Heart failure, the global pandemic: A call to action consensus statement from the global presidential conclave at the platinum jubilee conference of cardiological society of India 2023.

Heart failure (HF) is emerging as a major public health problem both in high- and low - income countries. The mortality and morbidity due to HF is substantially higher in low-middle income countries (LMICs). Accessibility, availability and affordability issues affect the guideline directed therapy implementation in HF care in those countries. This call to action urges all those concerned to initiate preventive strategies as early as possible, so that we can reduce HF-related morbidity and mortality. The most important step is to have better prevention and treatment strategies for diseases such as hypertension, ischemic heart disease (IHD), type-2 diabetes, and rheumatic heart disease (RHD) which predispose to the development of HF. Setting up dedicated HF-clinics manned by HF Nurses, can help in streamlining HF care. Subsidized in-patient care, financial assistance for device therapy, use of generic medicines (including polypill strategy) will be helpful, along with the use of digital technologies.

CSI clinical practice guidelines for dyslipidemia management: Executive summary.

Dyslipidemias are the most important coronary artery disease (CAD) risk factor. Proper management of dyslipidemia is crucial to control the epidemic of premature CAD in India. Cardiological Society of India strived to develop consensus-based guidelines for better lipid management for CAD prevention and treatment. The executive summary provides a bird's eye-view of the 'CSI: Clinical Practice Guidelines for Dyslipidemia Management' published in this issue of the Indian Heart Journal. The summary is focused on the busy clinician and encourages evidence-based management of patients and high-risk individuals. The summary has serialized various aspects of lipid management including epidemiology and categorization of CAD risk. The focus is on management of specific dyslipidemias relevant to India-raised low density lipoprotein (LDL) cholesterol, non-high density lipoprotein cholesterol (non-HDL-C), apolipoproteins, triglycerides and lipoprotein(a). Drug therapies for lipid lowering (statins, non-statin drugs and other pharmaceutical agents) and lifestyle management (dietary interventions, physical activity and yoga) are summarized. Management of dyslipidemias in oft-neglected patient phenotypes-the elderly, young and children, and patients with comorbidities-stroke, peripheral arterial disease, kidney failure, posttransplant, HIV (Human immunodeficiency virus), Covid-19 and familial hypercholesterolemia is also presented. This consensus statement is based on major international guidelines (mainly European) and expert opinion of lipid management leaders from India with focus on the dictum: earlier the better, lower the better, longer the better and together the better. These consensus guidelines cannot replace the individual clinician judgement who remains the sole arbiter in management of the patient.

Preterm Birth and Other Measures of Infant Biological Vulnerability: Associations with Maternal Sensitivity and Infant Cognitive Development.

INTRODUCTION: Low birth weight (LBW), biological vulnerability that includes preterm birth (PTB) and small for gestational age (SGA), is associated with reduced maternal sensitivity ("making accurate inferences about an infant's physical and emotional needs and responding appropriately") and impaired infant cognitive development. However, research does not examine if preterm birth, SGA, or both drive these associations. This study separated these measures of biological vulnerability to examine associations of LBW, PTB, and SGA with maternal sensitivity and infant cognitive development (controlling for maternal depression, breastfeeding, and demographic covariates). METHODS: The sample included 6900 9-month-old infants from the Early Childhood Longitudinal Study-Birth Cohort and used birth certificate data, maternal interviews, assessments of maternal sensitivity and infant cognitive development. Multiple linear regressions examined LBW, PTB, and SGA associations with concurrent measures of maternal sensitivity and infant cognition. RESULTS: Of the biological vulnerabilities, preterm birth had the strongest negative association with maternal sensitivity (F1,6450 = 29.48 versus 15.33 and 5.51, ps < .001) and infant cognitive development (F1,6450) = 390.65 versus 248.02 and 14.43, ps < .001). In the final regression model, preterm birth and maternal sensitivity were uniquely associated with infant cognitive development (R2 = .05, p < .001), after controlling for maternal depression, breastfeeding, and demographics. CONCLUSION: In this nationally representative infant sample infants, PTB had a stronger negative association with both maternal sensitivity and infant cognitive development in comparison to SGA or LBW. The LBW designation combines infants born preterm with SGA infants, potentially minimizing differences in developmental outcomes of PTB and SGA infants.

