Trends of humoral immune responses to heterologous antigenic exposure due to vaccination & omicron SARS-CoV-2 infection: Implications for boosting

Background & objectives: Vaccination and natural infection can both augment the immune responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but how omicron infection has affected the vaccine-induced and hybrid immunity is not well studied in Indian population. The present study was aimed to assess the durability and change in responses of humoral immunity with age, prior natural infection, vaccine type and duration with a minimum gap of six months post-two doses with either ChAdOx1 nCov-19 or BBV152 prior- and post-emergence of the omicron variant. Methods: A total of 1300 participants were included in this observational study between November 2021 and May 2022. Participants had completed at least six months after vaccination (2 doses) with either ChAdOx1 nCoV-19 or an inactivated whole virus vaccine BBV152. They were grouped according to their age (? or ?60 yr) and prior exposure of SARS-CoV-2 infection. Five hundred and sixteen of these participants were followed up after emergence of the Omicron variant. The main outcome was durability and augmentation of the humoral immune response as determined by anti-receptor-binding domain (RBD) immunoglobulin G (IgG) concentrations, anti-nucleocapsid antibodies and anti-omicron RBD antibodies. Live virus neutralization assay was conducted for neutralizing antibodies against four variants – ancestral, delta and omicron and omicron sublineage BA.5. Results: Before the omicron surge, serum anti-RBD IgG antibodies were detected in 87 per cent participants after a median gap of eight months from the second vaccine dose, with a median titre of 114 [interquartile range (IQR) 32, 302] BAU/ml. The levels increased to 594 (252, 1230) BAU/ml post- omicron surge (P<0.001) with 97 per cent participants having detectable antibodies, although only 40 had symptomatic infection during the omicron surge irrespective of vaccine type and previous history of infection. Those with prior natural infection and vaccination had higher anti-RBD IgG titre at baseline, which increased further [352 (IQR 131, 869) to 816 (IQR 383, 2001) BAU/ml] (P<0.001). The antibody levels remained elevated after a mean time gap of 10 months, although there was a decline of 41 per cent. The geometric mean titre was 452.54, 172.80, 83.1 and 76.99 against the ancestral, delta, omicron and omicron BA.5 variants in the live virus neutralization assay. Interpretation & conclusions: Anti-RBD IgG antibodies were detected in 85 per cent of participants after a median gap of eight months following the second vaccine dose. Omicron infection probably resulted in a substantial proportion of asymptomatic infection in the first four months in our study population and boosted the vaccine-induced humoral immune response, which declined but still remained durable over 10 months

Fenugreek seed extract alleviates hippocampal dendritic atrophy in streptozotocin induced diabetic rats / El extracto de semillas fenugreek alivia la atrofía dendrítica del hipocampo en ratas diabéticas inducidas por estreptozotocina

SUMMARY: Herbal extracts used for treatment of diabetes has focused mostly on the hypoglycaemic and anti-oxidant property.There are no studies which focused on its effect on dendritic architecture of pyramidal neurons of hippocampus caused by diabetes. This study was taken up to explore the effect of administration of Trigonella foenum-graecum (fenugreek) seed extract on diabetes induced dendritic atrophy in hippocampus. Experimental diabetes was induced in rats by administering single dose of Streptozotocin (60 mg/kg)intraperitoneally.Treatment groups of rats were orally administeredfenugreek seed extract of 1 g/kg body weight for 6 weeks. Followingly they were sacrificed and the brains were removed, processed for the Golgi-Cox stain method.The number of dendritic branching points and intersections were counted in successive radial segments of 20 µm up to a radial distance of 100 micron from soma and analysed by the Sholl's method. The rats with diabetes showed a significant decrease in the dendritic length and branching points in most of the apical and basal dendrites of CA1 and CA3 pyramidal neurons.Treatment with fenugreek seed extract were able to significantly alleviate the dendritic atrophy in most of the segments except in the apical branching points of the CA1 neuron. The present study demonstrates that fenugreek seed extract having a proven hypoglycaemic and anti-diabetic property also possess protection to the hippocampal pyramidal neurons form diabetes associated neuronal atrophy.

