Assessment of Radiation Induced Pneumonitis and Pericarditis in Patients Undergoing Breast Conservative Treatment Using Hypofractionated Simultaneous Integrated Boost Technique.

INTRODUCTION: To determine the proportion of radiationinduced pneumonitis and pericarditis in patients who have received Hypo-fractionated Radiation along with simultaneous integrated boost technique after breast conservative surgery using a prospective observational study from a tertiary hospital. MATERIALS & METHODS: The incidence of radiationinduced pneumonitis and pericarditis was evaluated in all adult patients with biopsy-proven early-stage unilateral breast cancer who underwent breast-conserving surgery followed by hypo-fractionated radiation with a simultaneous integrated boost technique. Baseline assessments including a six-minute walk test, highresolution computed tomography (HRCT), pulmonary function tests (PFTs), electrocardiography (ECG) and echocardiography (ECHO) were performed. At three months post-radiation treatment, patients underwent follow-up assessments with a six-minute walk test, ECG and ECHO. At six months post-radiation treatment, patients underwent further assessments with a six-minute walk test, ECG, ECHO, PFTs, and HRCT of the thorax. Data analysis was performed using SPSS version 19. RESULTS: Our study investigated the incidence of acute radiation-induced pneumonitis and pericarditis in patients treated with hypofractionated VMAT-SIB technique in 20 eligible early breast cancer patients. The study found that the technique is feasible and achieves encouraging dosimetric parameters, including well achieved ipsilateral lung and heart doses. The reduced treatment time of 3-4 weeks compared to the previous 6-7 weeks with sequential boost was also found to be desirable in resource-constrained settings. The incidence of acute radiation pneumonitis and pericarditis was acceptable and comparable to existing data, with 90% of patients experiencing grade 1 radiation pneumonitis according to CTCAE v5.0. Post-treatment pulmonary function tests showed significant changes, particularly in patients who had received neoadjuvant chemotherapy and nodal irradiation. The six-minute walk test and Borg scale also showed a significant positive correlation with pulmonary function tests. There was no significant pericarditis during the follow-up. The study proposes that the hypofractionated radiotherapy using VMAT-SIB is a suitable alternative to conventional fractionation, with acceptable acute toxicities, but longer follow-up is required to assess the impact on late toxicities. CONCLUSION: Our research has shown that hypofractionated adjuvant radiotherapy with SIB is a safe and feasible treatment for patients with early breast cancer. This treatment method doesn't pose any significant short-term risks to the lungs or heart, and the SIB technique provides better coverage, conformity and sparing of organs at risk. Additionally, patients have reported positive cosmetic outcomes with this treatment. However, to make more accurate conclusions, we need to conduct further studies with larger sample sizes and longer follow-up periods to evaluate the potential longterm side effects of this treatment using VMAT in whole breast radiation.

Influence of sleep disturbance, depression, anxiety, and stress on quality of life in people with epilepsy.

OBJECTIVES: We assessed the quality of life, sleep, depression, anxiety, and stress in people with pharmacoresistant epilepsy (PRE) and newly diagnosed epilepsy (NDE). We also assessed the influence of sleep, depression, anxiety, and stress on the quality of life (QOL) and the complex association between these factors. METHODS: We recruited 80 PRE and 70 NDE people attending the epilepsy clinic. We assessed QOL, sleep quality, daytime sleepiness, and mood using the quality of life in epilepsy-31 inventory (QOLIE-31), Pittsburgh sleep quality index (PSQI), Epworth sleepiness scale (ESS), and depression anxiety stress scale (DASS-21). We compared the results between the two groups of epilepsy populations. We performed univariate and multivariate linear regression to determine the factors affecting the QOLIE-31 total score. We applied Spearman's rank correlation to find the interrelationship between variables influencing QOL. RESULTS: We found significantly lower QOLIE-31 total scores (p = .001) in PRE compared to NDE. The PSQI and ESS did not differ significantly between the PRE and NDE groups. Anxiety (p = .002) and stress (p = .003) scores were significantly higher in PRE than in NDE. QOLIE-31 total scores showed a negative correlation with PSQI as well as symptoms of depression, anxiety, and stress scores in both groups. Multiple linear regression analysis revealed depression as a major factor influencing the QOLIE-31 total score in PRE (p = .001) and NDE (p = .003). We found significant complex associations between PSQI, depression, anxiety, stress, and QOLIE total scores in both groups. SIGNIFICANCE: The QOL is poorer for people with PRE than for those with NDE. Depression is a major determinant of QOL in PWE. These factors need to be considered to improve the QOL in epilepsy.

Cardiovascular autonomic function and baroreflex sensitivity in drug-resistant temporal lobe epilepsy.

