COVID-19 vaccines effectiveness against SARS-CO-V-2 infection among persons attending RT-PCR centre at a medical College Hospital in Telangana: A case control study

BackgroundIn January 2021, India drug regulator issued restricted emergency approval for COVAXIN and COVISHIELD which were manufactured in India. On mid-January 2021, in India, there were 10.5million confirmed cases and 0.15 million deaths. ObjectivesThe objectives were to evaluate vaccine effectiveness (VE) of India made Covid-19 vaccines against SARS-CoV-2 infection. MethodsA test negative case control study was conducted from May 2021 to December 2021 for duration of 8months among people attending an RT-PCR centre at a medical college Hospital for RT-PCR test. The baseline characteristics and RT-PCR report; and preliminary data about vaccine status were collected from the RT-PCR centre. The exposure to vaccination was enquired via Phone call or was checked with data available with the health authorities. ResultsAfter applying inclusion exclusion criteria, case and control definitions, a total of 380 participants (95cases and 285 controls) were included. The adjusted VE of two doses of COVISHIED vaccine against symptomatic SARS-CoV-2 infection was 52.2% (95% CI, 41.7 to 62.1) and single dose was 40.88% (95% CI, 31.26 to 51.29). The adjusted VE of two doses of COVAXIN vaccine against SARS-CoV-2 infection was 39% (95% CI, 29.40 to 49.27). The overall VE was 48.20% (95% CI, 37.90 to 58.22) for two doses of any vaccines. ConclusionsIndia made vaccines were nearly 50% effective. Similar results show by different studies with a margin of 10-25% difference. Further new studies should be conducted as new variants of SARS-CoV-2 are emerging, and we dont know how the vaccine works against the variants and booster doses were required or not.

Effectiveness of COVID-19 Vaccines against SARS-CoV-2 Infection among Persons Attending the RT-PCR center at a Medical College Hospital in Telangana: A Case- Control Study.

Background: In January 2021, India's drug regulator issued restricted emergency approval for COVISHIELD and COVAXIN, which were manufactured in India. In mid-January 2021, in India, there were 10.5 million confirmed cases and 0.15 million deaths. The objectives were to evaluate vaccine effectiveness (VE) of coronavirus disease 2019 (COVID-19) vaccines made in India against severe acute respiratory syndrome coronavirus disease 2 (SARS-CoV-2) infection. Materials and Methods: A test-negative case-control study was conducted from May 2021 to December 2021 for a duration of 8 months among people attending a reverse transcriptase polymerase chain reaction (RT-PCR) center at a medical college hospital for RT-PCR test for SARS-CoV-2. The baseline characteristics and RT-PCR report were collected from the RT-PCR center. The exposure to COVID-19 vaccines was enquired via phone call or was checked with data available with the health authorities. Results: After applying inclusion and exclusion criteria and case and control definitions, a total of 380 participants (95 cases and 285 controls) were included. The adjusted VE of two doses of COVISHIED vaccine against symptomatic SARS-CoV-2 infection was 52.2% (41.7 to 62.1), and that of a single dose was 40.88% (31.26 to 51.29). The adjusted VE of two doses of COVAXIN vaccine against SARS-CoV-2 infection was 39% (29.40 to 49.27). The overall VE was 48.20% (37.90 to 58.22) for two doses of any vaccines. Conclusions: Vaccines made in India were nearly 50% effective. Further new studies should be conducted as new variants of SARS-CoV-2 are emerging. We do not know the VE against the variants, and whether booster doses are required or not is not yet established.

A combination of LCPUFA ameliorates airway inflammation in asthmatic mice by promoting pro-resolving effects and reducing adverse effects of EPA.

