Nuclear Mitochondrial Disorder Due to a Variant in NAXE in Two Unrelated Indian Children.

Progressive encephalopathy with brain edema and/or leukoencephalopathy type 1 (PEBEL1) is a nuclear mitochondrial disorder involving the NAD(P)HX repair mechanism due to a NAXE variation. PEBEL1 is characterized by rapid neurologic deterioration culminating in death following high-grade fever during infancy. Currently, 23 patients from 14 families are described in the literature, with only three survivors. The authors report two living children from unrelated families with PEBEL1. Both children presented in infancy with ptosis, squint, and ataxia with no skin manifestations. Whole-exome sequencing revealed previously reported c.804_807delInsA (p.Lys270del) variation in exon 6 of NAXE. This is the first Indian report of PEBEL1.

Procalcitonin Guided Antibiotic Stewardship in Pediatric Sepsis and Lower Respiratory Tract Infections.

OBJECTIVES: To determine the impact of procalcitonin-guided antibiotic stewardship protocol (PCT-ASP) in children admitted with sepsis and lower respiratory tract infection on the duration of antibiotic therapy and clinical outcome. METHODS: This was a single-center study involving children with infections treated with antibiotic therapy according to the PCT-ASP as the study group. The control group consisted of children with same age and diagnosis who were treated with antibiotics according to individual unit protocol before the implementation of PCT-ASP. The primary outcome was median duration of antibiotic therapy and hospital stay. RESULTS: Among 127 patients, 66 were enrolled in the study and 61 in the control group respectively. The median (IQR) PCT values at admission, day 4 and day 6 of antibiotic therapy were 5.59 (61.3), 2.57 (47.35), and 0.35 (0.47) ng/ml respectively, and showed a decreasing trend. All the children in the control group received antibiotics at admission while 12% of children in the study group were not initiated on antibiotics. In the study group, 53% of the children received antibiotics only for three days in the absence of treatment failure. The duration of antibiotics (p = 0.001) and hospital stay (p = 0.03) were less in the study group when compared to the control group. CONCLUSIONS: PCT-ASP reduces the duration of antibiotics and duration of hospital stay without increasing morbidity and mortality.

Understanding Childhood Constipation through the Prism of the Caretaker.

Aims: Childhood constipation is presenting with increasing frequency at pediatric surgical clinics. The caregiver's role in prevention and management is pivotal. This study aimed at determining mothers' knowledge, attitudes, and practices with regard to childhood constipation and the association of these with demographic variables. Materials and Methods: This was a survey-based descriptive study conducted at a tertiary care hospital in South India. Randomly selected mothers of children aged 1-10 years consulting for any problem other than constipation were included in the study. Data collection was done by means of a pretested and prevalidated questionnaire. Results: There were 169 mothers with a median age of 30 years. Over half were homemakers and of a rural background. Urban mothers scored better than their rural counterparts in the attitude section (P = 0.034). Mothers with greater knowledge had better attitude (P = 0.001) and practice (P = 0.020) scores. Those with higher attitude scores also fared better in the practice section (P = 0.04). Conclusions: Knowledge, attitude and practice concerning childhood constipation are connected to each other. South Indian mothers are sufficiently aware of the nuances surrounding childhood constipation, but focused large-scale outreach programs and health education are necessary to bridge the gaps.

Role of Nuclear Factor-Kappa B Activation and Inflammatory Biomarkers in Critically Ill Children.

Mortality prediction is important for cautious monitoring and optimal management of critically ill children. The serum cytokine levels are elevated early in critical illness before the physiological parameters are deranged. This cross-sectional descriptive study included the critically ill children admitted in intensive care unit. Serial serum levels of IL-6, NF-κB and PELOD 2 scoring were measured and compared in 45 children (40 survivors, 5 non-survivors). The median IL-6 levels at 24 h and 72 h were significantly high in non-survivors when compared to survivors [median (IQR) = 1122 (1305) pg/ml vs. 564.39 (153) pg/ml and 1263 (626) pg/ml vs. 82 (191) pg/ml respectively; p <0.0001)]. There was an increasing trend of IL-6 in non-survivors when compared to the survivors. The NF-κB values were comparable. The IL-6 levels correlated well with the illness severity. IL-6 had superior prognostic value compared with NF-κB in predicting mortality.