OBJECTIVE: Temporal lobe epilepsy (TLE) is often associated with autonomic manifestations. Sudden unexpected death in epilepsy (SUDEP) is a leading cause of mortality in epilepsy. Cardiac disturbances and autonomic dysfunction are the potential mechanisms behind SUDEP. Though heart rate variability (HRV) and autonomic function tests are well studied in drug-resistant temporal lobe epilepsy, there is a paucity of data on baroreflex sensitivity (BRS), a better marker of cardiac mortality in this population. We aimed to study the interictal cardiac autonomic function and BRS in people living with drug-resistant temporal lobe epilepsy compared to healthy controls. MATERIALS AND METHODS: Thirty drug-resistant temporal lobe epilepsy (TLE) individuals and thirty healthy volunteers were recruited. Heart rate variability at rest, heart rate and blood pressure (BP) at rest, during deep breathing, postural change, BP response to isometric handgrip exercise, and baroreflex sensitivity were recorded in all study participants. The results were analyzed and compared between the two groups. RESULTS: Compared to controls, the resting heart rate, HRV, parasympathetic reactivity test, and BRS significantly differed in people living with drug-resistant TLE. Time-domain indices including SDNN (p < 0.001), RMSSD (p < 0.001), NN50 (p < 0.001), and pNN50 (p < 0.001) were significantly reduced in the patients compared to controls. In frequency-domain indices, the total power was reduced (p < 0.001) in drug-resistant TLE. The parasympathetic reactivity such as changes in heart rate during deep breathing (E: I) (p < 0.02) and postural change (30:15) (p < 0.005) were significantly reduced in the patients. Baroreflex sensitivity was also significantly reduced in the drug-resistant TLE group (p < 0.001). CONCLUSION: The present study findings are suggestive of parasympathetic dysfunction in drug-resistant TLE. Reduced HRV and BRS may increase the risk of SUDEP in people living with epilepsy.

Role of Ventromedial Hypothalamus in Sucrose-Induced Obesity on Metabolic Parameters.

BACKGROUND: Obesity is because of excessive fat accumulation that affects health adversely in the form of various diseases such as diabetes, hypertension, cardiovascular diseases, and many other disorders. Our Indian diet is rich in carbohydrates, and hence the sucrose-induced obesity is an apt model to mimic this. Ventromedial hypothalamus (VMH) is linked to the regulation of food intake in animals as well as humans. PURPOSE: To understand the role of VMHin sucrose-induced obesity on metabolic parameters. METHODS: A total of 24 adult rats were made obese by feeding them on a 32% sucrose solution for 10 weeks. The VMH nucleus was ablated in the experimental group and sham lesions were made in the control group. Food intake, body weight, and biochemical parameters were compared before and after the lesion. RESULTS: Male rats had a significant weight gain along with hyperphagia, whereas female rats did not have a significant weight gain inspite of hyperphagia. Insulin resistance and dyslipidemia were seen in both the experimental and control groups. CONCLUSION: A sucrose diet produces obesity which is similar to the metabolic syndrome with insulin resistance and dyslipidemia, and a VMH lesion further exaggerates it. Males are more prone to this exaggeration.

Link of neurocognitive deficit to impaired cardiovagal modulation in prehypertensives is comparable to newly diagnosed hypertensives in young Indian population.

BACKGROUND: Hypertension has been reported to cause impaired cardiovagal modulation and a wide variety of cognitive loss. However, the link cardiovagal modulation to neurocognitive impairment has not been studied yet. The present study has compared the link cardiovagal modulation to neurocognitive impairment between prehypertension and newly diagnosed hypertension in young adults. METHODS: One hundred forty-seven subjects (42 normotensives, 54 prehypertensives and 51 newly diagnosed hypertensives) aged between 18-44 years were included in this case-control study. The demographic, anthropometric, basal parameters, heart rate variability (HRV), cardiovascular autonomic function tests (CAFTs), event-related potential P300 and biochemical parameters were recorded in all the groups. Association of various parameters with neurocognitive deficit was studied by Pearson correlation analysis and independent contribution of various factors to cognitive deficit was assessed by multiple regression analysis in the study groups. RESULTS: Total power (TP) of HRV, the marker of cardiovagal modulation was reduced in both prehypertensives and hypertensives compared to controls. Among CAFTs, the ΔDBPIHG was increased, and 30:15 ratio and E:I ratio were decreased in both study groups. The latency of P300 (the marker of neurocognition) was significantly prolonged in prehypertensives and hypertensives and P300 latency was significantly associated with reduction in TP in both the groups. HOMA-IR was increased, and total oxidant capacity was decreased in prehypertensives and hypertensives, and both these parameters had independent contribution to P300. CONCLUSION: Prehypertensives had considerable autonomic imbalance, reduced cardiovagal modulation and neurocognitive deficit that were comparable to newly diagnosed hypertensives. Though the causal relationship between cardiovagal modulation and neurocognitive impairment can't be established from the findings of the present study, it appears that neurocognitive deficit might have some possible link to the decreased cardiovagal modulation and metabolic derangements in young prehypertensives and hypertensives.

