Phenytoin is a first-generation anticonvulsant medicine that efficiently cures a wide range of seizures, including status epilepticus, complex partial seizures, and generalized tonic-clonic seizures (GCTS). The major advantage of phenytoin is that its neurological functions are preserved. Phenytoin works by inhibiting voltage-dependent membrane Na channels, which are essential to generate action potential. This function inhibits the positive feedback, leading to high-frequency repeated firing, reducing seizure spread in the focal region. A purple color rash on the chest, abdomen, and trunk developed in a 21-year-old female patient after being treated with phenytoin is being reported. The presentation, pathophysiology, and management are also reviewed.
Methotrexate (MTX) is a well-established drug for the use of various neoplastic disorders. Recently, it has been widely used as a disease-modifying antirheumatic drug (DMARD) in low doses, mainly for rheumatoid arthritis (RA) and psoriasis. The drug is known to cause renal damage as well as be excreted via the kidneys, thus causing a higher incidence of adverse effects in patients with impaired renal function. The side effects of MTX toxicity range from mucocutaneous ulcers to nephrotoxicity and bone marrow depression, all of which are seen in this case. Here, we report an elderly male in his late 60s who was prescribed MTX 15 mg once a week along with folic acid 5 mg for RA by a general practitioner. Despite being prescribed once weekly, he continued to take MTX daily without following up with a physician for a span of five months. Following this, he presented to the medicine outpatient department with odynophagia due to oral ulcers for 10 days. He was diagnosed with MTX toxicity, causing nephropathy, myelosuppression, and mucocutaneous ulcerations. He was treated with injectable leucovorin 100 mg thrice a day until the toxicity subsided, leading to his eventual recovery.
Reversible posterior leukoencephalopathy syndrome, often referred to as posterior reversible encephalopathy syndrome (PRES), is a disorder characterized by acute cerebral dysfunction and is seen in conjunction with vasogenic edema on brain imaging. Headaches, visual issues, seizures, abnormal mentation, disturbances in awareness, and focal neurological symptoms are its defining features. In this case report, we present a 40-year-old male patient who developed PRES after experiencing a high-voltage electric shock.
Foodborne pathogens, food adulterants, allergens, and toxic chemicals in food can cause major health hazards to humans and animals. Stringent quality control measures at all stages of food processing are required to ensure food safety. There is, therefore, a global need for affordable, reliable, and rapid tests that can be conducted at different process steps and processing sites, spanning the range from the sourcing of food to the end-product acquired by the consumer. Current laboratory-based food quality control tests are well established, but many are not suitable for rapid on-site investigations and are costly. Microfluidic paper analytical devices (µPADs) are a fast-growing field in medical diagnostics that can fill these gaps. In this review, we describe the latest developments in the applications of microfluidic paper analytic device (µPAD) technology in the food safety sector. State-of-the-art µPAD designs and fabrication methods, microfluidic assay principles, and various types of µPAD devices with food-specific applications are discussed. We have identified the prominent research and development trends and future directions for maximizing the value of microfluidic technology in the food sector and have highlighted key areas for improvement. We conclude that the µPAD technology is promising in food safety applications by using novel materials and improved methods to enhance the sensitivity and specificity of the assays, with low cost.
Echinococcus granulosus is the tapeworm that causes hydatidosis. The liver is the most frequently impacted region, although it can also affect the spleen, lung, and peritoneum. Dogs are the definite hosts, whereas humans are the unintentional accidental hosts. The peritoneum is an unusual site for hydatid cysts. We report the case of a 42-year-old male who had abdominal distension. A CT scan revealed hydatid cysts in the liver, spleen, and peritoneum. The patient was managed conservatively with albendazole and advised for surgical intervention and removal of daughter cysts. This case highlights the uncommon presentation of hydatid disease involving multiple intra-abdominal organs concurrently. The successful management of such cases necessitates a multidisciplinary approach, encompassing accurate diagnosis, timely intervention, and comprehensive treatment strategies. Furthermore, this case emphasizes the importance of clinical suspicion in endemic regions to optimize patient outcomes and enhance quality of life.
