Clinical and Molecular Profile of Duchenne Muscular Dystrophy (DMD): Case-Record Analysis From Uttar Pradesh, India.

OBJECTIVE: To assess the clinical and molecular profile of patients with Duchenne Muscular Dystrophy (DMD) presenting to a tertiary center in Eastern Region of Uttar Pradesh, India. METHODS: In this retrospective study, case records of all patients diagnosed as DMD were analyzed to ascertain the clinical phenotype and molecular profile. Multiplex polymerase chain reaction (PCR) technique, Multiplex Ligation Dependent Probe Amplification (MLPA) and Next Gen Sequencing (NGS) were used for establishing the molecular diagnosis. Leiden Open Variation Database (LOVD) frame checker online tool was used to predict clinical severity of the cases. RESULTS: Records of 112 children with DMD were analyzed. The median (IQR) age of onset and clinical presentation of disease was 60 (12, 132) months and 90 (33, 156) months, respectively. The most common clinical presentations were difficulty in standing from sitting position (n = 107), difficulty in climbing stairs (n = 106), and difficulty in walking (n = 99). Bilateral calf muscle hypertrophy and a positive Gower's sign was seen in 110 and 108 patients at presentation. The median (IQR) creatinine phosphokinase (CPK) levels at diagnosis were 6296.5 (4320, 7432.5) U/L. The genetic mutations in 111 patients were reported as deletion (n = 105), duplication (n = 3), and point variation (n = 3). 22 patients could benefit from the available exon skipping therapy. Exondys (exon 51 skipping) could be used in 14 patients. CONCLUSION: Deletion mutations were recorded in a much higher proportion of patients compared to previous studies from India. There were 22 patients who could have been benefitted by present available exon skipping therapy.

Pre-hospital care, pre-hospital delay, and in-hospital delay in patients with traumatic brain injury in getting neurosurgical care in a tertiary care center: A Cross-Sectional study.

INTRODUCTION: Timely institution of pre-hospital therapies aimed at damage control and the appropriately timed decision of transfer to higher centers for definitive neurosurgical management are crucial in determining the outcome of patients following traumatic brain injury. This study aimed to evaluate the factors determining pre-hospital care and delay in patients with traumatic brain injury. METHODS: This was a descriptive cross-sectional study conducted in a tertiary care center after obtaining ethical approval from the Institutional Review Board (approval number 392 (6-11) E2). All patients with traumatic brain injury who presented to the emergency department from 1 July, 2018 to 15 June, 2019 were enrolled. Data related to patient demographics, the primary cause of the incident, grading of traumatic brain injury on admission, pre-hospital care, and variables that cause pre-hospital delay were collected. RESULTS: In this study of 144 patients with traumatic brain injury, we found that 70 (48.61%) experienced transfer delays exceeding one hour. There were 71 (49.31%) patients aged 15-44 years, and 100 (69.44%) were males , with falls being the primary cause of 119 (82.64%). Most patients had mild traumatic brain injury 80 (55.56%). Out of 144, 20 (13.89%) received prehospital care, and 28 (19.44%) underwent a computed tomography scan of the head before arrival. CONCLUSIONS: Our study highlights the challenges in pre-hospital care and delays in reaching for neurosurgical care in patients with traumatic brain injury. Falls, road accidents, and physical assaults were the leading causes.

Geochemical and mineralogical assessment of environmentally sensitive elements in Neyveli lignite deposits, Cauvery Basin, India.

This research work presents an examination of the concentrations and modes of occurrence of environmentally sensitive elements within lignite deposits, located in Neyveli, within the Cauvery Basin of India. Coal is one of the most complex geologically formed materials, consisting of organic and inorganic matter. The inorganic mineral matter including the crystalline minerals, non-crystalline mineraloids, and elements with non-mineral associations. These lignite samples underwent complete analysis encompassing macroscopic, microscopic and geochemical assessments. The analysis reveals that the total mineral matter (MM) content, comprising significant proportions of sulphides, carbonate and argillaceous components. Geochemical characterization further elucidates the lignite's properties, with proximate analysis yielding values such as ash, volatile matter and fixed carbon and the Ultimate components analysis reveals the carbon, hydrogen, nitrogen, sulphur and oxygen. Inorganic mineral matters play a significant role in coal utilization, and also such modes of occurrence of elements provide useful geochemical information on coal formation and coal-bearing basin evolution. In this paper, we assess the associations of elements and minerals, as well as the associations of selected elements including environmentally-sensitive (e.g., S, As, U, and Hg), and some major elements (e.g., Ca, Mg, Fe, Al, and Ti) that have largely occurred in non-mineral forms in these low-rank coals. And also, comparative analysis is conducted between the concentrations of elements within the lignite samples and the values reported for World Clarke Brown Coals (WCBC). Particularly, some of these elements exhibit significantly high environmental sensitivity, demanding careful consideration in lignite extraction and utilization practices.

