Atypical Case of Highly Mutated h-TERT Promoter in Germline Genome from Buccal Mucosa Cancer.

Buccal mucosa cancer has an aggressive nature as it rapidly grows and penetrates with high recurrence rate. Strikingly, carcinoma of buccal mucosa is the most common cancer of oral cavity in India. Recently, telomerase and telomere biology have been implicated in the pathogenesis and progression in various cancers via regulation of telomere maintenance by telomerase expression which is controlled by telomerase reverse transcriptase (TERT) promoter. Strikingly, h-TERT promoter mutations have been incriminated in regulation of telomerase gene expression. Here, we present a 35 years old male with intense coughing, short breathlessness and fever since 15 days, was admitted to the pulmonary unit. He was a chronic smoker and gutka user. The cytopathological analysis of gastric aspirate revealed buccal mucosa carcinoma of IV stage. We identified h-TERT promoter mutations in isolated genomic DNA from whole blood using DNA sequencer. Genetic analysis disclosed that h-TERT promoter region was highly mutated in this patient. Identified mutations include C.-248 del G, C.-272 del G, C.-279 del G, C.-331 del G, C.-349 del G, C.-351 del C, C.-360 G > A, C.-362 T > A, C.-371 del T and C.-372 del T. Further, all identified mutations were subjected to predict the pathologic functional consequences using bioinformatics tools viz TFsitescan and CiiiDER which showed either loss or gain of transcription factors binding sites in h-TERT promoter. This is a unique case in which total 9 mutations were observed in h-TERT promoter in a single case. In conclusion, all together these mutations in h-TERT promoter may alter the epigenetics and subsequently the tenacity of binding transcription factors which are of functional significance.

Potential molecular mechanisms of zinc- and copper-mediated antiviral activity on COVID-19.

Novel coronavirus disease 2019 (COVID-19) has spread across the globe; and surprisingly, no potentially protective or therapeutic antiviral molecules are available to treat severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. However, zinc (Zn) and copper (Cu) have been shown to exert protective effects due to their antioxidant, anti-inflammatory, and antiviral properties. Therefore, it is hypothesized that supplementation with Zn and Cu alone or as an adjuvant may be beneficial with promising efficacy and a favorable safety profile to mitigate symptoms, as well as halt progression of the severe form of SARS-CoV-2 infection. The objective of this review is to discuss the proposed underlying molecular mechanisms and their implications for combating SARS-CoV-2 infection in response to Zn and Cu administration. Several clinical trials have also included the use of Zn as an adjuvant therapy with dietary regimens/antiviral drugs against COVID-19 infection. Overall, this review summarizes that nutritional intervention with Zn and Cu may offer an alternative treatment strategy by eliciting their virucidal effects through several fundamental molecular cascades, such as, modulation of immune responses, redox signaling, autophagy, and obstruction of viral entry and genome replication during SARS-CoV-2 infection.

Prediction of hospital outcome in emergency medical admissions using modified early warning score (MEWS): Indian experience.

OBJECTIVE: To evaluate the applicability of modified early warning (MEWS) Score for prediction of hospital outcomes of medical emergency patients. DESIGN: Prospective hospital based observational study. SETTING: A tertiary care level medicine emergency unit in a medical college of North India. STUDY POPULATION: 300 Patients admitted in medicine emergency. METHOD: Patients of both sexes of age more than 18 years who were admitted in medical emergency unit at MMIMSR, Ambala were evaluated. Patients who were in cardiac arrest at arrival and those who died within the first 24 hours were excluded and 300 patients were included. Modified Early Warning Score based on physiological parameters was recorded at admission for each patient and monitored over the next 24 hours in the emergency unit. Hospital outcome of the patient in terms of mortality, need for critical care, prolonged stay and uneventful discharge were recorded and correlated with MEWS scores over the first 24 hours in the emergency unit. Receiver Operating Characteristic (ROC) curves was generated to evaluate the utility of MEWS as a tool to predict patient outcome in medical emergency setting. RESULT: Of the 300 patients studied, the mean age of patients was 49 years, and the majority of the patients were male (61%). A MEWS Score of >5 at 24 hours of admission was associated significantly with in-hospital mortality of patients (p < 0.0001). The ROC (Receiver Operator Characteristic) curve revealed that in those patients who had a 24 hours MEWS >/= 5, the area under curve was (AUC) = 0.9. (95% CI: 0.95-0.98). Thus, MEWS was an effective predictor of in hospital mortality with sensitivity (78%) and specificity (94%). CONCLUSION: MEWS, a scoring system based on easily recordable physiological parameters can be used as an effective tool to triage and monitor patients in medical emergency units, to identify patients who are at greater risk of clinical deterioration and need close monitoring or early transfer for critical care or other timely interventions. Thus, application of MEWS in medical emergency units can be a useful tool to improve patient care, ensure optimal utilization of resources and prevent inappropriate discharge or neglect of sick patients.

Association of Systemic Lupus Erythematosus and Beta Thalassaemia Trait- A Case Report.

Systemic Lupus Erythematosus (SLE) is a multisystem chronic inflammatory disease of autoimmune aetiology. It has a predilection for female gender and presence of photosensitive rash over the sun exposed area gives a clue to the diagnosis. Diagnosis in a male patient with atypical manifestations is unusual and difficult. A 25-year-old male presented with fever, fatigue, vomiting, abdominal pain and loss of weight. He had sustained injury on his right arm following which he developed abscess at the trauma site and severe anaemia. Further evaluation revealed pancytopenia and peritonitis. Though peritonitis is rare in SLE, it was considered in the differential diagnosis after ruling out bacterial and tubercular peritonitis. Positive anti-dsDNA and antiSm antibodies confirmed the diagnosis. While evaluating for microcytic anaemia it was found that iron studies were normal and A2 fraction was raised in haemoglobin electrophoresis. The symptoms and laboratory parameters improved remarkably with steroid therapy. Beta thalassaemia trait is rare in patients with SLE, but when they co-exist the manifestations can be severe. High degree of suspicion is required to diagnose SLE in male patients in absence of typical photosensitive rash. Beta thalassaemia trait often does not require any treatment except genetic counseling. However empirical treatment with iron should be avoided.