INTRODUCTION: We undertook the first study from India to evaluate the long-term health effects of coronavirus disease 2019 (COVID-19). METHODS: The patients enrolled in our post-COVID-19 clinic were followed up for assessment at 1, 3, 6 and 12 months after recovery from acute disease prospectively. RESULTS: 200 patients with mean age of 50.72 years and 57.5% males were analysed. 42.5% had severe and 17% had moderate disease at the time of diagnosis. The persistence of symptoms beyond 1 month of diagnosis was seen in 72.5% (145/200) patients. 8% (16/200) of the patients had post-COVID-19 complications that required rehospitalisation after discharge or recovery from acute COVID-19. The complications included respiratory failure (2%), lung cavities (3.5%), fungal infection, pericardial effusion, pneumothorax and death. The symptoms were persistent beyond 3 months in 51% (102/200) and beyond 6 months in 17.5% (35/200) of cases. The patients with persistent symptoms beyond 3 months and 6 months had significantly higher intensive care unit (ICU) admission during acute COVID-19, severe disease during acute COVID-19, and higher prevalence of comorbidities compared to the recovered patients. The clinical recovery was attained in 95.5% (91/200) patients, and the radiological recovery was attained in 97.92% patients at 1 year. The mean duration to clinical recovery was 174.2 days. CONCLUSIONS: COVID-19 recovery takes longer time. However, clinico-radiological recovery is attained in >95% cases by one year.
Molecular docking is by far the most preferred approach in structure-based drug design for its effectiveness to predict the scoring and posing of a given bioactive small molecule into the binding site of its pharmacological target. Herein, we present MzDOCK, a new GUI-based pipeline for Windows operating system, designed with the intent of making molecular docking easier to use and higher reproducible even for inexperienced people. By harmonic integration of python and batch scripts, which employs various open source packages such as Smina (docking engine), OpenBabel (file conversion) and PLIP (analysis), MzDOCK includes many practical options such as: binding site configuration based on co-crystallized ligands; generation of enantiomers from SMILES input; application of different force fields (MMFF94, MMFF94s, UFF, GAFF, Ghemical) for energy minimization; retention of selectable ions and cofactors; sidechain flexibility of selectable binding site residues; multiple input file format (SMILES, PDB, SDF, Mol2, Mol); generation of reports and of pictures for interactive visualization. Users can download for free MzDOCK at the following link: https://github.com/Muzatheking12/MzDOCK.
Endothelial dysfunction, linked to reduced eNOS expression and nitric oxide (NO) availability, contributes to cardiovascular diseases (CVDs). Large cardamom exhibits antihypertensive effects by augmenting NO levels and antioxidant activity. To decipher its mechanisms, selected constituents were docked with eNOS-associated target genes such as GTP cyclohydrolase I (GTPCH-1) and (dihydrofolate reductase [DHFR]). Endothelial damage induced by L-NAME and fructose was countered by assessing nitric oxide metabolites (NOx), tetrahydrobipterin (BH4 levels), GCH-I expression and super oxide dismutase (SOD) activity after constituent incubation. Cyanidin-3-O-glucoside and petunidin-3-O-glucoside notably restored impaired vascular markers in both models. These phytoconstituents are likely to activate GCH-BH4-eNOS pathways, upregulating SOD and NO expression, maintaining endothelial integrity. Large cardamom's antihypertensive effects may stem from these components, synergistically enhancing endothelial NO release via the eNOS pathway.
Enhanced Recovery After Surgery (ERAS) protocols have emerged as a promising approach to optimize perioperative care and improve outcomes in various surgical specialties. Despite feasibility studies on ERAS in various surgeries, there remains a paucity of research focusing on gastrointestinal cancer surgeries in the Indian context. The primary objective is to evaluate the compliance rate of the ERAS protocol and secondary objectives include the compliance rate of individual components of the protocol, the complications, the length of hospital stay, and the challenges faced during implementation in patients undergoing gastrointestinal cancer surgeries in our tertiary care cancer center. In this prospective interventional study (CTRI/2022/04/041657; registered on 05/04/2022), we evaluated 50 patients aged 18 to 70 years undergoing surgery for gastrointestinal malignancies and implemented a refined ERAS protocol tailored to our institutional resources and conditions based on standard ERAS society recommendations for gastrointestinal surgeries and specific recommendations for colorectal, pancreatic, and esophageal surgeries.Our study's mean overall compliance rate with the ERAS protocol was 88.54%. We achieved a compliance rate of 91.98%, 81.66%, and 92.00% for pre-operative, intraoperative, and post-operative components respectively. Fourteen (28%) patients experienced complications during the study. The median length of stay was 6.5 days (5.25-8). Challenges were encountered during the preoperative, intraoperative, and postoperative phases. The study highlighted the feasibility of implementing the ERAS protocol in a cancer institute, but specific challenges need to be addressed for its optimal success in gastrointestinal cancer surgeries. Supplementary Information: The online version contains supplementary material available at 10.1007/s13193-024-01897-y.
