Closed-loop digital meditation for neurocognitive and behavioral development in adolescents with childhood neglect.

Adverse childhood experiences are linked to poor attentive behaviors during adolescence, as well as increased risk for mental health disorders in adults. However, no study has yet tested targeted interventions to optimize neurocognitive processes in this population. Here, we investigated closed-loop digital interventions in a double-blind randomized controlled study in adolescents with childhood neglect, and evaluated the outcomes using multimodal assessments of neuroimaging, cognitive, behavioral, and academic evaluations. In the primary neuroimaging results, we demonstrate that a closed-loop digital meditation intervention can strengthen functional connectivity of the dorsal anterior cingulate cortex (dACC) in the cingulo-opercular network, which is critically developing during the adolescent period. Second, this intervention enhanced sustained attention and interference-resolution abilities, and also reduced behavioral hyperactivity at a 1-year follow-up. Superior academic performance was additionally observed in adolescents who underwent the digital meditation intervention. Finally, changes in dACC functional connectivity significantly correlated with improvements in sustained attention, hyperactivity, and academic performance. This first study demonstrates that closed-loop digital meditation practice can facilitate development of important aspects of neurocognition and real-life behaviors in adolescents with early childhood neglect

Single-step Aerosol Methods for Lignin Valorization: From Fundamentals to Scale-up

Growing consumption of fossil resources for energy and materials production has significantly increased greenhouse gas emissions, which will have an increasingly negative, and potentially catastrophic, environmental impact in the future. Lignocellulosic biomass is one of the few sustainable carbon resources that has the abundance and geographical distribution to displace fossil-based fuels and materials. However, the under-utilization of by-products such as lignin fraction remains a key challenge in expanding the utilization of lignocellulosic materials, necessitating the development of technologies for valorization of lignin into high-value products. Lignin is a promising precursor for the synthesis of a diverse range of high-value nanomaterials. However, the conventional solvothermal techniques to obtain lignin-based nanomaterials often involve multistep batch processes and large volumes of solvents/activating agents that are not cost-effective and environmentally benign, thereby limiting their scalability. Therefore, to advance scalable (i.e., environmentally benign and economically viable) valorization of lignin to lignin-based nanomaterials, it is essential to develop alternative techniques. This thesis demonstrates the development of gas-phase aerosol techniques for the valorization of lignin to lignin-based nanoparticles (NPs). Key features of the aerosol technique include ultrafast processing (seconds), continuous and single-step operation, minimal use of solvents, and precise control over material properties. This thesis is divided into three sections concerning the: (1) demonstration of a furnace aerosol reactor (FuAR) for the controlled synthesis of lignin-based NPs; (2) design and development of a novel aerosol reactor for the in-situ synthesis of lignin-based nanocomposites; and (3) scalability assessment of FuAR for the synthesis of carbon nanoparticles (CNPs) from lignin. The first section demonstrates the application of FuAR for the controlled synthesis of lignin-based NPs, specifically lignin nanoparticles (LNPs) and CNPs, from bulk lignin. The key operating parameters of FuAR, lignin concentration, temperature, and residence time, are systematically investigated for their roles in determining the nanoparticle size, morphology, surface area, and chemical structure. Furthermore, the impacts of various inter/intra particle processes (such as nucleation, reactions, collision, and sintering) on nanoparticle properties are illustrated to enable controlled synthesis of NPs. To determine the kinetics of simultaneous reaction and sintering, a generalized geometric model (GM) predicting the size and shape evolution of multiparticle aggregates is presented. Using the experimental results on nanoparticle properties and knowledge of reaction and sintering kinetics of lignin obtained from the GM, a detailed mechanism for the evolution of bulk lignin to LNPs and CNPs in FuAR is proposed. The as-synthesized LNPs and CNPs are evaluated for their performance in UV protection and supercapacitor applications, respectively. CNPs exhibited a specific capacitance of 247 F/g at 0.5 A/g with excellent capacity retainment of over 98% after 10,000 cycles, which is a clear demonstration of their superior performance compared with supercapacitors synthesized earlier from lignin. Moreover, the FuAR approach requires significantly less time for CNPs synthesis: on the order of seconds in comparison to hours for conventional solvothermal methods, highlighting significant promise for rapid valorization of lignin. The second section focuses on the design and development of a novel aerosol-based reactor to advance the application of the FuAR system for in-situ synthesis of lignin-based carbon nanocomposites, specifically Carbon-Silicon (C-Si) and Carbon-Sulfur (C-S). The fundamentals involved in the aerosol reactor design and the impact of processing parameters on composite properties are systematically investigated. Based on the analysis results, detailed mechanisms for the formation of C-S and C-Si composites in the respective FuAR-based systems are proposed. The impact of the distribution and loading of Si in C-Si and S in C-S on their performance as electrodes in Li-ion batteries is investigated to establish property function relationships. The third section assesses the scalability of the FuAR system for the synthesis of CNPs using a comprehensive life cycle assessment (LCA). Initially, the assessment is focused on lab-scale FuAR to investigate the significance of various processing parameters on the environmental impact of CNPs synthesis. Based on the LCA of lab-scale FuAR, an optimized scaled-up FuAR design, that incorporates recirculation of exhaust gas, heat recovery, and H2O recovery, is proposed. The scaled-up FuAR exhibited a global warming potential of 28.31 kg CO2 eq./kg of carbon material and 0.117 kg CO2 eq./F of capacitance based on mass and energy storage performance in supercapacitors, respectively. The superior sustainability along with the simple (single-step, continuous, and rapid) operation indicates the significant promise of using FuAR for the synthesis of CNPs from lignin. Finally, this dissertation also includes the demonstration of electrospray for lignin valorization. In summary, this dissertation comprehensively covers all aspects, from fundamentals to scale-up, for advancing scalable valorization of lignin to high-value nanomaterials using single-step aerosol techniques

