Whitaker syndrome: A case report of autoimmune polyendocrine syndrome type 1 with dilated cardiomyopathy.

Key Clinical Message: This case report highlights dilated cardiomyopathy as a cardiovascular complication in autoimmune polyendocrine syndrome type 1 (APS-1), emphasizing the need for early recognition and a multidisciplinary approach. Comprehensive care and regular follow-up are crucial in managing these atypical presentations to optimize patient outcomes. Abstract: APS-1, also known as Whitaker syndrome, is characterized by a triad of mucocutaneous candidiasis, adrenal insufficiency, and hypoparathyroidism. This rare autosomal recessive disorder results from mutations in the autoimmune regulator (AIRE) gene. Cardiovascular and pulmonary manifestations in APS-1 are infrequently reported in the literature. We present a case of a 28-year-old male who presented with shortness of breath and pedal edema. Physical examination revealed alopecia, absence of eyebrows, hyperpigmentation on joints, oral candidiasis, and nail dystrophy. Echocardiography demonstrated dilated cardiomyopathy (DCM) and pericardial effusion. Chest x-ray showed left-sided pleural effusion. Laboratory investigations revealed hypocalcemia, hyperphosphatemia, low parathyroid hormone (PTH), low cortisol, and high adrenocorticotropic hormone (ACTH) levels. The combination of chronic mucocutaneous candidiasis (CMC), hypoparathyroidism, and adrenal insufficiency confirmed the diagnosis of APS-1. To the best of our knowledge, this is the first Pakistani and second worldwide reported case of APS-1 presenting with such a combination of manifestations. Early recognition and multidisciplinary management are crucial for improving outcomes in these patients.

Pheochromocytoma and Thyroid Storm Presenting as ST-Elevation Myocardial Infarction in a Patient with Non-Obstructive Coronary Arteries.

Introduction: Pheochromocytomas can present as a diagnostic challenge, given their diverse clinical manifestations. Though classically taught as presenting with headaches, palpitations and paroxysmal hypertension, only 1 in 4 present with such a triad. Catecholamines affect the myocardium in various ways, ranging from beta-adrenergic receptor-mediated myofibril dysfunction to direct myocardial injury by catecholamine oxidation products. Case description: We report the case of a 41-year-old female with no significant past medical history, who presented with acute coronary syndrome. She was found to have myocardial infarction with non-obstructive coronary arteries (MINOCA), and her clinical course was complicated by erratic blood pressure management. Laboratory findings and imaging findings confirmed the diagnosis of pheochromocytoma. Post-cardiac catheterisation, she developed a thyroid storm and fatal cardiac arrest. Conclusions: The combination of hyperthyroidism with pheochromocytoma is rare but often fatal; iodinated angiography contrast likely precipitated her thyroid storm. This case underscores the importance of considering pheochromocytoma early in patients with MINOCA, particularly in those with erratic blood pressure. Pheochromocytomas have been reported to be associated with MINOCA in rare cases and have significant mortality. Current guidelines do not include pheochromocytoma as a possible differential diagnosis; recognition and early diagnosis are crucial for improved outcomes. LEARNING POINTS: Pheochromocytoma and thyroid disease should be added as recommended differential diagnoses in patients with myocardial infarction with non-obstructive coronary artery disease (MINOCA) despite current guidelines not including them in the routine work-up.For patients with erratic blood pressure and MINOCA, the possibility of a pheochromocytoma should be considered early, as a prompt diagnosis can result in favourable outcomes.

Utilization of Aspergillus niger for the fermentative production of azaphilone dye in YEPB medium.

The current research focuses on the production and optimization of a natural yellowish-brown Azaphilone dye using Aspergillus niger. A variety of culture media were tested to ascertain the best conditions for dye synthesis. The formation of the yellowish-brown dye was confirmed by a color shift in the reaction mixture, and UV-Vis spectroscopy detected the dye at 450 nm. Static conditions were found to be more favorable than shaking for higher dye yields, and fed-batch fermentation was more effective than batch fermentation. Maximum dye production was achieved after 28 days of incubation. Factors such as temperature, pH, and inoculum percentage were shown to influence dye synthesis, with the highest production (2.5 ml) occurring at 30 °C, pH 7, and a 3% spore suspension in yeast extract peptone broth (YEPB) medium under static conditions. Gas chromatography-mass spectrometry (GC-MS) analysis validated the presence of Azaphilone dye in the culture filtrate. The dye was successfully applied to a pretreated cotton cloth. These findings advance our understanding of optimizing fungal dye production for sustainable and eco-friendly textile coloration applications. This study appears to be the first of its kind to report azaphilone dye production by A. niger in the YEPB medium.