Acute necrotic arachnidism with necrotising fasciitis and recurrent pneumothorax.

A male infant presented with swelling of the left leg and fever. Over the next 2 days, the area developed fasciitis extending to the left thigh, abdomen, and lower chest. Meanwhile, the parents found a giant brown spider within the infant's cot belonging to the genus Loxosceles, otherwise called the brown recluse spider. The dermo-myonecrosis progressed to deeper tissues involving the lung parenchyma requiring invasive ventilation. CT of the thorax showed multiple pneumatoceles, and lung biopsy showed alveolar necrosis. The infant was treated with intravenous antibiotics and corticosteroids. We drained the pneumothoraces by thoracostomy and insertion of intercostal drainage tubes. The infant required respiratory support initially by conventional ventilation, which was escalated to high-frequency oscillatory ventilation. He had refractory hypoxaemia and died. This is the first fatal case of acute spider envenomation described in India. Spider envenomation must be considered in patients with sudden onset, rapidly progressive necrotising fasciitis unresponsive to antibiotic therapy.

Sirtuin 6 inhibition protects against glucocorticoid-induced skeletal muscle atrophy by regulating IGF/PI3K/AKT signaling.

Chronic activation of stress hormones such as glucocorticoids leads to skeletal muscle wasting in mammals. However, the molecular events that mediate glucocorticoid-induced muscle wasting are not well understood. Here, we show that SIRT6, a chromatin-associated deacetylase indirectly regulates glucocorticoid-induced muscle wasting by modulating IGF/PI3K/AKT signaling. Our results show that SIRT6 levels are increased during glucocorticoid-induced reduction of myotube size and during skeletal muscle atrophy in mice. Notably, overexpression of SIRT6 spontaneously decreases the size of primary myotubes in a cell-autonomous manner. On the other hand, SIRT6 depletion increases the diameter of myotubes and protects them against glucocorticoid-induced reduction in myotube size, which is associated with enhanced protein synthesis and repression of atrogenes. In line with this, we find that muscle-specific SIRT6 deficient mice are resistant to glucocorticoid-induced muscle wasting. Mechanistically, we find that SIRT6 deficiency hyperactivates IGF/PI3K/AKT signaling through c-Jun transcription factor-mediated increase in IGF2 expression. The increased activation, in turn, leads to nuclear exclusion and transcriptional repression of the FoxO transcription factor, a key activator of muscle atrophy. Further, we find that pharmacological inhibition of SIRT6 protects against glucocorticoid-induced muscle wasting in mice by regulating IGF/PI3K/AKT signaling implicating the role of SIRT6 in glucocorticoid-induced muscle atrophy.

Smokeless Tobacco Exposure and Fetal Iron Status: An Analytical Study.

Objectives: To compare the cord serum ferritin and fetal iron status in newborns with and without maternal occupational smokeless tobacco exposure and determine the influencing factors. Methods: This cross-sectional study included mother-infant dyads with occupational tobacco exposure (exposed) and an unexposed group. Umbilical cord serum ferritin was compared in both groups. Fetal nicotine absorption was established by cord cotinine. Results: A total of 140 newborns each were analyzed in each group. There was no significant mean difference (MD) (P = 0.900) between the cord serum ferritin in the tobacco exposed and unexposed group. Fetal nicotine absorption was seen in 43.6% of the exposed group. Cord serum ferritin was 14.1 µg/L (95% confidence interval [(95% CI:-43.1, 14.9); P=0.338] lower in this group compared with the group without fetal nicotine absorption. A higher adjusted MD for ferritin was present for maternal hypertension (12.5 [95% CI: -75.5, 100.5]; P = 0.777) and gestational diabetes mellitus (21.4 [95% CI: -54.0, 96.9]; P = 0.571) in the group with fetal nicotine absorption. Fetal nicotine absorption exaggerated fetal iron depletion in maternal anemia [aOR 4.8 (95%CI: 1.2, 19.0); P=0.025]. Conclusion: Cord serum ferritin and fetal iron status were comparable in tobacco exposed and unexposed groups. In those with fetal nicotine absorption, cord ferritin levels reflect the fetal inflammatory state.