Comparison of locking compression plating vs retrograde intramedullary nailing in distal femur extra-articular fractures

Background: The purpose of the study was to compare the outcome of distal femur extra articular fractures treated with locking plate and retrograde intramedullary nail.Methods: 86 patients’ distal femur extra-articular fractures were included in the study. 44 patients were operated with intramedullary nailing; 42 patients were operated with locking plate. Results of the 2 groups were compared with regards to clinical and radiological outcome, intraoperative timing and blood loss. Post-operative status of the patients was evaluated using the visual analogue scale, neer score, knee range of motion and radiological union on plain radiographs. Patients were followed-up at 4 weekly intervals from 8 to 28 weeks and then at 1 year.Results: Mean operative time and blood loss was less in intramedullary nailing group whereas intraoperative blood loss was less in the plating group. 6 patients developed surgical site infection in the plating group. Mean-time till radiological union was significantly better in intramedullary nailing group. 7 patients in plating group had issues with union (5 non-union, 2 delayed union) whereas 1 patient in IMN group had nonunion. 93% of intramedullary nailing cases were able to bear full weight at 12 weeks compared to 66% cases in plate group. Knee pain at 6 months was more in intramedullary nailing group.Conclusions: IMN proved to be a better modality of fixation of distal femur fracture fixation in our study in terms of operative time, union rates, infection rates and overall patient outcome if done with proper principles and techniques of intramedullary fixation

Factors contributing to acute heart failure after a first acute coronary syndrome episode