Lipid mediators derived from omega (n)-3 and n-6 long-chain polyunsaturated fatty acids (LCPUFA) play key roles in bronchoconstriction, airway inflammation, and resolution processes in asthma. This study compared the effects of dietary supplementation with either a combination of LCPUFAs or eicosapentaenoic acid (EPA) alone to investigate whether the combination has superior beneficial effects on the outcome of asthmatic mice. Mice were sensitized with house dust mite (HDM) extract, and subsequently supplemented with either a combination of LCPUFAs or EPA alone in a recall asthma model. After the final HDM and LCPUFA administration, airway hyperresponsiveness (AHR), bronchoalveolar lavages, and lung histochemistry were examined. Lipid mediator profiles were determined by liquid chromatography coupled with tandem mass spectrometry (LC-MS-MS). The LCPUFA combination reduced AHR, eosinophilic inflammation, and inflammatory cytokines (IL-5, IFN-γ, and IL-6) in asthmatic mice, whereas EPA enhanced inflammation. The combination of LCPUFAs was more potent in downregulating EPA-derived LTB5 and LTC5 and in supporting DHA-derived RvD1 and RvD4 (2.22-fold and 2.58-fold higher levels) than EPA alone. Ex vivo experiments showed that LTB5 contributes to granulocytes' migration and M1-polarization in monocytes. Consequently, the LCPUFA combination ameliorated airway inflammation by inhibiting adverse effects of EPA and promoting pro-resolving effects supporting the lipid mediator-dependent resolution program.

Low-dose irradiation prior to bone marrow transplantation results in ATM activation and increased lethality in Atm-deficient mice.

Ataxia telangiectasia is a genetic instability syndrome characterized by neurodegeneration, immunodeficiency, severe bronchial complications, hypersensitivity to radiotherapy and an elevated risk of malignancies. Repopulation with ATM-competent bone marrow-derived cells (BMDCs) significantly prolonged the lifespan and improved the phenotype of Atm-deficient mice. The aim of the present study was to promote BMDC engraftment after bone marrow transplantation using low-dose irradiation (IR) as a co-conditioning strategy. Atm-deficient mice were transplanted with green fluorescent protein-expressing, ATM-positive BMDCs using a clinically relevant non-myeloablative host-conditioning regimen together with TBI (0.2-2.0 Gy). IR significantly improved the engraftment of BMDCs into the bone marrow, blood, spleen and lung in a dose-dependent manner, but not into the cerebellum. However, with increasing doses, IR lethality increased even after low-dose IR. Analysis of the bronchoalveolar lavage fluid and lung histochemistry revealed a significant enhancement in the number of inflammatory cells and oxidative damage. A delay in the resolution of γ-H2AX-expression points to an insufficient double-strand break repair capacity following IR with 0.5 Gy in Atm-deficient splenocytes. Our results demonstrate that even low-dose IR results in ATM activation. In the absence of ATM, low-dose IR leads to increased inflammation, oxidative stress and lethality in the Atm-deficient mouse model.

Bone marrow transplantation improves the outcome of Atm-deficient mice through the migration of ATM-competent cells.

Ataxia telangiectasia (A-T) is a highly pleiotropic disorder. Patients suffer from progressive neurodegeneration, severe bronchial complications, immunodeficiency, hypersensitivity to radiotherapy and elevated risk of malignancies. Leukemia and lymphoma, along with lung failure, are the main causes of morbidity and mortality in A-T patients. At present, no effective therapy for A-T exists. One promising therapeutic approach is bone marrow transplantation (BMT) that is already used as a curative therapy for other genomic instability syndromes. We used an established clinically relevant non-myeloablative host-conditioning regimen and transplanted green fluorescent protein (GFP)-expressing ataxia telangiectasia mutated (ATM)-competent bone marrow-derived cells (BMDCs) into Atm-deficient mice. GFP expression allowed tracking of the potential migration of the cells into the tissues of recipient animals. Donor BMDCs migrated into the bone marrow, blood, thymus, spleen and lung tissue of Atm-deficient mice showing an ATM-competent phenotype. BMT inhibited thymic lymphomas, normalized T-lymphocyte populations, improved weight gain and rearing activity of Atm-deficient mice. In contrast, no GFP(+) cells were found in the cerebellum or cerebrum, and we detected decreased size index in MRI imaging of the cerebellum in 8-month-old transplanted Atm-deficient mice in comparison to wild-type mice. The repopulation with ATM-competent BMDCs is associated with a prolonged lifespan and significantly improved the phenotype of Atm-deficient mice.

