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We present the case of an 82-year-old woman with persistent fatigue, exertional dyspnea, and dizziness related to a paravalvular leak following a self-expanding transcatheter aortic valve replacement. Successful closure was performed using a steerable sheath to negotiate a vascular plug closure device through the self-expanding valve structure.
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BACKGROUND: Inflammation is a major cause of kidney injury. The Interleukin (IL)-1 family cytokine IL-33 is released from damaged cells and modulates the immune response through its receptor ST2 expressed on many cell types, including regulatory T-cells (Tregs). While a proinflammatory role of IL-33 has been proposed, exogenous IL-33 expanded Tregs and suppressed renal inflammation. However, the contribution of endogenous IL-33/ST2 for the role of Tregs in the resolution of kidney injury has not been investigated. METHODS: We used murine renal ischemia-reperfusion injury and kidney organoids to delineate the role of the ST2 and amphiregulin (AREG) specifically in Treg cells using targeted deletion. Bulk and single-cell RNA sequencing was performed on flow-sorted Tregs from spleen and CD4 T-cells from post-ischemic kidneys respectively. The protective role of ST2-sufficient Tregs was analyzed using a novel co-culture system of syngeneic kidney organoids and Treg cells under hypoxic conditions. RESULTS: Bulk RNA-sequencing of splenic and single-cell-RNA-sequencing of kidney T-cells showed that ST2+ Tregs are enriched for genes related to Treg proliferation and function. Genes for reparative factors such as AREG were also enriched in ST2+ Tregs. Treg-specific deletion of ST2 or AREG exacerbated kidney injury and fibrosis in the unilateral ischemia reperfusion injury model. In co-culture studies, WT but not ST2-deficient Tregs preserved the hypoxia-induced loss of kidney-organoid viability, which was restored by AREG supplementation. CONCLUSIONS: Our study identified the role of the IL-33/ST2 pathway in Tregs for resolution of kidney injury. The transcriptome of ST2+ Tregs was enriched for reparative factors including AREG. Lack of ST2 or AREG in Tregs worsened kidney injury. Tregs protected kidney organoids from hypoxia in ST2 and AREG-dependent manner. Thus Treg-based approaches could be of benefit for resolution of renal injury.
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Despite the WHO's recommended treatment regimen, challenges such as patient non-adherence and the emergence of drug-resistant strains persist with TB claiming 1.5 million lives annually. In this study, we propose a novel approach by targeting the DNA replication-machinery of M.tb through drug-repurposing. The ß2-Sliding clamp (DnaN), a key component of this complex, emerges as a potentially vulnerable target due to its distinct structure and lack of human homology. Leveraging TBVS, we screened â¼2600 FDA-approved drugs, identifying five potential DnaN inhibitors, by employing computational studies, including molecular-docking and molecular-dynamics simulations. The shortlisted compounds were subjected to in-vitro and ex-vivo studies, evaluating their anti-mycobacterial potential. Notably, Dicoumarol, Paromomycin, and Posaconazole exhibited anti-TB properties with a MIC value of 6.25, 3.12 and 50 µg/ml respectively, with Dicoumarol and Paromomycin, demonstrating efficacy in reducing live M.tb within macrophages. Biophysical analyses confirmed the strong binding-affinity of DnaNdrug complexes, validating our in-silico predictions. Moreover, RNA-Seq data revealed the upregulation of proteins associated with DNA repair and replication mechanisms upon Paromomycin treatment. This study explores repurposing FDA-approved drugs to target TB via the mycobacterial DNA replication-machinery, showing promising inhibitory effects. It sets the stage for further clinical research, demonstrating the potential of drug repurposing in TB treatment.
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The amount of apically extruded debris following glide-path preparation of mesial root of 120 freshly extracted human mandibular molar teeth using Senseus ProFinder files, PathFile, G-Files, Scout-RaCe files, HyFlex glidepath files and V glide-path two file system is of interest. The Eppendorf tubes were used as test equipment for collecting debris and the average weight of the debris was measured using an electronic micro-balancing system. It was observed that regardless of the file system utilized, debris was expelled from the apex. The G files resulted in a lower quantity of debris being extruded (0.070 ± 0.002 mg). In contrast, the V glide-path two file system exhibited the highest amount of debris extrusion (0.110 ± 0.004 mg) compared to all other file systems.
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Coronary artery anomalies may place patients at risk for various adverse events. We present a case of a 62-year-old male with a two-year history of intermittent chest pain. A computed tomography coronary angiogram revealed a rare finding of an anomalous right coronary artery (ARCA) originating from the left ascending aorta, with high-risk features. This case highlights the complexities in diagnosing and managing ARCA, underscoring the importance of individualized care and careful consideration of invasive intervention risks versus potential benefits.