Sedation Usage in COVID-19 Acute Respiratory Distress Syndrome: A Multicenter Study.

BACKGROUND: Patients with COVID-19 acute respiratory distress syndrome (ARDS) have been shown to have high sedation requirements. OBJECTIVE: The purpose of this study was to compare sedative use between patients with COVID-19 ARDS and non-COVID-19 ARDS. METHODS: This was a retrospective study of patients with COVID-19 ARDS compared with historical controls of non-COVID-19 ARDS who were admitted to 2 hospitals from March 1, 2020, to April 30, 2020, and April 1, 2018, to December 31, 2019, respectively. The primary outcome was median cumulative dose of propofol (µg/kg) at 24 hours after intubation. RESULTS: There were 92 patients with COVID-19 ARDS and 37 patients with non-COVID-19 ARDS included. Within the first 24 hours of intubation, patients with COVID-19 ARDS required higher total median doses of propofol: 51 045 µg/kg (interquartile range, 26 150-62 365 µg/kg) versus 33 350 µg/kg (9632-51 455 µg/kg; P = 0.004). COVID-19 patients were more likely receive intravenous lorazepam (37% vs 14%; P = 0.02) and higher cumulative median doses of midazolam by days 5 (14 vs 4 mg; P = 0.04) and 7 of intubation (89 vs 4 mg; P = 0.03) to achieve the same median Richmond Analgesia-Sedation Scale scores. COVID-19 ARDS patients required more ventilator days (10 vs 6 days; P = 0.02). There was no difference in 30-day mortality. CONCLUSION AND RELEVANCE: Patients with COVID-19 ARDS required higher doses of propofol and benzodiazepines than patients with non-COVID-19 ARDS to achieve the same median levels of sedation.

The Young Heart Tears Easily Apart: A Case Report of Spontaneous Coronary Artery Dissection.

Spontaneous coronary artery dissection (SCAD) is a rare cause of acute coronary syndrome (ACS), seen mostly in young females. The rarity and limited knowledge of the disease make its management challenging. Prompt diagnosis of the condition is extremely important to decrease both long- and short-term complications. Treatment options depend on hemodynamic stability and the location of the dissection- with more distal lesions treated more conservatively as opposed to proximal lesions which are treated with percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG). The following are the two cases with different presentation, management and outcomes. Our first patient was a 35-year-old woman with no medical history who presented with acute, anginal pain, diaphoresis and palpitations. She was hemodynamically stable on presentation, with work-up significant for electrocardiogram (ECG) with sinus bradycardia, ST elevation in leads V1-V6, and elevated troponin level of 4 ng/ml. There was no evidence of a pulmonary embolism on computed tomography (CT) of the chest. A coronary angiogram showed 100% dissection of the proximal to mid-left anterior descending (LAD) artery. Attempts to place a stent in the proximal to mid LAD were unsuccessful as the true lumen of the LAD was not accessible. The patient became hemodynamically unstable, and an emergent CABG was done, restoring blood flow. The patient recovered during her hospital stay and was discharged with dual antiplatelet therapy (DAPT), beta-blockers, and atorvastatin. The second patient was a 28-year-old woman, with a history of hypertension who presented with anginal chest pain. Workup showed ECG with minimal ST elevations in anteroseptal leads, with elevated troponin level to 0.71 ng/ml. Coronary angiogram showed 40-50% stenosis of the mid LAD with an aneurysmal segment. An echocardiogram showed no evidence of wall motion abnormalities, and she had a normal left ventricular ejection fraction (LVEF). She was discharged home the next day, on medical management. After two days, she returned to the hospital with similar complaints, with work-up significant for ECG with non-specific ST-T abnormality, and troponin level which peaked at 2.22 ng/ml. She was started on a heparin drip, and a repeat left heart catheterization revealed type 2 dissection of the mid to distal LAD, with intravascular ultrasound showing a fractional flow reserve of 0.76. She was discharged home on DAPT, beta-blocker, calcium channel blocker (CCB), and atorvastatin, with close cardiology follow up. These two cases highlight the importance of keeping in mind the possibility of SCAD, especially when relatively healthy young women present with anginal symptoms. Early diagnosis of the condition and prompt management are extremely important to ensure favourable outcomes. The two cases also describe the coronary angiogram findings in SCAD, and the different strategies employed in the management of this condition.

