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Author(s): Samatharman Purushothaman [sup.1], Pankaj Kundra [sup.1], Muthapillai Senthilnathan [sup.1], Sarath Chandra Sistla [sup.2], Shathish Kumar [sup.3] Author Affiliations: (1) grid.414953.e, 0000000417678301, Department of Anaesthesiology and Critical Care, Second Floor, [...], Purpose and objectives Phantom limb pain (PLP) is a major cause of physical limitation and disability accounting for about 85% of amputated patients. Mirror therapy is used as a therapeutic modality for patients with phantom limb pain. Primary objective was to study the incidence of PLP at 6 months following below-knee amputation between the mirror therapy group and control group. Methods Patients posted for below-knee amputation surgery were randomized into two groups. Patients allocated to group M received mirror therapy in post-operative period. Two sessions of therapy were given per day for 7 days and each session lasted for 20 min. Patients who developed pain from the missing portion of the amputated limb were considered to have PLP. All patients were followed up for six months and the time of occurrence of PLP and intensity of the pain were recorded among other demographic factors. Results A total of 120 patients completed the study after recruitment. The demographic parameters were comparable between the two groups. Overall incidence of phantom limb pain was significantly higher in the control group (Group C) when compared to the mirror therapy (Group M) group [Group M = 7 (11.7%) vs Group C = 17 (28.3%); p = 0.022]. Intensity of PLP measured on the Numerical Rating Scale (NRS) was significantly lower at 3 months in Group M compared to Group C among patients who developed PLP [NRS - median (Inter quartile range): Group M 5 (4,5) vs Group C 6 (5,6); p 0.001]. Conclusion Mirror therapy reduced the incidence of phantom limb pain when administered pre-emptively in patients undergoing amputation surgeries. The severity of the pain was also found to be lower at 3 months in patients who received pre-emptive mirror therapy. Trial Registration This prospective study was registered in the clinical trial registry of India. Trial Registration number: CTRI/2020/07/026488.

Author(s): Pankaj Kundra (corresponding author) [1]; Muthapillai Senthilnathan [1] The art of educating the trainees is always challenging to the medical fraternity. Teaching is much more challenging in the speciality [...]

Ovarian cancer is the deadliest gynecological cancer. Cytoreductive surgery to remove primary and intraperitoneal tumor deposits remains as the standard therapeutic approach. However, lack of an intraoperative image-guided approach to enable the visualization of all tumors can result in incomplete cytoreduction and recurrence. We engineered nano-sized particles derived from erythrocytes that encapsulate the near infrared (NIR) fluorochrome, indocyanine green, as potential imaging probes for tumor visualization during cytoreductive surgery. Herein, we present the first demonstration of the use of these nanoparticles in conjunction with spatially-modulated illumination (SMI), at spatial frequencies in the range of 0-0.5 mm-1, to fluorescently image intraperitoneal ovarian tumors in mice. Results of our animal studies suggest that the nanoparticles accumulated at higher levels within tumors 24 h post-intraperitoneal injection as compared to various other organs. We demonstrate that, under the imaging specifications reported here, use of these nanoparticles in conjunction with SMI enhances the fluorescence image contrast between intraperitoneal tumors and liver, and between intraperitoneal tumors and spleen by nearly 2.1, and 3.0 times, respectively, at the spatial frequency of 0.2 mm-1 as compared to the contrast values at spatially-uniform (non-modulated) illumination. These results suggest that the combination of erythrocyte-derived NIR nanoparticles and structured illumination provides a promising approach for intraoperative fluorescence imaging of ovarian tumor nodules at enhanced contrast.

Author(s): Pankaj Kundra [1]; Stalin Vinayagam (corresponding author) [1] Supraglottic airway (SGA) devices are widely used for elective airway management and rescue devices in difficult airway management. According to the [...]

PurposeVarious excitation strategies have been proposed for dynamic imaging of hyperpolarized agents such as [1-13 C]-pyruvate, but the impact of these strategies on quantitative evaluation of signal evolution remains unclear. To better understand their relative performance, we compared the accuracy and repeatability of measurements made using variable excitation angle strategies and conventional constant excitation angle strategies.MethodsSignal evolution for constant and variable excitation angle schedules was simulated using a pharmacokinetic model of hyperpolarized pyruvate with 2 chemical pools and 2 physical compartments. Noisy synthetic data were then fit using the same pharmacokinetic model with the apparent chemical exchange term as an unknown, and fit results were compared with simulation parameters to determine accuracy and reproducibility.ResultsConstant excitations and a variable excitation strategy that maximizes the HP lactate signal yielded data that supported quantitative analyses with similar accuracy and repeatability. Variable excitation angle strategies that were designed to produce a constant signal level resulted in lower signal and worse quantitative accuracy and repeatability, particularly for longer acquisition times.ConclusionsThese results suggest that either constant excitation angle or variable excitation angles that attempt to maximize total signal, as opposed to maintaining a constant signal level, are preferred for metabolic quantification using hyperpolarized pyruvate.