Adaptive evolution and functional significance of the PPARGC1A gene across diverse animal species.

Codon-based analyses of the PPARGC1A gene across 38 vertebrate species were deployed to elucidate patterns of evolutionary change. Employing maximum likelihood assessments through MEGA, we scrutinized 447 codon positions addressing the entire coding region, excluding positions mired by gaps or missing data. Distinct codons manifested variance in selection pressures, particularly codons 4, 11, 66, and 123, which exhibited positive dN-dS values suggestive of positive selection. Codon 137 displayed the most pronounced dN-dS value, signifying intensified selective advantage. Meanwhile, codons 30 and 90 portrayed near-neutral scores, indicative of purifying selection. Complementary computational methods (IFEL, REL, FUBAR, and SLAC) confirmed positive selection at specific codon sites, with varying degrees of corroboration. The integration of mixed-effect modeling (MEME) identified episodic diversifying selection, pinpointing codons that underwent selection episodes in certain lineages. Refined codon model selection lent insight into substitution rates, revealing nuanced degrees of evolutionary conservation among different codons. Supporting these genetic insights, the phylogenetic analysis highlighted relationships among the PPARGC1A sequences and domain analysis confirmed conserved features across species, while protein-protein interaction networks suggested a complex web of functional interdependencies. These findings advance our understanding of the PPARGC1A gene's evolutionary trajectory and underscore the gene's potential adaptive significance within diverse vertebrate lineages.

Metabolomics reveals a key role of salicylic acid in embryo abortion underlying interspecific hybridization between Hydrangea macrophylla and H. arborescens.

KEY MESSAGE: Embryo abortion at the heart-shaped stage is the main reason for the failure of interspecific hybridization of hydrangea, and salicylic acid plays a key role during embryo abortion. Difficulties in obtaining seeds from interspecific hybridization between Hydrangea macrophylla and H. arborescens had severely restricted the process of breeding new hydrangea varieties. To clarify the cause of reproductive barriers, an interspecific hybridization was made between H. macrophylla 'Endless Summer' (female parent) and H. arborescens 'Annabelle' (male parent). The results showed that both parents' floral organs developed normally, 'Annabelle' had high pollen viability (84.83% at 8 h after incubation), and the pollen tube could enter into the ovule of 'Endless Summer' at 72 h after pollination. Therefore, the pre-fertilization barrier was not the main reason for the failure of interspecific hybridization. However, observation of the embryo development by paraffin sections showed that the embryo was aborted at the heart-shaped stage. In addition, salicylic acid (SA) content was significantly higher (fourfold, P < 0.01) at 21 days after pollination (DAP) as compared to that of 17 DAP, which means SA may be closely correlated with embryo development. A total of 957 metabolites were detected, among which 78 were significantly different. During the embryo abortion, phenylpropanoids and polyketides were significantly down-regulated, while organic oxygen compounds were significantly up-regulated. Further analysis indicated that the metabolic pathway was enriched in the shikimic acid biosynthesis pathway, which suggests that more SA was synthesized. Taken together, it can be reasonably speculated that SA plays a key role leading to embryo abortion underlying the interspecific hybridization between Hydrangea macrophylla and H. arborescens. The result is helpful to direct the breeding of hydrangea through distant hybridization.

Graphene oxide-based materials as proton-conducting membranes for electrochemical applications.

