Management of Rhinosporidiosis: by Coblation.

Rhinosporidiosis is a granulomatous disease commonly affecting the mucous membrane. It is caused by Rhinosporidium seeberi, an aquatic parasite & seen affecting the nose, paranasal sinuses most commonly. A retrospective study was conducted at a tertiary care hospital situated in Indian peninsula and five patients who were diagnosed and treated for rhinosporidiosis were analysed. Surgical excision by coblator along with medical management using Dapsone 100 mg once daily for 6 months given promising results in view of reducing recurrence. Combined approach of management including surgical excision using coblator and medical therapy with dapsone is effective in managing the rhinosporidiosis with no recurrence.

Targeting long non-coding RNAs in cancer therapy using CRISPR-Cas9 technology: A novel paradigm for precision oncology.

Cancer is the second leading cause of death worldwide, despite recent advances in its identification and management. To improve cancer patient diagnosis and care, it is necessary to identify new biomarkers and molecular targets. In recent years, long non-coding RNAs (lncRNAs) have surfaced as important contributors to various cellular activities, with growing proof indicating their substantial role in the genesis, development, and spread of cancer. Their unique expression profiles within specific tissues and their wide-ranging functionalities make lncRNAs excellent candidates for potential therapeutic intervention in cancer management. They are implicated in multiple hallmarks of cancer, such as uncontrolled proliferation, angiogenesis, and immune evasion. This review article explores the innovative application of CRISPR-Cas9 technology in targeting lncRNAs as a cancer therapeutic strategy. The CRISPR-Cas9 system has been widely applied in functional genomics, gene therapy, and cancer research, offering a versatile platform for lncRNA targeting. CRISPR-Cas9-mediated targeting of lncRNAs can be achieved through CRISPR interference, activation or the complete knockout of lncRNA loci. Combining CRISPR-Cas9 technology with high-throughput functional genomics makes it possible to identify lncRNAs critical for the survival of specific cancer subtypes, opening the door for tailored treatments and personalised cancer therapies. CRISPR-Cas9-mediated lncRNA targeting with other cutting-edge cancer therapies, such as immunotherapy and targeted molecular therapeutics can be used to overcome the drug resistance in cancer. The synergy of lncRNA research and CRISPR-Cas9 technology presents immense potential for individualized cancer treatment, offering renewed hope in the battle against this disease.

Effects of early adjunctive pharmacotherapy on serum levels of brain injury biomarkers in patients with traumatic brain injury: a systematic review of randomized controlled studies.

Objectives: Traumatic brain injury (TBI) is one of the top causes of morbidity and mortality worldwide. The review aimed to discuss and summarize the current evidence on the effectiveness of adjuvant neuroprotective treatments in terms of their effect on brain injury biomarkers in TBI patients. Methods: To identify relevant studies, four scholarly databases, including PubMed, Cochrane, Scopus, and Google Scholar, were systematically searched using predefined search terms. English-language randomized controlled clinical trials reporting changes in brain injury biomarkers, namely, neuron-specific enolase (NSE), glial fibrillary acid protein (GFAP), ubiquitin carboxyl-terminal esterase L1 (UCHL1) and/or S100 beta (S100 ß), were included. The methodological quality of the included studies was assessed using the Cochrane risk-of-bias tool. Results: A total of eleven studies with eight different therapeutic options were investigated; of them, tetracyclines, metformin, and memantine were discovered to be promising choices that could improve neurological outcomes in TBI patients. The most utilized serum biomarkers were NSE and S100 ß followed by GFAP, while none of the included studies quantified UCHL1. The heterogeneity in injury severity categories and measurement timing may affect the overall evaluation of the clinical efficacy of potential therapies. Therefore, unified measurement protocols are highly warranted to inform clinical decisions. Conclusion: Few therapeutic options showed promising results as an adjuvant to standard care in patients with TBI. Several considerations for future work must be directed towards standardizing monitoring biomarkers. Investigating the pharmacotherapy effectiveness using a multimodal biomarker panel is needed. Finally, employing stratified randomization in future clinical trials concerning potential confounders, including age, trauma severity levels, and type, is crucial to inform clinical decisions. Clinical Trial Registration: [https://www.crd.york.ac.uk/prospero/dis], identifier [CRD42022316327].