High-sensitivity C-reactive protein (hsCRP) has emerged as a critical biomarker in inflammation, offering insights into various chronic diseases. However, traditional blood-based assays for hsCRP measurement pose limitations regarding invasiveness and cost. In recent years, saliva has garnered attention as an alternative diagnostic medium, presenting a noninvasive and easily accessible option for biomarker analysis. Salivary hsCRP has thus emerged as a promising avenue for research and clinical application, offering potential advantages over blood-based assays. This comprehensive review aims to elucidate the biological basis of salivary hsCRP, its clinical applications, and methodologies for measurement. By exploring its diagnostic potential, prognostic value, and implications for treatment monitoring, this review highlights the potential impact of salivary hsCRP in modern medicine. Moreover, it emphasizes the need for continued exploration, validation, and integration of salivary hsCRP into routine clinical practice to realize its full potential for enhancing patient care and advancing personalized medicine approaches.
Robust monitoring of heterogeneity in biopharmaceutical development is crucial for producing safe and efficacious biotherapeutic products. Multiattribute monitoring (MAM) has emerged as an efficient tool for monitoring of mAb heterogeneities like deamidation, sialylation, glycosylation, and oxidation. Conventional biopharma analysis during mAb development relies on use of one-dimensional methods for monitoring titer and charge-based heterogeneity using non-volatile solvents without direct coupling with mass spectrometry (MS). This approach requires analysis of mAb harvest by ProA for titer estimation followed by separate cation exchange chromatography (CEX) analysis of the purified sample for estimating charge-based heterogeneity. This can take up to 60-90 min due to the required fraction collection and buffer exchange steps. In this work, a native two-dimensional liquid chromatography (2DLC) mass spectrometry method has been developed with Protein A chromatography in the first dimension for titer estimation and cation exchange chromatography (CEX) in the second dimension for charge variant analysis. The method uses volatile salts for both dimensions and enables easy coupling to MS. The proposed 2DLC method exhibits a charge variant profile that is similar to that observed via the traditional methods and takes only 15 min for mass identification of each variant. A total of six charge variants were separated by the CEX analysis after titer estimation, including linearity assessment from 5 µg to 160 µg of injected mAb sample. The proposed method successfully estimated charge variants for the mAb innovator and 4 of its biosimilars, showcasing its applicability for biosimilarity exercises. Hence, the 2D ProA CEX MS method allows direct titer and charge variant estimation of mAbs in a single workflow.
Over the last three decades, neurodegenerative diseases (NDs) have increased in frequency. About 15% of the world's population suffers from NDs in some capacity, which causes cognitive and physical impairment. Neurodegenerative diseases, including Amyotrophic Lateral Sclerosis, Parkinson's disease, Alzheimer's disease, and others represent a significant and growing global health challenge. Neuroinflammation is recognized to be related to all NDs, even though NDs are caused by a complex mix of genetic, environmental, and lifestyle factors. Numerous genes and pathways such as NFκB, p38 MAPK, Akt/mTOR, caspase, nitric oxide, and COX are involved in triggering brain immune cells like astrocytes and microglia to secrete inflammatory cytokines such as tumor necrosis factor-α, interleukin (IL)-1ß, and IL-6. In AD, the binding of Aß with CD36, TLR4, and TLR6 receptors results in activation of microglia which start to produce proinflammatory cytokines and chemokines. Consequently, the pro-inflammatory cytokines worsen and spread neuroinflammation, causing the deterioration of healthy neurons and the impairment of brain functions. Gene therapy has emerged as a promising therapeutic approach to modulate the inflammatory response in NDs, offering potential neuroprotective effects and disease-modifying benefits. This review article focuses on recent advances in gene therapy strategies targeting neuroinflammation pathways in NDs. We discussed the molecular pathways involved in neuroinflammation, highlighted key genes and proteins implicated in these processes, and reviewed the latest preclinical and clinical studies utilizing gene therapy to modulate neuroinflammatory responses. Additionally, this review addressed the prospects and challenges in translating gene therapy approaches into effective treatments for NDs.