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BACKGROUND: Ni-kshay Poshan Yojana (NPY), a direct benefit transfer scheme under the National Tuberculosis Elimination Program (NTEP) in India, provides a monthly benefit of INR500 for nutritional support of persons with TB (PwTB). OBJECTIVES: To determine the proportion of PwTB receiving atleast one NPY instalment and pattern of utilisation; to ascertain factors associated with NPY non-receipt and association of NPY receipt with TB treatment outcome. METHODS: In our cross-sectional study, we used multi-stage sampling to select PwTB whose treatment outcome was declared between May 2022 and February 2023. A cluster-adjusted, generalized linear model was used to identify factors associated with the non-receipt of NPY and determine association between NPY receipt and TB treatment outcome. RESULTS: Among 3201 PwTB, 2888 (92.7%; 95% CI 89.8%, 94.8%) had received at least one NPY instalment, and 1903 (64.2%; 95% CI 58.9%, 69.2%) self-reported receipt of benefit. The median (IQR) time to receipt of first instalment was 105 (60,174) days. Non-receipt was significantly higher among PwTB from states with low TB score (aPR = 2.34; 95%CI 1.51, 3.62), who do not have bank account (aPR = 2.48; 95%CI 1.93, 3.19) and with unknown/missing diabetic status (aPR = 1.69; 95%CI 1.11, 2.55). Unfavorable treatment outcomes were associated with non-receipt of NPY (aPR 4.93; 95%CI 3.61,6.75) after adjusting for potential confounders. CONCLUSION: Majority of the PwTB received atleast one NPY instalment, but they experience significant delays. Most of the recipients utilised NPY for nutrition. Longitudinal follow-up studies are required to study the impact of NPY on treatment outcomes.
Main findings: Five years since implementation, almost ninety percent of persons with tuberculosis in India had received at least one benefit under Ni-kshay Poshan Yojana, most of whom utilise it for nutrition.Added knowledge: Persons with tuberculosis in India experience a median delay of over three months to receive the first instalment of the benefit.Global health impact for policy and action: Ensuring timely credit of benefits is crucial to enable its utilisation by persons with tuberculosis for better nutrition and favourable treatment outcomes.
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Tuberculosis , Humanos , India , Masculino , Femenino , Estudios Transversales , Adulto , Tuberculosis/tratamiento farmacológico , Persona de Mediana Edad , Antituberculosos/uso terapéutico , Adulto Joven , Adolescente , Resultado del Tratamiento , Programas Nacionales de SaludRESUMEN
BACKGROUND: Older adults discharged from our emergency department (ED) do not receive comprehensive fall risk evaluations. We conducted a quality improvement project using an existing Community Tele-Paramedicine (CTP) program to perform in-home fall risk assessment and mitigation after ED discharge. METHODS: High falls-risk patients, as defined by STEADI score >4, were referred for a CTP home visit by community paramedics supervised virtually by emergency physicians. Home hazards assessment, Timed Up and Go test (TUG), medication reconciliation, and psychosocial evaluation were used to develop fall risk mitigation plans. Outcomes assessed at 30 days post ED-discharge included: completed CTP visits, falls, ED revisits, hospital admissions, and referrals. RESULTS: Between November 2022 and June 2023, 104 (65%) patients were discharged and referred to CTP. The mean age of enrolled patients was 80 years, 66% were female, 63% White, 79% on Medicare or Medicaid, most lived with a family member (50%) or alone (38%). Sixty-one (59%) patients received an initial CTP visit, 48 (79%) a follow-up visit, and 12 (11%) declined a visit. Abnormal TUG tests (74%), home hazards (67%), high-risk medications (36%), or need for outpatient follow-up (49%) or additional home services (41%) were frequently identified. At 30 days, only one of the CTP patients reported a fall, one patient had a fall-related ED visit, and one patient was admitted secondary to a fall. CONCLUSIONS: A quality improvement initiative using CTP to perform fall risk reduction after ED discharge identified areas of risk mitigation in the home where most falls take place. Further controlled studies are needed to assess the impact of CTP on clinical outcomes important to patients and health systems.