Does breastfeeding account for the association between maternal sensitivity and infant cognitive development in a large, nationally representative cohort?

BACKGROUND: Previous research has established that exposure to high maternal sensitivity is positively associated with advances in infant cognitive development. However, there are many fixed and modifiable factors that influence this association. This study investigates whether the association between maternal sensitivity and infant cognitive development in the first year of life is accounted for by other factors, such as breastfeeding, maternal depressive symptoms, maternal alcohol use, infant birth weight or demographic covariates. METHODS: Using data from the Early Childhood Longitudinal Study-Birth (ECLS-B) Cohort, a nationally representative sample of U.S. born children, multi-variable regression analyses was used to examine whether breastfeeding, maternal depressive symptoms and alcohol use were associated with maternal sensitivity, as measured by the Nursing Child Assessment Teaching Scale (NCATS), and with infant cognitive development, as measured by the Bayley Scales of Infant Development, Short Form, Research Edition, after controlling for demographic covariates (infant sex, maternal age, education, race/ethnicity, income, parity, family structure) and infant birth weight. RESULTS: Breastfeeding, depressive symptoms and alcohol use were not associated with maternal sensitivity scores after controlling for demographic covariates and infant birth weight. However, breastfeeding (ß = .079, p < .001), depressive symptoms (ß = -.035, p < .05), and maternal sensitivity (ß = .175, p < .001) were each significantly associated with infant cognitive development scores, even after controlling for demographic covariates and birthweight (R2 = .053, p < .001). The association between maternal sensitivity and infant cognitive development did not attenuate after adjusting for breastfeeding. Instead, both sensitivity and breastfeeding independently contributed to higher infant cognitive development scores. CONCLUSION: Maternal sensitivity and breastfeeding are separate means to advancing infant cognitive development. This study is significant because it is the first to examine breastfeeding, maternal depressive symptoms and alcohol use together, upon the association between maternal sensitivity and infant cognitive development, after adjusting for demographic covariates and infant birthweight. Maternal sensitivity, a measurable quality, advances infants' cognitive development. Moreover, sensitivity and breastfeeding had independent effects upon cognitive development after controlling for multiple fixed and modifiable covariates. Understanding factors impacting the association between sensitivity and infant cognitive development provide avenues for developing more effective parenting interventions.

Comparative evaluation of Babesia bigemina truncated C-terminal rhoptry associated protein-1 and 200 kDa merozoite protein in indirect enzyme-linked immunosorbent assay.

Babesia bigemina is an intra-erythrocytic apicomplexan protozoon which causes an acute as well as chronic disease in cattle and is transmitted by ixodid ticks throughout the world. Due to low sensitivity of microscopy for detection of the parasite, there is a need for developing effective diagnostic tests that can be used to identify carrier animals in endemic areas. In the present study, C-terminal fragment of rhoptry associated protein-1 (RAP-1/CT) and 200 kDa merozoite protein (P200/CT) of B. bigemina were cloned into pET-32a(+) expression vector and expressed in Escherichia coli as thioredoxin-fusion proteins for use in an indirect ELISA. The rRAP-1/CT and rP200/CT showed no cross reactivity with plasma from cattle infected with other common parasites namely Theileria annulata, Trypanosoma evansi, Cryptosporidium parvum and Anaplasma marginale in the standardized ELISA. Examination of 116 blood samples collected from cattle suspected for haemoprotozoan infections revealed that 17 (14.6%), 46 (39.6%), 52 (44.8%) and 53 (45.7%) were positive for B. bigemina by microscopy, nested PCR, rRAP-1/CT based and rP200/CT based indirect ELISA, respectively. The diagnostic sensitivities of rRAP-1/CT and rP200/CT indirect ELISAs were 97.8% and 91.3%, while the diagnostic specificities were 90% and 84.3%, respectively, when nested PCR was taken as a reference test. An almost perfect agreement (Kappa value -0.859) between rRAP-1/CT ELISA and nested PCR results, and a substantial agreement (Kappa value -0.737) between rP200/CT ELISA and nested PCR were noticed. The findings of the present study suggest that rRAP-1/CT is a better diagnostic candidate antigen than rP200/CT for diagnosis of B. bigemina infection and it may be used in an ELISA for surveillance or diagnosis of B. bigemina infection in bovines.