Isolation and Identification of Yeasts in Marcha, a Rice Wine Starter Culture From Nepal.

Nepal harbors a rich diversity of cultures and traditions, including the unique practice of creating an indigenous grain called Marcha by various ethnic groups such as Newar, Tamang, Sherpa, Rai, Limbu, Gurung, Magar, and Tharu people. In the eastern region of Nepal, Marcha producers utilize over 42 different plants, including Vernonia cinerea, Clematis grewiae, Polygala arillata, Buddleja asiatica, Inula sp., Scoparia, and more, which shows regional diversity. The primary objective of the study was to explore the diversity of yeast present in Marcha samples. The studied Marcha samples were collected from 10 different geographic regions of Nepal, which included altogether 27 samples. The isolates were grouped into Groups A, B, and C based on morphological and physiological characteristics. Notably, Group B yeast displayed high amylase production, an enzyme responsible for starch breakdown, and exhibited the ability to produce ethanol. To further investigate the potential of these isolates, stress exclusion tests were conducted, with 30 isolates (70%) showing positive responses. The yeast isolates demonstrated resilience to high glucose concentrations of up to 36% (w/v) at a pH above 3 and a temperature of 37°C, which is the ideal growth condition. The study observed a direct correlation between the yeast isolates' ethanol production capabilities and their tolerance to different ethanol concentrations. Considering that all tested Marcha samples contained yeast capable of starch degradation and ethanol production, it was expected that these yeast isolates would actively participate in the fermentation of starch-based alcohol.

Ileal perforation peritonitis secondary to accidental ingestion of a chicken bone: A case report.

INTRODUCTION AND IMPORTANCE: Ileal perforation is a rare but serious condition that can arise from accidental ingestion of foreign objects. This report discusses an unusual case of ileal perforation peritonitis caused by ingestion of a chicken bone. CASE PRESENTATION: A 60-year-old male presented with acute generalized abdominal pain, fever, nausea, and vomiting for three days. A physical examination revealed signs of peritonitis. Imaging results were unremarkable. Emergency laparotomy revealed perforation in the ileum caused by the chicken bone. The perforated segment was resected, and primary anastomosis was performed. CLINICAL DISCUSSION: Ingestion of foreign bodies, although common, rarely leads to gastrointestinal perforations. Among these foreign bodies, chicken bones are rarely reported, making the diagnosis challenging because of nonspecific symptoms and low clinical suspicion. Prompt surgical intervention is crucial for managing complications such as peritonitis and sepsis. CONCLUSION: This case highlights the importance of considering foreign body ingestion in the differential diagnosis of acute abdominal pain, particularly in patients without an obvious cause of peritonitis. Early detection and timely surgical intervention are essential to improve patient outcomes.

Atypical case of tuberous sclerosis with isolated neurologic findings: A case report.

Tuberous sclerosis (TSC) is an autosomal dominant neurocutaneous disorder. This case highlights rare isolated neurologic finding in a TSC patient emphasizing the need for heightened suspicion even in the absence of any cutaneous findings and family history.

Investigational new drugs for the treatment of leishmaniasis.