Background: Mpox is a viral zoonotic disease that has seen a resurgence in recent years, with outbreaks reaching beyond its traditional endemic zones in Central and West Africa to parts of Europe and North America. The relationship between human immunodeficiency virus (HIV) infection and mpox outcomes, particularly hospitalization rates, remains underexplored despite the known immunosuppressive effects of HIV. This systematic review and meta-analysis aimed to clarify the association between HIV infection and the likelihood of hospitalization in mpox cases. Methods: A literature search was conducted through PubMed, Embase, Web of Science, Scopus, and the Cochrane Library up until August 10, 2024. The eligibility criteria focused on observational studies that evaluated hospitalization rates among mpox cases, distinguishing between HIV-positive and HIV-negative individuals. Newcastle-Ottawa Scale was used for evaluating study quality. The meta-analysis used a random-effects model to accommodate expected study heterogeneity using R software (V. 4.4). Results: The search yielded 686 records, with 14 studies meeting the inclusion and exclusion criteria after screenings and full-text assessments. The pooled analysis revealed a 56.6% increased risk of hospitalization among HIV-positive mpox cases compared to HIV-negative individuals (95% CI: 18.0–107.7%). Notable heterogeneity (I² = 76%) was observed, likely reflecting variations in study settings and methodologies. Sensitivity analysis confirmed the robustness of these findings, and no significant publication bias was detected (Egger's test p-value = 0.733). Conclusion: HIV infection is associated with a statistically significant increased risk of hospitalization in mpox cases. There is a critical need for integrated care and enhanced surveillance, especially in populations with high HIV prevalence. Our findings emphasize the importance of ongoing research to better understand HIV and mpox co-infection and to refine management strategies for this vulnerable group. Future studies should focus on long-term outcomes and the effectiveness of various management strategies across different healthcare settings. [ABSTRACT FROM AUTHOR]

Easy-to-fabricate, flexible optoelectronic devices based on conducting organic polymers are in high demand due to their cost-effectiveness and low weight. The hole and electron transport layers (HTL/ELT) are central to the working of these devices. Conductive polymers are now extensively used (HTL/ETL) in solar cells, as hole injection layers in OLEDs, and as electrodes or active channel layers in organic thin film transistors. Poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) is the mainstay of these devices. The energy levels of the tailored PEDOT:PSS determine the work function, the efficiency of charge separation, and the device’s performance. Transparent electrodes are another requirement for the efficient functioning of devices, with indium tin oxide (ITO) being a common choice. To overcome problems associated with ITO, researchers are focusing on conducting polymer materials such as PEDOT:PSS as transparent electrode materials. Flexibility, water processability, high electrical conductivity, good optical transparency, biocompatibility, and good thermoelectric properties make functionalized PEDOT:PSS a versatile conductive polymer. Priced for its versatility and good performance, it is used in cutting-edge applications including LEDs, solar cells, and sensors. Cost-effective production and easy production scalability make it a default material for optoelectronic applications despite some challenges. This review highlights recent research with special emphasis on tuning the work function of PEDOT:PSS to enhance the performance of optoelectronic devices. [ABSTRACT FROM AUTHOR]

Background: Atrial fibrillation (AF) is the most prevalent form of sustained cardiac arrhythmia, with vascular endothelial growth factor (VEGF) increasingly recognized for its potential role in the pathogenesis of AF through mechanisms involving atrial remodeling, inflammation, and fibrosis. This systematic review aims to synthesize available evidence on the association between VEGF and AF, exploring the implications of VEGF as a biomarker and therapeutic target. Methods: We conducted a comprehensive search across PubMed, Embase, and Web of Science until November 10 2024, selecting studies based on pre-defined criteria that involve adults with AF and measurements of VEGF levels. The selected studies included observational and experimental designs, excluding non-English and methodologically insufficient publications. Narrative synthesis was used for summarising the results. Results: Eight studies met the inclusion criteria. The studies show a general trend of elevated VEGF levels in AF patients compared to controls, with significant heterogeneity in findings across studies. VEGF subtypes such as VEGF-A and VEGF-D demonstrated stronger associations with AF risk compared to VEGF-C. These variations point to the complex role of VEGF in AF, influencing factors like angiogenesis, endothelial function, and inflammatory responses. Conclusion: VEGF is potentially a significant contributor to AF pathophysiology, with its levels reflecting disease activity. The variability observed across studies suggests a need for standardized measurement approaches and further investigation into VEGF subtypes. Future research should focus on longitudinal studies to better understand the causal relationships and the potential of VEGF as a therapeutic target and biomarker in AF management. Clinical trial number: Not applicable. [ABSTRACT FROM AUTHOR]