Effects of 12 Weeks Practice of Yoga on Heart Rate Variability in Males with Type 2 Diabetes Receiving Oral Antidiabetic Drugs: A Randomized Control Trial.

Objective: To investigate the effects of 12 weeks practice of a structured yoga module on heart rate variability (HRV) and cardiometabolic risks in patients with type 2 diabetes (T2D) receiving similar kind of oral antidiabetic drugs (OAD) with yoga therapy and without yoga therapy, matched for all the known confounders. Design: Parallel design interventional (randomized control trial) study. Subjects: Eighty treatment-naive males with T2D were randomized into control group (n = 40) and study group (n = 40). Intervention: Study group participants received a structured yoga therapy that included asana and pranayama practice for 12 weeks in addition to OAD, whereas control group participants received OAD alone. Outcome measures: Before and after intervention, BP parameters, rate pressure product (RPP) as the marker of myocardial stress, total power (TP) of HRV, low-frequency to high-frequency (LF-HF) ratio of HRV, homeostatic model of insulin resistance (HOMA-IR), lipid profile and lipid risk factors, malondialdehyde (MDA), and high-sensitive C-reactive protein (hsCRP) were measured. TP of HRV was defined as the primary outcome. Association of TP (the marker of HRV) and LF-HF ratio (the marker of sympathovagal balance) with cardiometabolic parameters was assessed by correlation and regression analyses. Results: After 12 weeks yoga therapy, there was significant reduction in cardiometabolic risks (TP of HRV, RPP, lipid risks factors, levels of MDA, and hsCRP) in study group subjects compared with control subjects that did not receive yoga therapy. All cardiometabolic risk factors were significantly correlated with TP in study group, having maximum significance with homeostatic model of insulin secretion (r = 0.502, p ≤ 0.001). Multiple regression analysis demonstrated the independent contribution of decrease in RPP, HOMA-IR, hsCRP, and MDA to increased TP and decreased LF-HF ratio in T2D patients after yoga therapy. Conclusion: From the results of this study, the authors conclude that 12 weeks practice of a structured yoga module improves TP of HRV, sympathovagal balance, and metabolic functions, and reduce cardiovascular (CV) risks in patients with diabetes who received routine antidiabetic medicines along with yoga therapy, compared with the patients with diabetes who received antidiabetic medicines alone. The reduction in cardiometabolic risks in these patients is linked to the improvement in TP of HRV. Future studies should also include a control group with rapid walking or a similar exercise program of equal time to the yoga intervention group to discern whether it is in fact yoga that is leading to these results and not simply increased CV activity. Clinical Trial Registry of India (No. CTRI/2021/06/034074).

Effects of Three Months of Honey Supplementation on Quality of Life and Neuropathy in Type 2 Diabetic Patients.

CONTEXT: Diabetic neuropathy, a common debilitating complication of type 2 diabetes, can occur despite adequate treatment. To date, no studies have occurred on the use alternative medicine as an adjunct therapy for treating diabetic neuropathy. OBJECTIVE: The study assessed the effects of three months of honey supplementation on insulin resistance, lipid profiles, oxidant status, nerve conduction, and QOL in patients with diabetic neuropathy. METHODS/DESIGN: The research team designed a single-arm, open-label pilot study. SETTING: The study took place at the Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER) in Puducherry, India. PARTICIPANTS: The study included 48 patients with diabetic neuropathy at the institute, with a mean age of 58.91 ± 7.976 years. INTERVENTION: Participants took honey for three months at a dose of 0.5 gm/Kg of body weight per day. OUTCOME MEASURES: Participants completed the Neuropathy Total Symptom Score-6 (NTSS-6) questionnaire and the Norfolk QOL Diabetic Neuropathy (Norfolk QOL-DN) questionnaire at baseline and postintervention. Also, participants' glucose levels, lipid profiles, and biochemical markers were obtained and a nerve conduction study was completed at baseline and postintervention. RESULTS: A significant reduction occurred in the NTSS-6 score (P < .0001) and the Norfolk QOL-DN total score (P < .0001) from baseline to postintervention. Participants' fasting blood glucose (FBG), triglycerides (TG), and total cholesterol (TC) decreased significantly, at P = .0192, P = .0371, and P = .0049, respectively. Their malondialdehyde (MDA), and inflammatory markers interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) also decreased significantly, and MDA showed a significant correlation with neuron specific enolase (NSE). CONCLUSIONS: Three months honey supplementation reduced participants' subjective pain scores and symptoms from diabetic neuropathy and improved their QOL. However, the nerve conduction study showed that no significant change had occurred in motor velocity.

