TGF-ß ligand cross-subfamily interactions in the response of Caenorhabditis elegans to a bacterial pathogen.

The Transforming Growth Factor beta (TGF-ß) family consists of numerous secreted peptide growth factors that play significant roles in cell function, tissue patterning, and organismal homeostasis, including wound repair and immunity. Typically studied as homodimers, these ligands have the potential to diversify their functions through ligand interactions that may enhance, repress, or generate novel functions. In the nematode Caenorhabditis elegans, there are only five TGF-ß ligands, providing an opportunity to dissect ligand interactions in fewer combinations than in vertebrates. As in vertebrates, these ligands can be divided into bone morphogenetic protein (BMP) and TGF-ß/Activin subfamilies that predominantly signal through discrete signaling pathways. The BMP subfamily ligand DBL-1 has been well studied for its role in the innate immune response in C. elegans. Here we show that all five TGF-ß ligands play a role in survival on bacterial pathogens. We also demonstrate that multiple TGF-ß ligand pairs act nonredundantly as part of this response. We show that the two BMP-like ligands-DBL-1 and TIG-2-function independently of each other in the immune response, while TIG-2/BMP and the TGF-ß/Activin-like ligand TIG-3 function together. Structural modeling supports the potential for TIG-2 and TIG-3 to form heterodimers. Additionally, we identify TIG-2 and TIG-3 as members of a rare subset of TGF-ß ligands lacking the conserved cysteine responsible for disulfide linking mature dimers. Finally, we show that canonical DBL-1/BMP receptor and Smad signal transducers function in the response to bacterial pathogens, while components of the DAF-7 TGF-ß/Activin signaling pathway do not play a major role in survival. These results demonstrate a novel potential for BMP and TGF-ß/Activin subfamily ligands to interact and may provide a mechanism for distinguishing the developmental and homeostatic functions of these ligands from an acute response such as the innate immune response to bacterial pathogens.

Identification, Characterization, and Electronic Structures of Interconvertible Cobalt-Oxygen TAML Intermediates.

The reaction of Li[(TAML)CoIII]·3H2O (TAML = tetraamido macrocyclic tetraanionic ligand) with iodosylbenzene at 253 K in acetone in the presence of redox-innocent metal ions (Sc(OTf)3 and Y(OTf)3) or triflic acid affords a blue species 1, which is converted reversibly to a green species 2 upon cooling to 193 K. The electronic structures of 1 and 2 have been determined by combining advanced spectroscopic techniques (X-band electron paramagnetic resonance (EPR), electron nuclear double resonance (ENDOR), X-ray absorption spectroscopy/extended X-ray absorption fine structure (XAS/EXAFS), and magnetic circular dichroism (MCD)) with ab initio theoretical studies. Complex 1 is best represented as an S = 1/2 [(Sol)(TAML•+)CoIII---OH(LA)]- species (LA = Lewis/Brønsted acid and Sol = solvent), where an S = 1 Co(III) center is antiferromagnetically coupled to S = 1/2 TAML•+, which represents a one-electron oxidized TAML ligand. In contrast, complex 2, also with an S = 1/2 ground state, is found to be multiconfigurational with contributions of both the resonance forms [(H-TAML)CoIV═O(LA)]- and [(H-TAML•+)CoIII═O(LA)]-; H-TAML and H-TAML•+ represent the protonated forms of TAML and TAML•+ ligands, respectively. Thus, the interconversion of 1 and 2 is associated with a LA-associated tautomerization event, whereby H+ shifts from the terminal -OH group to TAML•+ with the concomitant formation of a terminal cobalt-oxo species possessing both singlet (SCo = 0) Co(III) and doublet (SCo = 1/2) Co(IV) characters. The reactivities of 1 and 2 at different temperatures have been investigated in oxygen atom transfer (OAT) and hydrogen atom transfer (HAT) reactions to compare the activation enthalpies and entropies of 1 and 2.

A Guide to Tris(4-Substituted)-triphenylmethyl Radicals.