RESUMEN: Los extractos de hierbas para el tratamiento de la diabetes se han basado principalmente en las propiedades hipoglucémicas y antioxidantes. En la literatura no hay estudios basados en su efecto sobre la arquitectura dendrítica de las neuronas piramidales del hipocampo, causadas por la diabetes. El objetivo de este estudio fue investigar el efecto de la administración de extracto de semilla de Trigonella foenum graecum (fenogreco) sobre la atrofia dendrítica inducida por la diabetes en el hipocampo. Se indujo diabetes experimental en ratas mediante la administración de una dosis única de estreptozotocina (60 mg / kg) por vía intraperitoneal. Se administró a grupos de ratas extracto de semilla de fenogreco a razón de 1 g / kg de peso corporal durante 6 semanas. Las ratas fueron sacrificadas posteriormente y se procesaron los cerebros mediante método de tinción de Golgi-Cox. El número de puntos de ramificación dendrítica e intersecciones se contaron en segmentos radiales sucesivos de 20 µm hasta una distancia radial de 100 micras del soma y se analizaron mediante el método de Sholl. Las ratas con diabetes mostraron una disminución significativa en la longitud dendrítica y los puntos de ramificación en la mayoría de las dendritas apicales y basales de las neuronas piramidales CA1 y CA3. El tratamiento con extracto de semilla de fenogreco alivió significativamente la atrofia dendrítica en la mayoría de los casos, excepto en los puntos de ramificación apical de la neurona CA1. El estudio demuestra que el extracto de semilla de fenogreco además de tener propiedades hipoglucémicas y antidiabéticas, también protege las neuronas piramidales del hipocampo contra la atrofia neuronal asociada a la diabetes.

Prognostic Value of Aortic Pulse Wave Velocity as Index of Arterial Stiffness in the General Population

Background: During a person’s lifetime, as part of the aging process or as a consequence of hypertension, atherosclerosis, or other pathological processes, the aorta stiffens. Accordingly, the forward pulse wave travels faster, and the arterial waves reflected from the periphery reach the heart early during systole, which leads to higher systolic but lower diastolic blood pressure, an augmentation of the cardiac workload, and a decrease of the coronary perfusion pressure. The aortic pulse wave velocity (APWV) reflects central arterial stiffness. Some studies addressed the prognostic significance of APWV above and beyond other cardiovascular risk factors. Furthermore, pulse pressure, an indirect measure of increased arterial stiffness, predicts a poor prognosis in treated and untreated hypertensive subjects. Methods: The study was conducted on a sex- and age-stratified random sample of 167 rural and suburban population of Haryana state aged 40 to 70 years. Results: Cox regression analysis was used to investigate the prognostic value of APWV, pulse pressure (PP) and other covariates. We adjusted for sex, age, body mass index. MAP measured in the office (conventional PP) and APWV by Periscope TM. With these adjustments, APWV maintained its prognostic significance in relation to each end point (P<0.05), whereas office PP lost their predictive value (P>0.19). In sensitivity analyses, APWV still predicted all cardiovascular events after standardization to a heart rate of 60 beats per minute, after adjustment for MAP. Conclusions: In a general population of Haryana, APWV predicted a composite of cardiovascular outcomes above and beyond traditional cardiovascular risk factors.

Assessment of maternal vascular stiffness indices in three trimesters of normal pregnancy.