The rapid advancements of graphene oxide (GO)-based membranes necessitate the understanding of their properties and application potential. Generally, proton (H+)-conducting membranes, including GO-based ones, are crucial components in various energy-relevant devices, significantly determining the transport process, selectivity, and overall efficiency of these devices. Particularly, GO-based membranes exhibit great potential in electrochemical applications owing to their remarkable conductivity and ease of undergoing further modifications. This review is aimed at highlighting recent functionalization strategies for GO with diverse substrates. It is also aimed at emphasizing how these modifications can enhance the electrochemical performances of GO-based membranes. Notably, key aspects, such as the enhanced H+-transfer kinetics, improved conductivity, functionalities, and optimization, of these membranes for specific applications are discussed. Additionally, the existing challenges and future directions for the field of functionalized GO are addressed to achieve precise control of the functionalities of these membranes as well as advance next-generation electrochemical devices.

Effect of Intensive Blood Pressure Lowering on the Risk of Incident Silent Myocardial Infarction: A Post Hoc Analysis of a Randomized Controlled Trial.

BACKGROUND: Silent myocardial infarction (SMI) frequently goes undetected, yet it is associated with increased cardiovascular morbidity and mortality. The impact of intensive systolic blood pressure (SBP) lowering on the risk of SMI in those with hypertension remains uncertain. METHODS: In this post hoc analysis of the Systolic Blood Pressure Intervention Trial (SPRINT), participants with serial electrocardiograms (ECGs) during the trial were included. SPRINT investigated the benefit of intensive SBP lowering, aiming for < 120 mmHg compared to the standard SBP goal of < 140 mmHg. Incident SMI was defined as evidence of new MI on an ECG without adjudicated recognized myocardial infarction (RMI). RESULTS: During a median follow-up of 3.9 years, a total of 234 MI events (55 SMI and 179 RMI) occurred. Intensive, compared to standard, SBP lowering resulted in a lower rate of SMI (incidence rate 1.1 vs. 2.3 cases per 1000 person-years, respectively; HR [95% CI]: 0.48 [0.27-0.84]). Similarly, intensive, compared to standard, BP lowering reduced the risk of RMI (incidence rate 4.6 vs. 6.5 cases per 1000 person-years, respectively; HR [95% CI]: 0.71 [0.52-0.95]). No significant differences were noted between the strength of the association of intensive BP control on lowering the risk of SMI and RMI (p-value for HR differences = 0.23). CONCLUSIONS: This study shows that in adults with hypertension, the benefits of intensive SBP lowering, compared with standard BP lowering, go beyond the prevention of RMI to include the prevention of SMI. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01206062.

Assessment of Respiratory Health Implications of Vaping: A Systematic Review of Toxicity Mechanisms and Adverse Effects of Electronic Nicotine Delivery Systems.

E-cigarettes are thought to aid in tobacco smoking cessation, but there are concerns about their overall effectiveness and safety for the general population, particularly adults. This review aims to investigate the mechanisms of toxicity and adverse effects of e-cigarettes on the respiratory system, comparing these effects with those of conventional smoking. A systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Searches were performed on PubMed, Embase, and the Cochrane Library using keywords, controlled vocabulary, and text words, with the following criteria: studies published in English from 2014 to 2024, open access, peer-reviewed, and full-text availability. Study selection, quality assessment, and data extraction were carried out by two independent reviewers. The Cochrane Risk of Bias 2.0 tool was used to evaluate the risk of bias in included randomized controlled trials, and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) tool was employed to assess the strength of evidence and determine its generalizability. Electronic nicotine delivery systems (ENDS) have diverse mechanisms of toxicity, including inflammation, hypoxia, cardiovascular stress, and metabolic changes. Reported adverse effects include cough, throat irritation, nausea, and hemodynamic changes. However, ENDS are associated with fewer risks compared to conventional cigarette smoking. ENDS users experience fewer respiratory and cardiovascular issues and have lower levels of biomarkers such as NNAL and CO compared to traditional smokers. Additionally, ENDS are more effective than nicotine replacement therapy (nicotine patches) for smoking cessation, particularly in pregnant women. The side effects of ENDS and nicotine-free vaping are similar to those of conventional smoking in pregnant women, with the exception of a lower birth weight among newborns exposed to ENDS (p < 0.05). ENDS present a complex balance of benefits and risks regarding respiratory health. While there are adverse effects, ENDS are considered less detrimental than conventional smoking and a viable option for smoking cessation. Longitudinal studies are needed to evaluate their safety with long-term use (>16 weeks). Policymakers and health practitioners should use these findings to develop balanced public health policies that weigh the benefits of ENDS against potential health risks, enabling informed decision-making for users.