Triphenylmethyl (trityl, Ph3C•) radicals have been considered the prototypical carbon-centered radical since their discovery in 1900. Tris(4-substituted)-trityls [(4-R-Ph)3C•] have since been used in many ways due to their stability, persistence, and spectroscopic activity. Despite their widespread use, existing synthetic routes toward tris(4-substituted)-trityl radicals are not reproducible and often lead to impure materials. We report here robust syntheses of six electronically varied (4-RPh)3C•, where R = NMe2, OCH3, tBu, Ph, Cl, and CF3. The characterization reported for the radicals and related compounds includes five X-ray crystal structures, electrochemical potentials, and optical spectra. Each radical is best accessed using a stepwise approach from the trityl halide, (RPh)3CCl or (RPh)3CBr, by controllably removing the halide with subsequent 1e- reduction of the trityl cation, (RPh)3C+. These syntheses afford consistently crystalline trityl radicals of high purity for further studies.

Organic Mixed-Valence Compounds and the Overhauser Effect in Insulating Solids.

Recent experiments have shown that the organic free radical 1,3-bisdiphenylene-2-phenylallyl (BDPA) can induce an Overhauser effect dynamic nuclear polarization in insulating solids, a feat previously considered not to be possible. Here, we establish that this peculiar ability of the BDPA radical stems from its mixed-valence nature and the ensuing intramolecular charge transfer. Using state-of-the-art DMRGSCF calculations, we confirm the class II mixed-valence nature of BDPA with the characteristic double-well potential energy surface, and we investigate the mechanism of the consequent electron hopping. A two-component vibronic Hamiltonian is then employed to compute the rate of electron hopping from a quantum dynamical time-propagation of the density matrix. The predicted hyperfine coupling oscillations indeed fall within the frequency range required for an Overhauser effect. The paradigm of mixed-valence compounds as a mining source opens many possibilities for the development and fine tuning of novel polarizing agents.

Tissue specific tumor-gene link prediction through sampling based GNN using a heterogeneous network.

A tissue sample is a valuable resource for understanding a patient's symptoms and health status in relation to tumor growth. Recent research seeks to establish a connection between tissue-specific tumor samples and genetic markers (genes). This breakthrough has paved the way for personalized cancer therapies. With this motivation, the proposed model constructs a heterogeneous network based on tumor sample-gene relation data and gene-gene interaction data. This network also incorporates tissue-specific gene expression and primary site-based gene counts as features, enabling tissue-specific predictions. Graph neural networks (GNNs) have proven effective in modeling complex interactions and predicting links within this network. The proposed model has successfully predicted tumor-gene associations by leveraging sampling-based GNNs and link layer embedding. The model's performance metrics, such as AUC-ROC scores, reached approximately 94%, demonstrating the potential of this heterogeneous network in predicting tissue-specific tumor sample-gene links. This paper's findings highlight the importance of tissue-specific associations in cancer research.

A Rare Presentation of Systemic Lupus Erythematosus (SLE) With Hemoptysis and Hematuria: A Case Report.

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by type II and type III hypersensitivity reactions that affect multiple organs, including the joints, heart, lungs, brain, skin, and kidneys. Patients with SLE can experience a range of symptoms, ranging from fever and joint pain to a distinctive butterfly facial rash. Severe complications may encompass conditions such as diffuse alveolar hemorrhage (DAH), pulmonary hypertension, and lupus nephritis, among others. Among them, DAH, a critical pulmonary complication in SLE, involves bleeding from interstitial capillaries and alveoli due to immune complex damage. This case report describes a patient who was initially misdiagnosed but later confirmed to have SLE. The patient presented with persistent symptoms, including cough, dyspnea, and fever, over two weeks and subsequently developed hematuria and hemoptysis within the last two days. The progression of symptoms led to an acute exacerbation, resulting in her admission to the emergency department. Subsequent evaluations confirmed the diagnosis of lupus nephritis and DAH. This case highlights the importance of considering SLE in the differential diagnosis of unexplained systemic symptoms and underscores the urgent need for medical intervention in DAH to substantially reduce mortality.