Lower socioeconomic factors are associated with higher mortality in patients with septic shock.

BACKGROUND: Previous studies have explored the relationship between socioeconomic status and sepsis outcomes OBJECTIVES: The purpose of this investigation is to determine if race, ethnicity, economic stability, neighborhood environment, and access to health care are predictive of mortality in patients with septic shock. METHODS: Retrospective study of septic shock patients admitted to two medical centers. RESULTS: Caucasian patients had higher proportion of outpatient physician visits in the year prior to admission and were less likely to be Medicare or Medicaid beneficiaries. Thirty-day mortality was lower for the Caucasian cohort (39.3% vs. 48.7%, p < 0.01). Multivariate logistic regression found several predictors of 30-day mortality including Minority race/ethnicity (OR 1.44, 95% CI 1.12-1.86), unemployment (OR 1.40, 95% CI 1.09-1.81), and neighborhood poverty rate ≥10% (OR 1.43, 95% CI 1.01-2.01). CONCLUSIONS: Minority patients, unemployed patients, and those living in neighborhoods with poverty rates greater than 10% suffered from higher 30-day mortality when admitted for septic shock.

Electrocardiometry for Hemodynamic Categorization and Assessment of Fluid Responsiveness in Pediatric Septic Shock: A Pilot Observational Study.

AIM: To evaluate the utility of noninvasive electrocardiometry (ICON®) for hemodynamic categorization and assessment of fluid responsiveness in pediatric septic shock. MATERIALS AND METHODS: Pilot prospective observational study in a 12-bedded tertiary pediatric intensive care unit (PICU) in children aged between 2 months and 16 years with unresolved septic shock after a 20 mL/kg fluid bolus. Those with cardiac index (CI) <3.3 L/min/m2 and systemic vascular resistance index (SVRI) >1600 dyn sec/cm5/m2 were classified as vasoconstrictive shock-electrocardiometry (VCEC) and those with CI >5.5 L/min/m2 and SVRI <1000 dyn sec/cm5/m2 as vasodilated shock-electrocardiometry (VDEC). Fluid responsiveness was defined as a 10% increase in CI with a 20 mL/kg fluid bolus. Sepsis-induced myocardial dysfunction (SMD) was diagnosed on echocardiography. Outcomes studied included clinical shock resolution, length of PICU stay, and mortality. RESULTS: Thirty children were enrolled over 6 months with a median (interquartile range) age and pediatric risk of mortality (PRISM) III score of 87(21,108) months and 6.75(1.5,8.25), respectively; 14(46.6%) were boys and 4(13.3%) died. Clinically, 19(63.3%) children had cold shock and 11(36.7%) had warm shock; however, 16(53.3%) children had VDEC (including five with clinical cold shock) and 14(46.7%) had VCEC using electrocardiometry. Fluid responsiveness was seen in 16(53.3%) children, 10 in the VCEC group and 6 in the VDEC group. In the VCEC group, the responders had a significant rise in CI and a fall in SVRI, while the responders in the VDEC group had a significant rise in CI and SVRI. Fluid responders, compared to nonresponders, had a significantly higher stroke volume variation (SVV) before fluid bolus (24.1 ± 5.2% vs. 18.2 ± 3.5%, p < 0.001) and a higher reduction in SVV after fluid bolus (10.0 ± 2.8% vs. 6.0 ± 4.5%, p = 0.006), higher lactate clearance (p = 0.03) and lower vasoactive-inotropic score (p = 0.04) at 6 hours, higher percentage of clinical shock resolution at 6 (p = 0.01) and 12 hours (p = 0.01), and lesser mortality (p = 0.002). Five (16.6%) children with VCEC had SMD and were less fluid responsive (p = 0.04) with higher mortality (p = 0.01) compared to those without SMD. CONCLUSIONS AND CLINICAL SIGNIFICANCE: Continuous, noninvasive hemodynamic monitoring using electrocardiometry permits hemodynamic categorization and assessment of fluid responsiveness in pediatric septic shock. This may provide real-time guidance for optimal interventions, and thus, improve the outcomes. HOW TO CITE THIS ARTICLE: Rao SS, Reddy M, Lalitha AV, Ghosh S. Electrocardiometry for Hemodynamic Categorization and Assessment of Fluid Responsiveness in Pediatric Septic Shock: A Pilot Observational Study. Indian J Crit Care Med 2021;25(2):185-192.