Intraoperative Ketamine and Pain after Video-Assisted Thoracoscopic Surgery (VATS): A Systematic Review and Meta-analysis.

BACKGROUND: Video-assisted thoracoscopic surgery (VATS) reduces postoperative discomfort and expedites recovery compared to open thoracotomy. Effective postoperative pain management is crucial to enhance recovery and reduce complications. Ketamine, an NMDA receptor antagonist, has shown promise, though its efficacy in VATS remains uncertain. This meta-analysis aims to evaluate the efficacy and safety of ketamine in reducing acute pain in VATS patients. METHODS: A comprehensive search of MEDLINE (PubMed), CENTRAL, Embase, Science Direct, Scopus, and clinicaltrials.gov was conducted. Eligible studies were randomized controlled trials (RCTs) comparing intraoperative intravenous ketamine with normal saline in VATS patients and reporting postoperative pain scores. Statistical analyses were performed using R version 4.3.3. Cochrane risk of bias (RoB2) tool was used to assess the quality of included studies. RESULTS: A total of 10 RCTs with 1,151 participants were included. Ketamine was associated with a significant reduction in postoperative pain at 12 (MD -0.65, p = 0.04) and 48 hours (MD -0.55 points, p < 0.01) post-surgery. No significant difference was observed in pain scores within the first 3 hours, at 6 and 12 hours, 24-h postoperative opioid consumption, urine output, surgery duration, rescue analgesia, mean arterial pressure, infusion volume, heart rate, extubation time, and blood loss. The certainty of evidence ranged from moderate to low across the outcomes. CONCLUSIONS: Intraoperative intravenous ketamine effectively reduces acute postoperative pain in VATS patients but does not significantly impact opioid consumption, hemodynamic parameters, and adverse events. Large-scale studies are needed to confirm these findings and explore ketamine's potential benefits for chronic pain management. REGISTRATION: PROSPERO (CRD42024527858).

Genome wide analysis of HMA gene family in Hydrangea macrophylla and characterization of HmHMA2 in response to aluminum stress.

Aluminum toxicity poses a significant threat to plant growth, especially in acidic soils. Heavy metal ATPases (HMAs) are crucial for transporting heavy metal ions across plant cell membranes, yet their role in Al3+ transport remains unexplored. This study identified eight HmHMA genes in the genome of Hydrangea macrophylla, categorizing them into two major clades based on phylogenetic relationships. These genes were found unevenly distributed across six chromosomes. Detailed analysis of their physicochemical properties, collinearity, and gene structure was conducted. RNA-seq and qRT-PCR analyses revealed that specific HmHMA genes, notably HmHMA2, were predominantly expressed in roots and flowers under Al3+ stress, indicating their potential role in Al3+ tolerance. HmHMA2 showed significant expression in roots, especially under Al3+ stress conditions, and when expressed in yeast cells, it conferred resistance to aluminum and zinc but increased sensitivity to cadmium. Overexpression of HmHMA2 in hydrangea leaf discs significantly improved Al3+ tolerance, reduced oxidative stress markers like hydrogen peroxide and malondialdehyde, and enhanced antioxidant enzyme activity such as SOD, POD and CAT compared to controls. These findings shed lights on the potential role of HmHMAs in Al transport and tolerance in H. macrophylla.

Coincidence of HCV and chronic kidney disease-a systematic review and meta-analysis.

BACKGROUND: There are reported studies of Hepatitis C and chronic kidney disease association. However, how this liver virus infection affects the general population's susceptibility to the onset of the kidney disease is still unknown. METHODS: To determine if a positive anti-HCV serologic status is linked to a greater incidence of chronic kidney disease in the general adult population, a systematic evaluation of the published medical literature since 2015 was conducted. A summary estimate of the relative risk of chronic kidney disease with HCV was produced using a random-effects model. Moreover, stratified analysis and meta-regression were performed. RESULTS: Twelve studies (n = 605858 patients) were filtered and included. Meta-analyses were conducted according to the outcome. Pooling results of longitudinal studies (n = 06 studies, n = 347120 unique patients) demonstrated an association between positive anti-HCV serologic status and increased incidence of CKD. The summary estimate for adjusted hazard ratio was 1.21 with (95% confidence interval 1.13; 1.29, P = 0.001), and between studies heterogeneity was noted (P value by Q test < 0.001). In the subset of Asian surveys, the risk of the occurrence of chronic kidney disease linked to HCV was 1.70 (95% confidence interval 1.40; 2.00) without heterogeneity (P value by Q test = 0.6). CONCLUSIONS: We found a strong correlation between HCV infection and a higher risk of chronic renal disease in general global population.