Dysphagia in a Patient With Lewy Body Dementia and Incidental Anterior Cervical Osteophyte: A Case Report.

One of the common problems affecting the elderly is dysphagia, which can be brought on by several things, including the presence of anterior cervical osteophytes. In this case study, a patient with Lewy body dementia is shown to have a case of dysphagia. The patient's primary complaint was dysphagia, which prompted questions regarding the development of underlying Lewy body dementia combined with gradual cognitive deterioration and motor control problems. An upper GI endoscopy was conducted during the patient's hospitalization after a barium swallow suggested esophageal obstruction but found no internal obstruction or any other abnormalities. Following the endoscopic procedure, the patient complained of neck aches. An anterior cervical osteophyte was subsequently discovered by computed tomography, which may have been the primary cause of the patient's dysphagia. The importance of considering coexisting medical conditions in elderly individuals, as well as the significance of promptly assessing and diagnosing dysphagia in the presence of neurodegenerative disorders such as Lewy body dementia, is emphasized by this example.

A Diagnostic Dilemma: A Case of Complicated Pneumonia With Pyelonephritis and Subclinical Myocarditis.

A 41-year-old woman presented with a 3.5-month history of fever, weakness, productive cough, and burning micturition along with generalized weakness and significant weight loss. Chest X-ray revealed bilateral infiltrates and bilateral pleural effusion, and the workup suggested community-acquired pneumonia (CAP). However, the course was complicated by persistent fevers, elevated inflammatory markers, elevated N-terminal pro-B-type natriuretic peptide (NT-proBNP), and pelvic fluid collection. Extensive investigations, including bronchoscopy and lung biopsy, failed to identify a specific pathogen. Pulmonary vasculitis and lymphoma were ruled out. Antibiotic and corticosteroid therapy resulted in clinical improvement. While the cause remains unknown, brucellosis and aspergillosis were considered but ruled out with advanced testing. The underlying etiology remains elusive, highlighting the diagnostic challenges in CAP with atypical presentations.

Critical Role of Pleural Wrap and Post-operative Neonatal Protocol in Long-gap Oesophageal Atresia: A Team Effort.

BACKGROUND: The objectives of this study were to bring out the results of application of pleural wrap in primary repair of tracheo - esophageal fistula (TEF) with long-gap oesophageal atresia (LGEA) and also define the role of neonatologists and paediatric intensivists in post-operative management in these patients by laying down standard neonatal management protocol. MATERIALS AND METHODS: This was a retrospective descriptive observational study conducted between March 2011 and April 2019 on 23 cases of LGEA with TEF. The study was conducted at two tertiary care paediatric surgery centres in Northern part of India wherein these newborn babies were operated by two paediatric surgeons with variable experience of 8-12 years. It also describes the neonatal management protocol used in post-operative period. RESULTS: Out of 23 patients, 15 were boys and 8 were girls, with a mean age of 32.25 weeks and a mean birth weight of 2.02 kg. The mean hospital stay was 23.5 ± 8 days. Eleven cases had gap between 3 and 3.5 cm, 8 cases between 3.5 and 4 cm and 4 cases had gap more than 4 cm. The incidence of associated anomalies was 52%. Anastomotic leak rate was 8.69%, and 3 (13.04%) patients died in the post-operative period. All the operated patients were managed postoperatively as per strict neonatal management protocol exclusively by the team of neonatologists and neonatal intensivists. CONCLUSION: Application of pleural wrap over anastomosis following primary repair of LGEA with TEF significantly reduced the incidence of anastomotic leak in our study. Apart from the pleural wrap, the key to successful outcome also is contributed by the little prolonged, controlled ventilation and patience and perseverance in post-operative feeds. This post-operative management protocol that has been followed by us in our study is easily reproducible and can be adopted by paediatric surgeons working alongside neonatologists as a team.

Unravelling the potential of L-carnosine analog-based nano-assemblies as pH-responsive therapeutics in treating glioma: an in vitro perspective.