Maternal Occupational Tobacco Exposure and Newborn Umbilical Cord Serum Leptin Concentration.

OBJECTIVE: To assess the effect of maternal occupational tobacco handling (bidi rolling) on cord serum leptin levels. METHODS: We enrolled 64 neonates born to women who were bidi-rollers, and 64 small for gestational age (SGA) neonates and 57 term appropriate for gestational age (AGA) neonates born to mothers with no tobacco exposure. Cord blood leptin levels between the groups were compared. Adjusted mean difference in leptin was calculated using regression model. RESULTS: Cord leptin showed moderate correlation with birthweight (r=0.16; P=0.027) across the groups. Mean (SD) cord serum leptin levels (ng/mL) of study group was 19.79 (13.32), in comparison to 21.4 (13.4) of SGA (P=0.497), and 27.70 (13.96) of term AGA (P=0.002). Maternal occupational tobacco exposure contributed to significant decrease in cord leptin (adjusted mean difference (95%CI): -4.5 ng/mL (-8.82, -0.19); P=0.041). CONCLUSIONS: Maternal occupational tobacco exposure causes signifi-cant reduction in fetal leptin levels.

A multicomponent oxygen delivery strategy for COVID-19 patients in a step-down intensive care unit: A case series.

Coronavirus disease 2019 (COVID-19) is the cause of the pandemic that has affected millions of people worldwide with pulmonary manifestations ranging from mild pneumonia to ARDS and characterized by hypoxia. This has led to questions regarding the most efficacious and least harmful oxygen delivery strategies that minimize exposure to health care workers. In this case series, we present the hospital course of 4 patients that were managed with a multi-component oxygen delivery method in a COVID-19 step down unit.

Damned If You Drain, Damned If You Don't: A Case of Pericardial Decompression Syndrome.

Pericardial decompression syndrome (PDS) is an unusual clinical scenario with a reported incidence of 5% in all surgical or percutaneously managed pericardial tamponade patients. It is defined as a paradoxical hemodynamic instability leading to left ventricular (LV), right ventricular (RV), or biventricular dysfunction. An 84-year-old female with a history of a chronic pericardial effusion presented with symptoms of tamponade. She had had multiple prior admissions with an extensive and unyielding workup for the etiology of her pericardial effusion. During the present admission, a transthoracic echocardiogram (TTE) confirmed an augmenting pericardial effusion causing cardiac tamponade. She underwent a pericardial window with the removal of 1.2 liters of serous fluid. Postoperatively, she went into cardiogenic shock from right heart failure. Unfortunately, there also was re-accumulation of the pericardial effusion and worsening hemodynamic instability. Due to her poor prognosis, she was transitioned to comfort care. Although the etiology of PDS is unknown, it has been theorized to be caused by an imbalance of sympathetic-parasympathetic states after a rapid decompression. Currently, there are no clear guidelines or recommendations regarding the quantity of fluid that can be removed safely. More awareness leading to a more cautious and staged pericardial drainage might be the required solution.

A Rare Case of a Large, Deceitfully Quiet Brainstem Arteriovenous Malformation Presenting Only as Dizziness.