Genetic characterization and phylogenetic analysis of Sarcocystis suihominis infecting domestic pigs (Sus scrofa) in India.

A total of 57 tissue samples of domestic pigs (Sus scrofa) were collected from the meat outlets of five north Indian states and examined for sarcocystosis by histological and molecular methods. The genomic DNA extracted from five representative positive isolates was subjected to PCR amplification of the partial 18S rRNA gene followed by cloning and sequencing. Sequence analysis of the newly generated Indian isolates recorded 96.9-100.0% identity with published sequences of Sarcocystis suihominis. Two new haplotypes that have not been previously described manifested 99.5-100.0% nucleotide homology within themselves. In the phylogenetic analysis, Indian isolates of S. suihominis grouped together with S. suihominis originating from Italy, and they collectively formed a sister clade with Sarcocystis miescheriana within a clade containing various Sarcocystis spp. of ruminants having felids as final hosts. At the same time, this clade separated from a sister clade containing Sarcocystis spp. of bovid or cervid ruminants using canids as known or surmised definitive host. The current study established the phylogenetic relationship of Indian isolates of S. suihominis with various Sarcocystis spp. as well as with other taxa of Sarcocystidae family based on 18S rRNA gene for the first time.

Genetic characterization of Theileria species infecting bovines in India.

Genetic characterization of Theileria species infecting bovines in India was attempted targeting the 18S ribosomal RNA region of the parasite. Blood samples of bovines (n = 452), suspected for haemoprotozoan infections, from 9 different states of the country were microscopically examined for Theileria species infection. Four Theileria spp. positive blood samples from each state were randomly utilized for PCR amplification of the 18S rRNA gene (approx. 1529 bp) followed by cloning and sequencing. The sequence data analysis of all the 36 isolates revealed that 33 isolates had high sequence similarity with published sequences of T. annulata, whereas 3 isolates (MF287917, MF287924 and MF287928) showed close similarity with published sequences of T. orientalis. Sequence homology within the isolates ranged between 95.8 and 100% and variation in the length of targeted region was also noticed in different isolates (1527-1538 nt). Phylogenetic tree created for T. annulata sequences revealed that a total of 24 Indian isolates formed a major clade and grouped together with isolates originating from countries like China, Spain, Turkey and USA. Remaining 09 isolates clustered in a separate group and were closely related to the TA5 isolate of T. annulata (a new genotype) originating from India and also with the isolates from East Asian countries like Japan and Malaysia. All the three T. orientalis isolates had minimal intraspecific variation (99-100% homology) amongst themselves. Further, in the phylogenetic analysis T. orientalis Indian isolates were found to cluster away from other 14 isolates of T. buffeli/sergenti/orientalis originating from different countries (Australia, China, Indonesia and Spain). However, these 3 isolates clustered together with the T. buffeli Indian isolate (EF126184). Present study confirmed the circulation of different genotypes of T. annulata in India, along with T. orientalis isolates.

Immunoprophylactic evaluation of recombinant gametocyte 22 antigen of Eimeria tenella in broiler chickens.

