Changes in Energy Dynamics in Arsenic Exposure Based Neurotoxicity: A Comprehensive Review.

BACKGROUND: The by-product of naturally occurring rock, soil with different agricultural and industrial processes contaminated groundwater with a toxic metalloid- Arsenic (As3+), which results in different toxicities within the human body and in developing fetus. AIM: The present study emphasizes evaluating the presence of oxidative stress and excessive generation of reactive oxygen species (ROS) resulting in mitochondrial dysfunction and caspase activation followed by apoptosis due to arsenic-induced neurotoxicity along with epigenetic modifications at different molecular targets. METHODS: Published articles available on PubMed and Scopus were studied and summarized. RESULTS: The precise mechanism causing arsenic-induced neurotoxicity at a critical stage of brain development is still unknown, while increased oxidative stress led to mitochondrial dysfunctions which are known to play a prominent role in this. AMPK acts as a metabolic checkpoint and restores ATP levels through a different anabolic pathway in energy starvation. At the same time, arsenic-induced AMPK activation leads to autophagy and neuronal cell death. CONCLUSION: This review summarized the molecular mechanisms involved in arsenic-induced neurotoxicity, which can help develop suitable future ameliorative and therapeutic strategies.

Dehydrozingerone ameliorates arsenic-induced reproductive toxicity in male Wistar rats.

Arsenic (As3+), a significant environmental pollutant that has garnered global attention, is widely recognized for its adverse effects on reproductive health. This study assesses the aphrodisiac activity of Dehydrozingerone (DHZ) against As3+ induced sexual dysfunction in male Wistar rats. Male Wistar rats were divided into control, As3+, and As3++DHZ groups. The As3+ group received 5 mg/kg sodium arsenite (NaAsO2) orally while As3++DHZ group received 50 mg/kg synthesized DHZ along with As3+ for 42 days. Following administration, mount and intromission latency, frequency, and average time were measured to assess aphrodisiac and reproductive toxicity in male Wistar rats which had 1:1 coitus with female rats. On days 14th, 28th, and 42nd, sexual behaviour was measured. Further on 43rd day, animals were sacrificed, blood was collected to measure oxidative parameters and LH hormone, and then testes were collected to profile reproductive damage. As3+ treated rats had lower sperm counts, motility, and abnormalities. These alterations reduced sexual hormones. In addition, As3+ toxicity depleted antioxidant indicators including SOD, GSH and elevated ROS. Compared to the As3+ group, As3++DHZ showed a substantial (p < 0.05) increase in sperm count, motility, and reduced abnormalities. DHZ also reversed the rise in luteinizing hormone caused by As3+ therapy, restored oxidative indicators, and improved seminiferous tubule structural damage. 42 days As3+ exposure slightly increased rats' sexual desire but not sperm quality. However, As3++DHZ lower libido and sperm quality. Thus, DHZ therapy enhanced rat sexual desire and sperm quality compared to As3+.

Naringin and temozolomide combination suppressed the growth of glioblastoma cells by promoting cell apoptosis: network pharmacology, in-vitro assays and metabolomics based study.

Introduction: Glioblastoma, which affects a large number of patients every year and has an average overall lifespan of around 14.6 months following diagnosis stands out as the most lethal primary invasive brain tumor. Currently, surgery, radiation, and chemotherapy with temozolomide (TMZ) are the three major clinical treatment approaches. However, the ability to treat patients effectively is usually limited by TMZ resistance. Naringin, a bioflavonoid with anti-cancer, antioxidant, metal-chelating, and lipid-lowering effects, has emerged as a promising therapeutic option. Methods: To explore the targets and pathways of naringin and TMZ in glioblastoma network pharmacology, cell line-based ELISA, flow cytometry, immunocytochemistry, western blotting, and LC-HRMS based metabolomics study were used. Results: The findings through the network pharmacology suggested that the key targets of naringin in the chemosensitization of glioblastoma would be Poly [ADP-ribose] polymerase 1 (PARP-1), O-6-Methylguanine-DNA Methyltransferase (MGMT), and caspases. The functional enrichment analysis revealed that these targets were significantly enriched in important pathways such as p53 signaling, apoptosis, and DNA sensing. Further, the results of the in-vitro study in U87-MG and T98-G glioblastoma cells demonstrated that TMZ and naringin together significantly reduced the percentage of viability and inhibited the DNA repair enzymes PARP-1 and MGMT, and PI3K/AKT which led to chemosensitization and, in turn, induced apoptosis, which was indicated by increased p53, caspase-3 expression and decreased Bcl2 expression. Additionally, a metabolomics study in T98-G glioblastoma cells using liquid chromatography high-resolution mass spectrometry (LC-HRMS) revealed downregulation of C8-Carnitine (-2.79), L-Hexanoylcarnitine (-4.46), DL-Carnitine (-2.46), Acetyl-L-carnitine (-3.12), Adenine (-1.3), Choline (-2.07), Propionylcarnitine (-1.69), Creatine (-1.33), Adenosine (-0.84), Spermine (-1.42), and upregulation of Palmitic Acid (+1.03) and Sphingosine (+0.89) in the naringin and TMZ treatment groups. Discussion: In conclusion, it can be said that naringin in combination with TMZ chemosensitized TMZ antiglioma response and induced apoptosis in tumor cells.