Background: Neurological disorders are a major global health concern, especially in BRICS nations (Brazil, Russia, India, China, South Africa), where demographic and socio-economic changes have amplified their impact. This study evaluates trends in incidence, prevalence, mortality, and Disability-Adjusted Life Years (DALYs) associated with neurological diseases in these countries from 1990 to 2021, focusing on sex disparities and key risk factors. Methods: Data were obtained from the Global Burden of Disease (GBD) 2021 database. Join point regression and Estimated Annual Percentage Change (EAPC) analyses were used to assess trends in neurological disease burden. Age-standardized rates for incidence, prevalence, and mortality were calculated, along with DALYs, and key risk factors were analyzed. Results: China showed the largest increase in incidence (7541.89 to 8031.37 per 100,000) and prevalence (26494.85 to 28534.79 per 100,000). Mortality increased in India (21.01 to 24.27 per 100,000) and South Africa (27.66 to 30.65 per 100,000), while China showed a decline (39.59 to 37.30 per 100,000). Brazil experienced a substantial rise in DALYs (1610.65 to 42024.59). Sex disparities showed higher DALY rates for females across all nations. Conclusion: The research highlights the rising burden of neurological disorders in BRICS nations, especially in China and Brazil due to aging populations and metabolic risks. It emphasizes the need for targeted interventions in India and South Africa, where increasing mortality rates and DALYs are concerning. Effective health policies should focus on early detection, managing metabolic risks, and implementing sex-specific strategies to address these issues. [ABSTRACT FROM AUTHOR]

Long noncoding RNAs (lncRNAs) are commonly dysregulated in tumors, but only a handful are known to play pathophysiological roles in cancer. We inferred lncRNAs that dysregulate cancer pathways, oncogenes, and tumor suppressors (cancer genes) by modeling their effects on the activity of transcription factors, RNA-binding proteins, and microRNAs in 5,185 TCGA tumors and 1,019 ENCODE assays. Our predictions included hundreds of candidate onco- and tumor-suppressor lncRNAs (cancer lncRNAs) whose somatic alterations account for the dysregulation of dozens of cancer genes and pathways in each of 14 tumor contexts. To demonstrate proof of concept, we showed that perturbations targeting OIP5-AS1 (an inferred tumor suppressor) and TUG1 and WT1-AS (inferred onco-lncRNAs) dysregulated cancer genes and altered proliferation of breast and gynecologic cancer cells. Our analysis indicates that, although most lncRNAs are dysregulated in a tumor-specific manner, some, including OIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergistically dysregulate cancer pathways in multiple tumor contexts.

Hotspot mutations in splicing factor genes have been recently reported at high frequency in hematological malignancies, suggesting the importance of RNA splicing in cancer. We analyzed whole-exome sequencing data across 33 tumor types in The Cancer Genome Atlas (TCGA), and we identified 119 splicing factor genes with significant non-silent mutation patterns, including mutation over-representation, recurrent loss of function (tumor suppressor-like), or hotspot mutation profile (oncogene-like). Furthermore, RNA sequencing analysis revealed altered splicing events associated with selected splicing factor mutations. In addition, we were able to identify common gene pathway profiles associated with the presence of these mutations. Our analysis suggests that somatic alteration of genes involved in the RNA-splicing process is common in cancer and may represent an underappreciated hallmark of tumorigenesis.

Protein ubiquitination is a dynamic and reversible process of adding single ubiquitin molecules or various ubiquitin chains to target proteins. Here, using multidimensional omic data of 9,125 tumor samples across 33 cancer types from The Cancer Genome Atlas, we perform comprehensive molecular characterization of 929 ubiquitin-related genes and 95 deubiquitinase genes. Among them, we systematically identify top somatic driver candidates, including mutated FBXW7 with cancer-type-specific patterns and amplified MDM2 showing a mutually exclusive pattern with BRAF mutations. Ubiquitin pathway genes tend to be upregulated in cancer mediated by diverse mechanisms. By integrating pan-cancer multiomic data, we identify a group of tumor samples that exhibit worse prognosis. These samples are consistently associated with the upregulation of cell-cycle and DNA repair pathways, characterized by mutated TP53, MYC/TERT amplification, and APC/PTEN deletion. Our analysis highlights the importance of the ubiquitin pathway in cancer development and lays a foundation for developing relevant therapeutic strategies.