Gametocyte proteins are being explored as potential vaccine candidates against Eimeria sp. in chicken since they are the components of the resilient oocyst wall. The aim of this study was to investigate the immunoprophylactic efficacy of recombinant Eimeria tenella gametocyte antigen 22 (EtGam22) in chickens against homologous oocyst challenge. Broiler chicks were subcutaneously immunized individually with 100 µg of recombinant EtGam22 adjuvanted with Montanide ISA 71 VG at 7 days of age and boosted 2 weeks later. The immunized chickens were challenged individually with 1 × 104 sporulated oocysts of E. tenella 1 week post-booster immunization. The anti-EtGam22 IgY and serum cytokine response was measured post-immunization. The results showed that the anti-EtGam22 IgY antibody, serum IFN-γ, IL-2, TGF-ß, and IL-4 levels in chickens vaccinated with recombinant protein were significantly increased post-immunization as compared to unimmunized challenged controls (P < 0.05). The peripheral blood lymphocyte proliferation activity was also found significantly higher in EtGam22-immunized group on day 28, i.e., pre-challenge (P < 0.05). Upon homologous oocyst challenge, chickens immunized with rEtGam22 exhibited a significant drop in the total oocyst output per bird (246.78 ± 36.9 × 106, 45.23% reduction) and a significantly higher weight gain (497.7 ± 19.2 g) as compared to unimmunized challenged controls. Taken together, these data indicate that EtGam22 is a potent immunogen for use as a subunit vaccine against cecal coccidiosis in chickens as it induces a diverse and robust immune response involving multiple cytokines and strong antibody titers.

KIR2DL4-HLAG interaction at human NK cell-oligodendrocyte interfaces regulates IFN-γ-mediated effects.

Interactions between germline-encoded natural killer (NK) cell receptors and their respective ligands on tumorigenic or virus-infected cells determine NK cell cytotoxic activity and/or cytokine secretion. NK cell cytokine responses can be augmented in and can potentially contribute to multiple sclerosis (MS), an inflammatory disease of the central nervous system focused upon the oligodendrocytes (OLs). To investigate mechanisms by which NK cells may contribute to MS pathogenesis, we developed an in vitro human model of OL-NK cell interaction. We found that activated, but not resting human NK cells form conjugates with, and mediate cytotoxicity against, human oligodendrocytes. NK cells, when in conjugate with OLs, rapidly synthesize and polarize IFN-γ toward the OLs. IFN-γ is capable of reducing myelin oligodendrocyte and myelin associated glycoproteins (MOG and MAG) content. This activity is independent of MHC class-I mediated inhibition via KIR2DL1, but dependent upon the interaction between NK cell-expressed KIR2DL4 and its oligodendrocyte-expressed ligand, HLA-G. NK cells from patients with MS express higher levels of IFN-γ following conjugation to OLs, more actively promote in vitro reduction of MOG and MAG and have higher frequencies of the KIR2DL4 positive population. These data collectively suggest a mechanism by which NK cells can promote pathogenic effects upon OLs.

Colossal dielectric permittivity in Co-doped ZnO ceramics prepared by a pressure-less sintering method.

Dielectric properties and impedance spectroscopic studies of single phase Zn1- xCoxO (0 ≤ x ≤ 0.05) ceramics, synthesized by a pressure-less solid state reaction method, have been carried out to investigate the origin of colossal dielectric permittivity (CP), ε' ∼ 105, in a wide frequency (2 × 101-2 × 106 Hz) range. These results show that a defect density within the grain is present in the materials due to the use of pressure-less sintering at high temperature for a long duration of time. The colossal dielectric response is essentially due to this electronic inhomogeneous conduction mechanism within the material due to the production of absorption current in the thin grain boundary region which accumulates charge at the interface and induces Maxwell-Wagner interfacial polarization. Moreover, this defect structure further increases with the addition of Co ions and enhances the CP property. An effective way to control the colossal dielectric properties is to control the defect density within a grain by using a proper sintering method.

Immune response and protective efficacy of Eimeria tenella recombinant refractile body protein, EtSO7, in chickens.