Dizziness is one of the most frequent complaints encountered in the medical practice affecting 15%-20% of adults yearly, and can be challenging to assess. Most patients use dizziness as a non-specific term, and thus suffer prejudice from the physicians' end and can be disregarded frequently. Dizziness can be a symptom of various diseases, some with sinister pathologies. We present a case of garden-variety vertigo that unfurled to be not-so-simple, emphasizing the importance of a thorough history and physical examination again even in the era of technology. A 32-year-old male patient with no past medical history presented with dizziness, later clarified as gradually progressive vertigo for two years, with unstable gait, dysarthria, and occasional diplopia. Physical examination found sustained nystagmus that changed direction with horizontal gaze, vertical nystagmus with upward gaze, dysarthria, and a wide-based ataxic gait. CT head without contrast revealed indeterminate hypodense areas in the left midbrain, pons, and cerebellar hemisphere. MRI brain identified a 2.8 x 3.4 x 4.2 cm Spetzler-Martin grade IV brainstem arteriovenous malformation (AVM) involving the left midbrain, pons, and cerebellum. Feeders were mostly from the posterior circulation, with three intranidal aneurysms, all draining into the deep venous system. The AVM was deemed inoperable, and the patient was treated with onyx embolization for two/three feeding vessel aneurysms. After treatment, the symptoms persisted, and the patient was diagnosed with major depressive disorder (MDD) six months after diagnosis, and was admitted a year later with suicidal ideation and substance use disorder. Brain AVMs are rare clinical entities that present in 0.1% of the population, mostly presenting as intracranial bleeds. When they do rarely present with isolated focal neurologic deficits, it has been attributed to a vascular steal phenomenon, hemorrhage, or a mass effect. The isolated findings of vertigo and dysarthria are highly non-specific; with such presentation, clinicians should consider etiologies under the realm of vertigo of central origin. An untreatable AVM reduces patients' quality of life and has been linked to depression and anxiety, and thus patients may benefit from psychosocial therapy. Although preventing intracranial hemorrhage (ICH) is the primary concern with brain AVMs, the rest of the patient's profile should not be forgotten.

Et Tu, B12? Cobalamin Deficiency Masquerading As Pseudo-Thrombotic Microangiopathy.

Vitamin B12 deficiency is classically associated with megaloblastic anemia. Possible cobalamin deficiency is not investigated once hemolysis is seen. Around 2.5% of cases can present as pseudo-thrombotic microangiopathy (TMA). A swift identification of this means the difference between an easy solution and a protracted one for the patient. A 74-year-old man with no past medical history presented with exertional dyspnea, fatigue, and increasing anorexia over two weeks. Physical examination including a neurological examination was normal. Laboratory tests revealed pancytopenia, unconjugated hyperbilirubinemia, elevated LDH (lactate dehydrogenase), low haptoglobin, and fragmented red blood cells (RBCs) on the peripheral smear, but normal FDP (fibrinogen degradation product) and fibrinogen. The absolute reticulocyte count was reduced as opposed to the expected elevation. Vitamin B12 levels were undetectable, and severe cobalamin deficiency from pernicious anemia was found to be the paramount etiology. Cobalamin deficiency causing pseudo-TMA baffles most physicians. Advanced pernicious anemia is thought to cause intramedullary hemolysis, resulting in peripheral pancytopenia. The fragile RBCs are easily sheared, producing schistocytosis without platelet microthrombi. In contrast to hemolytic anemias, reticulocyte count is low given the unavailability of B12 for erythropoiesis. Reticulocytopenia is a universal finding in cases of pseudo-TMA. Around 38.8% of cases with pseudo-TMA are misdiagnosed as thrombotic thrombocytopenic purpura and treated with plasma product therapy. Keeping an eye out for reticulocytopenia in cases of hemolysis could mean a world of difference for the patient.

Toll-like receptor 2 deficiency hyperactivates the FoxO1 transcription factor and induces aging-associated cardiac dysfunction in mice.