INTRODUCTION: Over the past 20 years, significant progress has been made in anti-leishmanial therapy. Three new drugs/formulations are available for the treatment of various forms of leishmaniasis, namely oral miltefosine, paromomycin and liposomal amphotericin B. However, these advances in drug development have added considerable complexity for clinicians including toxicity, emergence of resistance and decreased sensitivity of available drugs. The development of newer drugs with less toxicity and more efficacy is urgently needed. AREAS COVERED: This review comprehensively examines the latest developments and current status of antileishmanial drugs for the treatment of leishmaniasis across the world. Several new investigational drugs that showed anti-leishmanial activity under in vitro or in vivo conditions and either underwent the phase-I/II clinical trials or are on the verge of entering the trials were reviewed. We also delve into the challenges of drug resistance and discuss the emergence of new and effective antileishmanial compounds. EXPERT OPINION: The available treatments for leishmaniasis are limited in number, toxic, expensive, and demand extensive healthcare resources. Every available antileishmanial drug is associated with several disadvantages, such as drug resistance and toxicity or high cost. Miltefosine is potentially teratogenic. New antileishmanial drugs/treatment modalities are sorely needed for expanding future treatment options.

Quality by design (QbD) based approach for development of itraconazole-loaded transferosomes for skin cancer: in vitro, ex vivo and cell line studies.

OBJECTIVE: Itraconazole (ITZ), a widely used systemic antifungal drug, has been ingeniously repurposed for its antitumor effects. In the present work, we have prepared and optimized the ITZ-loaded transferosomes by Quality by Design (QbD) approach and repurposed them for skin cancer. METHODS: The transferosomal formulation was optimized by employing a QbD approach with the design of experiment. A combination of screening and optimization design was used for formulation optimization. The optimized formulation was characterized by particle size, PDI, zeta potential, FTIR, XRD, and surface morphology using TEM. In vitro and ex vivo studies were performed using Franz diffusion cells. An in vitro cell line study was performed on the human melanoma A375 cell line. RESULTS: The optimized formulation has a particle size of 192.37 ± 13.19 nm, PDI of 0.41 ± 0.03, zeta potential -47.80 ± 3.66, and an entrapment efficiency of 64.11 ± 3.75%. In vitro release studies showed that ITZ encapsulated transferosomes offer higher and sustained release than pure drugs. Ex vivo drug penetration and retention studies show that the penetration and retention of transferosomes are more visible in the skin than in the drug. The cell viability study confirms that ITZ encapsulated transferosomes have almost 2-fold more potency against the A375 cell line than pure drug. CONCLUSION: ITZ encapsulated transferosomes were successfully prepared and optimized using a combination of screening and optimization designs. Based on ex vivo and cell line studies, we conclude that ITZ-loaded transferosomes could aid melanoma management alongside standard therapies.

Rh(III)-catalyzed aldehydic and aryl C-H alkylation with cyclopropanols via C-H/C-C bond activation.

Herein, we report Rh(III) catalyzed aldehydic or aryl C-H alkylation via C-C bond activation of cyclopropanols, facilitating the synthesis of ß-functionalized ketones. The protocol employs cyclopropanol as the alkylating agent with 2-aminobenzaldehyde or aniline derivatives to access a variety of unsymmetrical 1,4-diketones or ß-aryl ketones, respectively. The practicality of these transformations is showcased through the modification of natural products, gram-scale synthesis, broad substrate scope and postfunctionalizations.

A cub and sushi domain-containing protein with esterase-like activity confers insecticide resistance in the Indian malaria vector Anopheles stephensi.

Chemical insecticides (organophosphates and pyrethroids) in the form of IRS (Indoor Residual Sprays) and LLINs (Long Lasting Insecticidal Nets) are the cornerstone for vector control, globally. However, their incessant use has resulted in widespread development of resistance in mosquito vectors, warranting continuous monitoring and investigation of the underlying mechanisms of resistance. Here, we identified a previously uncharacterized- Cub and Sushi Domain containing Insecticide Resistance (CSDIR) protein and generated evidence for its role in mediating insecticide resistance in the Anopheles stephensi. A strong binding affinity of the CSDIR protein towards different classes of insecticide molecules-malathion (KD 6.43 µM) and deltamethrin (KD 46.7 µM) were demonstrated using MD simulation studies and Surface Plasmon Resonance (SPR) experiments. Further, the recombinant CSDIR913-1190 protein exhibited potent esterase-like activity (α-naphthyl acetate (α-NA)- 1.356 ± 0.262 mM/min/mg and ß-naphthyl acetate (ß -NA)- 1.777 ± 0.220 mM/min/mg). Interestingly, dsRNA-mediated gene silencing of the CSDIR transcripts caused >60% mortality in resistant An. stephensi upon 1-h exposure to deltamethrin and malathion insecticides, compared to the control group. A significant reduction in the esterase-like activity was also observed against α-NA (p = 0.004) and ß-NA (p = 0.025) in CSDIR silenced mosquitoes compared to the control group. Using computational analysis and experimental data, our results provided significant evidence of the involvement of the CSDIR protein in mediating insecticide resistance in Anopheles mosquitoes. Thereby making the CSDIR protein, a novel candidate for exploration of novel insecticide molecules. These data would also be helpful in further understanding the development of metabolic resistance by the Anopheles vector.