Refractile body protein, SO7, is a highly immunogenic protein which is essentially involved in the early development of Eimeria species infecting the domestic chicken. In the present study, the immune response and protective efficacy of recombinant Eimeria tenella SO7 (rEtSO7) protein was assessed in broiler chickens following homologous oocyst challenge. Broiler chicks were subcutaneously immunized with rEtSO7 antigen adjuvanted with Montanide ISA 71 VG on 7 and 21 days of age and protective efficacy of vaccination was evaluated in terms of body weight gain, lesion score and reduction in oocyst output. The peripheral blood lymphocyte proliferation, serum IgY response, and levels of interferon gamma (IFN-γ), interleukin 2 (IL-2), interleukin 4 (IL-4), tumor growth factor beta (TGF-ß) and nitric oxide (NO) were assessed. The results revealed significant reduction (p < 0.05) in the oocyst output and increased weight gain in immunized birds as compared to unimmunized birds. Significantly increased levels of serum IgY, IFN-γ and proliferation of lymphocytes were evident in rEtSO7 immunized chickens. The results demonstrated that the recombinant protein could effectively elicit the cellular and humoral immune responses in immunized chickens, and provided significant protection against caecal coccidiosis in chickens.

Evaluation of Echinococcus granulosus recombinant EgAgB8/1, EgAgB8/2 and EPC1 antigens in the diagnosis of cystic echinococcosis in buffaloes.

Three recombinant proteins of Echinococcus granulosus including two antigen B sub-units EgAgB8/1 and EgAgB8/2 and Echinococcus protoscolex calcium binding protein 1 (EPC1) were expressed in prokaryotic expression vectors. The diagnostic potential of these three recombinant proteins was evaluated in the detection of cystic echinococcosis in buffaloes in IgG-ELISA. The EgAgB8/1 and EgAgB8/2 recombinant proteins reacted fairly with the hydatid infected buffaloes with sensitivity of 75.0% and 78.6%, respectively and specificity of 75.8% while EPC1 recombinant protein showed higher sensitivity (89.3%) but lower specificity (51.5%). Cross-reactivity of these three antigens was assayed with buffalo sera naturally infected with Explanatum explanatum, Paramphistomum epiclitum, Gastrothylax spp., Fasciola gigantica and Sarcocystis spp. EgAgB8/1 and EPC1 antigens cross-reacted with all these sera while EgAgB8/2 showed no cross-reaction with Sarcocystis spp. and reacted with some of the E. explanatum infected buffalo sera. This study explores the potential of three hydatid antigens viz. EgAgB8/1, EgAgB8/2 and EPC1 for their diagnostic potential in buffaloes positive for cystic echinococcosis.

Trypanosomiasis in a Young Infant from Rural Gujarat, India.

BACKGROUND: Human trypansomiasis due to infection by animal trypanosomes is rarely reported from India. CASE CHARACTERISTICS: We describe clinical presentation of a 2-month-old boyfrom a rat infested house in rural Gujarat who was diagnosed to be havinginfection with the rodent parasite Trypanosoma lewisi. OBSERVATION: The fever and parasitemia resolved on treatment with liposomal amphotericin B, Ceftriaxone and Amikacin, and there was no recurrence of parasitemia over a 2 month follow-up. MESSAGE: The case highlights the need for increased awareness and heightened surveillance for this rare zoonotic infection.

Prevalence of vitamin B12 deficiency in healthy Indian school-going adolescents from rural and urban localities and its relationship with various anthropometric indices: a cross-sectional study.

