Molecular insights into codon usage analysis of mitochondrial fission and fusion gene: relevance to neurodegenerative diseases.

Mitochondrial dysfunction is the leading cause of neurodegenerative disorders like Alzheimer's disease and Parkinson's disease. Mitochondria is a highly dynamic organelle continuously undergoing the process of fission and fusion for even distribution of components and maintaining proper shape, number, and bioenergetic functionality. A set of genes governs the process of fission and fusion. OPA1, Mfn1, and Mfn2 govern fusion, while Drp1, Fis1, MIEF1, and MIEF2 genes control fission. Determination of specific molecular patterns of transcripts of these genes revealed the impact of compositional constraints on selecting optimal codons. AGA and CCA codons were over-represented, and CCC, GTC, TTC, GGG, ACG were under-represented in the fusion gene set. In contrast, CTG was over-represented, and GCG, CCG, and TCG were under-represented in the fission gene set. Hydropathicity analysis revealed non-polar protein products of both fission and fusion gene set transcripts. AGA codon repeats are an integral part of translational regulation machinery and present a distinct pattern of over-representation and under-representation in different transcripts within the gene sets, suggestive of selective translational force precisely controlling the occurrence of the codon. Out of six synonymous codons, five synonymous codons encoding for leucine were used differently in both gene sets. Hence, forces regulating the occurrence of AGA and five synonymous leucine-encoding codons suggest translational selection. A correlation of mutational bias with gene expression and codon bias and GRAVY and AROMA signifies the selection pressure in both gene sets, while the correlation of compositional bias with gene expression, codon bias, protein properties, and minimum free energy signifies the presence of compositional constraints. More than 25% of codons of both gene sets showed a significant difference in codon usage. The overall analysis shed light on molecular features of gene sets involved in fission and fusion.

Synthetic biology approach revealed enhancement in haeme oxygenase-1 gene expression by codon pair optimization while reduction by codon deoptimization.

Haem oxygenase-1 (HO-1) is a ubiquitously expressed gene involved in cellular homoeostasis, and its imbalance in expression results in various disorders. To alleviate such disorders, HO-1 gene expression needs to be modulated. Codon usage bias results from evolutionary forces acting on any nucleotide sequence and determines the gene expression. Like codon usage bias, codon pair bias also exists, playing a role in gene expression. In the present study, HO-1 gene was recoded by manipulating codon and codon pair bias, and four such constructs were made through codon/codon pair deoptimization and codon/codon pair optimization to reduce and enhance the HO-1 gene expression. Codon usage analysis was done for these constructs for four tissues brain, heart, pancreas and liver. Based on codon usage in different tissues, gene expression of these tissues was determined in terms of the codon adaptation index. Based on the codon adaptation index, minimum free energy, and translation efficiency, constructs were evaluated for enhanced or decreased HO-1 expression. The analysis revealed that for enhancing gene expression, codon pair optimization, while for reducing gene expression, codon deoptimization is efficacious. The recoded constructs developed in the study could be used in gene therapy regimens to cure HO-1 over or underexpression-associated disorders.

A small frontal lobe cavernoma presenting with headache mimicking migraine and complex focal seizure: A case report.

Cavernoma, or cerebral cavernous angioma, are hamartomatous lesions formed by sinusoidal vascular spaces without cerebral parenchyma in between. Cavernoma is a rare disorder that is diagnosed infrequently and incidentally, so it is called incidentaloma. However, cavernoma can present with seizures, headaches, and other focal neurological deficits, with seizures being the most frequent presentation. Cavernoma is angiographically concealed, and it's diagnosis is challenging. So, the cavernoma is diagnosed based on an MRI. We present the rare case of a patient who presented with a complex focal seizure and migraine-like headache caused by a small frontal lobe cavernoma.

Dengue fever complicated with ST elevation myocardial infarction with atypical features: A case report.

Dengue fever is an arboviral infection whose presentation ranges from a mild febrile illness to a multisystem complicated syndrome. We report a case of 58-year-old female presenting with fever, myalgia, arthralgia, and vomiting who was found to be infected with dengue and had electrocardiography changes revealing ST-segment elevation myocardial infarction, a rare manifestation in dengue. Dengue fever can affect the cardiovascular system leading to conduction abnormalities, hypotension, arrhythmias, myocarditis, cardiomyopathy, and occasionally myocardial infarction, which has been reported in only a few case reports prior to this. The differentiation between myocarditis and myocardial infarction is essential for which echocardiography and coronary angiography can be helpful. It is essential to keep an eye on the cardiovascular complications in a dengue patient as the presentation can be quite subtle with devastating consequences.