Gene pyramiding improved cell membrane stability under heat stress in cotton (Gossypium hirsutum L.).

Climate change has been drastically affecting cotton not only in Pakistan but also all over the world. Normally cotton is known as heat tolerant when compared with other crops, but if the high temperature occurs during flowering period the yield decreases significantly. Marker assisted gene pyramiding provides a sustainable solution to improve heat tolerance. A total of seven genotypes were developed by a series of crossing seven tolerant genotypes over the period of three years. Tolerant genotypes were selected by screening for important transcription factors (GHSP26, HSP3, HSFA2, DREB1A, HSP101, DREB2A, GhNAC2, HSPCB, GhWRKY41, TPS, GbMYB5, ANNAT8, GhMPK17, GhMKK1, GhMKK3, GhMPK2, HSC70, APX1 and GhPP2A1). The seven genotypes were evaluated under normal and heat stress in a multi-year trial. The traits related to heat tolerance, such as cell membrane stability, relative water content, excised leaf water loss, plant height, number of nodes, internodal length, number of buds, number of bolls and leaf area was observed under normal and heat stress conditions. The developed genotypes showed improvement in cell membrane stability and relative water content under heat stress. The genotypes [(VH-305×MNH-886)×MNH-1035)×NIAB-78)], [(MNH-1035×MNH-886)×MNH-886)×SM-431] and [(MNH-1035×MNH-886)×MNH-886)×SS-32] depicted heat tolerance and could be used as heat tolerant material for variety development in breeding programs.

Dual-energy CT: Impact of detecting bone marrow oedema in occult trauma in the Emergency.

Dual-energy computed tomography (DECT) is an advanced imaging technique that acquires data using two distinct X-ray energy spectra, typically at 80 and 140 kVp, to differentiate materials based on their atomic number and electron density. This capability allows for the enhanced visualisation of various pathologies, including bone marrow oedema (BMO), by providing high-resolution images with notable energy spectral separation while maintaining radiation doses comparable to conventional CT. DECT's ability to create colour-coded virtual non-calcium (VNCa) images has proven particularly valuable in detecting traumatic bone marrow lesions (BMLs) and subtle fractures, offering a reliable alternative or complement to MRI. DECT has emerged as a significant tool in the detection and characterisation of bone marrow pathologies, especially in traumatic injuries. Its ability to generate high-resolution images and distinguish between different tissue types makes it a valuable asset in clinical diagnostics. With its comparable diagnostic accuracy to MRI and the added advantage of reduced examination time and increased availability, DECT represents a promising advancement in the imaging of BMO and related conditions.

Cholecystocolonic fistula secondary to ascending colon diverticular disease: A case report.

Cholecystocolonic fistula occurring as a complication of colonic diverticular disease is a rarely encountered clinical entity in which the patient may remain asymptomatic or present with vague abdominal or systemic symptoms. Imaging studies are usually not very reliable or effective in detecting direct communication between gallbladder and colon. However, indirect signs such as pneumobilia, gallstones, gallbladder adherent to colon and colonic diverticulosis may help reach the diagnosis. Treatment of cholecystocolonic fistula in symptomatic patients is usually surgical. However, in asymptomatic patients or patients with risk factors and comorbidities, non-surgical options such as conservative management or biliary stenting can be considered.

Isolated diastolic hypertension and cardiovascular outcomes across different diagnostic guidelines: a systematic review and meta-analysis.