Conditioned medium from renal tubular epithelial cells initiates differentiation of human mesenchymal stem cells.

OBJECTIVES: Mesenchymal-epithelial interactions play a pivotal role in tubular morphogenesis and in maintaining the integrity of the kidney. During renal repair, similar mechanisms may regulate cellular reorganization and differentiation. We have hypothesized that soluble factors from proximal tubular epithelial cells (PTC) induce differentiation of adipose-derived adult mesenchymal stem cells (ASC). This hypothesis has been tested using cultured ASC and PTC. MATERIAL AND METHODS: Conditioned medium was prepared from injured PTC and transferred to ASC cultures. ASC proliferation was analysed by a fluorometric and photometric assay. Signal transduction was analysed by phosphorylation of extracellular signal-regulated kinase 1 and 2 (ERK1/ERK2). Grade of ASC differentiation was assessed by morphological analysis and cell expression of characteristic markers. RESULTS: Conditioned medium significantly induced proliferation and phosphorylation of ERK1/ERK2 of ASC. After 12 days of incubation, cell morphology changed to an epithelial-like monolayer. Expression of cytokeratin 18 was induced by conditioned medium, while alpha-smooth muscle actin, CD49a and CD90 expression decreased. These alterations strongly indicate onset of the differentiation process to the epithelial lineage. In summary, soluble factors from PTC induce signal transduction and differentiation of ASC. CONCLUSIONS: Our study shows that conditioned medium from renal tubular epithelial cells provides a convenient source of inductive signals to initiate differentiation of ASC towards epithelial lineage. We deduce that these interactions may play an important role during renal repair mechanisms.

Safety and immunogenicity of a cluster specific immunotherapy in children with bronchial asthma and mite allergy.

BACKGROUND: Cluster specific immunotherapy (SIT) is a modern form of allergen immunotherapy allowing safe administration of high allergen doses in a short time interval compared to classic SIT. In the current study, we investigated the safety profile and immunological effect of cluster SIT in children with allergic asthma due to house dust mite allergy. METHODS: A total of 34 children (6-18 years) with allergic asthma were assigned to cluster (n = 22) or classic SIT (n = 12). To achieve a maintenance dose of allergen extract, cluster patients received 14 injections of house dust mite allergen within 6 weeks, whereas the classic SIT group received 14 injections within 14 weeks. Safety was monitored by recording adverse events. Immunogenicity was measured by specific IgG(Mite) and IgG4(Mite), by antibody-blocking properties on basophil activation, and by the T cell subset transcription factors Foxp3, T-bet, and GATA-3. RESULTS: There were no significant differences in local and systemic side effects between the two groups. In the cluster group, serum levels of specific IgG(Mite) (p < 0.001) and specific IgG4(Mite) (p < 0.001) significantly increased after 8 weeks, while it took 12 weeks in the classic SIT group. These data were confirmed by blocking CD63 expression as well as release of cysteinyl leukotrienes after in vitro basophil stimulation. No differences in transcription factor expression were found in the two groups. CONCLUSION: Cluster SIT is safe in children. Additionally, our data demonstrated an even more rapid induction of specific immune tolerance. Cluster SIT is an attractive alternative to conventional up-dosing schedules with fewer consultations for the patients.

C-reactive protein induced activation of MAP-K and RANTES in human renal distal tubular epithelial cells in vitro.