Unravelling wheat genotypic responses: insights into salinity stress tolerance in relation to oxidative stress, antioxidant mechanisms, osmolyte accumulation and grain quality parameters.

BACKGROUND: Salt stress is a prominent abiotic stressor that imposes constraints on grain yield and quality across various crops, including wheat (Triticum aestivum). This study focused on assessing the genetic diversity of 20 wheat genotypes categorized as tolerant, moderately tolerant, and sensitive with three genotypes of unknown tolerance. To address salinity stress-related problems, different morpho-physiological, osmoprotectant, biochemical, yield, and grain quality-related parameters were analyzed under control (pH 8.0, EC 3.9) and saline-sodic (pH 9.4, EC 4.02) conditions in field. RESULTS: Findings revealed noteworthy variations among the genotypes in response to salinity stress. Greater accumulation of Na+ and lower K+ content were observed in response to salt stress in the sensitive varieties HD1941 and K9162. Proline, a stress indicator, exhibited significantly (p ≤ 0.05) greater accumulation in response to salinity stress, particularly in the tolerant cultivars KRL210 and KH65. Salt stress induced the most significant decrease (p ≤ 0.05) in spike length, thousand-grain weight, and hectolitre weight coupled with increased protein content in sensitive varieties, resulting in diminished yield. CONCLUSION: Correlation analysis of parameters under salinity stress showed that SOD, proline, and K+ contents can be used as the most efficient screening criteria for salinity stress during early developmental stages. Principal component analysis revealed that DBW187, DBW303, and DBW222 varieties were tolerant to salinity stress and exhibited an effective antioxidant system against salinity. This study will facilitate salt-tolerant wheat breeding in terms of the identification of tolerant lines by screening for limited traits in a wide range of germplasms.

Acute myocardial infarction or Takotsubo syndrome in a patient with stunned myocardium due to myocardial bridging? A case report of diagnostic dilemma clarified after serial workup.

BACKGROUND: Myocardial bridging is a cardiac anomaly where a segment of epicardial coronary arteries runs through the myocardium and can rarely cause MI. Takotsubo syndrome is a stress-induced cardiomyopathy that can mimic MI. Catecholamine surge during stress can contribute to Takotsubo syndrome, but whether this surge can trigger an inconspicuous myocardial bridging to manifest symptomatically remains unclear, and alternately, whether a myocardial bridge might cause worsening of Takotsubo syndrome is also a matter that needs further research. CASE PRESENTATION: We report the case of a patient who initially presented with features of acute exacerbation of bronchiectasis and subsequently developed symptoms and ECG features suggestive of acute myocardial infarction. Echocardiography revealed features of takotsubo syndrome, and complete myocardial bridging was revealed via coronary angiography. The patient was managed conservatively with pharmacological treatment, and after a few days, echocardiographic features were reversed. As such, the diagnosis shifted toward Takotsubo syndrome with myocardial stunning due to co-existent myocardial bridging. CONCLUSION: We report a rare case of a patient with acute bronchiectasis exacerbation with features suggestive of acute myocardial infarction who had findings of Takotsubo syndrome and complete myocardial bridging. In the beginning, it was difficult to determine whether the symptoms arose due to acute MI resulting from myocardial bridging or were solely due to takotsubo syndrome because of stress from bronchiectasis. Although myocardial bridging is often overlooked as an etiology for acute MI, this case highlights the importance of expanding the differential diagnosis to myocardial bridging in the work-up for the cause of acute MI and how Takotsubo syndrome can mimic acute MI and pose a diagnostic challenge.

Atypical Aggressive Hemangioma of Thoracic Vertebrae Associated With Thoracic Myelopathy-A Case Report and Review of the Literature.