Skin cancer is one of the most life-threatening diseases caused by the abnormal growth of the skin cells, when exposed to ultraviolet radiation. Early detection seems to be more crucial for reducing aberrant cell proliferation because the mortality rate is rapidly rising. Although multiple researches are available based on the skin cancer detection, there still exists challenges in improving the accuracy, reducing the computational time and so on. In this research, a novel skin cancer detection is performed using a modified falcon finch deep Convolutional neural network classifier (Modified Falcon finch deep CNN) that efficiently detects the disease with higher efficiency. The usage of modified falcon finch deep CNN classifier effectively analyzed the information relevant to the skin cancer and the errors are also minimized. The inclusion of the falcon finch optimization in the deep CNN classifier is necessary for efficient parameter tuning. This tuning enhanced the robustness and boosted the convergence of the classifier that detects the skin cancer in less stipulated time. The modified falcon finch deep CNN classifier achieved accuracy, sensitivity, and specificity values of 93.59%, 92.14%, and 95.22% regarding k-fold and 96.52%, 96.69%, and 96.54% regarding training percentage, proving more effective than literary works.
Neural Networks, Computer , Skin Neoplasms , Skin Neoplasms/diagnosis , Skin Neoplasms/classification , Skin Neoplasms/pathology , Humans , Finches , Animals , Male , Early Detection of Cancer/methods , Female , Sensitivity and Specificity
Renal infarction is an uncommon illness that can have serious side effects. Patients may be predisposed to the disease by factors including smoking, atrial fibrillation, thrombus, infective endocarditis, myocardial infarction, and prosthetic valves. Patients are most susceptible from 24 hours to 15 days after myocardial infarction, with an increased rate of left ventricular (LV) thrombus development, which raises the probability of thromboembolic events in the cerebrovascular system and might exacerbate morbidity and mortality rate. This can be diagnosed by two-dimensional echocardiography. Different risk factors can contribute to the development of an LV thrombus. Renal infarcts from LV clots are less common but can occur bilaterally in certain situations. A 30-year-old male diagnosed with anterior wall myocardial infarction presented at our hospital and was suspected to have bilateral renal infarcts, possibly due to the LV thrombi. The patient was managed on anti-thrombolytics and was reported to be doing well at a follow-up of one month.
Hemangiosarcoma and angiosarcoma are soft-tissue sarcomas of blood vessel-forming cells in dogs and humans, respectively. These vasoformative sarcomas are aggressive and highly metastatic, with disorganized, irregular blood-filled vascular spaces. Our objective was to define molecular programs which support the niche that enables progression of canine hemangiosarcoma and human angiosarcoma. Dog-in-mouse hemangiosarcoma xenografts recapitulated the vasoformative and highly angiogenic morphology and molecular characteristics of primary tumors. Blood vessels in the tumors were complex and disorganized, and they were lined by both donor and host cells. In a series of xenografts, we observed that the transplanted hemangiosarcoma cells created exuberant myeloid hyperplasia and gave rise to lymphoproliferative tumors of mouse origin. Our functional analyses indicate that hemangiosarcoma cells generate a microenvironment that supports expansion and differentiation of hematopoietic progenitor populations. Furthermore, gene expression profiling data revealed hemangiosarcoma cells expressed a repertoire of hematopoietic cytokines capable of regulating the surrounding stromal cells. We conclude that canine hemangiosarcomas, and possibly human angiosarcomas, maintain molecular properties that provide hematopoietic support and facilitate stromal reactions, suggesting their potential involvement in promoting the growth of hematopoietic tumors.
Enhancing the electrical conductance through amorphous nondoped polymers is challenging. Here, we show that vibrational strong coupling (VSC) of intrinsically nonconducting and amorphous polymers such as polystyrene, deuterated polystyrene, and poly(benzyl methacrylate) to the vacuum electromagnetic field of the cavity enhances the electrical conductivity by at least 6 orders of magnitude compared to the uncoupled polymers. Remarkably, the observed extraordinary conductance is vibrational mode selective and occurs only under the VSC of the aromatic C-H(D) out-of-plane bending modes of the polymers. The conductance is thermally activated at the onset of strong coupling and becomes temperature-independent as the collective strong coupling strength increases. The electrical characterizations are performed without external light excitation, demonstrating the role of vacuum electromagnetic field-matter strong coupling in enhancing long-range transport even in amorphous nonconducting polymers.