AIMS: C-reactive protein (CRP) is a component of the acute-phase reaction to inflammation, severe tissue injury, and infection. Investigations have shown that CRP concentration is highly increased in the urine during acute renal graft dysfunction and, therefore, may affect tubular cell metabolism. Nevertheless, no data about the effects of CRP on human renal tubular epithelial cells are available. METHODS: Human renal distal tubular cells (DTC) were isolated immunomagnetically and cultured. Cells were stimulated with affinity chromatography pure native CRP from human ascites (10 - 0.001 microg/ml). Phosphorylation of MAP-K was assessed by Westernblot analysis. Release of RANTES and interleukin-6 was evaluated with an enzyme immunoassay. Cytotoxic effects of CRP were determined by a commercially available Live/Dead assay and MTT assay. Effects on cell proliferation were analyzed by a fluorimetric assay. RESULTS: Westernblot analysis clearly showed that CRP activates the MAP-K pathway of DTC. CRP upregulated RANTES expression of DTC in a significant and dose-dependent manner. CRP (10 microg/ml) induced a 12.3-fold upregulation, CRP 1 or 0.1 microg/ml induced a 6.3-/2.8-fold RANTES upregulation, respectively. Interleukin-6 synthesis was not influenced. Cytotoxic, proliferative or apoptotic effects were not observed at the concentrations used. CONCLUSIONS: We demonstrated an activating effect of CRP on DTC in vitro. In vivo, this effect of CRP might be part of the immune activation cascade during episodes of renal graft rejection or bacterial infections.

Biphasic urethral sphincter responses to acetic acid infusion into the lower urinary tract in anesthetized cats.

PURPOSE: Varying the concentration of infused acetic acid produced bladder irritation and dose dependent increases in external urethral sphincter electromyography activity in cats. We further characterized acetic acid induced external urethral sphincter electromyography activity in intact and acute spinal cord injured animals. MATERIALS AND METHODS: Bladder cystometrography and external urethral sphincter electromyography were continuously recorded in chloralose anesthetized cats. Dilute 0.05% to 0.8% acetic acid was infused into the lower urinary tract through the bladder dome. Intravesical or intraurethral infusion was performed separately in bladder neck ligated preparations. In some animals the spinal cord was transected at L1 to L2 2 to 8 hours before the study. RESULTS: Acetic acid infusion into the lower urinary tract elicited dose dependent increases in tonic external urethral sphincter activity. However, a prolonged infusion of 0.7% to 0.8% acetic acid usually inhibited external urethral sphincter activity. The excitatory external urethral sphincter response was elicited by intraurethral but not by intravesical infusion. This response remained in acute spinal cord injured animals. The inhibition of tonic external urethral sphincter activity during 0.7% to 0.8% acetic acid infusion was observed when there was extreme bladder irritation characterized by continual contractions. Induced tonic external urethral sphincter activity was attenuated by intrathecal administration of prazosin or scopolamine and abolished by hexamethonium. CONCLUSIONS: Acetic acid infusion into the lower urinary tract elicits biphasic external urethral sphincter responses. The early excitatory response is a spinal urethrourethral reflex and the late inhibitory phase results from negative vesicourethral feedback control. Spinal muscarinic cholinergic and alpha-adrenergic receptors are involved in acetic acid induced excitatory external urethral sphincter responses.

Developmental, family, and ethnic influences on adolescent alcohol usage: a growth curve approach.

The influence of the developmental process of individuation, family conflict and cohesion, and ethnicity on adolescent alcohol use was examined in a 3-year longitudinal study. Participants included non-Hispanic White, Mexican American, and African American adolescents (n = 6,522) from 6th, 7th, and 8th grades. They were surveyed annually for 3 years. Depending on which aspect of individuation was measured, hierarchical linear modeling indicated that changes in adolescent individuation were related to either increases or decreases in alcohol use over the 3-year period. Separation and family conflict were related to increases in alcohol use, and intergenerational individuation and family cohesion were related to decreases in alcohol use. White and Mexican American adolescents had a faster rate of increase in alcohol use than did African American youth. Separation and family process similarly influenced adolescent alcohol use from different ethnic groups. Implications for prevention and intervention programs are discussed.

External resorption associated with tooth eruption.

