Evaluation of Anti-Angiogenic Therapy Combined with Immunotherapy and Chemotherapy as a Strategy to Treat Locally Advanced and Metastatic Non-Small-Cell Lung Cancer.

Immunotherapy has made recent improvements in disease-free survival (DFS) and/or overall survival (OS) in all stages of non-small-cell lung cancer (NSCLC). Here, we review the tumor microenvironment and its immunosuppressive effects and discuss how anti-angiogenic therapies may potentiate the anti-carcinogenic effects of immunotherapy. We also review all the past literature and discuss strategies of combining anti-angiogenic therapy and immunotherapy +/- chemotherapy and hypothesize how we can use this strategy for non-small-cell lung cancer in metastatic previously untreated/previously treated settings in previously treated EGFR-mutated NSCLC for the upfront treatment of brain metastases prior to radiation therapy and for the incorporation of this strategy into stage III unresectable disease.

Alpha-synuclein interaction with mitochondria is the final mechanism of ferroptotic death induced by erastin in SH-SY5Y cells.

Ferroptosis has been characterized as a form of iron-dependent regulated cell death accompanied by an accumulation of reactive oxygen species and lipid oxidation products along with typical morphological alterations in mitochondria. Ferroptosis is activated by diverse triggers and inhibited by ferrostatin-1 and liproxstatin-1, apart from iron chelators and several antioxidants, and the process is implicated in multiple pathological conditions. There are, however, certain ambiguities about ferroptosis, especially regarding the final executioner of cell death subsequent to the accumulation of ROS.

Exosomal Dynamics and Brain Redox Imbalance: Implications in Alzheimer's Disease Pathology and Diagnosis.

Oxidative burden plays a central role in Alzheimer's disease (AD) pathology, fostering protein aggregation, inflammation, mitochondrial impairment, and cellular dysfunction that collectively lead to neuronal injury. The role of exosomes in propagating the pathology of neurodegenerative diseases including AD is now well established. However, recent studies have also shown that exosomes are crucial responders to oxidative stress in different tissues.

Assessing risk of bias in the meta-analysis of round 1 of the Health Care Innovation Awards.

Background: Systematic reviews of observational studies can be affected by biases that lead to under- or over-estimates of true intervention effects. Several tools have been reported in the literature that attempt to characterize potential bias. Our objective in this study was to determine the extent to which study-specific bias may have influenced intervention impacts on total costs of care (TCOC) in round 1 of the Health Care Innovation Awards.

Enhancing Anti-cancer Activity: Green Synthesis and Cytotoxicity Evaluation of Turmeric-Gold Nanocapsules on A549 Lung Cancer Cells.

Background Lung cancer remains a major global health concern, with a notable increase in new cases in recent years. This study aims to investigate the cytotoxic effects of polymeric turmeric-gold nanocapsules on A549 human lung cancer cells, utilizing green-synthesized gold nanoparticles from . and ethyl cellulose-based nanocapsules.

Meta-Analysis of the Impact of Four Advanced Primary Care Redesign Initiatives on Medicare Expenditures.

We conducted a secondary analysis of the evaluations of 22 sites participating in four primary care redesign initiatives funded by the Centers for Medicare and Medicaid Services or the Center for Medicare and Medicaid Innovation. Our objectives were to determine the overall impact of the initiatives on Medicare expenditures and whether specific site-level program features influenced expenditure findings. Averaged over sites, the mean intervention effect was a statistically insignificant US$26 per beneficiary per year.

Visceral adiposity index and lipid accumulation product index: The promising role in assessing cardiometabolic risk in non-obese patients of PCOS.

Background: The combination of metabolic disorders like obesity, insulin resistance, reduced glucose tolerance, diabetes mellitus, and dyslipidemia poses an increased risk of cardiovascular events in patients with PCOS which is closely related to increased visceral fat accumulation. This study explored the noninvasive adiposity markers like Visceral Adiposity Index (VAI) and Lipid Accumulation Product (LAP) levels in non-obese PCOS patients and their associations with clinico-metabolic parameters.

Methods And Materials: The case-control study was conducted with a total of 66 PCOS cases and 40 healthy controls (aged 18-35).

Evaluating ChatGPT's Ability to Solve Higher-Order Questions on the Competency-Based Medical Education Curriculum in Medical Biochemistry.

Background Healthcare-related artificial intelligence (AI) is developing. The capacity of the system to carry out sophisticated cognitive processes, such as problem-solving, decision-making, reasoning, and perceiving, is referred to as higher cognitive thinking in AI. This kind of thinking requires more than just processing facts; it also entails comprehending and working with abstract ideas, evaluating and applying data relevant to the context, and producing new insights based on prior learning and experience.