Alkynyl nicotinamides show antileukemic activity in drug-resistant acute myeloid leukemia.

Activating mutations of FLT3 contribute to deregulated hematopoietic stem and progenitor cell (HSC/Ps) growth and survival in patients with acute myeloid leukemia (AML), leading to poor overall survival. AML patients treated with investigational drugs targeting mutant FLT3, including Quizartinib and Crenolanib, develop resistance to these drugs. Development of resistance is largely due to acquisition of cooccurring mutations and activation of additional survival pathways, as well as emergence of additional FLT3 mutations. Despite the high prevalence of FLT3 mutations and their clinical significance in AML, there are few targeted therapeutic options available. We have identified 2 novel nicotinamide-based FLT3 inhibitors (HSN608 and HSN748) that target FLT3 mutations at subnanomolar concentrations and are potently effective against drug-resistant secondary mutations of FLT3. These compounds show antileukemic activity against FLT3ITD in drug-resistant AML, relapsed/refractory AML, and in AML bearing a combination of epigenetic mutations of TET2 along with FLT3ITD. We demonstrate that HSN748 outperformed the FDA-approved FLT3 inhibitor Gilteritinib in terms of inhibitory activity against FLT3ITD in vivo.

Grid-free algorithms for direction-of-arrival trajectory localization.

Direction-of-arrival (DOA) estimation algorithms are crucial in localizing acoustic sources. Traditional localization methods rely on block-level processing to extract the directional information from multiple measurements processed together. However, these methods assume that DOA remains constant throughout the block, which may not be true in practical scenarios. Also, the performance of localization methods is limited when the true parameters do not lie on the parameter search grid. In this paper, two trajectory models are proposed, namely the polynomial and harmonic trajectory models, to capture the DOA dynamics. To estimate trajectory parameters, two gridless algorithms are adopted: (i) Sliding Frank-Wolfe (SFW), which solves the Beurling LASSO problem, and (ii) Newtonized orthogonal matching pursuit (NOMP), which is improved over orthogonal matching pursuit (OMP) using cyclic refinement. Furthermore, our analysis is extended to include multi-frequency processing. The proposed models and algorithms are validated using both simulated and real-world data. The results indicate that the proposed trajectory localization algorithms exhibit improved performance compared to grid-based methods in terms of resolution, robustness to noise, and computational efficiency.

SMAC Mimetics for the Treatment of Lung Carcinoma: Present Development and Future Prospects.