Self-assembled small peptide-based nanoparticles (NPs) constitute a major section of the biomimetic smart NPs owing to their excellent compatibility and minimal adverse effects in the biological system. Here, we have designed a modified L-carnosine dipeptide analog, "Fmoc-ß-Ala-L-His-(Trt)-o-methyl formate", which was assembled along with a modified single amino acid, Fmoc-Arg-(Pbf)-OH and zinc ions to form stable and mono-dispersed L-carnosine analog NPs (CaNPs) with inherent anti-cancer properties. Furthermore, the CaNPs demonstrated an average size of ∼200 nm, making them suitable to invade the tumor site by following the enhanced permeability and retention (EPR) effect. Our studies depicted a remarkable cancer cell killing ability of the NPs of ∼82% in C6 glioma cells. Thereafter, cellular investigations were performed in C6 cells to analyze the influence of the NPs on cellular cytoskeleton integrity by using a phalloidin assay and anti-cancer efficacy by using calcein AM/PI, and an apoptosis assay further indicated their anti-cancer effect. Additionally, the NPs negatively impacted the ability of C6 cells to migrate across a premade scratch (∼44% wound closure) demonstrating their tendency to halt cancer cell migration and metastasis. Also, our NPs depicted ∼19.51 ± 0.17% permeability across the bEnd.3 transwell model establishing their BBB penetrability. Collectively, our results could positively implicate the successful anti-cancer potential of the minimalistic, biologically compliant, L-carnosine analog (Ca)-based nanostructures in glioma.

Carpal Tunnel Syndrome as an Atypical Presentation of Chikungunya: A Case Report.

Chikungunya virus (CHIKV) is an arbovirus endemic to tropical and subtropical regions, primarily known for causing fever and severe joint pain. However, its capacity to induce neurological complications is less frequently documented. This case report highlights a rare presentation of carpal tunnel syndrome (CTS) following CHIKV infection, expanding the spectrum of CHIKV manifestations beyond its common arthropathic effects. We detail the case of a 45-year-old male who developed acute CTS symptoms, including pain, numbness, and motor dysfunction in the right thumb, six weeks after experiencing typical CHIKV symptoms of high-grade fever and arthralgia. Despite an initial treatment regimen of corticosteroids aimed at reducing inflammation, the patient's symptoms showed minimal improvement, prompting surgical intervention. Following carpal tunnel release surgery, the patient experienced significant relief and functional recovery. This case underscores the importance of considering CHIKV in the differential diagnosis of CTS in endemic areas, particularly when preceded by typical viral infection symptoms. It also supports surgical intervention as a viable treatment option for CTS associated with CHIKV when conservative management is ineffective, highlighting the need for an interdisciplinary approach in treating atypical manifestations of CHIKV infections.

Deep Learning Models for Health-Driven Forecasting of Indoor Temperatures in Heat Waves in Canada: An Exploratory Study Using Smart Thermostats.

In Canada, extreme heat occurrences present significant risks to public health, particularly for vulnerable groups like older individuals and those with pre-existing health conditions. Accurately predicting indoor temperatures during these events is crucial for informing public health strategies and mitigating the adverse impacts of extreme heat. While current systems rely on outdoor temperature data, incorporating real-time indoor temperature estimations can significantly enhance decision-making and strengthen overall health system responses. Sensor-based technologies, such as ecobee smart thermostats installed in homes, enable effortless collection of indoor temperature and humidity data. This study evaluates the efficacy of deep learning models in predicting indoor temperatures during heat waves using smart thermostat data, to enhance public health responses. Utilizing ecobee smart thermostats, we analyzed indoor temperature trends and developed forecasting models. Our findings indicate the potential of integrating IoT and deep learning into health warning systems, enabling proactive interventions, and improving sustainable health care practices in extreme heat scenarios. This approach highlights the role of digital health innovations in creating the resilient and sustainable healthcare systems against climate-related health adversities.

Cutaneous Anaplastic T-Cell Lymphoma Mimicking a Small Abscess: A Case Report.