A case is presented with severe resorption on the mesial root of the mandibular first permanent molar in a patient with Juvenile Periodontitis. The follicle of the bicuspid is seen in contact with mesial root of the molar.

Adolescent individuation and alcohol use in multi-ethnic youth.

OBJECTIVE: A structural equation modeling approach is used to assess adolescent alcohol use as a function of two measures of individuation in the context of other family and peer psychosocial factors for adolescents in three ethnic groups. The separation measure captures aspects of individuation related to detachment or rebelliousness. Intergenerational individuation measures increasing self-reliance and control with maintenance of supportive family bonds. METHOD: A sample of 1,200 sixth through eighth grade black, Mexican-American and non-Hispanic white adolescents participated. A structural equation model describing adolescent alcohol use as a function of two measures of individuation, family conflict, communication with mother, stress and peer use of alcohol was tested and compared for the three ethnic groups. RESULTS: Significant direct and indirect paths to adolescent alcohol use were indicated for individuation measures and family use, peer use and stress variables. The proposed model fit for each of the groups, although the way in which separation related to stress was different in the black group. CONCLUSIONS: The findings support the role of individuation as a contributing factor in adolescent alcohol use for each ethnic group. They indicate the importance of family and parent-adolescent relationships in adolescent alcohol use and suggest directions for both family-based and school-based preventive interventions.

Induction of RANTES, HLA-DR, and intercellular adhesion molecule-1 on highly purified distal tubular cells from human kidney.

BACKGROUND: Expression of proinflammatory molecules by tubular epithelial cells plays an important role in renal allograft rejection and inflammatory kidney diseases. Different studies from patients with acute rejection point to the involvement of distal tubular segments. At present no in vitro system for the human distal tubule is established. METHODS: Human distal tubular cells were isolated immunomagnetically. Cultured cells were stimulated with cytokines (interferon-gamma, tumor necrosis factor-alpha, interleukin-1beta, or a cytokine mix). Secretion of RANTES (regulated upon activation, normal T-cell expressed and secreted) was evaluated with an enzyme-linked immunoassay. Expression of HLA-DR and intercellular adhesion molecule (ICAM)-1 was assessed by flow cytometric analysis and immunofluorescence studies. RESULTS: Our data clearly indicate that distal tubular cells express RANTES, HLA-DR, and ICAM-1 in response to a mixture of specific cytokines. Dexamethasone inhibited the induced expression of RANTES and HLA-DR significantly, but not that of ICAM-1. CONCLUSIONS: We demonstrate an appropriate in vitro system for the human distal tubule. The present study proves the involvement of the distal tubular segment during inflammatory kidney diseases.

Effects of mycophenolic acid on human renal proximal and distal tubular cells in vitro.

BACKGROUND: Mycophenolic acid has been shown to be effective for the prevention and treatment of renal allograft rejection. Rejection episodes were found to be associated with an infiltration of lymphocytes and macrophages/monocytes into the diseased kidney. Expression of RANTES, HLA-DR and ICAM-1 may be important for the pathogenesis of this leukocyte infiltration. Therefore the aim of this study was to evaluate the effect of the antiproliferative and immunosuppressive agent mycophenolic acid (MPA) on cell growth and cytokine-induced expression of RANTES, HLA-DR and ICAM-1 of highly purified proximal (PTC) and distal tubular cells (DTC) from human kidney. METHODS: Human PTC and DTC were cultured in the presence of different concentrations of MPA (0.25-50 microM) or MPA plus guanosine (100 microM). Total cell number (DNA content) was determined after 4 days of cell culture by a non-radioactive fluorescence assay. Cells were stimulated by a combination of cytokines (IL1beta+gammaIFN+TNFalpha=cytomix) or cytomix plus MPA. Secretion of RANTES protein was evaluated with an enzyme-linked-immunosorbent assay. Cell surface expression of HLA-DR and ICAM-1 was assessed by flow cytometric analysis. RESULTS: MPA inhibited cell growth of PTC and DTC in a dose-dependent manner. This effect was totally abolished by the addition of guanosine. Cytokine-induced RANTES expression was synergistically increased in the presence of MPA, an effect that was partially prevented by the addition of guanosine. Cytokine stimulation resulted in de novo expression of HLA-DR and a marked increase of ICAM-1 expression, which was partially inhibited by dexamethasone. Addition of MPA did not influence this stimulated expression. CONCLUSIONS: We demonstrate that MPA has an effect on cell growth and chemokine release of tubular epithelial cells, and that these effects are dependent on the inhibition of cellular guanosine production. The clinical consequences of this possible pro-inflammatory effect of MPA on RANTES release may be abolished by a concomitant treatment with steroids.