Normal pregnancy is associated with intense alterations in the maternal cardiovascular system. The aim of the present study was, to assess the influence of normal pregnancy on maternal central aortic pressures, arterial stiffness, and arterial wave reflection using non-invasive PC based cardiovascular risk analysis system (PeriscopeTM). The current study was conducted on 137 women with, normotensive, healthy, singleton pregnancies at first trimester (n=42), second trimester (n=48), third trimester (n=47) of pregnancy and 35 age matched non-pregnant controls. There was no significant correlation between the estimated means for age and systolic and diastolic blood pressure. There was progressive and significant increase in BMI as pregnancy progresses (p=0.0001). Heart rate rose significantly from Pre-pregnant to second and second to third trimesters (P<0.003). There were no significant changes observed in central aortic diastolic pressure (AoDiaBP) as pregnancy progressed (p=0.235) however Post Hoc comparisons showed a significant increase in central aortic systolic blood pressure (AoSysBP) and central aortic pulse pressure (AoPP) during first trimester when compared with non pregnant control group (p=0.039 and 0.048 respectively). There was significant increase in central aortic augmentation pressure (AoAugP) in first trimester compared to non pregnant control group (p=0.024). All the parameters of central aortic pressures were increased in the first trimester but decreased in the second trimester and again increased in the third trimester of pregnancy. There was a significant drop in Brachial-Ankle Pulse wave Velocity (baPWV) during first trimester of pregnancy compared to non-pregnant control group (p=0.0001) after that there is a progressive increase in baPWV in second and third trimester of pregnancy. In the third trimester baPWV is increased to more than non-pregnant control group but it was non significant (p=0.562) however it was significantly higher than first trimester (p=0.0001). Carotid-femoral Pulse wave velocity (cfPWV) also followed the same sequence as BaPWV but the drop in cfPWV during first trimester was not significant (P=0.135). All of the variables of hemodynamic and arterial compliance differed between participants with various trimester of pregnancy and non-pregnant control group. A significant up and down changes in Augmentation index (Aix) was observed from control to first, second and third trimester of pregnancy (3.14 to 6.74 to 2.63 to 10.51 respectively, P<0.0001). To summarize our report show that normal pregnancy is associated with a significant cardiovascular adaptation indicated by alteration in central aortic blood pressure, augmentation index and pulse wave velocity.

Assessment of Myocardial Mechanics in Overweight and Obese Indian Subjects.

Obesity is associated with increased cardiovascular morbidity and mortality. A direct effect of isolated obesity on cardiac function is not well established. The study was designed to determine the direct effect of various grades of isolated obesity on Echocardiographic indices of systolic and diastolic left ventricular function. Forty five overweight & obese and 30 normal weight, serving personnel without any other pathological condition were studied. Group I (n=23) consisted of subjects with normal weight and body mass index (BMI 18.5-22.9 kg/m2), Group II (n=28) of overweight subjects (BMI 23-24.9 kg/m2) and Group III (n=24) of obese subjects (BMI ≥25 kg/m2). Echocardiographic indices of systolic and diastolic function were obtained and dysfunction was assumed when at least two values differed by ≥2 SD from the normal weight group. Ejection fraction was increased (p=0.001) in group II and III however fractional shortening was increased significantly in group III (<0.001). Left ventricular dimensions (EDD & ESD) were increased (P<0.001, 0.002) but relative wall thickness was unchanged in group II & III. Systolic dysfunction was not observed in any of the obese patients. The deceleration time was increased (P<0.01) in overweight and obese subjects compared to normal group individuals. No difference was found between obesity subgroups. Subclinical diastolic dysfunction in the form of reduced E/A ratio and increased deceleration time was more prevalent among obese subjects. BMI correlated significantly with indices of left ventricular systolic and diastolic function. Subclinical left ventricular diastolic dysfunction was noted in all grades of obesity which correlates with BMI.

Correlation of Age and Antimullerian Hormone in Assisted Reproductive Technology Program Outcome.