BACKGROUND: Uncontrolled cell growth and proliferation, which originate from lung tissue often lead to lung carcinoma and are more likely due to smoking as well as inhaled environmental toxins. It is widely recognized that tumour cells evade the ability of natural programmed death (apoptosis) and facilitates tumour progression and metastasis. Therefore investigating and targeting the apoptosis pathway is being utilized as one of the best approaches for decades. OBJECTIVE: This review describes the emergence of SMAC mimetic drugs as a treatment approach, its possibilities to synergize the response along with current limitations as well as future perspective therapy for lung cancer. METHOD: Articles were analysed using search engines and databases namely Pubmed and Scopus. RESULT: Under cancerous circumstances, the level of Inhibitor of Apoptosis Proteins (IAPs) gets elevated, which suppresses the pathway of programmed cell death, plus supports the proliferation of lung cancer. As it is a major apoptosis regulator, natural drugs that imitate the IAP antagonistic response like SMAC mimetic agents/Diablo have been identified to trigger cell death. SMAC i.e. second mitochondria activators of caspases is a molecule produced by mitochondria, stimulates apoptosis by neutralizing/inhibiting IAP and prevents its potential responsible for the activation of caspases. Various preclinical data have proven that these agents elicit the death of lung tumour cells. Apart from inducing apoptosis, these also sensitize the cancer cells toward other effective anticancer approaches like chemo, radio, or immunotherapies. There are many SMAC mimetic agents such as birinapant, BV-6, LCL161, and JP 1201, which have been identified for diagnosis as well as treatment purposes in lung cancer and are also under clinical investigation. CONCLUSION: SMAC mimetics acts in a restorative way in the prevention of lung cancer.

Therapeutic approaches for the treatment of Interstitial Lung Disease: An exploratory review on molecular mechanisms.

BACKGROUND: Interstitial Lung Diseases (ILDs) are characterized by shortness of breath caused by alveolar wall inflammation and/or fibrosis. OBJECTIVE: Our review aims to study the depth of various variants of ILD, diagnostic procedures, pathophysiology, molecular dysfunction and regulation, subject and objective assessment techniques, pharmacological intervention, exercise training and various modes of delivery for rehabilitation. METHOD: Articles are reviewed from PubMed and Scopus and search engines. RESULTS: ILD is a rapidly progressing disease with a high mortality rate. Each variant has its own set of causal agents and expression patterns. Patients often find it challenging to self-manage due to persistent symptoms and a rapid rate of worsening. The present review elaborated on the pathophysiology, risk factors, molecular mechanisms, diagnostics, and therapeutic approaches for ILD will guide future requirements in the quest for innovative and tailored ILD therapies at the molecular and cellular levels. CONCLUSION: The review highlights the rationale for conventional and novel therapeutic approaches for better management of ILD.

Association of Serum Ferritin Level in Early Second Trimester of Pregnancy with Development of Gestational Diabetes Mellitus: A Prospective Observational Study.

Background: Gestational diabetes mellitus (GDM) is associated with various maternal and perinatal morbidities. Serum ferritin is a major storage protein of iron and also acts as acute phase reactant which is increased in inflammatory conditions. GDM is a state of insulin resistance and associated with inflammation. The aim of this study was to find the correlation between serum ferritin and development of GDM. Objectives: To determine the serum ferritin concentration in nonanemic pregnant women and its correlation with subsequent development of GDM. Methodology: In this prospective observational study, 302 nonanemic pregnant women with singleton gestation between 14 and 20 weeks, attending antenatal OPD, were enrolled. Serum ferritin was measured at the time of enrolment, and they were followed till 24-28 weeks of gestation and subjected to blood glucose test by DIPSI method. A total of 92 women had blood glucose level ≥ 140 mg/dl and were labeled as GDM, and 210 pregnant women with blood glucose level < 140 mg/dl were labeled as non-GDM. Result: Mean serum ferritin level of women with GDM (56.44 ± 19.19 ng/ml) was found to be higher as compared to non-GDM (27.62 ± 12.11 ng/ml), and this difference was found to be statistically significant (p < 0.001). The cutoff value of serum ferritin > 37.55 ng/ml was found to be 85.9% sensitive and 81.9% specific. Conclusion: We can infer that serum ferritin is associated with development of GDM. Based on the findings of the current study, serum ferritin level can be used a predictive marker for the development of GDM.

Tumor-associated macrophages employ immunoediting mechanisms in colorectal tumor progression: Current research in Macrophage repolarization immunotherapy.