Effect of honey and insulin treatment on oxidative stress and nerve conduction in an experimental model of diabetic neuropathy Wistar rats.

Diabetic neuropathy is the most common complication affecting more than 50% of patients with longstanding diabetes. Till date, there are no reports to explain the scientific basis of alternative medicine as an adjunct therapy for treating diabetic neuropathy. Hence, we studied the effect of honey and insulin treatment on hyperglycemia, dyslipidemia, oxidant and anti-oxidant status and nerve conduction in experimental diabetic neuropathy Wistar rats. In this experimental study, forty healthy male Wistar albino rats of 10-12 weeks age, weighing between 150 to 200g were obtained from our institute central animal house. After acclimatization, the rats were divided into control (n = 8) and experimental (n = 32) groups randomly. In the experimental group, type 2 diabetic neuropathy was induced with high fat and high sugar diet for 8 weeks followed by streptozotocin at a dose of 35 mg/kg body weight. Three days after streptozotocin injection, blood glucose levels of rats were measured from fasting samples to confirm diabetes. After the development of diabetes, rats were given standard rodent chow and allowed four more weeks to remain diabetic and to develop neuropathy. Every second week, nerve conduction study was done to confirm neuropathy. All the diabetic rats of experimental group developed neuropathy after 4 weeks of developing diabetes, which was confirmed by significant reduction in conduction velocity of sensory and motor nerve when compared to non-diabetic control group. After the development of neuropathy, these rats were randomly divided into diabetic neuropathy with no treatment group (n = 8) and three treatment groups (n = 8, each). The rats of treatment group were administered with either honey or insulin or honey+insulin for six weeks. After six-weeks of intervention, there was significant decrease in blood glucose and lipids in honey, insulin and honey+insulin treated neuropathy rats, when compared with no treatment group. Malondialdehyde was reduced and total anti-oxidant status improved in all the three treatment groups. There was no significant increase in conduction velocity of sciatic tibial motor nerve in treatment groups when compared with no treatment group. However, the sensory nerve conduction velocity improved significantly in honey+insulin treated neuropathy rats. In conclusion, six-week honey treatment helped in reducing dyslipidemia and oxidative stress. Honey given along with insulin for six-weeks improved sensory nerve conduction velocity in experimental diabetic neuropathy Wistar rats.

Decreased baroreflex sensitivity is associated with cardiometabolic risks and prehypertension status in early-postmenopausal women.

OBJECTIVE: We studied the link of decreased baroreflex sensitivity (BRS) to cardiometabolic risks and prehypertension status in postmenopausal women during their early menopausal phase. METHODS: Premenopausal women (n = 55) and early-postmenopausal women (n = 50) of age group between 40 and 55 years were recruited for the study, and their anthropometric parameters, complete battery of autonomic function tests (AFT), BRS, hormone levels, and cardiometabolic risk parameters were measured and compared between two groups. Correlation analysis of BRS with various physiological and biochemical parameters in these two groups were performed. Multiple regression analysis of BRS with various other associated factors in postmenopausal subjects and bivariate logistic regression analysis for assessing prediction of prehypertension status by BRS in postmenopausal group were performed. RESULTS: There was a significant difference in AFT and metabolic parameters between premenopausal and postmenopausal women. Sympathovagal imbalance (increased sympathetic and decreased parasympathetic) was prominent in early-postmenopausal women. Decreased BRS, the marker of cardiovascular (CV) risk was found to be significant (P < .001) and correlated with various cardiometabolic parameters in early-postmenopausal subjects. Multiple regression analysis demonstrated that decreased BRS is independently linked to parameters of decreased vagal activity, inflammation, and oxidative stress in early-postmenopausal group. Decreased BRS could predict prehypertension status in early-postmenopausal subjects as confirmed by bivariate logistic regression analysis. CONCLUSION: Sympathovagal imbalance, decreased BRS and considerable metabolic derangements were observed in women in their early phase of menopause. Decreased BRS appears to be associated with the cardiometabolic risks in these women. Prehypertension status in early-postmenopausal subjects could be predicted by decreased BRS.

Pulmonary function severity in relation to interleukin-23 levels in patients with psoriasis vulgaris.