Acute oral poisoning due to pretilachlor herbicide - a rare case report from Nepal.

Introduction: Acute oral intoxication of pretilachlor, a synthetic chloroacetanilide herbicide, can present similar clinical manifestations of organophosphorus toxicity in humans. Case presentation: A 15-year-old male was admitted after suicidal ingestion of pretilachlor poison, with decreased consciousness and blood-mixed vomiting. Discussion: Pretilachlor is a colorless and odorless liquid that can cause neurotoxicity and carcinogenicity due to its prolonged exposure. The effects of acute oral exposure are mild and may differ from chronic exposure. Individuals exposed to chloroacetanilides may not show symptoms or experience vomiting and neurological issues. Clinical manifestations such as vomiting, excessive lacrimation, bowel and bladder incontinence, bradycardia, and hypotension can be observed in both organophosphate poisoning and pretilachlor poisoning, making accurate diagnosis challenging, particularly in resource-limited settings like ours. There is no specific antidote for pretilachlor poisoning. Treatment focuses on symptomatic care and monitoring the patient's hemodynamics as per standard protocol. Conclusion: This case underscores the need for prompt stabilization, vigilant monitoring, and supportive care to ensure timely recovery in pretilachlor poisoning cases despite similarities with organophosphate poisoning. It emphasizes the importance of educating and raising awareness among physicians about potential mimickers like organophosphates.

Giant multinodular goiter for 24 years; hidden in a village in Western Nepal.

Here, we present the case of a giant multinodular goiter with retrosternal extension in an old lady with dyspnea for 3 months. The patient was treated with microscopic-assisted total thyroidectomy without any postoperative complications.

Bell's palsy as a possible complication of mRNA-1273 (Moderna) vaccine against COVID-19.

Introduction: Vero Cell, AstraZeneca, Janssen, mRNA-1273 (Moderna), and Pfizer COVID-19 vaccines have been authorized for emergency use in Nepal. These vacines have been linked to some adverse effects, including fever, myalgia, and headache. Furthermore Bell's Palsy a rare adverse effect was also reported to be associated with the use of mRNA-1273 (Moderna) vaccine in some patients. Case presentation: In this case report we present a 17-year-old female who acquired Bell's Palsy following the administration of mRNA-1273 (Moderna) COVID-19 vaccination. Discussion: The possible etiology of BP that has been suggested is infection by reactivated viruses, such as the varicella-zoster virus (VZV), herpes simplex virus type 1 (HSV-1), human herpesvirus 6, and the Usutu virus, [1] the most accepted hypothesis is the one with reactivation of latent Herpes Simplex Virus type 1 in the geniculate ganglia of the facial nerves, an autoimmune mechanism through the mimicry of host molecules by the antigens of the vaccines. Conclusion: Though the extent of association between the mRNA vaccination and the development of Bell's Palsy has yet to be confirmed, this example highlights the need to closely monitor side effects and repercussions after receiving a new vaccine.

Hypertension and the Role of Dietary Fiber.

Hypertension (HTN) is a leading modifiable risk factor for multiple diseases. It has reached epidemic proportions, affecting nearly a third of the world's population. With such a high prevalence and an exhaustive list of potential complications, antihypertensive therapy has been a subject of focus for the scientific community for a long time. Recently, Dietary fiber is emerging as yet another promising candidate addressing this issue. It is a well-known fact that dietary modification alone can significantly impact a patient's health, with a noticeable effect on BP as well. But simply switching to healthy alternatives is not enough and must happen in tandem with dietary supplementation. The consumption of ultra-processed food has only increased in recent times. Hence, we feel the need to focus on dietary interventions in managing hypertension. This review aims to bring to light the current literature on the pathophysiology, risk factors, and treatment protocols of hypertension, focusing on dietary fibers and their role in hypertension management.

Snakebite in the Hills and Mountains of Nepal.

Snakebite is an important public health issue around the world. In Nepal, it affects a huge number of people mostly belonging to low-income households who are involved in agriculture. Although snakebite has a serious impact on the Terai population, a few studies suggest that snakebite also occurs frequently in hills and mountains. In the absence of sufficient studies related to snakebites in these geographical regions, it is tough to sketch a true picture and estimate the magnitude of snakebites in those areas. Because of this, the healthcare system is probably not prepared enough to handle the victims of snakebites. This demands a proper study of the burden of the issue in these regions and appropriate initiatives for addressing it. Keywords: antivenom; Nepal; snakebite.