Background: Factors that speed up the development of acute heart failure (AHF) after acute coronary syndrome (ACS), are understudied in developing country like India. Therefore, this study was aimed to determine the risk factor of heart failure (HF) among the post-ACS patients. Methods: This  descriptive  cross-sectional  study  was  performed  at Government General  Hospital  (GGH) Srikakulam, Andhra Pradesh, India. 108 patients who were admitted with HF cardiology unit of GGH after ACS from September 2023 to November 2024 were enrolled in the study. An established inclusion and exclusion criteria along with consecutive sampling technique were used for patients’ recruitment. A self-structured proforma was applied to gather data. Data analysis was done in the statistical package for the social sciences (SPSS) version 25.0. Results: Clinical features, including glucose levels, dyslipidemia, COPD, and medication history, were analyzed in patients with and without ACS. HF was more common in those aged≥40 years (69.23%), male (62.82%), and with anterior wall myocardial infarction (38.46%). Key risk factors included reduced ejection fraction (67.90%), left anterior descending artery pathology (17.95%), absence of myocardial revascularization (46.15%), diabetes mellitus (52.56%), hypertension (78.20%), anemia (53.85%), hyperlipidemia (75.64%), and smoking history (51.28%). Additionally, glucose dysregulation, dyslipidemia, COPD, and medication history influenced HF progression. Conclusions: Factors such as an age group with 40 years or above, male gender, anterior wall myocardial infarction, reduced ejection fraction, left anterior descending artery pathology, absence of myocardial revascularization procedure, diabetes mellitus, hypertension, anemia, hyperlipidemia, and history of smoking, all accelerate the development of HF among post-ACS patients

Enhancement of c-Myc degradation by BLM helicase leads to delayed tumor initiation

The spectrum of tumors that arise owing to the overexpression of c-Myc and loss of BLM is very similar. Hence, it was hypothesized that the presence of BLM negatively regulates c-Myc functions. By using multiple isogenic cell lines, we observed that the decrease of endogenous c-Myc levels that occurs in the presence of BLM is reversed when the cells are treated with proteasome inhibitors, indicating that BLM enhances c-Myc turnover. Whereas the N-terminal region of BLM interacts with c-Myc, the rest of the helicase interacts with the c-Myc E3 ligase Fbw7. The two BLM domains act as ‘clamp and/or adaptor’, enhancing the binding of c-Myc to Fbw7. BLM promotes Fbw7-dependent K48-linked c-Myc ubiquitylation and its subsequent degradation in a helicase-independent manner. A subset of BLM-regulated genes that are also targets of c-Myc were determined and validated at both RNA and protein levels. To obtain an in vivo validation of the effect of BLM on c-Myc-mediated tumor initiation, isogenic cells from colon cancer cells that either do or do not express BLM had been manipulated to block c-Myc expression in a controlled manner. By using these cell lines, the metastatic potential and rate of initiation of tumors in nude mice were determined. The presence of BLM decreases c-Myc-mediated invasiveness and delays tumor initiation in a mouse xenograft model. Consequently, in tumors that express BLM but not c-Myc, we observed a decreased ratio of proliferation to apoptosis together with a suppressed expression of the angiogenesis marker CD31. Hence, partly owing to its regulation of c-Myc stability, BLM acts as a ‘caretaker tumor suppressor’

The Use of Biomaterials in Gastrointestinal Endoscopy

Gastrointestinal endoscopy has evolved to become a therapeutic resource for multiple pathologic conditions, utilizing many techniques, tools and materials from the field of conventional surgery. Thermal, mechanical or chemical modalities are often employed to expedite the process of hemostasis and achieve a stable coagulum. Thermocoagulation coupled with devices for mechanical hemostasis have been adapted successfully to endoscopy. Chemical hemostasis from biomaterials can be obtained from biologically active materials such as thrombin and fibrin, absorbable products such as gelatins, collagen and oxidized cellulose or synthetic products and inorganic powders. Aside from hemostatic properties, biomaterials are also appealing due to its ability to promote wound healing. However, the use of biomaterials has not been as widespread in endoscopy as in conventional surgery, mainly because of the constraint of delivering these materials through an endoscope. Over the last decade, the options for biomaterials have expanded and its incorporation in endoscopy has slowly increased. Although the cost of biomaterials is higher compared to traditional hemostatics, this may be offset by the potential benefits of decreased bleeding related complications, procedure time, hospital stay and blood transfusions. Biomaterials have demonstrated an improvement in clinical outcomes during conventional surgery. Nevertheless, more studies are required to extrapolate these benefits to endoscopy