Background Interleukin-23 (IL-23), a key inflammatory regulator in the pathogenesis of psoriasis, is suspected to play a role in the onset of pulmonary dysfunction (chronic obstructive pulmonary disease) in psoriasis. Despite that, pulmonary function tests are rarely studied in these subjects. This study aims to seek a possible relation between pulmonary function in psoriasis patients serum IL-23. Methods For this analytical cross-sectional study, male psoriasis patients in the age group of 25-45 years were recruited from dermatology out patient department (n = 40). Age and BMI matched apparently healthy individuals were recruited as control group (n = 40). After obtaining demographic and personal details, anthropometric parameters and blood pressure were recorded. The severity of psoriasis was assessed using Psoriasis Area and Severity Index score. Pulmonary function was assessed using computerized spirometry, and serum IL-23 was measured using ELISA. Results Forced vital capacity, forced expiratory volume in 1 s, peak expiratory flow rate, and forced expiratory flow at 25%-75% of the pulmonary volume (FEF25%-75%) were significantly reduced in psoriasis. Based on the percentage of predicted values FEF25%-75% was significantly reduced in psoriasis. Serum IL-23 (pg/mL) was significantly higher in psoriasis. The increase in IL-23 in psoriasis subjects does not correlate with their pulmonary function. Conclusions Psoriasis may be associated with a reduced lung function even when the disease is in the mild stage. Increased IL-23 found in these subjects is suggestive of systemic inflammation, which indirectly lowers lung function.

Assessment of the association of heart rate variability and baroreflex sensitivity with depressive symptoms and stress experienced by women in pregnancy.

BACKGROUND: Pregnancy is a unique physiological state with systemic changes including cardiovascular, autonomic, hemodynamic and psychological. Increase in incidence of stress and depression in antenatal period has been reported. Autonomic changes in pregnancy and its dysfunction in depression are well documented. However, there is lack of evidence associating cardiovascular autonomic dysfunction to stress and depressed mood in pregnant women. METHODS: In this correlation study, we assessed cardiovascular autonomic functions of 172 pregnant women using heart rate variability (HRV) and baroreflex sensitivity (BRS). The Edinburg postnatal depression scale (EPDS) was used to evaluate depressive symptoms and perceived stress scale (PSS) was used to assess stress. The HRV and BRS parameters were correlated with EPDS and PSS. Multiple regression analysis was performed for EPDS and PSS individually to study their association with cardiac autonomic functions(CAF). RESULTS: HRV and BRS were well correlated to EPDS and PSS scores. The depression and stress were found to be significantly associated to autonomic dysfunctions as increased sympathetic and decreased parasympathetic activity. Among various CAF parameters, LF:HF ratio and BRS were found to be significantly associated with depression and stress among these women. CONCLUSION: LF:HF ratio and BRS may be associated with depression during antenatal period. The depression in antenatal period may add on to cardiovascular risk in expecting mothers.

Contribution of insulin resistance to decreased baroreceptor sensitivity & cardiometabolic risks in pre-obesity & obesity.

BACKGROUND & OBJECTIVES: Although insulin resistance (IR) is a known complication in obesity, the physiological mechanisms linking IR with cardiometabolic risks in obesity have not been well studied. This study was conducted to assess the difference in cardiovascular (CV) risk profile in IR and non-IR (NIR) conditions, and contribution of IR to cardiometabolic risks in pre-obese and obese individuals. METHODS: Basal CV, blood pressure variability, autonomic function test and cardiometabolic parameters were recorded in pre-obese (n=86) and obese (n=77) individuals during 2012 and 2015. The association of altered cardiometabolic parameters with homeostatic model for IR (HOMA-IR) in pre-obese and obese groups and with baroreceptor sensitivity (BRS) in IR and NIR groups was calculated by appropriate statistical analysis. RESULTS: Decreased BRS, a known CV risk and cardiometabolic parameters were significant in IR (pre-obese and obese) group compared to the NIR group. Sympathovagal imbalance in the form of increased sympathetic and decreased parasympathetic activities was observed in individuals with IR. There was no significant difference in the level of independent contribution of HOMA-IR to cardiometabolic parameters in pre-obese and obese groups. Adiponectin and inflammatory markers had an independent contribution to BRS in IR group. INTERPRETATION & CONCLUSIONS: Findings of the present study demonstrated that the intensity of cardiometabolic derangements and CV risk were comparable between IR, pre-obese and obese individuals. Pro-inflammatory state, dyslipidaemia and hypoadiponectinaemia might contribute to CV risk in these individuals with IR. IR could possibly be the link between altered metabolic profile and increased CV risks in these individuals independent of the adiposity status.

Effect of 12 Weeks of Yoga Therapy on Quality of Life and Indian Diabetes Risk Score in Normotensive Indian Young Adult Prediabetics and Diabetics: Randomized Control Trial.