Attention Deficit Hyperactivity Disorder: What Are Pharmacists' Roles and Associated Outcomes?

Globally, the prevalence of attention deficit hyperactivity disorder (ADHD) is increasing. The treatment for ADHD is multifaceted and requires long-term care and support. Pharmacists are capable of assisting patients and their caretakers in achieving desired outcomes. This work discusses and summarizes pharmacists' roles in ADHD care and their associated outcomes. Overall, pharmacists are positioned to educate on ADHD, optimize medications in a collaborative practice model, manage and monitor side effects, and provide remote and virtual pharmaceutical care. Pharmacists could directly contribute to ensuring medication safety and increasing awareness regarding the optimal use of ADHD medications. Patients with ADHD can benefit from pharmacist involvement in a variety of ways, including, but not limited to, initial screening and referral, the provision of clinical consultation and feedback, and the improvement of self-management and self-awareness of the illness. Pharmacists also play a significant role in therapeutic decision making regarding the initiation, intensification, and monitoring of ADHD treatment to ensure its effectiveness and quality of life improvement. Lastly, pharmacists could help identify more cost-effective treatment approaches for ADHD patients based on the clinical scenario that is encountered.

Risk Factors, Clinical Consequences, Prevention, and Treatment of Childhood Obesity.

Obesity might adversely affect the health and well-being of children and their families. Childhood obesity has crucial implications for health, both during childhood and as they age. It is highly associated with many acute problems and is commonly present during childhood, making visits and hospital admissions polarized in this group of children. The problems that may affect these children can be medical, such as asthma, chronic inflammation, orthopedic abnormalities, liver disease, diabetes mellitus or dyslipidemia. Long-term consequences of cardiovascular risk factors, the persistence of obesity and premature mortality are common among adults who had obesity during their early lives. Additionally, they could also suffer from psychological issues, such as low self-esteem, which puts them at risk of a much more serious psychosocial problem that may lead to depression, as well as a disruption in educational achievements and social relationships. A healthy diet, physical activity, adequate sleep, and limited screen time are all preventive measures that should be implemented at the family and community levels, preferably through well-structured programs. Furthermore, pharmacological management of childhood obesity is limited and only used after non-pharmacological interventions have failed or in the late stages of obesity. However, recent guidelines advocate the early use of medical interventions. Approved pharmacotherapeutic options include orlistat, phentermine/topiramate combination and liraglutide. There are several other options approved primarily for other specific forms of obesity or for other indications, including setmelanotide, metformin, lisdexamfetamine, zonisamide and fluoxetine. Bariatric surgery is a safe and effective option in cases with extreme obesity and comorbidities considering the need for long-term monitoring and support for cases and their families post-surgery. This review aims to discuss and highlight the recent evidence regarding risk factors, clinical consequences, prevention, and treatment of childhood obesity.

Efficacy of Nondiuretic Pharmacotherapy for Improving the Treatment of Congestion in Patients with Acute Heart Failure: A Systematic Review of Randomised Controlled Trials.

Diuretic therapy is the mainstay during episodes of acute heart failure (AHF). Diuretic resistance is often encountered and poses a substantial challenge for clinicians. There is a lack of evidence on the optimal strategies to tackle this problem. This review aimed to compare the outcomes associated with congestion management based on a strategy of pharmacological nondiuretic-based regimens. The PubMed, Cochrane Library, Scopus, and ScienceDirect databases were systematically searched for all randomised controlled trials (RCTs) of adjuvant pharmacological treatments used during hospitalisation episodes of AHF patients. Congestion relief constitutes the main target in AHF; hence, only studies with efficacy indicators related to decongestion enhancement were included. The Cochrane risk-of-bias tool was used to evaluate the methodological quality of the included RCTs. Twenty-three studies were included; dyspnea relief constituted the critical efficacy endpoint in most included studies. However, substantial variations in dyspnea measurement were found. Tolvaptan and serelaxin were found to be promising options that might improve decongestion in AHF patients. However, further high-quality RCTs using a standardised approach to diuretic management, including dosing and monitoring strategies, are crucial to provide new insights and recommendations for managing heart failure in acute settings.