Tumor-associated macrophages (TAMs) constitute the most prolific resident of the tumor microenvironment (TME) that regulate its TME into tumor suppressive or progressive milieu by utilizing immunoediting machinery. Here, the tumor cells construct an immunosuppressive microenvironment that educates TAMs to polarize from anti-tumor TAM-M1 to pro-tumor TAM-M2 phenotype consequently contributing to tumor progression. In colorectal cancer (CRC), the TME displays a prominent pro-tumorigenic immune profile with elevated expression of immune-checkpoint molecules notably PD-1, CTLA4, etc., in both MSI and ultra-mutated MSS tumors. This authenticated immune-checkpoint inhibition (ICI) immunotherapy as a pre-requisite for clinical benefit in CRC. However, in response to ICI, specifically, the MSIhi tumors evolved to produce novel immune escape variants thus undermining ICI. Lately, TAM-directed therapies extending from macrophage depletion to repolarization have enabled TME alteration. While TAM accrual implicates clinical benefit in CRC, sustained inflammatory insult may program TAMs to shift from M1 to M2 phenotype. Their ability to oscillate on both facets of the spectrum represents macrophage repolarization immunotherapy as an effective approach to treating CRC. In this review, we briefly discuss the differentiation heterogeneity of colonic macrophages that partake in macrophage-directed immunoediting mechanisms in CRC progression and its employment in macrophage re-polarization immunotherapy.

IgA Levels among Type 2 Diabetic and Non-Diabetic Patients with Periodontitis: A Prospective Clinical Study.

OBJECTIVES: To estimate gingival crevicular immunoglobulin A(IgA) using enzyme-linked immunosorbent assay (ELISA) among type II diabetic patients with periodontitis. MATERIALS AND METHODS: A non-randomized study was done of 40 periodontitis subjects with a mean age of 50 years and were recruited into two groups, Group A (Type II controlled diabetics with HbA1c < 7%) and Group B (non-diabetics with HbA1c between 4 and 6%). Both the groups underwent nonsurgical periodontal therapy (NSPT). The clinical parameters were recorded at baseline, 1, and 3 months. GCF sample was collected for the estimation of crevicular IgA at baseline and at 3 months. STATISTICAL ANALYSIS: Results were analyzed using parametric tests paired t-test and Student's t-test for every assessment point. The level of significance was set at p < 0.05. RESULTS: Difference in IgA levels and clinical parameters was seen between diabetic and non-diabetic groups, which was statistically significant. CONCLUSION: Changes in crevicular IgA levels in patients with diabetic periodontitis can be used as a novel biomarker in assessing the inflammatory status.

Role of PARP Inhibitors in Glioblastoma and Perceiving Challenges as Well as Strategies for Successful Clinical Development.

Glioblastoma multiform is the most aggressive primary type of brain tumor, representing 54% of all gliomas. The average life span for glioblastoma multiform is around 14-15 months instead of treatment. The current treatment for glioblastoma multiform includes surgical removal of the tumor followed by radiation therapy and temozolomide chemotherapy for 6.5 months, followed by another 6 months of maintenance therapy with temozolomide chemotherapy (5 days every month). However, resistance to temozolomide is frequently one of the limiting factors in effective treatment. Poly (ADP-ribose) polymerase (PARP) inhibitors have recently been investigated as sensitizing drugs to enhance temozolomide potency. However, clinical use of PARP inhibitors in glioblastoma multiform is difficult due to a number of factors such as limited blood-brain barrier penetration of PARP inhibitors, inducing resistance due to frequent use of PARP inhibitors, and overlapping hematologic toxicities of PARP inhibitors when co-administered with glioblastoma multiform standard treatment (radiation therapy and temozolomide). This review elucidates the role of PARP inhibitors in temozolomide resistance, multiple factors that make development of these PARP inhibitor drugs challenging, and the strategies such as the development of targeted drug therapies and combination therapy to combat the resistance of PARP inhibitors that can be adopted to overcome these challenges.

Comparison of Effect of Non-invasive Ventilation Delivered by Helmet vs Face Mask in Patients with COVID-19 Infection: A Randomized Control Study.