INTRODUCTION: India has become the epicentre for diabetes, a stress-related disorder affecting the working skills and day-to-day lifestyle management of younger population. Most of the studies have reported the effect of yoga on improving Quality of Life (QoL) in diabetic patients with other comorbidities. Till date, no randomized control trial reports are available to show the effect of yoga therapy on QoL and Indian Diabetes Risk Score (IDRS) in normotensive prediabetic and diabetic young individuals. AIM: To determine the effect of 12 weeks of yoga therapy on QoL and IDRS among normotensive prediabetic and diabetic young Indian adults. MATERIALS AND METHODS: A randomized control trial was conducted in Endocrinology Outpatient Department (OPD). Normotensive participants (n=310) aged 18-45 years were divided into healthy controls (n=62), prediabetics (n=124) and diabetics (n=124). Study group subjects were randomly assigned to Group II (n=62, prediabetes-standard treatment), Group III (n=62, prediabetes-standard treatment + yoga therapy), Group IV (n=62, diabetes-standard treatment) and Group V (n=62, diabetes-standard treatment + yoga therapy). Flanagan QoL scale, IDRS questionnaire, Fasting Plasma Glucose (FPG) and insulin were assessed pre and post 12 weeks of intervention. Statistical analysis was done using Student's paired t-test and one-way ANOVA. RESULTS: Pre-post intervention analysis showed significant improvement in QoL scale with p<0.01 in Group II and Group IV; p<0.001 in Group III and Group V respectively. There was significant reduction in IDRS in Group II (p<0.05); p<0.001 in Group III, Group IV and Group V respectively. Significant difference (p<0.001) in QoL scale and IDRS were found when study groups with standard treatment along with yoga therapy were compared to standard treatment alone. CONCLUSION: Yoga therapy along with standard treatment for 12 weeks improved QoL and attenuated the diabetes risk among Indian prediabetics and diabetics compared to standard treatment alone.

Decreased baroreflex sensitivity is linked to the atherogenic index, retrograde inflammation, and oxidative stress in subclinical hypothyroidism.

Purpose/aim of the study: The present study investigated the link of hyperlipidemia, inflammation and oxidative stress (OS) to cardiovascular (CV) risks in subclinical hypothyroidism (SCH). MATERIALS AND METHODS: We enrolled 81 subclinical hypothyroid patients and 80 healthy subjects as control. Their CV and autonomic functions were assessed by spectral analysis of heart rate variability (HRV), continuous blood pressure variability (BPV) measurement and conventional autonomic function testing. Thyroid profile, lipid profile, immunological, inflammatory and OS markers were estimated and correlated with the baro-reflex sensitivity (BRS), the marker of sympathovagal imbalance (SVI) & CV risk. RESULTS: Mean arterial pressure (MAP, P<0.0001), total peripheral resistance (TPR, P<0.0001), ratio of low-frequency to high-frequency power of HRV (LF-HF ratio) (P<0.0001) were significantly higher and BRS (P<0.0001) was significantly lower in SCH group than the control group. BRS significantly correlated with heart rate, MAP, LF-HF ratio, lipid risk factors, anti-thyroperoxidase antibody, thyroid-stimulating hormone, high-sensitive C-reactive protein (hsCRP), malondialdehyde (MDA) and SCH. CONCLUSIONS: It was concluded that SVI is associated with SCH. Though dyslipidemia, inflammation and OS contributed to decreased BRS, SCH per se contributed maximally to it. Decreased BRS could be a physiological basis of increased CV risks in patients with SCH.

Decreased baroreflex sensitivity is linked to sympathovagal imbalance, low-grade inflammation, and oxidative stress in pregnancy-induced hypertension.

Pregnancy-induced hypertension (PIH) has been reported as a cardiovascular (CV) risk. We assessed the sympathovagal imbalance (SVI) and the association of inflammation and oxidative stress (OS) with CV risks in PIH. A total of 125 pregnant women having a risk factor for PIH were followed till term and the incidence of PIH was observed. Retrospectively, they were divided into two groups: Group I (those who did not develop PIH, n = 82) and Group II (those who developed PIH, n = 43). Blood pressure variability (BPV) parameters including baroreflex sensitivity (BRS), spectral heart rate variability (HRV), autonomic function tests (AFTs), inflammatory markers (interleukin-6, TNF-α, interferon-γ), and OS markers were measured in both the groups. Alterations in parasympathetic and sympathetic components of AFTs were analyzed. Link of various parameters to BRS was assessed by correlation and multiple regression analysis. Parasympathetic components of AFTs were decreased from the early part of pregnancy and sympathetic components were increased toward the later part of pregnancy. Decreased BRS, the marker of CV risk, was more prominent in Group II subjects. Independent contribution of interleukin-6 (ß = 0.276, P = 0.020), TNF-α (ß = 0.408, P = 0.002), interferon-γ (ß = 0.355, P = 0.008), and thiobarbituric-acid reactive substance (ß = 0.287, P = 0.015) to BRS was found to be significant. It was concluded that sympathetic overactivity that develops more in the later part (third trimester) of pregnancy contributes to SVI and genesis of PIH. In PIH women, CV risks are present from the beginning of pregnancy that intensifies in the later part of pregnancy. Retrograde inflammation and oxidative stress contribute to the decreased BRS in PIH.