Non-healing ulcers display a noteworthy demonstrative challenge for clinicians. While often attributed to common causes like infections, these persistent wounds can occasionally mask a more sinister underlying condition: malignancy. This case report presents a 39-year-old Indian man with a non-healing ulcer on his right gluteal region. Despite initial treatments for a presumed bacterial infection, the ulcer persisted. Biopsy ultimately revealed a malignant neoplasm of possible hematopoietic origin, positive for CD30 and focally positive for CD45. Further investigations, including MRI, FNAC, and X-rays, were indicative of lymphoma. Non-healing ulcers present a challenge due to diverse etiologies. A thorough understanding of potential causes, including infectious, vascular, autoimmune, and malignant etiologies, is crucial for navigating the diagnostic process. This case highlights the critical role of maintaining a broad differential diagnosis for non-healing ulcers and the importance of a biopsy in reaching a definitive diagnosis. Early recognition of malignancy in such cases is essential for optimal patient management. This case underscores the importance of considering malignancy in patients with persistent ulcers and performing biopsies for a definitive diagnosis. While the initial presentation mimicked an infectious process, the biopsy revealed a possible cutaneous anaplastic T-cell lymphoma. Further investigations are necessary to definitively classify the specific lymphoma subtype and guide further treatment decisions.

Cyclical Exacerbation of Asthma Symptoms in Relation to the Menstrual Cycle: A Case Report on Catamenial Asthma.

Catamenial asthma, marked by cyclical exacerbations of symptoms linked to the menstrual cycle, poses distinctive diagnostic and therapeutic challenges. This report discusses a 34-year-old woman who experienced significant asthma flare-ups 3-5 days before menstruation, as confirmed by spirometry (forced expiratory volume in one second (FEV1) dropped from 2.5 to 1.75 liters). Despite adhering to standard asthma treatments, her symptoms remained poorly controlled during these periods. A comprehensive management plan encompassing inhaled corticosteroids, short-acting beta-agonists, montelukast, and oral contraceptives, along with lifestyle modifications and patient education, led to a significant improvement in FEV1 and reduced symptom severity. This case underscores the need for personalized treatment strategies that take hormonal influences into account, suggesting that integrating hormonal therapies with conventional asthma management can yield significant benefits.

Acute Radial Artery Thromboembolic Occlusion During Transcatheter Aortic Valve Replacement: A Case Report and Review of Management Strategies.

Acute limb ischemia requires prompt diagnosis and treatment. Thromboembolic events are common, especially in patients with multiple risk factors. This case report describes a rare complication of transcatheter aortic valve replacement (TAVR) involving thromboembolic occlusion of the radial artery and highlights the risk of embolic complications during TAVR. While TAVR is minimally invasive and preferred for high-risk patients, it carries the risk of complications such as paravalvular leakage and cerebrovascular events. Prompt recognition and management are crucial. Various mechanisms, including catheter manipulation and altered hemodynamics, contribute to embolic risks during TAVR. Awareness and management of rare embolic complications during TAVR are essential. Further research is needed to prevent these complications and improve patient outcomes.

Aortic Dissection Masquerading as Pneumonia: A Case Report of an Atypical Presentation.

Aortic dissection is a critical and life-threatening condition that can present with atypical symptoms, often leading to misdiagnosis and delayed treatment. The report presents a case of a 65-year-old male who initially exhibited fever, right-sided chest pain, and a productive cough, resulting in an initial diagnosis of pneumonia. Despite empirical antibiotic therapy, his symptoms persisted, prompting further investigation. A computed tomography (CT) scan ultimately revealed a Type B aortic dissection. The patient was then transferred to a specialized tertiary care facility for successful endovascular intervention. This case underscores the importance of considering aortic dissection in patients presenting with persistent, atypical symptoms that do not respond to standard treatments, such as unexplained fever and chest pain. It highlights the crucial role of advanced imaging techniques, such as CT scans, in achieving an accurate and timely diagnosis. Clinicians must maintain a high index of suspicion and ensure prompt referral to specialized centers to improve patient outcomes in this potentially fatal condition.

Navigating Infertility in Kartagener's Syndrome: A Clinical Case Report.