Oxidative stress in the pathophysiology of type 2 diabetes and related complications: Current therapeutics strategies and future perspectives.

Type 2 diabetes (T2DM) is a persistent metabolic disorder rising rapidly worldwide. It is characterized by pancreatic insulin resistance and ß-cell dysfunction. Hyperglycemia induced reactive oxygen species (ROS) production and oxidative stress are correlated with the pathogenesis and progression of this metabolic disease. To counteract the harmful effects of ROS, endogenous antioxidants of the body or exogenous antioxidants neutralise it and maintain bodily homeostasis. Under hyperglycemic conditions, the imbalance between the cellular antioxidant system and ROS production results in oxidative stress, which subsequently results in the development of diabetes. These ROS are produced in the endoplasmic reticulum, phagocytic cells and peroxisomes, with the mitochondrial electron transport chain (ETC) playing a pivotal role. The exacerbated ROS production can directly cause structural and functional modifications in proteins, lipids and nucleic acids. It also modulates several intracellular signaling pathways that lead to insulin resistance and impairment of ß-cell function. In addition, the hyperglycemia-induced ROS production contributes to micro- and macro-vascular diabetic complications. Various in-vivo and in-vitro studies have demonstrated the anti-oxidative effects of natural products and their derived bioactive compounds. However, there is conflicting clinical evidence on the beneficial effects of these antioxidant therapies in diabetes prevention. This review article focused on the multifaceted role of oxidative stress caused by ROS overproduction in diabetes and related complications and possible antioxidative therapeutic strategies targeting ROS in this disease.

A randomized comparative study of methylcobalamin, methylcobalamin plus pregabalin and methylcobalamin plus duloxetine in patients of painful diabetic neuropathy.

CONTEXT: Diabetic neuropathy affects 10.5%-32.2% of diabetic population posing clinical burden onto society. AIMS: We aimed to study the efficacy, safety, and tolerability of methylcobalamin, methylcobalamin plus pregabalin, and methylcobalamin plus duloxetine in patients of painful diabetic neuropathy. SETTINGS AND DESIGN: It is a prospective, randomized, open-label, interventional, and parallel-group study done in patients of painful diabetic neuropathy. MATERIALS AND METHODS: A total of 100 patients were recruited and randomized to three study groups A, B, and C on methylcobalamin, methylcobalamin and pregabalin, and methylcobalamin and duloxetine, respectively. Patients were assessed at day 0 and 4, 8, and 12 weeks. The tuning fork test, monofilament test, Thermal Sensitivity testing, and Visual Analog Scale (VAS) were used to analyze vibration, pressure, thermal sensitivity, and pain. STATISTICAL ANALYSIS USED: The results are expressed as mean ± standard deviation. Appropriate statistical methods were used to calculate P value (<0.05 - significant). RESULTS: The increase in number of patients with vibration perception is 11.6%, 37.9%, and 41.4%; pressure sensation is 7.6%, 37.9%, and 37.9%; and thermal sensitivity is 15.4%, 31.1%, and 37.9% in Groups A, B, and C, respectively. The decrease in VAS scores is 0.58 ± 0.14, 3.82 ± 0.05, and 4.17 ± 0.48 in Groups A, B, and C correspondingly. The adverse effects reported in Groups A, B, and C are 0%, 6.9%, and 10.3%, respectively. CONCLUSIONS: Group C is more efficacious when compared to Groups A and B while Group B is safer.

Associations between Socio-Demographic Factors and Hypertension Management during the COVID-19 Pandemic: Preliminary Findings from Malaysia.