Endothelial nitric oxide synthase gene polymorphisms are associated with cardiovascular risks in prehypertensives.

Though endothelial nitric oxide synthase (eNOS) gene polymorphism is documented in the causation of hypertension, its role in prehypertension has not been investigated. The present study was conducted in 172 subjects divided into prehypertensives (n = 57) and normotensives (n = 115). Cardiovascular (CV) parameters including baroreflex sensitivity (BRS) by continuous BP variability assessment and sympathovagal imbalance (SVI) by heart rate variability analysis were recorded. Biochemical parameters for insulin resistance (homeostatic model for assessment of insulin resistance), oxidative stress, lipid risk factors, renin, and inflammatory parameters were measured. Genotyping for eNOS polymorphisms rs1799983 (298G>T) and rs2070744 (-786T>C) was performed by polymerase chain reaction-restriction fragment length polymorphism method. Multiple regression analysis was done to assess the association between SVI and metabolic markers, and multivariate logistic regression was done to determine the prediction of prehypertension status by genotype, BRS, and ratio of low-frequency to high-frequency in these subjects. The BP variability, heart rate variability, and biochemical parameters were significantly altered in prehypertensives. The eNOS polymorphisms were found to be associated with prehypertension. BRS, the marker of SVI, was significantly associated with BP, homeostatic model for assessment of insulin resistance, and tumor necrosis factor alpha in 298GG genotype of prehypertensive population. The eNOS gene polymorphisms appear to be associated with prehypertension. 298G>T and -786T>C contribute to SVI in young prehypertensives attributed by insulin resistance and inflammation. The CV risks were associated with prehypertension status in prehypertensives expressing both 298GG and -786TT genotypes. Association of CV risks with SVI appears to be stronger in prehypertensives expressing GG genotype.

Gender Difference in the Role of Posterodorsal Amygdala on the Regulation of Food Intake, Adiposity and Immunological Responses in Albino Wistar Rats.

Lesion of posterodorsal amygdala (PDA) has been known to produce hyperphagia and obesity in animal models. However, the influence of gender on food intake (FI), body weight (BW) and immunological parameters following PDA lesion is not yet known. The present work was carried out to study the effect of gender on the regulation of FI, BW and immunological parameters following lesions of PDA in albino Wistar rats. Twenty-four albino Wistar rats were divided equally into 2 groups - PDA group and control group - with 6 male and 6 female rats in each. In the experimental group, bilateral electrolytic lesion of the respective nuclei was performed by stereotaxy and post-lesion parameters were recorded. In the control group, sham lesion was made. Male-female difference in each parameter was determined. Following PDA lesion, FI increased significantly in both male (p < 0.001) and female rats (p < 0.01) but the percentage increase in FI was significantly more in female rats (p < 0.001). BW also increased in both the sexes but the increase in BW was significant only in male rats (p < 0.05). Both male and female rats showed increase in the concentration of cluster of differentiation 4 (CD4), but the significant increase in CD4 concentration (p < 0.01) was seen only in male rats. CD8 concentration increased significantly in male rats (p < 0.05). The liver weight-BW ratio was significantly greater in female rats (p < 0.001) following PDA lesions. Lesion of PDA results in accentuation of FI and BW gain and activation of immunity. There is a gender difference in the inhibitory control of PDA on FI, BW and immunity.

Attenuated baroreflex sensitivity in normotensive prediabetes and diabetes in Indian adults.

PURPOSE/AIM OF THE STUDY: Though attenuated baroreflex sensitivity (BRS) is known to promote cardiovascular disease (CVD) risk in diabetics, its status in prediabetes has not been reported. Also, the link of BRS to CVD risk in normotensive diabetics has not been reported. This study aimed to evaluate the association of BRS to CVD risk in normotensive prediabetics and diabetics. MATERIALS AND METHODS: Participants (n = 154) of 18-45 years were divided into normoglycemics (n = 52), prediabetics (n = 64) and diabetics (n = 38) based on American Diabetes Association criteria. Body mass index, waist-hip ratio, waist-height ratio, body fat mass index, basal heart rate, systolic blood pressure, diastolic blood pressure, rate pressure product, BRS, heart rate variability (HRV), fasting plasma glucose, fasting insulin, lipid profile and atherogenic index of plasma (AIP) were measured. Indian Diabetes Risk Score (IDRS) and homeostatic model assessment of insulin resistance were calculated. RESULTS: There was significant increase in all the parameters except BRS, HRV and high-density lipoprotein in prediabetics and diabetics compared to normoglycemics. All these parameters were significantly altered in prediabetics compared to diabetics. Significant negative correlation was found between BRS and other parameters in prediabetics and diabetics. CONCLUSIONS: BRS was attenuated in normotensive prediabetics and diabetics with high IDRS, insulin resistance, AIP, dyslipidemia and reduced HRV that predisposes them to CVD risk. The study demonstrates CVD risk quite early in the prediabetics with reduced HRV, high body fat, hyperinsulinemia, insulin resistance, AIP and rate pressure product.