Background and aims: We compared the effectiveness of non-invasive ventilation (NIV) provided by helmet mask vs face mask in patients with COVID-19. Methods and materials: Between March and May 2021, a single-center, prospective, open-label randomized controlled research was undertaken. Sixty patients were randomly assigned to one of two groups based on the NIV delivery interface. In group I (n = 30) helmet mask was used and in group II (n = 30) face mask was used for delivery of NIV. The proportion of patients in each group who required endotracheal intubation was the primary outcome. The duration of NIV, length of stay in the intensive care unit (ICU), hospital mortality, ratio of partial pressure of oxygen to fraction of inspired oxygen (PaO2/FiO2), respiratory rate, patient comfort, and complications were all documented as secondary outcomes. Results: In both groups, demographics, clinical characteristics, and treatment received were comparable. Around 10% of patients in the helmet mask group were intubated, while 43.3% of patients in the face mask group were intubated (p = 0.004). The two groups demonstrated similar hemodynamic patterns. The use of a helmet mask, on the other hand, resulted in enhanced oxygenation (263.57 ± 31.562 vs 209.33 ± 20.531, p = 0.00), higher patient satisfaction (p = 0.001), a lower risk of complications, and a shorter NIV and ICU stay (p = 0.001) (4.53 ± 0.776 vs 7.60 ± 1.354, p = 0.00 and 6.37 ± 0.556 vs 11.57 ± 2.161, p = 0.00). Conclusion: Helmet mask could be a reliable interface for delivery of NIV in COVID-19 and results in a lower rate of endotracheal intubation, better oxygenation with greater patient comfort and shorter ICU stay as compared to face mask used for NIV. How to cite this article: Saxena A, Nazir N, Pandey R, Gupta S. Comparison of Effect of Non-invasive Ventilation Delivered by Helmet vs Face Mask in Patients with COVID-19 Infection: A Randomized Control Study. Indian J Crit Care Med 2022;26(3):282-287.

Newborn thermal care in western Uttar Pradesh - gap analysis between knowledge and practices.

BACKGROUND: The provision of health care services including maternal and newborn care is a dynamic system of entitlement and obligations among the community, the service providers, and the government. Thermal control remains poor in newborns owing to immaturity of the thermoregulatory center and newborn become vulnerable to hypothermia especially premature babies, intrauterine growth retardation and LBW babies, and even normal babies.This study aimed to assess the knowledge & practices regarding thermal protection their determinants. METHODS: Cross-sectional study was conducted in the Amroha district. The study population comprised women of reproductive age (15 to 49 years) who have delivered a live baby within the past 12 weeks before the conduct of the study. Out of 6 blocks, 2 most populous villages were selected. Total 61 villages from 6 blocks were covered under the study. Knowledge and practices regarding newborn thermal care were expressed in percentages and compared. RESULTS: The knowledge domain on thermal protection of baby, 60.9% of the respondents were well aware of how to keep baby warm after delivery, 71.4% of respondents knew that baby should be dried soon after birth, 64.9% of the respondents had an idea of time to dry the baby, 69.6% of the respondents knew that baby should be wrapped soon after birth. CONCLUSION: The findings of the study provides an insight into the existing knowledge and necessitate a need for quantitative studies in the study area to access knowledge & practices related to thermal protection of newborns. The authors emphasize a need for improving community awareness for the promotion of newborn care and improve the health system to meet the demands of birthing mothers and the needs of newborns.

Stressor Combat Strategies and Motivating Factors Among Health Care Service Providers During COVID-19 Pandemic.

Context Since its inception in December 2019 in Wuhan, China, the severe acute respiratory syndrome coronavirus-2, the etiological agent for coronavirus disease 2019 (COVID-19), is spreading rapidly both locally and internationally, and became certified as a pandemic by the World Health Organization (WHO) in March 2020. Working in an environment of high risk, coupled with adherence to quarantine and stressors related to the job, has been found to exacerbate the psychological health of frontline healthcare workers. Aims To assess the perceived stressors, combat strategies, and motivating factors among health care service providers during the COVID-19 pandemic. Setting and design A cross-sectional study was conducted among healthcare workers at a tertiary care hospital in the north-central region of India from May to September 2020. Methods and materials A convenience sample of 150 health care workers was taken. A self-reported pretested structured "COVID 19 staff questionnaire" was used as a study tool. The health care workers (HCWs) included nurses, physicians, laboratory technicians, and radiology technicians who worked in high-risk areas (isolation ward, COVID intensive care unit, emergency department, and outpatient cough outdoor walk-in clinics) during the outbreak constituted our study population.  Statistical analysis used The varying levels of stress or effectiveness of measures were reported as mean and standard deviation, as appropriate. Descriptive statistics were used for data presentation. A Mann-Whitney U test was used to analyse differences between two groups of non-normally distributed data. A p-value of less than 0.05 was considered statistically significant. Results As compared to doctors, paramedical staffs were more stressed with frequent protocol changes (88%), emotional exhaustion (68%), and conflicts with duties (62.7%). The factors like seeing colleague getting better (78.7%) and hoping for financial compensation (49.3%) were reported as stress busters; family compensation in case of death at the workplace and disability benefits in case of disease-related disability development were more effective motivational factors for paramedical staff in case of future outbreaks (p-value <0.05). Conclusions It is needful that secondarily traumatized team members should be always observed, educated, and properly handled. Certain personal coping strategies adopted by health workers should be well addressed and motivated if scientifically sustainable. We have to include psychiatric preparedness and stress monitoring also for health care teams along with emphasizing hygiene, temperature monitoring, and fever management, in planning to fight the pandemic.