Role of written examination in the assessment of attitude ethics and communication in medical students: Perceptions of medical faculties.

Background: The study aims to record the perceptions of medical faculties regarding the effectiveness of theory-based examination to assess the newly introduced competencies of attitude ethics and communication (AETCOM) in the competency-based medical curriculum for Indian medical graduates.

Materials And Methods: This is an analytical cross-sectional study performed on the month of February 2020 where a prevalidated questionnaire consisting of components of AETCOM was e-mailed to the teaching faculties of IQ City Medical College via Google Forms. Consenting faculties responded.

Experimental Observation of Ultrashort Hyperchaotic Dark Multisoliton Complexes in a Magnonic Active Ring Resonator.

We report on the self-generation of ultrashort hyperchaotic dark multisoliton sequences with two positive large Lyapunov exponents in an active ring resonator consisting of a multifunctional L-shaped magnonic waveguide and a saturable amplifier. The irregular magnonic waveguide supports the converting of backward volume magnetostatic spin waves with negative dispersion to magnetostatic surface spin waves with positive dispersion that is accompanied by a transition from four-wave to three-wave nonlinear spin-wave interactions. Each multisoliton complex consists of four dark parametric pulses containing the soliton trains of four dark incoherent spin-wave envelope solitons possessing a subnanosecond duration.

Making Evidence Actionable: Interactive Dashboards, Bayes, and Health Care Innovation.

The results of many large-scale federal or multi-site evaluations are typically compiled into long reports which end up sitting on policymaker's shelves. Moreover, the information policymakers need from these reports is often buried in the report, may not be remembered, understood, or readily accessible to the policymaker when it is needed. This is not a new challenge for evaluators, and advances in statistical methodology, while they have created greater opportunities for insight, may compound the challenge by creating multiple lenses through which evidence can be viewed.

Access to Household Water Quality Information Leads to Safer Water: A Cluster Randomized Controlled Trial in india.

Household-specific feedback on the microbiological safety of drinking water may result in changes to water management practices that reduce exposure risks. We conducted a randomized, controlled trial in India to determine if information on household drinking water quality could change behavior and improve microbiological quality as indicated by Escherichia coli counts. We randomly assigned 589 participating households to one of three arms: (1) a messaging-only arm receiving messaging on safe water management ( n = 237); (2) a standard testing arm receiving the same messaging plus laboratory E.

Profile of Justice-Involved Marijuana and Other Substance Users: Demographics, Health and Health Care, Family, and Justice System Experiences.

Substance users are more likely to have co-occurring health problems, and this pattern is intensified among those involved with the criminal justice system. Interview data for 1977 incarcerated men in 5 states from the Multi-site Family Study on Incarceration, Parenting, and Partnering that was conducted between December 2008 and August 2011 were analyzed to compare pre-incarceration substance use patterns and health outcomes between men who primarily used marijuana, primarily used alcohol, primarily used other drugs, and did not use any illicit substances during that time. Using regression modeling, we examined the influence of substance use patterns on physical and mental health.

Measuring job satisfaction among healthcare staff in the United States: a confirmatory factor analysis of the Satisfaction of Employees in Health Care (SEHC) survey.

Objective: To validate the Satisfaction of Employees in Health Care (SEHC) survey with multidisciplinary, healthcare staff in the United States (U.S.).

Impact Of Health Care Delivery System Innovations On Total Cost Of Care.

Using delivery system innovations to advance health care reform continues to be of widespread interest. However, it is difficult to generalize about the success of specific types of innovations, since they have been examined in only a few studies. To gain a broader perspective, we analyzed the results of forty-three ambulatory care programs funded by the first round of the Center for Medicare and Medicaid Innovation's Health Care Innovations Awards.

Screening of Oral Potentially Malignant Disorders Using Exfoliative Cytology: A Diagnostic Modality.

. Oral exfoliative cytology (OEC) has been implemented in the diagnosis of pathologic lesions for ages. The present study was undertaken to evaluate the cytomorphological features of some of the commonest potentially malignant disorders (leukoplakia, lichen planus, and oral submucous fibrosis) through a simple procedure and illustrate its importance in mass screening.

Ceramide and Sphingosine-1-Phosphate in Cell Death Pathways : Relevance to the Pathogenesis of Alzheimer's Disease.