Serum ferritin has garnered considerable attention as a prognostic marker in intensive care units (ICUs), offering valuable insights into patient outcomes and clinical management strategies. This comprehensive review examines the role of serum ferritin in predicting outcomes among critically ill patients, with a particular focus on its implications for ischemic heart disease (IHD). Elevated serum ferritin levels have consistently been associated with adverse outcomes in ICU settings, including increased mortality, prolonged hospital stays, and higher morbidity rates. Furthermore, the relationship between serum ferritin levels and IHD underscores its potential as a biomarker for cardiovascular risk assessment in critically ill populations. The review synthesizes existing literature to highlight the predictive value of serum ferritin in assessing illness severity and guiding clinical decision-making in the ICUs. It also explores potential mechanisms linking serum ferritin to adverse outcomes and discusses implications for clinical practice. Integrating serum ferritin measurements into routine assessments could enhance prognostication and risk stratification in ICU patients, while further research is needed to elucidate optimal management strategies and therapeutic targets. Collaborative efforts between clinicians and researchers are essential to advance our understanding of serum ferritin's prognostic value in the ICUs and translate this knowledge into improved patient care and outcomes.
This article presents a dataset on bacterial community structure associated with Ready-to-eat (RTE) vegetable salads sold in Kampala City, Uganda. The Illumina Miseq sequencing of 16S rRNA gene amplicon unveiled the bacterial communities and generated a metagenomic library from RTE vegetable salads to understand the diversities and distribution. The metagenome contained a total of 23,805 sequences with 35,420 Taxonomic units (OTUs). Metagenome sequence information is obtainable at NCBI under the Bioproject assigned accession number PRJNA1064313. Taxonomic hits distribution from VSEARCH analysis at phylum level classification of NN-3 discovered predominantly Proteobacteria (65.34%) followed by Firmicutes (31.60%) and Bacteroidota (0.14%). Deinococcota (0.01%) and Planctomycetota (0.01%) were also detected. Also, VSEARCH-assisted analysis of NN-4 detected a higher prevalence of Firmicutes (65.68%) than Proteobacteria (33.25%), while Bacteroidota (0.04%) indicating the presence of contaminants of faecal sources.
Uncontrolled diabetes can trigger a movement disorder called hemichorea-hemiballismus, characterized by non-ketotic hyperglycemia-related chorea/ballism and usually reversible basal ganglia abnormalities on CT and/or MRI. The condition is diagnosed clinically and is mostly based on radiological imaging. Here, we report a case of a 68-year-old female presenting with right-sided and facial involuntary movements owing to uncontrolled hyperglycemia who was treated with antidiabetic and anticholinergic medications. The patient responded well to the treatment and showed a favorable outcome with no complications.
Introduction Digital ischemia is alike any other visceral ischemic event leading to severe tissue damage ultimately causing necrosis of the involved extremity. It's like a preview of the upcoming systemic disorder and can present itself in any specialty and hence everyone, be it a physician or a surgeon must be primed toward how to proceed with a case of digital ischemia. In this case series, we present six such cases that presented with digital ischemic events either as a sole presentation or were followed by other systemic manifestations that led to their evaluation and ultimately the etiology behind it. Material and method Patients visiting Rheumatology OPD with complaints suggestive of digital ischemia were included in this study. All patients underwent thorough history taking and clinical examination to establish the cause of digital ischemia. Patients with probable infective, trauma, cardiac, and drug-induced causes and malignancies were excluded. As per probable autoimmune causes, patients underwent evaluation via antinuclear antibodies by immunofluorescence (ANA by IF), antiphospholipid antibodies like lupus anticoagulant (LAC), anticardiolipin antibodies (AcL) and anti Beta2GP1 antibodies, extractable nuclear antigens (ENA) and in cases of suspected vasculitis doppler ultrasound and angiography. Results Six patients were identified as cases primarily presenting with digital ischemia or with a prior history of digital ischemia. Two patients were of the pediatric age group, one 16-year-old male presenting with acute arthritis and a history of digital ischemia one year back, and the other was a 12-year-old female with blackening of the second toe in her left foot with a history of similar complaints in the left great toe for which she underwent amputation of that toe. Other four cases were of the adult age group, with two cases of scleroderma, one with systemic lupus erythematosus, and one with Takayasu arteritis. All of these patients primarily presented to departments other than rheumatology. Conclusion Digital ischemia is a pan-specialty problem with the etiologies spreading across a vast spectrum of rheumatological disorders, many of which may present to different specialties initially, later discovered to be part of the systemic manifestation of autoimmune diseases. Hence, it becomes imperative to have a rheumatological perspective in these cases of digital ischemia which all specialities should be aware of, and timely referral may prevent permanent loss of the digits and in some cases the entire limb.