Kartagener's syndrome is a genetic condition that is caused by a triad of symptoms, which includes bronchiectasis, chronic sinusitis, and situs inversus, and is considered rare. It is caused by defective ciliary motility, leading to impaired mucociliary clearance. We report a case of a 24-year-old male who presented with primary infertility and a long-standing history of recurrent respiratory infections. Physical examination revealed dextrocardia and digital clubbing. Radiological investigations confirmed situs inversus totalis and bronchiectasis. Semen analysis revealed azoospermia. Genetic analysis was not done due to financial constraints. However, the constellation of clinical features was diagnostic of Kartagener's syndrome. The patient was managed with antibiotics and chest physiotherapy. In vitro fertilization (IVF) was advised for infertility. A successful pregnancy was achieved through IVF, indicating viable sperm despite immotility. The aforementioned case underscores the significance of maintaining a heightened sense of suspicion for Kartagener's syndrome in individuals exhibiting unexplained bronchiectasis and infertility. Early diagnosis can prevent chronic respiratory morbidity and enable parenthood through assisted reproduction.

Schnitzler-Like Syndrome Presenting With IgG Kappa Monoclonal Gammopathy: A Case Report and Review of Diagnostic and Therapeutic Challenges.

Schnitzler syndrome (SS) is a rare autoinflammatory disorder characterized by a constellation of symptoms that include chronic urticarial rash, recurrent fever, arthralgias/arthritis, and monoclonal gammopathy, typically involving immunoglobulin M (IgM). However, cases with overlapping clinical features but lacking specific criteria fall under the umbrella of Schnitzler-like syndromes. This case report describes a 40-year-old male with Schnitzer-like syndrome and underscores the diagnostic complexities and therapeutic challenges of Schnitzer-like syndrome with IgG kappa monoclonal gammopathy, highlighting the need for a comprehensive diagnostic approach and targeted therapy.

Muir-Torre Syndrome: A Case Report and a Literature Review of Genetic Insights and Cancer Surveillance.

Muir-Torre syndrome (MTS) is a rare autosomal dominant genetic disorder that manifests through the co-occurrence of sebaceous skin tumors and internal malignancies, primarily due to mutations in mismatch repair (MMR) genes such as MSH2, MLH1, and MSH6. This paper presents a detailed case report of a 57-year-old female diagnosed with MTS, highlighting her extensive medical history and the critical role of genetic testing and multidisciplinary management. The patient's dermatological and oncological assessments revealed multiple sebaceous carcinomas and recurrent urothelial carcinoma, confirmed by a pathogenic MSH2 mutation. Through comprehensive preventive surgeries and rigorous follow-up, this case underscores the necessity of proactive cancer surveillance. The discussion integrates findings from key genetic studies and emphasizes the importance of immunohistochemistry in diagnosis. Recommendations for clinical practice include routine genetic testing, stringent surveillance, and multidisciplinary management, underscoring the need for ongoing research to understand better and manage this complex syndrome.

Left Ventricular Non-compaction and Associated Cardiomyopathy Presenting With Cardiac Failure: A Case Report.

The characteristic structural anomaly of the heart in the left ventricular non-compaction (LVNC) is identified with a prominent layer of the trabecular meshwork, thin compacted myocardium, and intertrabecular recesses within the depths of the left ventricle. Despite growing clinical recognition, the prevalence of LVNC in adults and the full clinical spectrum remain poorly explored. The disease shows heterogeneous phenotypes from an asymptomatic presentation to severe cardiac complications like cardiac failure, arrhythmias, and thromboembolic events. Current diagnostic practices for LVNC lack standardized guidelines, making patient management difficult. We here report a case of an adult patient who presented with features of congestive cardiac failure and on detailed imaging with echocardiogram and magnetic resonance imaging (MRI) was diagnosed to have LVNC. We here also emphasize that there is a great need for refined diagnostic criteria that include genetic, clinical, and imaging data. Cases of LVNC with full-blown phenotypic expression should be used for diagnostic criteria.