Restoring and preserving capacity of self-affirmation for well-being in Indian adults with non-clinical depressive tendencies.

BACKGROUND: Although self-affirmation has been reported to enhance well-being and other positive life outcomes in normal adults, little is known about its capacity to restore and preserve well-being in adults with depressive tendencies. The current study attempts to expound the restoring and preserving capacity of self-affirmation for well-being in Indian adults with non-clinical depressive tendencies. PARTICIPANTS AND PROCEDURE: The study used a sequential research design. Eighty participants (22-27 years) with depressive tendencies were chosen through purposive sampling and were randomly assigned equally to the experimental and control conditions. Their depressive tendencies and well-being were measured through standard scales at three intervals: pre-intervention, post-intervention and follow-up. RESULTS: The results revealed significant restoring and preserving capacity of self-affirmation for the well-being of the experimental group participants as compared to the control group. The main effects of conditions (experimental, control) and treatment intervals (pre, post, follow-up) were significant along with the interaction effects of conditions × treatment intervals. The significant differences in the mean well-being scores for pre-intervention, post-intervention and follow-up points of time showed the restoring and preserving capacity of self-affirmation intervention. CONCLUSIONS: The findings showed that self-affirmation helps to restore well-being as well as preserve it after a significant gap, which is evident in higher well-being mean scores of the experimental group taken at post-intervention and follow-up intervals. The positive effects of self-affirmation on well-being may have remained active even after the cessation of the intervention due to the underlying mechanisms of enhanced self-worth, positive values, inner strengths, positive attributions and interpersonal relationships.

Positive, not negative, self-compassion mediates the relationship between self-esteem and well-being.

OBJECTIVES: The study examined the predictive strengths of self-esteem, and positive and negative self-compassion for hedonic and eudaimonic well-being as well as assessed the relative mediating roles of positive and negative self-compassion for the relationships among self-esteem, and hedonic and eudaimonic well-being. DESIGN: A correlational design was employed through which self-esteem, self-compassion, and hedonic and eudaimonic well-being were measured. METHODS: One hundred thirty-four male (M = 25.11, SD = 1.66) and 138 female (M = 21.89, SD = 1.87) participants were chosen by a convenient sampling. RESULTS: The findings evinced that there were significant positive correlations among self-esteem, positive self-compassion, and hedonic and eudaimonic well-being while negative self-compassion exhibited small positive correlations with both the well-being measures (criterion). The regression analyses showed that self-esteem and positive self-compassion reflected significant predictive strengths for hedonic as well as eudaimonic well-being while negative self-compassion did not. This was also true for the social and psychological aspects of well-being. The ß values reflected that positive self-compassion did show a higher contribution for both the well-being measures as compared to self-esteem. CONCLUSIONS: The findings evinced that positive, not negative, self-compassion mediated the relationship between self-esteem and hedonic well-being as well as self-esteem and eudaimonic well-being. Moreover, self-esteem and self-compassion have predictive strengths for both kinds of well-being. The findings showed the relevance of self-esteem and self-compassion to underscore well-being. The implications and directions for future researchers have been discussed. PRACTITIONER POINTS: Contrary to the earlier findings suggesting self-esteem and self-compassion carrying relevance to explicate performance and well-being of people with individualistic and collectivistic cultures, respectively, the findings of this study suggest both the constructs to be useful to understand the well-being of people with both the values belonging especially to the fast-changing societies like India. The study also suggests reconceptualization and empirical verification of self-compassion that will make it more effective for enhancing and promoting interventions for positive life outcomes.