BACKGROUND: This systematic review aims to determine the impact of isolated diastolic hypertension (IDH) on cardiovascular outcomes. METHODS: We searched only English language articles on PubMed and SCOPUS until July 31, 2023 to investigate the association between IDH and cardiovascular outcomes. RESULTS: This meta-analysis of 19 studies evaluated the impact of different hypertension diagnostic guidelines (ACC/AHA: American Heart Association/American College of Cardiology; JNC7: Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure; NICE/ESC: National Institute for Health and Care Excellence/European Society of Cardiology) on hypertension-related outcomes. Studies had varying sample sizes (173 to 2,969,679 participants) and study designs. In cohort studies using JNC7 guidelines, IDH was linked to increased cardiovascular disease (CVD) risk (HR: 1.45, 95% CI 1.17, 1.74), CVD mortality (HR: 1.54, 95% CI 1.23, 1.84), and coronary heart disease (CHD) risk (HR: 1.65). In studies using ACC/AHA guidelines, associations with CVD risk and CVD mortality were weaker [HR: 1.16 (95% CI 1.06, 1.25) and 1.10 (95% CI 0.95, 1.25), respectively]. Subgroup analysis revealed differences in outcomes on the basis of age and sex. Cross-sectional studies did not show significant associations with JNC7 and ACC guidelines; NICE guidelines were not used in cross-sectional studies. CONCLUSION: IDH is associated with an increased risk of CVD. Higher diastolic blood pressure cutoffs were associated with higher cardiovascular risk. This association varied by study design and effect modification by sex and race influenced the association.

Kinetics of cellulase-free endo xylanase hyper-synthesis by Aspergillus Niger using wheat bran as a potential solid substrate.

The present study deals with the production of cellulase-free endoxylanase by Aspergillus niger ISL-9 using wheat bran as a solid substrate. Endoxylanase was produced under a solid-state fermentation. Various growth parameters were optimized for the improved production of the enzyme. The Substrate level of 15 g was optimized as it provided the fungus with balanced aeration and nutrition. Among the six moisture contents investigated, Moisture Content 5 (MC5) was optimized (g/l: malt extract, 10; (NH4)2HPO4, 2.5; urea, 1.0) and 10 mL of MC5 was found to give the highest production of endoxylanase. The pH and time of incubation were optimized to 6.2 and 48 h respectively. The Inoculum size of 2 mL (1.4 × 106 spores/mL) gave the maximum enzyme production. After optimization of these growth parameters, a significantly high endoxylanase activity of 21.87 U/g was achieved. Very negligible Carboxymethylcellulase (CMCase) activity was observed indicating the production of cellulase-free endoxylanase. The notable finding is that the endoxylanase activity was increased by 1.4-fold under optimized conditions (p ≤ 0.05). The overall comparison of kinetic parameters for enhanced production of endoxylanase by A. niger ISL-9 under Solid State Fermentation (SSF) was also studied. Different kinetic variables which included specific growth rate, product yield coefficients, volumetric rates and specific rates were observed at 48, 72 and 96 h incubation time and were compared for MC1 and MC5. Among the kinetic parameters, the most significant result was obtained with volumetric rate constant for product formation (Qp) that was found to be optimum (1.89 U/h) at 72 h incubation period and a high value of Qp i.e.1.68 U/h was also observed at 48 h incubation period. Thus, the study demonstrates a cost-effective and environmentally sustainable process for xylanase production and exhibits scope towards successful industrial applications.

Expanding the Potential Window through Synergistic Design and Oriented Heterostructure for Supercapacitor.

Metal telluride-based nanomaterials have recently gained attention as promising candidates for enhancing the performance of electrodes in energy storage devices. In this study, Co-Zr-Te@CuO electrode materials engineered through strategic approach are introduced, involving the deposition of a Co-Zr metal-organic framework (MOF) on CuO nanowires, followed by a tellurization. This composite material demonstrates an expanded potential window of 1.2 V, making it potential electrode material for supercapacitor applications. Electrochemical evaluations reveal that the Co-Zr-Te@CuO electrode exhibits 576 C g-1, 1.8 times higher than Co-Zr-MOF@CuO. Furthermore, density functional theory (DFT) calculations confirm enhancements in conductivity and explains the synergistic effects present within the heterostructure. Hybrid supercapacitor (HSC) device achieves a peak energy density of 69.4 Wh kg-1 at a power density of 1.4 kW kg-1. This evidence of Co-Zr-Te@CuO effective electrode performance demonstrates its potential and robust stability for real-world energy storage applications.