The perspectives of hypertensive patients on the state of hypertension control during the ongoing pandemic restrictions have not been extensively studied in Malaysia. Therefore, this study aimed to assess the impact of socio-demographic factors, health literacy, and adherence on the overall hypertension management in a group of Malaysian hypertensive patients during the COVID-19 pandemic. An anonymous, online cross-sectional study was conducted over three months that involved a group of Malaysian adults with hypertension. A validated, self-administered 30-item questionnaire was prepared in Malay and English languages on Google Forms. The link was then distributed to participants on social media (Facebook and WhatsApp). Following survey validation, a pilot study with 30 participants who met the inclusion criteria was carried out. The total scores for health literacy, adherence, and pandemic impact on hypertension control were calculated and compared across all independent variables. In a total of 144 study participants, controlled blood pressure was reported in 77% (N = 111). There were good levels of adherence and health literacy scores but moderate levels of pandemic impact scores. The total adherence scores showed a statistically significant difference between age groups (χ2 = 6.48, p = 0.039) and those who reported having controlled and uncontrolled blood pressure (U = 1116, p = 0.001). Moreover, the analysis revealed statistically significant differences in total pandemic impact scores based on the age group (χ2 = 15.008, p = 0.001), household income (χ2 = 6.887, p = 0.032), employment (U = 1712, p = 0.006), and marital status (U = 520.5, p < 0.001). The youngest age group (18-39) years, the lowest income group, unemployed and unmarried individuals, had significantly higher pandemic impact scores. This denotes that those individuals were more prone to be negatively affected by the pandemic regarding their hypertension management. Most participants reported relatively controlled blood pressure and good levels of health literacy as well as adherence amidst the pandemic. To a moderate extent, study participants perceived that the pandemic had a negative effect on hypertension management. The perceived negative impact of the pandemic was attributed to several socio-demographic factors, such as age, household income, employment, and marital status.

Pancreas transplant in type 1 diabetes mellitus: the emerging role of islet cell transplant.

Pancreas transplant, both whole pancreas and islet cell, is a known therapeutic option for treatment of type 1 diabetes mellitus. Islet cell transplant began as an experimental therapy but is emerging to be quite beneficial due to less surgical risk and fewer complications. It is also considered a promising option in pediatric patients. In this review the authors discuss the indications, procedure, and benefits of islet cell transplant along with newer strategies for improving outcomes.

Emerging role of non-coding RNA in health and disease.

Human diseases have always been a significant turf of concern since the origin of mankind. It is cardinal to know the cause, treatment, and cure for every disease condition. With the advent and advancement in technology, the molecular arena at the microscopic level to study the mechanism, progression, and therapy is more rational and authentic pave than a macroscopic approach. Non-coding RNAs (ncRNAs) have now emerged as indispensable players in the diagnosis, development, and therapeutics of every abnormality concerning physiology, pathology, genetics, epigenetics, oncology, and developmental diseases. This is a comprehensive attempt to collate all the existing and proven strategies, techniques, mechanisms of genetic disorders including Silver Russell Syndrome, Fascio- scapula humeral muscular dystrophy, cardiovascular diseases (atherosclerosis, cardiac fibrosis, hypertension, etc.), neurodegenerative diseases (Spino-cerebral ataxia type 7, Spino-cerebral ataxia type 8, Spinal muscular atrophy, Opitz-Kaveggia syndrome, etc.) cancers (cervix, breast, lung cancer, etc.), and infectious diseases (viral) studied so far. This article encompasses discovery, biogenesis, classification, and evolutionary prospects of the existence of this junk RNA along with the integrated networks involving chromatin remodelling, dosage compensation, genome imprinting, splicing regulation, post-translational regulation and proteomics. In conclusion, all the major human diseases are discussed with a facilitated technology transfer, advancements, loopholes, and tentative future research prospects have also been proposed.

Pancreas transplant in type 1 diabetes mellitus: the emerging role of islet cell transplant

Pancreas transplant, both whole pancreas and islet cell, is a known therapeutic option for treatment of type 1 diabetes mellitus. Islet cell transplant began as an experimental therapy but is emerging to be quite beneficial due to less surgical risk and fewer complications. It is also considered a promising option in pediatric patients. In this review the authors discuss the indications, procedure, and benefits of islet cell transplant along with newer strategies for improving outcomes.

Pancreas transplant in type 1 diabetes mellitus: the emerging role of islet cell transplant

Pancreas transplant, both whole pancreas and islet cell, is a known therapeutic option for treatment of type 1 diabetes mellitus. Islet cell transplant began as an experimental therapy but is emerging to be quite beneficial due to less surgical risk and fewer complications. It is also considered a promising option in pediatric patients. In this review the authors discuss the indications, procedure, and benefits of islet cell transplant along with newer strategies for improving outcomes.

