Advances in Thyroid Function Tests: Precision Diagnostics and Clinical Implications.

This narrative review explores the evolving field of thyroid function testing, explicitly highlighting the significance of precision diagnostics and their substantial impact on clinical practice. Commencing with a comprehensive examination of the historical progression of thyroid diagnostics, the discourse proceeds to explore recent developments, highlighting the paramount importance of accuracy in testing methods. The primary issue under consideration is the crucial requirement for accuracy in the field of therapeutic practice. The review critically examines the problems related to the interpretation, standardization, and ethical considerations in examining advanced laboratory techniques, novel biomarkers, and state-of-the-art technologies like immunoassays, molecular testing, and automation. The focus on the paradigm shift towards precision diagnostics brings attention to the complex connection between test results and their direct influence on patient care. This investigation expands upon the incorporation of imaging and molecular diagnostics, highlighting the rising significance of precision in customizing treatment strategies. In summary, the study provides a prospective viewpoint, recognizing the persistent obstacles and highlighting the want for dependable, uniform methodologies in thyroid diagnostics. This narrative's primary objective is to guide physicians, researchers, and stakeholders in effectively navigating the intricate nature of contemporary thyroid function tests, with a particular emphasis on resolving the fundamental issue of precision.

An Uncommon Presentation of Paraneoplastic Leukemoid Reaction (PLR) in a Rare Case of Adenosquamous Carcinoma (ASC) of the Gallbladder (GB): A Case Report.

This case report describes an unusual paraneoplastic leukemoid response presenting in a rare instance of gallbladder (GB) adenosquamous carcinoma (ASC). Adenocarcinoma is the most prevalent histological subtype of GB carcinoma, which is most frequently diagnosed in people in their sixth and seventh decades of life. Adenosquamous and squamous variations are uncommon. Rarely have reports of paraneoplastic leukemoid reaction (PLR) in GB carcinoma been made; this reaction is characterized by a white cell count exceeding 50,000/mm3 in combination with solid malignancy. PLR has most commonly been found in association with lung carcinoma.  In this instance, a 40-year-old man presented with right upper abdominal pain and a total leukocyte count of 26 x 109/L. The patient was initially treated on the lines of acute cholecystitis. But when the abdominal symptoms and leukocytosis did not settle, open cholecystectomy was performed. The results of the histopathological analysis showed that the GB had adenosquamous cancer. The white cell count increased even after surgery. Leukocytosis in the patient was looked into further to rule out hematological malignancy and other possible reasons. Sadly, the patient expired before any treatment could be started. The cancer GB carcinoma is uncommon and aggressive. Despite its rarity, ASC should be included in the differential diagnosis. PLR is an unusual manifestation associated with GB carcinoma. A thorough investigation, including a complete blood count, can help identify this paraneoplastic syndrome in patients with elevated white cell counts.

Concurrent Typhoid Fever and Dengue Hemorrhagic Fever: A Case Report.

Dengue virus can co-infect with a number of viruses, bacteria, and parasites of which dengue malaria co-infection is most well-known. We report a rare case of dengue virus co-infection with typhoid fever and the development of dengue hemorrhagic fever (DHF) during a dengue outbreak. The second spike of high-grade fever following initial defervescence with antibiotic therapy, hemorrhagic manifestations, new onset leucopenia and thrombocytopenia, and evidence of plasma leakage raised suspicion of DHF. Diagnosis of dengue co-infection was made by seroconversion for anti-dengue immunoglobulin M (IgM) antibodies by enzyme-linked immunosorbent assay (ELISA) on the seventh day of new-onset fever. Early recognition and judicious use of fluid therapy prevented the patient from developing shock and its complications. Prompt diagnosis, early recognition of plasma leakage, and appropriate management of DHF can reduce morbidity and mortality.

Combined deep learning and molecular docking simulations approach identifies potentially effective FDA approved drugs for repurposing against SARS-CoV-2.

The ongoing pandemic of Coronavirus Disease 2019 (COVID-19) has posed a serious threat to global public health. Drug repurposing is a time-efficient approach to finding effective drugs against SARS-CoV-2 in this emergency. Here, we present a robust experimental design combining deep learning with molecular docking experiments to identify the most promising candidates from the list of FDA-approved drugs that can be repurposed to treat COVID-19. We have employed a deep learning-based Drug Target Interaction (DTI) model, called DeepDTA, with few improvements to predict drug-protein binding affinities, represented as KIBA scores, for 2440 FDA-approved and 8168 investigational drugs against 24 SARS-CoV-2 viral proteins. FDA-approved drugs with the highest KIBA scores were selected for molecular docking simulations. We ran around 50,000 docking simulations for 168 selected drugs against 285 total predicted and/or experimentally proven active sites of all 24 SARS-CoV-2 viral proteins. A list of 49 most promising FDA-approved drugs with the best consensus KIBA scores and binding affinity values against selected SARS-CoV-2 viral proteins was generated. Most importantly, 16 drugs including anidulafungin, velpatasvir, glecaprevir, rifapentine, flavin adenine dinucleotide (FAD), terlipressin, and selinexor demonstrated the highest predicted inhibitory potential against key SARS-CoV-2 viral proteins. We further measured the inhibitory activity of 5 compounds (rifapentine, velpatasvir, glecaprevir, anidulafungin, and FAD disodium) on SARS-CoV-2 PLpro using Ubiquitin-Rhodamine 110 Gly fluorescent intensity assay. The highest inhibition of PLpro activity was seen with rifapentine (IC50: 15.18 µM) and FAD disodium (IC50: 12.39 µM), the drugs with high predicted KIBA scores and binding affinities.