Abstract : Increasing female literacy and employment have resulted in a clear rise in the age at which women conceive. As fertility starts to decline with advancing age more and more number of women are facing the problem of infertility and are seeking medical attention to over come this problem. This resulted in more number of women seeking medical help to over come the problem of Infertility. This age related decline in ovarian reserve is not uniform in all women of reproductive age. A number of ovarian reserve tests were developed to overcome this problem. But to date there is no ideal marker for predicting ovarian reserve and pregnancy outcome in assisted reproductive technology program (ART). Recent studies indicate that anti mullein hormone is a promising marker for predicting ovarian reserve and pregnancy out come. The aim of this study was to assess the influence of age on Anti-Mullerian Hormone (AMH) in ART program outcomes. Ninety-three subjects in the age group of 25 to 42 years were recruited to the study. All these subjects underwent controlled ovarian stimulation (COS) and later intracytoplasmic sperm injection (ICSI). Subjects were divided into four groups. AMH levels in positive and negative pregnancy subjects in the above and below 35years age groups were compared. AMH levels were correlated with other ovarian reserve parameters and clinical pregnancy out come in both the age groups. Statistically significant differences were found in AMH levels between positive and negative pregnancy subjects in the age group of 35 and above, but not in the age group below 35 years. There were positive correlations between AMH and other ovarian reserve markers and clinical pregnancy outcome in this age group. AMH and the number of retrieved oocytes (r=0.784, P<0.01), Antral Follicle count (AFC) (r=0.749, P<0.01) and Mature Oocytes (MII) (r=0.407, P<0.01) followed by Grade-I Embryos (r=0.433, P<0.01). The current study revealed that AMH levels are better correlated with ovarian reserve and clinical pregnancy out come in subjects aged 35 years and above.

Myocardial performance in asymptomatic essential hypertension.

Prevalence, determinants, and prognostic value of left ventricular function in subjects with asymptomatic essential hypertension are still incompletely known. The goal of this study was to investigate the effects of asymptomatic untreated essential hypertension on left ventricular structure and function. The left ventricular functions were assessed among 127 hypertensive and 80 healthy subjects. American society of echocardiography (ASE) convention was applied to measure the stroke volume, percentage ejection fraction, percentage fractional fiber shortening, cardiac output and cardiac index. The stroke volume, cardiac output and cardiac index were normal but significantly high among hypertensive compared to normotensive subjects (P<0.05). The percentage ejection fraction and fractional fiber shortening were significantly reduced among hypertensives compared to normotensives (P<0.05). The significant impairment of percentage fractional fiber shortening is due to alteration in dimension of left ventricular wall thickness, left ventricular cavity and left ventricular geometry. This carries prognostic implication and requires further documentations, investigations and researches. Percentage ejection fraction and fractional fiber shortening is considered a hallmark of normal left ventricular function. The left ventricular contractile state was negatively correlated to left ventricular after load parameters. So the main objective of management of hypertensive subjects should be, to reduce the after load to improve the left ventricular contractile state.

Prediction and stratification of the future cardiovascular arrhythmic events: Signal averaged electrocardiography versus ejection fraction.

Cardiac arrhythmias as cause of sudden cardiac death remains an important public health problem. The availability of effective treatment in terms of the implantable defibrillator makes it critical to identify individuals at risk. An essential step in this process is the use of noninvasive techniques to screen patients and identify those at risk. The detection of ventricular late potential using the SAECG as a non-invasive technique is being explored for this purpose. The objective of the study was to stratify the future cardiovascular events including life threatening cardiac arrhythmias, in different cardiac diseases through positive and negative predictive values of SAECG and comparing with EF% another mechanical determinant. The study was conducted on 152 subjects selected from the OPD and admitted case of the New Civil Hospital and Govt. Medical College, Surat; between 25 to 75 years of age group, from August 2001 to June 2004. 80 healthy subjects free from any major acute/chronic illness were selected as a control using our own normative values for SAECG. The statistical analysis was performed using SPSS package. The results obtained were analyzed for significance by using Chi square and Independent ‘t’ test. When we compared the cardiac arrhythmic events on 6 month follow-up study, based on SAECG and EF% separately we found that negative predictive value of SAECG was more (99.1%) than negative predictive value of EF% (93.6%). However positive predictive values for cardiac arrhythmic events of SAECG were less (28.9%) compare to EF% (42.9%).When both the parameters SAECG and EF% are considered together the negative as well as positive predictive values of these tests were quite high (100% and 50% respectively). In this study conducted on 152 patients we found that SAECG and EF% together were an accurate predictor of the cardiac arrhythmic events in terms of positive and negative predictive value while SAECG or EF% alone were not. However SAECG has got a more negative predictive value compare to EF%. In this study SAECG compared favorably or even better than EF% for risk stratification. SAECG and EF% together (and not separately) may be considered as a better investigational tool to stratify future cardiovascular arrhythmic events.