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"Singh, Tulika"
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Zika virus: Can India win the fight?
2017
Zika virus is an emerging arbovirus of public health importance transmitted by Aedes mosquito which also transmits dengue, chikungunya and yellow fever. The disease has been spreading at an alarming rate in Africa, Pacific Islands, and the Americas. Given the expansion of environments where mosquitoes can live and breed, facilitated by urbanization and globalization, there is potential for major urban epidemics of Zika virus disease to occur globally. World Health Organization (WHO) has declared Zika virus disease to be a Public Health Emergency of International Concern (PHEIC). Our failed attempts to control dengue epidemics in the past call for concern and we need to be to prepared to fight Zika virus before it arrives at our doors.
Journal Article
Qualitative evaluation of survey questions to assess treatment preference for daily oral or long‑acting injectable antiretroviral therapy among people living with HIV
by
Chounta, Vasiliki
,
Díaz De Santiago, Alberto
,
Dretler, Robin
in
Administration, Oral
,
Adult
,
Adults
2024
Treatment of HIV has historically required taking daily oral antiretroviral therapy (ART). A recent alternative to daily oral ART is long-acting injectable ART with cabotegravir plus rilpivirine, administered monthly or every 2 months. The purpose of this qualitative study was to evaluate the concept relevance and interpretability of five previously developed questions: one treatment preference question and four questions designed to assess how the emotional burden associated with HIV treatment impacts treatment preferences. Thirty adults in the United States currently receiving HIV treatment were enrolled in a cross-sectional study involving one-on-one concept confirmation and cognitive debriefing interviews. Concept confirmation interviews included topics, questions, and probes designed to elicit information about the emotional burden of HIV and current perceptions of a participant’s treatment regimen. Cognitive debriefing assessed the relevance and clarity of instructions, questions, response options, and recall periods. Transcripts were analyzed with MAXQDA. Mean age of participants was 49 years (range: 29–68), with 60% being male and 40% female. Racial demographics included Blacks (40%), Whites (40%), and other (20%). During concept confirmation, participants endorsed concepts relevant to HIV treatment preference: fear of disclosure of HIV status (47%), forgetting to take daily oral medication (40%), and current treatment regimen as a bothersome daily reminder of HIV status (40%). During cognitive debriefing, participants interpreted the instructions, question, response options, and recall periods as intended for the treatment preference question. Additionally, participants confirmed that the preference question’s response options were appropriate and relevant to the experiences of people living with HIV. Participants also consistently interpreted the questions related to fear of disclosure of HIV status, anxiety associated with forgetting to take HIV medication, and HIV medication being an uncomfortable reminder of HIV status; however, participants provided variable responses to the question designed to assess treatment ease of use. These results support the concept relevance and interpretability of the single treatment preference question and three of the four emotional well-being questions among adults living with HIV.
Journal Article
Qualitative evaluation of survey questions to assess treatment preference for daily oral or long-acting injectable antiretroviral therapy among people living with HIV
by
Chounta, Vasiliki
,
Díaz De Santiago, Alberto
,
Dretler, Robin
in
Antiviral agents
,
Beliefs, opinions and attitudes
,
Dosage and administration
2024
Treatment of HIV has historically required taking daily oral antiretroviral therapy (ART). A recent alternative to daily oral ART is long-acting injectable ART with cabotegravir plus rilpivirine, administered monthly or every 2 months. The purpose of this qualitative study was to evaluate the concept relevance and interpretability of five previously developed questions: one treatment preference question and four questions designed to assess how the emotional burden associated with HIV treatment impacts treatment preferences. Thirty adults in the United States currently receiving HIV treatment were enrolled in a cross-sectional study involving one-on-one concept confirmation and cognitive debriefing interviews. Concept confirmation interviews included topics, questions, and probes designed to elicit information about the emotional burden of HIV and current perceptions of a participant's treatment regimen. Cognitive debriefing assessed the relevance and clarity of instructions, questions, response options, and recall periods. Transcripts were analyzed with MAXQDA. Mean age of participants was 49 years (range: 29-68), with 60% being male and 40% female. Racial demographics included Blacks (40%), Whites (40%), and other (20%). During concept confirmation, participants endorsed concepts relevant to HIV treatment preference: fear of disclosure of HIV status (47%), forgetting to take daily oral medication (40%), and current treatment regimen as a bothersome daily reminder of HIV status (40%). During cognitive debriefing, participants interpreted the instructions, question, response options, and recall periods as intended for the treatment preference question. Additionally, participants confirmed that the preference question's response options were appropriate and relevant to the experiences of people living with HIV. Participants also consistently interpreted the questions related to fear of disclosure of HIV status, anxiety associated with forgetting to take HIV medication, and HIV medication being an uncomfortable reminder of HIV status; however, participants provided variable responses to the question designed to assess treatment ease of use. These results support the concept relevance and interpretability of the single treatment preference question and three of the four emotional well-being questions among adults living with HIV.