Toll-like receptors (TLRs) are a family of pattern-recognition receptors involved in innate immunity. Previous studies have shown that TLR2 inhibition protects the heart from acute stress, including myocardial infarction and doxorubicin-induced cardiotoxicity in animal models. However, the role of TLR2 in the development of aging-associated heart failure is not known. In this work, we studied aging-associated changes in structure and function of TLR2-deficient mice hearts. Whereas young TLR2-KO mice did not develop marked cardiac dysfunction, 8- and 12-month-old TLR2-KO mice exhibited spontaneous adverse cardiac remodeling and cardiac dysfunction in an age-dependent manner. The hearts of the 8-month-old TLR2-KO mice had increased fibrosis, cell death, and reactivation of fetal genes. Moreover, TLR2-KO hearts displayed reduced infiltration by macrophages, increased numbers of myofibroblasts and atrophic cardiomyocytes, and higher levels of the atrophy-related ubiquitin ligases MuRF-1 and atrogin-1. Mechanistically, TLR2 deficiency impaired the PI3K/Akt signaling pathway, leading to hyperactivation of the transcription factor Forkhead box protein O1 (FoxO1) and, in turn, to elevated expression of FoxO target genes involved in the regulation of muscle wasting and cell death. AS1842856-mediated chemical inhibition of FoxO1 reduced the expression of the atrophy-related ubiquitin ligases and significantly reversed the adverse cardiac remodeling while improving the contractile functions in the TLR2-KO mice. Interestingly, TLR2 levels decreased in hearts of older mice, and the activation of TLR1/2 signaling improved cardiac functions in these mice. These findings suggest that TLR2 signaling is essential for protecting the heart against aging-associated adverse remodeling and contractile dysfunction in mice.

Knowledge, Attitude, and Practice of Yoga in Medical Students: Assessment of Anthropometry and Lifestyle Factors.

Medical students often experience significant stress during their undergraduate training. Evidence has shown short-term yoga to be effective in decreasing stress in students. This study aimed to assess knowledge about, attitude toward, and practice of (KAP) yoga among medical students. A secondary objective was to analyze their dietary habits and physical activity. Participants consisted of 224 medical students aged 18-23 years in pre- and paraclinical groups. A closed-ended KAP questionnaire was used to collect data. Anthropometric measurements were taken. Results showed that paraclinical students (70.5%) favorably perceived the health benefits of yoga. Nearly three-fourths of study subjects had previously practiced yoga; greater numbers intended to practice yoga in the future. About 95.5% of the preclinical students who had done yoga had discontinued the practice. Perceived barriers to the practice of yoga were lack of time, insufficient facilities, lack of company, and lack of interest. Consideration of the undergraduates' lifestyle revealed that 50.4% of preclinical students did not exercise, and they routinely consumed more junk food with fewer servings of fresh fruits/salads. Preclinical students exhibited higher BMI and waist circumference compared to paraclinical students. Findings suggest that knowledge of and attitude regarding yoga were good among medical undergraduates.

SIRT2 deacetylase represses NFAT transcription factor to maintain cardiac homeostasis.

Heart failure is an aging-associated disease that is the leading cause of death worldwide. Sirtuin family members have been largely studied in the context of aging and aging-associated diseases. Sirtuin 2 (SIRT2) is a cytoplasmic protein in the family of sirtuins that are NAD+-dependent class III histone deacetylases. In this work, we studied the role of SIRT2 in regulating nuclear factor of activated T-cells (NFAT) transcription factor and the development of cardiac hypertrophy. Confocal microscopy analysis indicated that SIRT2 is localized in the cytoplasm of cardiomyocytes and SIRT2 levels are reduced during pathological hypertrophy of the heart. SIRT2-deficient mice develop spontaneous pathological cardiac hypertrophy, remodeling, fibrosis, and dysfunction in an age-dependent manner. Moreover, young SIRT2-deficient mice develop exacerbated agonist-induced hypertrophy. In contrast, SIRT2 overexpression attenuated agonist-induced cardiac hypertrophy in cardiomyocytes in a cell-autonomous manner. Mechanistically, SIRT2 binds to and deacetylates NFATc2 transcription factor. SIRT2 deficiency stabilizes NFATc2 and enhances nuclear localization of NFATc2, resulting in increased transcription activity. Our results suggest that inhibition of NFAT rescues the cardiac dysfunction in SIRT2-deficient mice. Thus, our study establishes SIRT2 as a novel endogenous negative regulator of NFAT transcription factor.