The metabolic turnover of sphingolipids produces several signaling molecules that profoundly affect the proliferation, differentiation and death of cells. In particular, an enormous body of information is available that defines the varied role of ceramide and sphingosine-1-phosphate in cell death and survival. This review specifically examines the role of ceramide and sphingosine-1- phosphate in triggering neuronal death in Alzheimer's disease by analyzing the data from post-mortem studies and experimental research.

The Oral Iron Chelator, Deferasirox, Reverses the Age-Dependent Alterations in Iron and Amyloid-β Homeostasis in Rat Brain: Implications in the Therapy of Alzheimer's Disease.

The altered metabolism of iron impacts the brain function in multiple deleterious ways during normal aging as well as in Alzheimer's disease. We have shown in this study that chelatable iron accumulates in the aged rat brain along with overexpression of transferrin receptor 1 (TfR1) and ferritin, accompanied by significant alterations in amyloid-β (Aβ) peptide homeostasis in the aging brain, such as an increased production of the amyloid-β protein precursor, a decreased level of neprilysin, and increased accumulation of Aβ42. When aged rats are given daily the iron chelator, deferasirox, over a period of more than 4 months starting from the 18th month, the age-related accumulation of iron and overexpression of TfR1 and ferritin in the brain are significantly prevented.

Multiple mechanisms of age-dependent accumulation of amyloid beta protein in rat brain: Prevention by dietary supplementation with N-acetylcysteine, α-lipoic acid and α-tocopherol.

The aged brain may be used as a tool to investigate altered metabolism of amyloid beta protein (Aβ42) that may have implications in the pathogenesis of Alzheimer's disease (AD). In the present study, we have observed a striking increase in the amyloid precursor protein (APP) level in the brain cortex of aged rats (22-24 months) along with a mild but statistically significant increase in the level of APP mRNA. Moreover, the activity of β secretase is elevated (nearly 55%) and that of neprilysin diminished (48%) in brain cortex of aged rats compared to that in young rats (4-6 months).

Role of Carboplatin in the Treatment of Triple Negative Early- Stage Breast Cancer.

Triple negative breast cancer (TNBC) is more prevalent in younger patients and those carrying BRCA mutations. Although the incidence of breast cancer in general has dropped during the last years, TNBC has shown a relative increase. It is recognized as a breast cancer subtype with a high risk of tumor relapse and mortality.

Reactive oxygen species, redox signaling and neuroinflammation in Alzheimer's disease: the NF-κB connection.

Oxidative stress and inflammatory response are important elements of Alzheimer's disease (AD) pathogenesis, but the role of redox signaling cascade and its cross-talk with inflammatory mediators have not been elucidated in details in this disorder. The review summarizes the facts about redox-signaling cascade in the cells operating through an array of kinases, phosphatases and transcription factors and their downstream components. The biology of NF-κB and its activation by reactive oxygen species (ROS) and proinflammatory cytokines in the pathogenesis of AD have been specially highlighted citing evidence both from post-mortem studies in AD brain and experimental research in animal or cell-based models of AD.

α-Synuclein-induced mitochondrial dysfunction in isolated preparation and intact cells: implications in the pathogenesis of Parkinson's disease.

This study has shown that purified recombinant human α-synuclein (20 μM) causes membrane depolarization and loss of phosphorylation capacity of isolated purified rat brain mitochondria by activating permeability transition pore complex. In intact SHSY5Y (human neuroblastoma cell line) cells, lactacystin (5 μM), a proteasomal inhibitor, causes an accumulation of α-synuclein with concomitant mitochondrial dysfunction and cell death. The effects of lactacystin on intact SHSY5Y cells are, however, prevented by knocking down α-synuclein expression by specific siRNA.

Raised serum proinflammatory cytokines in Alzheimer's disease with depression.

The purpose of the present study was to identify the changes in the levels of proinflammatory cytokines like IL-1β, IL-6 and TNF-α in peripheral circulation in Alzheimer's disease (AD) subjects and to correlate these with associated depression and cognitive deficit. Fifty five AD subjects and thirty seven age and sex matched controls were included in the study. The AD patients were grouped as AD with depression (n= 31) and AD without depression (n= 24).

Altered serum levels of adipokines and insulin in probable Alzheimer's disease.

Cerebral hypometabolism of glucose, weight loss, and decreased food intake are characteristic features of sporadic Alzheimer's disease (AD). A systematic study on the serum levels of adipokines and insulin, the major hormones regulating energy metabolism, food intake, and body weight, in sporadic AD is necessary. The present study compares the serum levels of leptin, adiponectin, and insulin, measured by commercially available immuno-assay kits, between controls and sporadic AD subjects.