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Two-dimensional (2D) van der Waals heterostructures combine the distinct properties of individual 2D materials, resulting in metamaterials, ideal for emergent electronic, optoelectronic, and spintronic phenomena. A significant challenge in harnessing these properties for future hybrid circuits is their large-scale realization and integration into graphene interconnects. In this work, we demonstrate the direct growth of molybdenum disulfide (MoS2) crystals on patterned graphene channels. By enhancing control over vapor transport through a confined space chemical vapor deposition growth technique, we achieve the preferential deposition of monolayer MoS2 crystals on monolayer graphene. Atomic resolution scanning transmission electron microscopy reveals the high structural integrity of the heterostructures. Through in-depth spectroscopic characterization, we unveil charge transfer in Graphene/MoS2, with MoS2 introducing p-type doping to graphene, as confirmed by our electrical measurements. Photoconductivity characterization shows that photoactive regions can be locally created in graphene channels covered by MoS2 layers. Time-resolved ultrafast transient absorption (TA) spectroscopy reveals accelerated charge decay kinetics in Graphene/MoS2 heterostructures compared to standalone MoS2 and upconversion for below band gap excitation conditions. Our proof-of-concept results pave the way for the direct growth of van der Waals heterostructure circuits with significant implications for ultrafast photoactive nanoelectronics and optospintronic applications.
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Surgery forms the backbone of treatment for most locoregional or advanced oral cavity squamous cell carcinoma. Unfortunately, infectious complications (including orocutaneous fistulas) are common following such extensive surgery and can afflict over half of patients. These complications can lead to delays in adjuvant treatment, prolonged hospitalization, reconstructive failure, and decreased quality of life. The frequency and morbidity associated with infectious complications has led to the search for pre-disposing risk factors; and, several have been identified, including both patient (e.g. diabetes) and surgical (e.g. operative time) factors. However, these findings are inconsistently reproduced, and risk factor modification has had a limited impact on rates of infectious complications. This is striking given that the likely contaminant-the oral microbiome-is a well-studied microbial reservoir. Because many oral cavity cancer surgeries involve violation of oral mucosa and the spillage of the oral microbiome into normally sterile areas (e.g. the neck), variance in oral microbiome composition and function could underly differences in infectious complications. The goal of this perspective is to highlight 1) this knowledge gap and 2) opportunities for studies in this domain. The implication of this line of thought is that the identification of oral microbial dysbiosis in patients undergoing surgery for oral cavity cancer could lead to targeted pre-operative therapeutic interventions, decreased infectious complications, and improved patient outcomes.
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Microbiota , Neoplasias de la Boca , Humanos , Boca/microbiología , Boca/cirugía , Neoplasias de la Boca/cirugía , Neoplasias de la Boca/microbiología , Complicaciones Posoperatorias/microbiología , Factores de Riesgo , Infección de la Herida Quirúrgica/microbiología , Infección de la Herida Quirúrgica/etiologíaRESUMEN
OBJECTIVE: To evaluate the effect of prophylactic antibiotics on outcomes and complications following surgical reconstructions of nasal Mohs defects in the outpatient setting. STUDY DESIGN: Retrospective cohort study. SETTING: Single tertiary care center, July 2021 to June 2023. METHODS: All adult patients who underwent reconstruction of nasal Mohs defects in an outpatient office setting were examined. Patient demographics, surgical details, prophylactic postprocedural antibiotic use, and postprocedural complications (infection, flap or graft necrosis, wound dehiscence) were collected. Outcomes and complications were compared between patients who received and did not receive prophylactic antibiotics using χ2, Kruskal-Wallis, and multivariable logistic regression. RESULTS: A total of 211 patients met inclusion criteria. A majority of reconstructions utilized a local flap (70%), followed by a skin or composite graft (22%), then an interpolated flap (8%). Over half of patients (55%) were prescribed prophylactic antibiotics. Postprocedural complications were documented in 16 patients (7.6%), including infection (3.3%) and flap or graft loss or necrosis (1.4%). The rate of complications did not differ based on receipt of antibiotics. The only factors independently associated with the development of complications were history of chemoradiation and reconstruction with skin or composite grafts. CONCLUSION: Prophylactic antibiotics after nasal Mohs reconstructions performed in the office setting were not associated with any differences in the rate of postprocedural complications, including surgical site infections.