Aggressive thoracic hemangiomas are rare, benign tumors that extend into the spinal canal and cause neurological symptoms. Delayed diagnosis and treatment, due to a paucity of literature on optimal treatment strategies, can increase morbidity. This case report describes a 19-year-old male patient with aggressive thoracic hemangioma who presented with upper back pain and progressive weakness of the lower extremities. The patient underwent preoperative embolization and sclerotherapy, followed by decompression, posterior instrumentation, and stabilization. The final diagnosis was confirmed by biopsy, and there was a significant improvement in neurology after the surgical intervention. The diagnosis of rare lesions, such as aggressive hemangiomas, requires a high level of clinical suspicion and the assistance of imaging modalities in patients with features of compressive myelopathy. A combination of endovascular and surgical approaches can lead to optimal outcomes.

Neighborhood environment and quality of life of older adults in eastern Nepal: findings from a cross-sectional study.

INTRODUCTION: Quality of life (QoL) is a subjective measure reflecting individuals' evaluations based on their personal goals and values. While global research shows the role of neighborhood factors like ethnic diversity and socio-cultural dynamics on QoL, these are unexplored in the Nepali context. Therefore, this study examined the relationship between neighborhood environment and QoL among Nepali older adults in eastern Nepal. METHODS: This cross-sectional study involved 847 non-institutionalized older adults (aged ≥ 60 years) from two districts in eastern Nepal. QoL was evaluated using the 13-item brief Older People's Quality of Life questionnaire, where a mean score of < 3 indicated low/poor QoL. The neighborhood environment, conceptualized across three domains (demographic, socio-cultural, and built environment), included ethnic diversity, connections with family, friends, and neighbors, cultural ties, residential stability, and rurality. Their association with QoL was examined using multivariable logistic regression. RESULTS: Around 20% of older adults reported poor QoL. Higher ethnic diversity (adjusted Odds Ratio [aOR] = 0.12, 95% confidence interval [CI]: 0.04-0.36), moderate contact with family and relatives (aOR = 0.26, CI: 0.11-0.61), and high contact with neighbors (aOR = 0.09, CI: 0.03-0.21) were associated with lower odds of poor QoL. Conversely, high contact with friends (aOR = 2.29, CI: 1.30-4.04) and unstable residence (OR = 6.25, CI: 2.03-19.23) increased the odds of poor QoL. Additionally, among the covariates, chronic disease, tobacco use, unemployment, and lack of education were also significantly associated with poor QoL. CONCLUSION: Overall, the demographic environment, socio-cultural factors, and the built environment of the neighborhood influence QoL. Therefore, diversifying the neighborhood's ethnic composition, promoting social connections such as frequent contact with family, relatives, and neighbors, and ensuring residential stability can enhance the QoL of older adults.

Visualization of sheep kidney vasculature by modified corrosion cast technique.

Not applicable for Letter.

In vitro mutagenesis using habituation and PBR autotrophy based indirect somatic embryogenesis (ISE) system in Kinnow mandarin.

Solid mutant induction using specialized habituation and PBR (Plant bio-regulator) autotrophy-mediated suspension-based ISE system was the prime aim of present investigation. Based on survival of cell clumps after mutagen treatment, the probit analysis was calculated. The result revealed LD50 at 54.31 Gy in gamma, while for EMS (ethyl methanesulfonate), it was 0.1% for 3 h and 0.5% for 1 h. Based on embryogenesis efficiency, a dose rate of 100 Gy and 0.1% EMS for a 3-h exposure were selected for regeneration. As compared to control, significant decrease in the embryogenesis efficiency was recorded at 100 Gy (85.92%) with similar reduction trends in embryo production (79.49%), germination (13.43%), conversion (2.48%), establishment (15.78%) and acclimatization (60.92%). The growth-related parameters such as root and shoot length and number of leaves/regenerant were also significantly reduced to 67.29%, 30.19% and 5.03%, respectively, in the regenerated plants after gamma irradiation as compared to control. In the EMS treatment, at the dose rate of 0.1% for 3-h, the embryogenesis efficiency was reduced to 43.67% with similar diminution trends in embryo production (59.49%), germination (8.95%), conversion (1.94%), establishment (4.37%) and acclimatization (29.9%). The growth-related parameters in the EMS treatment, decreased to 91.00% (root length), 71.34% (shoot length) and 35.03% (no. of leaves). The molecular marker based varied amplifications confirmed the occurrence of mutations in both gamma and EMS induced M1 regenerants. The study highlights the alternative high frequency in vitro mutagenesis protocol for induction of solid mutants in Kinnow mandarin and related citrus species.