Evaluation of Efficacy of Coenzyme Q10 as an Adjunct to Nonsurgical Periodontal Therapy and Its Effect on Crevicular Superoxide Dismutase in Patients with Chronic Periodontitis.

OBJECTIVES: To assess the efficacy of coenzyme Q10 (CoQ10) as an adjunct to nonsurgical periodontal therapy and its effect on superoxide dismutase (SOD) in gingival crevicular fluid (GCF) in patients with chronic periodontitis (CP). MATERIALS AND METHODS: A total of 16 patients aged between 30 and 50 years having mild to moderate CP of both sexes having pocket depth of 5 to 7 mm in four nonadjacent interproximal sites were selected. The sites were randomized and divided into treatment and control groups. CoQ10 and a placebo gel were administered in the treatment and control sites, respectively, at baseline after scaling and root planing (SRP). GCF was collected using microcapillary method at baseline and 3 months and was assessed for SOD using enzyme-linked immunosorbent assay reader at 450 nm wavelength. Probing pocket depth, gingival index, and plaque index were assessed at baseline, 1 month, and 3 months, respectively. STATISTICAL ANALYSIS: For each assessment point, data were statistically analyzed using Student's t-test and paired t-test. Level of significance was set at p < 0.05. RESULTS: On intergroup comparison, there was no statistically significant difference between the clinical parameters of both the groups at all the time intervals (p > 0.05), but there was a significant increase in the level of SOD in the test group (p > 0.05) compared with the control group at 3 months. CONCLUSIONS: Adjunctive use of CoQ10 with SRP can boost the antioxidant concentration, but it is not superior to SRP in the treatment of CP.

Ibutilide with magnesium for conversion of atrial fibrillation or flutter in rheumatic heart disease patients: Ibutilide with magnesium for chemical cardioversion of atrial fibrillation or flutter.

BACKGROUND: Data on adjunctive use of magnesium with ibutilide for conversion of persistent rheumatic atrial fibrillation and flutter to sinus rhythm is lacking. AIM: We aimed to study the efficacy of adjunctive supplementation of intravenous magnesium with ibutilide for conversion of persistent rheumatic atrial fibrillation and flutter to sinus rhythm and to define a definite level of serum magnesium which leads to significant increase in rates of such conversion. METHODS AND RESULTS: This was a prospective study including 33 Rheumatic heart disease patients (13 males and 20 females) with mean age of 49.27 ± 11.4 years and persistent AF or AFl. All patients received intravenous magnesium to raise serum magnesium level in range of 4 mg/dl to 4.5 mg/dl prior to administration of Ibutilide. 25 out of 33 (76%) patients converted to sinus rhythm. Upon univariate analysis, presence of background beta blocker therapy, serum potassium and magnesium at time of Ibutilide injection were found to have significant relation with conversion to sinus rhythm. Upon multivariate analysis serum magnesium level at the time of Ibutilide injection was found to have significant contribution on post injection rhythm reversal (p-value = 0.006). The level of magnesium at 3.8 mg/dl was found to have maximum sensitivity of 96% and specificity of 62.5% for conversion to sinus rhythm by ibutilide with magnesium (p-value< 0.05). CONCLUSIONS: Ibutilide is highly effective in cardioversion of persistent rheumatic atrial fibrillation/flutter patients. Raising Serum Magnesium levels above 3.8 mg/dl significantly improves efficacy of ibutilide.

Driver Mutations in Leukemia Promote Disease Pathogenesis through a Combination of Cell-Autonomous and Niche Modulation.

Studies of patients with acute myeloid leukemia (AML) have led to the identification of mutations that affect different cellular pathways. Some of these have been classified as preleukemic, and a stepwise evolution program whereby cells acquire additional mutations has been proposed in the development of AML. How the timing of acquisition of these mutations and their impact on transformation and the bone marrow (BM) microenvironment occurs has only recently begun to be investigated. We show that constitutive and early loss of the epigenetic regulator, TET2, when combined with constitutive activation of FLT3, results in transformation of chronic myelomonocytic leukemia-like or myeloproliferative neoplasm-like phenotype to AML, which is more pronounced in double-mutant mice relative to mice carrying mutations in single genes. Furthermore, we show that in preleukemic and leukemic mice there are alterations in the BM niche and secreted cytokines, which creates a permissive environment for the growth of mutation-bearing cells relative to normal cells.