Use of Growth Hormone Treatment in Skeletal Dysplasia - A Review.

Skeletal dysplasias are the disorders of the skeletal and cartilaginous tissues. Short stature is the hallmark presentation. Achondroplasia is the commonest skeletal dysplasia. Growth hormone (GH) has been widely used in children with achondroplasia. Various studies have shown 1st year increase in height velocity is about 2-3cm. Apart from achondroplasia, studies have also shown positive effect of GH in hypochondroplasia children. However, in hypochondroplasia GH treatment seems to give better results when administered at puberty. Other forms of skeletal dysplasias are rare, so no conclusion on GH use in such patients can be drawn.

ACE2 Homo-dimerization, Human Genomic variants and Interaction of Host Proteins Explain High Population Specific Differences in Outcomes of COVID19

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a positive single-stranded RNA virus that causes a highly contagious Corona Virus Disease (COVID19). Entry of SARS-CoV-2 in human cells depends on binding of the viral spike (S) proteins to cellular receptor Angiotensin-converting enzyme 2 (ACE2) and on S-protein priming by host cell serine protease TMPRSS2. Recently, COVID19 has been declared pandemic by World Health Organization (WHO) yet high differences in disease outcomes across countries have been seen. We provide evidences to explain these population-level differences. One of the key factors of entry of the virus in host cells presumably is because of differential interaction of viral proteins with host cell proteins due to different genetic backgrounds. Based on our findings, we conclude that a higher expression of ACE2 is facilitated by natural variations, acting as Expression quantitative trait loci (eQTLs), with different frequencies in different populations. We suggest that high expression of ACE2 results in homo-dimerization, proving disadvantageous for TMPRSS2 mediated cleavage of ACE2; whereas, the monomeric ACE2 has higher preferential binding with SARS-CoV-2 S-Protein vis-a-vis its dimerized counterpart. Further, eQTLs in TMPRSS2 and natural structural variations in the gene may also result in differential outcomes towards priming of viral S-protein, a critical step for entry of the Virus in host cells. In addition, we suggest that several key host genes, like SLC6A19, ADAM17, RPS6, HNRNPA1, SUMO1, NACA, BTF3 and some other proteases as Cathepsins, might have a critical role. To conclude, understanding population specific differences in these genes may help in developing appropriate management strategies for COVID19 with better therapeutic interventions.

Feasibility of bisphosphonate therapy in an Indian pediatric patient of fibrodysplasia ossificans progressiva.

Fibrodysplasia ossificans progressiva, also known as myositis ossificans progressiva, is a rare autosomal dominant disorder (1 in 2 million). It produces a catastrophic and crippling illness in young people for which there is no effective treatment. This case report presents a case of 7-year-old child misdiagnosed as osteogenesis imperfecta admitted with severe disability and pain. He was diagnosed by clinical and radiological methods, treated with bisphosphonates for pain relief along with calcium and Vitamin D, and followed till 4 years.

A variable course of Cushing's disease in a 7 year old: diagnostic dilemma.

Background Cushing's syndrome (CS) or hypercortisolism results from disruption of the hypothalamus-pituitary-adrenal (HPA) axis with the resultant increase in the circulating serum and urinary cortisol levels and lack of cortisol circadian rhythm. The resultant effects cause the physical manifestation of hypercortisolism. The appearance of Cushing's disease in children is insidious, the most common features being growth failure, obesity, early puberty and facial appearance. Case presentation We report a case of a 7-year-old male with a very unusual course of the disease, which could have led to diagnostic delays.

Real-world efficacy and safety of insulin degludec with mealtime rapid-acting insulin in type 1 diabetes in Indian pediatric population.