BACKGROUND: Micronutrient deficiency is a global health burden, especially among developing countries. The present cross-sectional study aimed to determine the prevalence of vitamin B12 deficiency in healthy Indian school-going adolescents, based on area of residence, sex and body mass index (BMI). Furthermore, the relationship of serum B12 concentration with dietary vitamin B12 intake and anthropometric indices was assessed among adolescents from rural and urban India. METHODS: A total of 2403 school-going adolescents (11-17 years) from National Capital Region and rural areas of Haryana, India were selected. Serum B12 concentrations were estimated using an electrochemiluminescence immunoassay. Dietary assessments were conducted on 65% of total participants (n = 1556) by two 24-h diet recalls. RESULTS: The prevalence of vitamin B12 deficiency in the total study population was 32.4% (rural: 43.9% versus urban: 30.1%, P < 0.001; male: 34.4% versus female: 31.0%, P < 0.05; normal weight: 28.1%, versus overweight: 39.8%, versus obese: 51.2%, P < 0.001). More than half (51.2%) of obese adolescents were vitamin B12 deficient. On multiple linear regression analysis, serum B12 in rural adolescents was associated with age (ß = -0.12, P < 0.05). Among urban adolescents, serum B12 was associated with BMI (ß = -0.08, P < 0.05) and adjusted dietary vitamin B12 intake (ß = 0.14, P < 0.001). Serum vitamin B12 levels were found to be lower in rural females (ß = -0.12, P = 0.030) and urban males (ß: 0.11, P < 0.001) compared to their respective contemporaries. CONCLUSIONS: Vitamin B12 deficiency was higher among rural school-going adolescents. Boys had a higher B12 deficiency than girls. Inverse associations of serum B12 with adiposity indices were observed. Serum B12 levels were positively associated with dietary vitamin B12 intake.

Static and dynamic electro-optical properties of liquid crystals mediated by ferroelectric polymer films.

This paper reports the electro-optical properties of high resistivity nematic liquid crystals sandwiched between ferroelectric polymer films. Interactions between liquid crystals and the film result in a series of interesting optical and electro-optical features. For example, the visualization of ferroelectric domains by means of liquid crystals has been known for decades. However, here we demonstrate that liquid crystals can also reveal the fractal dimension of multi-domain poly(vinylidene fluoride)-based films. Unidirectionally rubbed films made of poly(vinylidene fluoride)-based (PVDF) materials align liquid crystals (LC) homogeneously, with the pretilt angle on the order of 1-2 degrees. This property was implemented in the design of hybrid cells composed of liquid crystals sandwiched between PVDF-based films. The designed PVDF|LC|PVDF cells exhibit tunable electro-optical performance originating from the presence of the PVDF-based films. More specifically, (i) the threshold voltage characterizing the transition of liquid crystals from a planar to a homeotropic state can be tuned by varying the film thickness, and (ii) total fall time (turn-off time) can be controlled by varying the frequency and amplitude of the driving voltage. This frequency dependence of the fall time is strongly pronounced at a relatively high voltage applied across the cell. In the low frequency regime, an increase in the turn-off time can be approximated as a linear function of the applied electric field. An electric-field induced polarization of the PVDF-based films is considered a major reason leading to the afore-mentioned amplitude and frequency dependence of the switching time.

Cord blood NK cells engineered to express IL-15 and a CD19-targeted CAR show long-term persistence and potent antitumor activity.

Chimeric antigen receptors (CARs) have been used to redirect the specificity of autologous T cells against leukemia and lymphoma with promising clinical results. Extending this approach to allogeneic T cells is problematic as they carry a significant risk of graft-versus-host disease (GVHD). Natural killer (NK) cells are highly cytotoxic effectors, killing their targets in a non-antigen-specific manner without causing GVHD. Cord blood (CB) offers an attractive, allogeneic, off-the-self source of NK cells for immunotherapy. We transduced CB-derived NK cells with a retroviral vector incorporating the genes for CAR-CD19, IL-15 and inducible caspase-9-based suicide gene (iC9), and demonstrated efficient killing of CD19-expressing cell lines and primary leukemia cells in vitro, with marked prolongation of survival in a xenograft Raji lymphoma murine model. Interleukin-15 (IL-15) production by the transduced CB-NK cells critically improved their function. Moreover, iC9/CAR.19/IL-15 CB-NK cells were readily eliminated upon pharmacologic activation of the iC9 suicide gene. In conclusion, we have developed a novel approach to immunotherapy using engineered CB-derived NK cells, which are easy to produce, exhibit striking efficacy and incorporate safety measures to limit toxicity. This approach should greatly improve the logistics of delivering this therapy to large numbers of patients, a major limitation to current CAR-T-cell therapies.