RECQL4 is essential for the transport of p53 to mitochondria in normal human cells in the absence of exogenous stress

Mutations in RECQL4 helicase are associated with Rothmund–Thomson syndrome (RTS). A subset of RTS patients is predisposed to cancer and is sensitive to DNA damaging agents. The enhanced sensitivity of cells from RTS patients correlates with the accumulation of transcriptionally active nuclear p53. We found that in untreated normal human cells these two nuclear proteins, p53 and RECQL4, instead colocalize in the mitochondrial nucleoids. RECQL4 accumulates in mitochondria in all phases of the cell cycle except S phase and physically interacts with p53 only in the absence of DNA damage. p53–RECQL4 binding leads to the masking of the nuclear localization signal of p53. The N-terminal 84 amino acids of RECQL4 contain a mitochondrial localization signal, which causes the localization of RECQL4–p53 complex to the mitochondria. RECQL4–p53 interaction is disrupted after stress, allowing p53 translocation to the nucleus. In untreated normal cells RECQL4 optimizes de novo replication of mtDNA, which is consequently decreased in fibroblasts from RTS patients. Wild-type RECQL4-complemented RTS cells show relocalization of both RECQL4 and p53 to the mitochondria, loss of p53 activation, restoration of de novo mtDNA replication and resistance to different types of DNA damage. In cells expressing Δ84 RECQL4, which cannot translocate to mitochondria, all the above functions are compromised. The recruitment of p53 to the sites of de novo mtDNA replication is also regulated by RECQL4. Thus these findings elucidate the mechanism by which p53 is regulated by RECQL4 in unstressed normal cells and also delineates the mitochondrial functions of the helicase

Clinical Presentation and Outcome of Sinonasal Mucormycosis in Pre COVID-19 Era from a Tertiary Care Centre in Uttarakhand: A Cross-sectional Study

Introduction: Sinonasal mucormycosis is an invasive fungal rhinosinusitis which rapidly involves orbits and brain either by direct extension or angioinvasion. Uncontrolled diabetics and immunocompromised patients are prone for this invasive fungal infection. The rapidity of severity of symptoms and morbidity of this invasive fungal infection warrant earliest diagnosis and appropriate management. This research work will be helpful in comparing sinonasal mucormycosis in Coronavirus Disease2019 (COVID-19) patients as all cases in present study were not associated with COVID-19 infection. Aim: To observe presenting features and estimate morbidity of mucormycosis patients in tertiary care hospital. Materials and Methods: This cross-sectional retroprospective study was conducted in Department of Otorhinolaryngology of a tertiary teaching hospital from July 2018 to March 2020. Total 25 sinonasal mucormycosis patients who underwent endoscopic debridement along with amphotericin B were included in this study. Patient was analysed regarding age, gender, chief complains, accompanying co-morbidity, extension of disease, medical treatment, surgical intervention and final outcome. Statistical analysis was done in the form of mean, mode, median and percentage wherever required. Results: Total 14 (56%) patients were male and 11 (44%) patients were female with median age of 48 years. Total 13 (52 %) patients had facial pain or headache while 13 (52%) had facial or orbital swelling followed by nasal symptoms in 5 (20%), vision loss in 4 (16%) and ptosis in 3 (12%) cases. Twenty four (96%) of cases were having uncontrolled diabetes mellitus. Only 3 (12%) had limited sinonasal disease while 22 (88%) had fungal invasion in orbit. Total 7 (28%) patients had intracranial extension. Out of 25 patients, 4 (16%) expired, 7 (28%) had permanent vision loss and 12 (48%) recovered completely and 2 (8%) left hospital against medical advice. Conclusion: Present study concluded that mucormycosis is strongly associated with uncontrolled diabetes mellitus. Most common presenting features were facial pain, headache and facial orbital swelling. Only half of the patients recovered with minimal morbidity. Mortality is associated with intracranial extension of mucormycosis. Early diagnosis, extensive and timely endoscopic debridement and appropriate use of amphotericin B is key for treatment of black fungus