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Profilaxis Antibiótica , Cirugía de Mohs , Humanos , Cirugía de Mohs/efectos adversos , Masculino , Femenino , Estudios Retrospectivos , Anciano , Persona de Mediana Edad , Colgajos Quirúrgicos , Neoplasias Nasales/cirugía , Infección de la Herida Quirúrgica/prevención & control , Complicaciones Posoperatorias/prevención & control , Antibacterianos/uso terapéutico , Procedimientos de Cirugía Plástica/métodos , Anciano de 80 o más Años , AdultoRESUMEN
ST segment elevations (STEs) on an electrocardiogram (EKG) gravitate immediate attention to the heart. However, these EKG changes can sometimes be the result of noncardiac pathologies. Here, we present an interesting case of small bowel obstruction (SBO) masquerading as an inferior wall myocardial infarction. A 77-year-old woman with a history of aortic stenosis status postsurgical aortic valve replacement presented with chest pain. Workup revealed elevated high-sensitivity troponins and STE in the inferior leads. She subsequently underwent a left heart catheterization, which showed no critical plaques or stenosis. Persistent abdominal pain prompted further evaluation with a computed tomography scan of the abdomen, which demonstrated evidence of SBO. Conservative treatment with bowel decompression resulted in symptom improvement and complete resolution of the STEs on a follow-up EKG. This case underscores the importance of considering noncardiac etiologies, such as SBO, in the differential diagnosis of STE on EKG for accurate diagnosis and management.
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Melanoma, originating through malignant transformation of melanin-producing melanocytes, is a formidable malignancy, characterized by local invasiveness, recurrence, early metastasis, resistance to therapy, and a high mortality rate. This review discusses etiologic and risk factors for melanoma, diagnostic and prognostic tools, including recent advances in molecular biology, omics, and bioinformatics, and provides an overview of its therapy. Since the incidence of melanoma is rising and mortality remains unacceptably high, we discuss its inherent properties, including melanogenesis, that make this disease resilient to treatment and propose to use AI to solve the above complex and multidimensional problems. We provide an overview on vitamin D and its anticancerogenic properties, and report recent advances in this field that can provide solutions for the prevention and/or therapy of melanoma. Experimental papers and clinicopathological studies on the role of vitamin D status and signaling pathways initiated by its active metabolites in melanoma prognosis and therapy are reviewed. We conclude that vitamin D signaling, defined by specific nuclear receptors and selective activation by specific vitamin D hydroxyderivatives, can provide a benefit for new or existing therapeutic approaches. We propose to target vitamin D signaling with the use of computational biology and AI tools to provide a solution to the melanoma problem.
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Atreye MajumdarSambit K. MohantyObjective This article identifies and evaluates the frequency of mutations in the BCR-ABL1 kinase domain (KD) of chronic myeloid leukemia (CML) patients who showed suboptimal response to their current tyrosine kinase inhibitor (TKI) regime and assesses their clinical value in further treatment decisions. Materials and Methods Peripheral and/or bone marrow were collected from 791 CML patients. Ribonucleic acid was extracted, reverse transcribed, and Sanger sequencing method was utilized to detect single-nucleotide variants (SNVs) in BCR-ABL1 KD. Results Thirty-eight different SNVs were identified in 29.8% ( n = 236/791) patients. T315I, E255K, and M244V were among the most frequent mutations detected. In addition, one patient harbored a novel L298P mutation. A subset of patients from the abovementioned harbored compound mutations (13.3%, n = 33/236). Follow-up data was available in 28 patients that demonstrated the efficacy of TKIs in correlation with mutation analysis and BCR-ABL1 quantitation. Molecular response was attained in 50% patients following an appropriate TKI shift. A dismal survival rate of 40% was observed in T315I-harboring patients on follow-up. Conclusion This study shows the incidence and pattern of mutations in one of the largest sets of Indian CML patients. In addition, our findings strengthen the prognostic value of KD mutation analysis among strategies to overcome TKI resistance.
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Stress-induced cardiomyopathy (SCM) is a cardiac systolic dysfunction caused by various stressful triggers. It is often transient and reversible upon the reversal of the underlying stressor. We present the case of a 70-year-old female with SCM in the setting of gastric volvulus and incarcerated para-esophageal hernia.
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Background Students' presentations are a teaching-learning tool where students not only study and understand a topic but also teach their peers, thereby learning the art and skill of effective presentation. Aims The study aimed to evaluate peer assessments in students' presentations and find their role and application in improving presentation skills among students through feedback and course correction. Methods A group of students every week from a class of 125 was assigned a topic to present to the rest of their batch students who evaluated their presentation on a rubric shared via a Google Form link. The number of students who gave responses was noted. The responses were also shared with the presenters. The evaluator faculty moderated and discussed the areas for possible improvement and course correction. The students also filled out a feedback form on the entire exercise after presentations from the entire batch. Results The quality of students' presentation skills improved with subsequent students over the period. The students learned about their areas of improvement. Through the feedback form, students shared their reasons not to give a presentation. However, most of them found the exercise beneficial. Conclusions Peer assessment can be a credible mode for improving presentation skills with the active participation of other students and provide a learning method based on others' performances. Peer responses provide for self-evaluation and self-reflection. This type of survey among different institutions will identify students' flaws, help them improve and self-evaluate, and add to the current literature.