Palladium(ii) complexes bearing mesoionic carbene ligands: catalytic application in domino Sonogashira coupling/cyclization reactions for one-pot synthesis of benzofuran and indole derivatives.

Bioactive heterocycles such as benzofuran and indole derivatives were synthesized from commercially available 2-iodoarenes and alkynes via domino Sonogashira coupling followed by cyclization reaction using well-defined palladium PEPPSI (Pyridine Enhanced Precatalyst Preparation Stabilization and Initiation) complexes (2a and 2b). These reactions tolerate a variety of 2-iodoarenes and diversely substituted terminal alkynes, resulting in the corresponding product in moderate to good yields in an open-air atmosphere. In particular, two palladium(ii) PEPPSI complexes 2a and 2b were synthesized in good yields from the reaction of corresponding 1,2,3-triazol-5-ylidene (MIC: mesoionic carbene), PdCl2, KI, and K2CO3 in pyridine at 110 °C and structurally characterized by various spectroscopic techniques including NMR spectroscopy, IR spectroscopy, HRMS and elemental analysis studies. Complex 2b is also characterized by X-ray crystallography.

Development and validation of stability indicating assay method for mitapivat: Identification of novel hydrolytic, photolytic, and oxidative forced degradation products employing quadrupole-time of flight mass spectrometry.

Mitapivat is a novel, first-in-class orally active pyruvate kinase activator approved by the US Food and Drug Administration in 2022 for the treatment of hemolytic anemia. There is no literature available regarding the identification of degradation impurities of mitapivat. The present study deals with the degradation behavior of mitapivat under various stress conditions such as hydrolytic, photolytic, thermal, and oxidative stress. The multivariate analysis found that the independent variables, that is, molarity, temperature, and time, are interacting with each other to affect the degradation of mitapivat. A specific, accurate, and precise high-performance liquid chromatographic (HPLC) method was developed to separate mitapivat from its degradation products. The separation was achieved on the C-18 column (250 mm × 4.6 mm × 5 µm) using the combination of 0.1% formic acid buffer and acetonitrile in gradient elution profile. The method was validated as per the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use Q2(R2) guideline. LC-electrospray ionization-Quadrupole-time of flight was employed to identify degradation products. A total of seven novel degradation products of mitapivat were identified based on tandem mass spectrometry and accurate mass measurement. In-silico toxicity of mitapivat and its degradation products was qualitatively evaluated by the DEREK toxicity prediction tool.

Tropical root responses to global changes: A synthesis.

Tropical ecosystems face escalating global change. These shifts can disrupt tropical forests' carbon (C) balance and impact root dynamics. Since roots perform essential functions such as resource acquisition and tissue protection, root responses can inform about the strategies and vulnerabilities of ecosystems facing present and future global changes. However, root trait dynamics are poorly understood, especially in tropical ecosystems. We analyzed existing research on tropical root responses to key global change drivers: warming, drought, flooding, cyclones, nitrogen (N) deposition, elevated (e) CO2, and fires. Based on tree species- and community-level literature, we obtained 266 root trait observations from 93 studies across 24 tropical countries. We found differences in the proportion of root responsiveness to global change among different global change drivers but not among root categories. In particular, we observed that tropical root systems responded to warming and eCO2 by increasing root biomass in species-scale studies. Drought increased the root: shoot ratio with no change in root biomass, indicating a decline in aboveground biomass. Despite N deposition being the most studied global change driver, it had some of the most variable effects on root characteristics, with few predictable responses. Episodic disturbances such as cyclones, fires, and flooding consistently resulted in a change in root trait expressions, with cyclones and fires increasing root production, potentially due to shifts in plant community and nutrient inputs, while flooding changed plant regulatory metabolisms due to low oxygen conditions. The data available to date clearly show that tropical forest root characteristics and dynamics are responding to global change, although in ways that are not always predictable. This synthesis indicates the need for replicated studies across root characteristics at species and community scales under different global change factors.