Intentions to use alcohol among fifth and sixth graders: the roles of social and stress/coping motives.

This study of children in grades five and six assessed the relationship between social and stress/coping motives and students' intentions to drink in junior high school. Whereas the two motives were not seen as separate by fifth graders, they were differentiated by sixth graders, for whom they were associated--social motives more strongly than stress/coping motives--with intentions to use alcohol. Implications for the design and timing of prevention programs are considered.

Transdifferentiation of distal but not proximal tubular epithelial cells from human kidney in culture.

Human renal proximal and distal (thick ascending limb and early distal convoluted tubule) epithelial cells have been isolated according to their specific antigen expression. The cells were well characterized by flow cytometry, enzyme cytochemistry and electron microscopy and cultured for up to 3 months. Cultured tubular cells coexpressed cytokeratin and vimentin as intermediate filament proteins. While primary isolated cells, proximal as well as distal, revealed the phenotypic characteristics of their nephron origin, cultured distal cells showed the tendency to dedifferentiate/transdifferentiate. Distal cells lost their characteristic expression of Tamm-Horsfall glycoprotein and started de novo expression of the proximal marker proteins aminopeptidase M, gamma-glutamyl transferase and dipeptidyl peptidase IV. The expression of these antigens by distal cells could be shown by flow-cytometric analysis and fluorescence microscopy. Enzyme activity assays revealed the activity of aminopeptidase M, gamma-glutamyl transferase and dipeptidyl peptidase IV, but not of the proximal marker enzyme alkaline phosphatase. This antigenic shift could not be prevented in different culture media, and the original phenotype could not be restored. Cultured cells displayed characteristic hormonal stimulation patterns indicative of their proximal and distal origins, as shown by activation of adenylate cyclase by different peptide hormones. These results indicate that distal tubular cells possibly transdifferentiate to a more proximal phenotype in view of loss of the distal marker enzyme Tamm-Horsfall protein and de novo expression of proximal marker enzymes like dipeptidyl peptidase IV and aminopeptidase M.

Adolescent individuation and alcohol use.

OBJECTIVE: This study evaluates a developmental psychosocial model of adolescent drinking. Specifically, the role of two aspects of adolescent individuation-separation and intergenerational individuation-is examined within the context of family dynamics, stress and peer associations. These measures parallel an ongoing debate regarding the nature of individuation. The separation measure captures aspects of individuation related to detachment or rebelliousness. Intergenerational individuation measures increasing self-reliance and control with maintenance of supportive family bonds. METHOD: A structural equation model describing adolescent alcohol use as a function of two measures of individuation, family conflict, communication with mother, stress and peer use of alcohol was tested in two independent samples. The first included 6th- through 12th-grade adolescents and the second was composed of 6th- through 8th-grade students. RESULTS: In both studies, significant direct and indirect paths were found from individuation measures and family, peer use and stress constructs to adolescent alcohol use. Separation had a stronger relationship to alcohol use than did intergenerational individuation and was associated with higher levels of stress and alcohol use by peers. CONCLUSIONS: The findings support the role of individuation as a contributing factor in adolescent alcohol use. They indicate the importance of family and parent-adolescent relationships in adolescent alcohol use and suggest directions for both family-based and school-based preventive interventions.