BACKGROUND: Insulin Degludec (IDeg) is a new ultra-long-acting basal insulin that has not been yet evaluated in Indian pediatric population. We aim to evaluate the efficacy and safety of IDeg as basal-bolus therapy in Indian pediatric patients affected by type 1 diabetes mellitus (T1DM). METHODS: A total of 30 pediatric and adolescent patients (17 boys, 13 girls; 22 were pre-pubertal) with T1DM who were on IDeg once daily participated in the study. All the patients received IDeg for at least 26 weeks along with rapid-acting mealtime insulin and their pre- and post-baseline characteristics (anthropometric data (BMI), age, duration of diabetes), metabolic (HbA1C), insulin requirement (unit/kg body weight per day) and number of hypoglycemia episodes were recorded along with the daily self-monitoring of blood glucose. RESULTS: There was a significant decline in HbA1c, FPG and bolus insulin dose from baseline to 26 weeks in the overall population (HbA1c: 9.65 ± 1.998% to 8.60 ± 1.631%, P = 0.0014; FPG: 156.93 ± 42.373 mg/dL to 109.37 ± 28.531 mg/dL, P = 0.000004; bolus insulin dose: 0.49 ± 0.208 U/kg/day to 0.35 ± 0.155 U/kg/day, P = 0.00032). The basal insulin dose was significantly higher at 26 weeks compared to baseline dose (0.42 ± 0.134 U/kg/day to 0.46 ± 0.139 U/kg/day, P = 0.04219). There was no significant change in BMI at 26 weeks.None of the patients experienced any DKA episode for 26 weeks. 16.7% patients had experienced at least one symptomatic hypoglycemia episode. On CGMS among the patients who were shifted from Glargine to degludec hypoglycemia were reduced significantly (overall hypoglycemia: 1.92 ± 1.26 to 0.35 ± 0.49 episodes over 3 days, P = 0.0026 while nocturnal hypoglycemia: 0.92 ± 0.47 to 0.21 ± 0.42 episodes, P = 0.0021). None of the patients had severe hypoglycemia episode. CONCLUSION: In our study IDeg is found to be safe and effective long-acting basal insulin that can be used in Indian pediatric population with T1DM. However further long term prospective studies are required to evaluate the long term effects.

Association of rheumatic fever & rheumatic heart disease with plausible early & late-stage disease markers.

BACKGROUND & OBJECTIVES: Rheumatic fever (RF) and rheumatic heart disease (RHD) are the autoimmune sequelae caused by Group A Streptococcus. RHD still remains a major concern in the developing countries due to its poor diagnosis, lack of vaccines and social awareness among population. This study was aimed to identify the plausible early- and late-stage disease markers associated with RF/RHD. METHODS: A total of 84 patients with confirmed pharyngitis (n=18), RF (n=23) and RHD (n=43) were included in the comparative analysis of different factors involved in host-pathogen interaction during RF/RHD pathogenesis. RESULTS: This study revealed high titre of serum antistreptolysin O (ASO) antibody in pharyngitis compared to RF and RHD patients, whereas procollagen type 1 C-peptide (PICP) level was elevated in RHD which showed an inverse correlation with serum ASO titre. The significant elevation of serum anti-peptide associated with RF (PARF) antibody in RF patients was correlated as a probable stage-specific determinant. In addition, pro-inflammatory cytokine profile revealed high levels of interleukin-12 (IL-12)/IL-23p40, IL-17A in RF, whereas IL-6 concentration was higher in RHD compared to healthy controls. INTERPRETATION & CONCLUSIONS: The overall assessment of the factors/ disease markers involved in host-pathogen interaction in RF/RHD may be suggestive of plausible disease marker in different groups of patients. Further studies with larger sample need to be done to better understand RF/RHD pathogenesis.

Novel mutation c.597_598dup in exon 5 of ABCC8 gene causing congenital hyperinsulinism.

Congenital hyperinsulinism (CHI), a clinically and genetically heterogeneous disease, characterized by the unregulated secretion of insulin from pancreatic ß-cells, is the most common cause of persistent hypoglycemia in infancy. Early diagnosis and maintenance of normoglycaemia are essential to prevent adverse neurodevelopmental outcomes. The most common and severe forms of CHI are caused by inactivating mutations in ABCC8 and KCNJ11 genes, encoding the two subunits of the pancreatic ß-cell ATP sensitive potassium channel (KATP). We report a case of neonatal CHI due to a novel homozygous recessive mutation in the ABCC8 gene.