Transitions from Injection-Drug-Use-Concentrated to Self-Sustaining Heterosexual HIV Epidemics: Patterns in the International Data

Background: Injecting drug use continues to be a primary driver of HIV epidemics in many parts of the world. Many people who inject drugs (PWID) are sexually active, so it is possible that high-seroprevalence HIV epidemics among PWID may initiate self-sustaining heterosexual transmission epidemics. Methods: Fourteen countries that had experienced high seroprevalence (,20%) HIV epidemics among PWID and had reliable data for injection drug use (IDU) and heterosexual cases of HIV or AIDS were identified. Graphs of newly reported HIV or AIDS cases among PWID and heterosexuals were constructed to identify temporal relationships between the two types of epidemics. The year in which newly reported cases among heterosexuals surpassed newly reported cases among PWID, aspects of the epidemic curves, and epidemic case histories were analyzed to assess whether it was ‘‘plausible’ ’ or ‘‘highly unlikely’ ’ that the HIV epidemic among PWID might have initiated the heterosexual epidemic in each country. Results: Transitions have occurred in 11 of the 14 countries. Two types of temporal relationships between IDU and heterosexual HIV epidemics were identified, rapid high incidence transitions vs. delayed, low incidence transitions. In six countries it appears ‘‘plausible’ ’ that the IDU epidemic initiated a heterosexual epidemic, and in five countries it appears ‘‘highly unlikely’ ’ that the IDU epidemic initiated a heterosexual epidemic. A rapid decline in incidence among PWID after the peak year of new cases and national income were the best predictors of the ‘‘highly unlikely’ ’ initiation of a heterosexua

Allogeneic Hematopoietic Cell Transplantation for Blastic Plasmacytoid Dendritic Cell Neoplasm: A CIBMTR Analysis

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematological malignancy with a poor prognosis and considered incurable with conventional chemotherapy. Small observational studies reported allogeneic hematopoietic cell transplantation (allo-HCT) offers durable remissions in patients with BPDCN. We report an analysis of patients with BPDCN who received an allo-HCT, using data reported to the Center for International Blood and Marrow Transplant Research (CIBMTR). We identified 164 patients with BPDCN from 78 centers who underwent allo-HCT between 2007 and 2018. The 5-year overall survival (OS), disease-free survival (DFS), relapse, and nonrelapse mortality (NRM) rates were 51.2% (95% confidence interval [CI], 42.5-59.8), 44.4% (95% CI, 36.2-52.8), 32.2% (95% CI, 24.7-40.3), and 23.3% (95% CI, 16.9-30.4), respectively. Disease relapse was the most common cause of death. On multivariate analyses, age of ≥60 years was predictive for inferior OS (hazard ratio [HR], 2.16; 95% CI, 1.35-3.46; P = .001), and higher NRM (HR, 2.19; 95% CI, 1.13-4.22; P = .02). Remission status at time of allo-HCT (CR2/primary induction failure/relapse vs CR1) was predictive of inferior OS (HR, 1.87; 95% CI, 1.14-3.06; P = .01) and DFS (HR, 1.75; 95% CI, 1.11-2.76; P = .02). Use of myeloablative conditioning with total body irradiation (MAC-TBI) was predictive of improved DFS and reduced relapse risk. Allo-HCT is effective in providing durable remissions and long-term survival in BPDCN. Younger age and allo-HCT in CR1 predicted for improved survival, whereas MAC-TBI predicted for less relapse and improved DFS. Novel strategies incorporating allo-HCT are needed to further improve outcomes