the role of Cyp4fs in regulating inflammatory response in vitro, in microglial cells and in vivo, in mouse brain using lipopolysacharide (LPS), as a model compound to generate inflammatory response. We demonstrate that mouse brain Cyp4fs are expressed ubiquitously in several cell types in the brain, including neurons and microglia, and modulate inflammatory response triggered by LPS, in vivo and in microglial cells, in vitro through metabolism of LTB(4) to the inactive 20-hydroxy LTB(4). Chemical inhibitor or shRNA to Cyp4fs enhance and inducer of Cyp4fs attenuates inflammatory response. Further, induction of Cyp4f expression lowers LTB(4) levels and affords neuroprotection in microglial cells or mice exposed to LPS. Thus, catalytic activity of Cyp4fs is a novel target for modulating neuroinflammation through hydroxylation of LTB(4).

Microscopic colitis in patients presenting with chronic diarrhea.

AIM: To investigate the prevalence of microscopic colitis among patients presenting with chronic watery diarrhea. MATERIAL AND METHODS: Colonic biopsies from 400 patients presenting with chronic watery diarrhea and other symptoms pertaining to lower gastrointestinal tract were studied. After a detailed clinical history and thorough physical examination full length colonoscopy was done using flexible colonoscope. Colonic biopsies were taken from abnormal and normal areas. Three to five micron thick sections were cut and stained with hematoxylin and eosin and Masson's trichrome stain to highlight sub epithelial collagen. RESULTS: Fifteen out of 400 (3.7%) colonic biopsies from patients presenting with chronic diarrhea had evidence of microscopic colitis. Five out of fifteen biopsies (33%) were diagnosed as collagenous colitis, 10 biopsies (67%) had evidence of lymphocytic colitis; 14/400(3.5%) histologically normal biopsies were taken as controls to compare various demographic and risk factors. Ten out of 15 patients (67%) were clinically diagnosed as irritable bowel syndrome. In the remaining five an infective etiology was suspected. On colonoscopy12/15 (80%) had no abnormality and 3/15 (20%) had mild hyperemia. CONCLUSION: A possibility of microscopic colitis should be considered while examining colonoscopic biopsy of a patient with chronic watery diarrhea and normal colonoscopy to avoid the misdiagnosis that may affect the treatment of patients.

Expression of mu- and delta-opioid receptors in song control regions of adult male zebra finches (Taenopygia guttata).

The opioid system is known to play a role in various aspects of learning and memory in diverse species of mammals and birds. Earlier studies have localized the endogenous opioids, met- and leu-enkephalin, in the song control regions of male zebra finches (Taenopygia guttata), a sexually dimorphic species of songbirds wherein only males sing. Recent research has shown that levels of enkephalin increase in some of the song control regions during singing and that blocking opioid receptors with the antagonist naloxone decreases the frequency of singing in songbirds. However, the distribution of receptors specific to the opioid system has not been studied in zebra finches. In the present study, we used reverse transcriptase PCR (RT-PCR) and quantitative real-time PCR (qRT-PCR) to demonstrate that the song control regions lateral magnocellular nucleus of the anterior nidopallium (LMAN), Area X, MSt (medial striatum), HVC and RA (robust nucleus of the arcopallium) expressed higher levels of mu-OR mRNA compared to delta-OR mRNA. In situ hybridization was used to demonstrate that neither LMAN nor Area X could be delineated from the surrounding brain regions [anterior nidopallium (ANP) and MSt, respectively], based on OR mRNA expression. However, HVC and RA neurons expressed marginally higher levels of mu-OR mRNA compared to the posterior nidopallium, which was confirmed by immunohistochemical localization. We also found that the dorsolateral subdivision of DLM (dorsolateral nucleus of the medial thalamus) demonstrated high levels of mu-OR immunoreactivity. Our results suggest that the ORs may be involved in modulating different aspects of vocalization and/or gating auditory input, as well as motor control.

Drug metabolism in human brain: high levels of cytochrome P4503A43 in brain and metabolism of anti-anxiety drug alprazolam to its active metabolite.

Cytochrome P450 (P450) is a super-family of drug metabolizing enzymes. P450 enzymes have dual function; they can metabolize drugs to pharmacologically inactive metabolites facilitating their excretion or biotransform them to pharmacologically active metabolites which may have longer half-life than the parent drug. The variable pharmacological response to psychoactive drugs typically seen in population groups is often not accountable by considering dissimilarities in hepatic metabolism. Metabolism in brain specific nuclei may play a role in pharmacological modulation of drugs acting on the CNS and help explain some of the diverse response to these drugs seen in patient population. P450 enzymes are also present in brain where drug metabolism can take place and modify therapeutic action of drugs at the site of action. We have earlier demonstrated an intrinsic difference in the biotransformation of alprazolam (ALP) in brain and liver, relatively more alpha-hydroxy alprazolam (alpha-OHALP) is formed in brain as compared to liver. In the present study we show that recombinant CYP3A43 metabolizes ALP to both alpha-OHALP and 4-hydroxy alprazolam (4-OHALP) while CYP3A4 metabolizes ALP predominantly to its inactive metabolite, 4-OHALP. The expression of CYP3A43 mRNA in human brain samples correlates with formation of relatively higher levels of alpha-OH ALP indicating that individuals who express higher levels of CYP3A43 in the brain would generate larger amounts of alpha-OHALP. Further, the expression of CYP3A43 was relatively higher in brain as compared to liver across different ethnic populations. Since CYP3A enzymes play a prominent role in the metabolism of drugs, the higher expression of CYP3A43 would generate metabolite profile of drugs differentially in human brain and thus impact the pharmacodynamics of psychoactive drugs at the site of action.

Activation of apoptosis signal regulating kinase 1 (ASK1) and translocation of death-associated protein, Daxx, in substantia nigra pars compacta in a mouse model of Parkinson's disease: protection by alpha-lipoic acid.

Parkinson's disease (PD), a neurodegenerative disorder, causes severe motor impairment due to loss of dopaminergic neurons in substantia nigra pars compacta (SNpc). MPTP, a neurotoxin that causes dopaminergic cell loss in mice, was used in an animal model to study the pathogenic mechanisms leading to neurodegeneration. We observed the activation of apoptosis signal regulating kinase (ASK1, MAPKKK) and phosphorylation of its downstream targets MKK4 and JNK, 12 h after administration of a single dose of MPTP. Further, Daxx, the death-associated protein, translocated to the cytosol selectively in SNpc neurons seemingly due to MPTP mediated down-regulation of DJ-1, the redox-sensitive protein that binds Daxx in the nucleus. Coadministration of alpha-lipoic acid (ALA), a thiol antioxidant, abolished the activation of ASK1 and phosphorylation of downstream kinases, MKK4, and JNK and prevented the down-regulation of DJ-1 and translocation of Daxx to the cytosol seen after MPTP. ALA also attenuated dopaminergic cell loss in SNpc seen after subchronic MPTP treatment. Our studies demonstrate for the first time that MPTP triggers death signaling pathway by activating ASK1 and translocating Daxx, in vivo, in dopaminergic neurons in SNpc of mice and thiol antioxidants, such as ALA terminate this cascade and afford neuroprotection.