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Objectives Iatrogenic injury to the internal carotid artery (ICA) is one of the most catastrophic complications of endoscopic sinus and skull base surgery. Previous research has shown that packing with a crushed muscle graft at the injury site can be an effective management technique to control bleeding and prevent the need for ICA sacrifice. Here, we describe a novel and readily available repair donor site-an autologous lateral tongue muscle patch. Design Three representative cases of a successful repair of ICA injuries using a lateral tongue muscle patch are included in this study. The graft measured approximately 2 × 3 cm and was taken from the lateral intrinsic tongue musculature. We describe the harvest of the graft, its advantages, and the details of operative repair. Results The lateral tongue provides a large and readily accessible source of muscle within the surgical field that can be quickly harvested during an endoscopic procedure. For the first case, an expanding parasellar ICA pseudoaneurysm was managed with a tongue muscle patch and nasal packing. In the second case, a cavernous ICA injury was sustained during craniopharyngioma resection. Case three involved an ICA injury during endonasal debridement of invasive fungal rhinosinusitis. None of the patients required embolization or neurovascular stenting. Postoperative angiograms and serial computed tomography angiograms showed complete resolution of the pseudoaneurysm, and the patients continued to do well at least 1 year after repair. Conclusion Lateral tongue muscle graft is an effective and efficient method to manage ICA injuries during endoscopic endonasal surgery. Advantages include the speed of harvest, donor site being readily accessible in the surgical field, and low donor site morbidity. It should be added to the repertoire of possible donor sites for addressing catastrophic sinonasal bleeding.
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Mosquito-borne diseases are a major public-health concern worldwide. The development of resistance in mosquitoes to the existing larvicides and the associated-risks necessitates the exploration of novel molecules to control vector-borne pathogens. This study demonstrates that N-alkylamides [2E,4E-N-isobutyl-undeca-2,4-diene-8,10-diynamide (1) and 2E,4E,8Z,10E-N-isobutyl-dodeca-2,4,8,10-tetraenamide (2)] of Acmella ciliata exhibit biocidal action against Aedes aegypti and Culex quinquefasciatus larvae. The LC50 for 1 and 2 were 44.19 and 18.28 ppm against Aedes larvae, and 30.89 and 11.75 ppm against Culex larvae, respectively. We further observed that the chain length, degree of unsaturation, and terminal methylation influence the larvicidal efficacy of N-alkylamides. HPLC-assisted quantification revealed that the content of both 1 (19.01 mg/g) and 2 (68.55 mg/g) was maximum in the flowers of A. ciliata. Thus, this study concludes that N-alkylamides are promising alternatives to control mosquito larvae and can be used as standard for quantitation in test samples.
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BACKGROUND: Data using real-world assessments of aortic regurgitation (AR) severity to identify rates of Heart Valve Team evaluation and aortic valve replacement (AVR), as well as mortality among untreated patients, are lacking. The present study assessed these trends in care and outcomes for real-world patients with documented AR. METHODS: Using a deidentified data set (January 2018-March 2023) representing 1,002,853 patients >18 years of age from 25 US institutions participating in the egnite Database (egnite, Inc.) with appropriate permissions, patients were classified by AR severity in echocardiographic reports. Rates of evaluation by the Heart Valve Team, AVR, and all-cause mortality without AVR were examined using Kaplan-Meier estimates and compared using the log-rank test. RESULTS: Within the data set, 845,113 patients had AR severity documented. For moderate-to-severe or severe AR, respectively, 2-year rates (95% confidence interval) of evaluation by the Heart Valve Team (43.5% [41.7%-45.3%] and 65.4% [63.3%-67.4%]) and AVR (19.4% [17.6%-21.1%] and 46.5% [44.2%-48.8%]) were low. Mortality at 2 years without AVR increased with greater AR severity, up to 20.7% for severe AR (p < 0.001). In exploratory analyses, 2-year mortality for untreated patients with left ventricular end-systolic dimension index > 25 mm/m2 was similar for moderate (34.3% [29.2%-39.1%]) and severe (37.2% [24.9%-47.5%]) AR. CONCLUSIONS: Moderate or greater AR is associated with poor clinical outcomes among untreated patients at 2 years. Rates of Heart Valve Team evaluation and AVR were low for those with moderate or greater AR, suggesting that earlier referral to the Heart Valve Team could be beneficial.