Decreased baroreflex sensitivity is linked to sympathovagal imbalance, body fat mass and altered cardiometabolic profile in pre-obesity and obesity.

OBJECTIVE: Though decreased baroreflex sensitivity (BRS), the predictor of cardiac morbidities and mortality has been reported in obesity, the mechanisms and metabolic biomarkers influencing BRS have not been studied. We aimed to assess the difference in cardiovascular (CV) risk profile in pre-obesity and obesity, and the contribution of body composition and cardiometabolic factors to CV risks in these two conditions. METHODS: Obesity indices, body composition, blood pressure variability and autonomic function test parameters were recorded in 223 subjects divided into controls (n=72), pre-obese (n=77) and obese (n=74) groups. Insulin resistance (HOMA-IR), atherogenic index (AI), leptin, adiponectin, inflammatory and oxidative stress parameters were measured. Association and independent contribution of altered cardiometabolic parameters with BRS were performed by Pearson's correlation and multiple regression analysis, respectively. RESULTS: BRS was significantly decreased in pre-obese and obese group compared to controls. Sympathovagal imbalance (SVI) in the form of increased sympathetic and decreased parasympathetic cardiac drives was observed in pre-obesity and obesity. There was significant difference in general markers of obesity (body mass index, and waist-to-hip ratio), between pre-obese and obese group, however no such difference was observed in body composition and cardiometabolic parameters between the two groups. AI, high sensitive C-reactive protein (hs-CRP) and ratio of basal metabolism to body fat (BM/BF) in pre-obese group, and AI, HOMA-IR, leptin, adiponectin, ratio of basal metabolism to body weight (BM/BW), BM/BF, inflammatory and oxidative stress markers in obese group had independent contribution to BRS. Among these metabolic biomarkers, BRS had maximum association with leptin (ß=0.532, p=0.000) in the obese group and hs-CRP (ß=0.445, p=0.022) in the pre-obese group. CONCLUSIONS: The present study demonstrates decreased BRS, an important marker of increased CV risk in pre-obesity and obesity. The intensity of cardiometabolic derangements and CV risk was comparable between pre-obese and obese subjects. BM/BF ratio appears to be a better marker of metabolic activity in pre-obesity and obesity. SVI and increased basal metabolism appear to be the physiological link between metabolic derangements and CV risks in both pre-obesity and obesity.

Prehypertension status, cardiometabolic risks, and decreased baroreflex sensitivity are linked to sympathovagal imbalance in salt-preferring individuals.

Salt preference has been reported to cause sympathovagal imbalance (SVI) and prehypertension. We investigated the role of inflammation, insulin resistance (IR), hyperlipidemia, and oxidative stress (OS) in genesis of SVI and cardiovascular (CV) risks in salt-preferring prehypertensives. The subjects were divided into no-salt-preferring (NSP, n = 87) and salt-preferring (SP, n = 89) group based on their preference for salted food. Body mass index (BMI), blood pressure (BP) variability parameters including baroreflex sensitivity (BRS), heart rate variability (HRV) indices, autonomic function tests, IR, lipid risk factors, inflammatory and OS markers, and renin were measured in both the groups. Based on the contribution of various cardiometabolic risks to low-frequency-high-frequency (LF-HF) ratio of HRV, the marker of SVI was assessed by multiple-regression analysis. Prediction of prehypertension status by the LF-HF ratio was assessed by bivariate logistic regression. BMI, heart rate, BP parameters, cardiac output, total peripheral resistance, LF-HF ratio, IR, atherogenic index, inflammatory, and OS markers were significantly increased, and BRS was significantly decreased in the SP group compared with the NSP group. There was an independent association of IR, atherogenic index, markers of inflammation and OS, and BRS with the LF-HF ratio in SP subjects, and the LF-HF ratio had significant prediction of prehypertension status in these subjects. It was concluded that IR, low-grade inflammation, atherogenic lipid profile, and OS contribute to SVI in SP subjects. Decreased BRS (the marker of CV risk) is linked to SVI, and SVI predicts prehypertension status in SP subjects.