Journal Article
Protection against symptomatic dengue infection by neutralizing antibodies varies by infection history and infecting serotype
2024
Dengue viruses (DENV1–4) are the most prevalent arboviruses in humans and a major public health concern. Understanding immune mechanisms that modulate DENV infection outcome is critical for vaccine development. Neutralizing antibodies (nAbs) are an essential component of the protective immune response, yet their measurement often relies on a single cellular substrate and partially mature virions, which does not capture the full breadth of neutralizing activity and may lead to biased estimations of nAb potency. Here, we analyze 125 samples collected after one or more DENV infections but prior to subsequent symptomatic or inapparent DENV1, DENV2, or DENV3 infections from a long-standing pediatric cohort study in Nicaragua. By assessing nAb responses using Vero cells with or without DC-SIGN and with mature or partially mature virions, we find that nAb potency and the protective NT50 cutoff are greatly influenced by cell substrate and virion maturation state. Additionally, the correlation between nAb titer and protection from disease depends on prior infection history and infecting serotype. Finally, we uncover variations in nAb composition that contribute to protection from symptomatic infection differently after primary and secondary prior infection. These findings have important implications for identifying antibody correlates of protection for vaccines and natural infections.
There is still a need to improve understanding of dengue-specific immunity. Here, by analyzing the antibody response in a pediatric cohort the authors show that the protective capacity of neutralizing antibodies depends on infection history and serotype, but its estimation varies by assay condition and virion maturation.
Journal Article
Lifestyle factors influencing medical and nursing student's health status at the rural health-care institute
2022
BACKGROUND: Noncommunicable diseases (NCDs) may be influenced by lifestyle behavior, acquired during transition in student life at university. Health is a major concern globally. The developing counties are facing a double burden of disease, both communicable and NCD. This study is aimed to assess the lifestyle and its associated factors that can affect the health status of medical and nursing students. MATERIALS AND METHODS: A community-based cross-sectional study was conducted among medical and nursing students of Sasaram, Bihar, by universal sampling. The study population consisted of 303 medical and 233 nursing students. The 536 students in the study, included 195 from rural areas and 341 from urban areas. Simple Lifestyle Indicator Questionnaire was used and Chi-square statistics was computed to determine the association of demographic variables with lifestyle behavior using Epi InfoTM 7 analysis software. RESULTS: Mean age and body mass index were 21 ± 2.59 years and 22.12 ± 3.77, respectively. After statistical analysis utilizing the Chi-square test, it was shown that the difference was found to be nonsignificant (P > 0.05) in all the following variables, such as gender, age, marital status except in designation, and alcohol and tobacco intake which showed the difference to be highly significant. CONCLUSIONS: The maximum number of students in the study population showed intermediate healthy lifestyle (57.1%), despite being the upcoming health-care providers of future. Fruits were rarely present in diet in 82%, no physical activity in 21.2%, and tobacco and alcohol were consumed by 11.7% and 13%, respectively. Targeted intervention for healthy diet, physical activity, stress, tobacco, and alcohol reduction can lead to healthy lifestyle. Independence and autonomy gained in the transition phase in student life needs guided supervision to raise responsible adults. It may help to assist or to plan accordingly in future to improve lifestyle of the students.
Journal Article
A Systematic Review of Action Imitation in Autistic Spectrum Disorder
by
Williams, Justin H. G.
,
Whiten, Andrew
,
Singh, Tulika
in
Action
,
Adolescent
,
Apraxias - etiology
2004
Imitative deficits have been associated with autistic spectrum disorder (ASD) for many years, most recently through more robust methodologies. A fresh, systematic review of the significance, characteristics, and underlying mechanism of the association is therefore warranted. From 121 candidates, we focused on 21 well-controlled studies involving 281 cases of ASD. Overall, children with ASD performed worse on imitative tasks (Combined Logit \"p\" value less than .00005). The emerging picture is of delayed development in imitation, implicating a deficit in mapping neural codings for actions between sensory and motor modalities, rather than in motivation or executive function. We hypothesise that ASD is characterised by abnormal development of these mappings, such that they are biased towards object-oriented tasks at the expense of those required for action imitation per se.
Journal Article
Human immune globulin treatment controls Zika viremia in pregnant rhesus macaques
2022
There are currently no approved drugs to treat Zika virus (ZIKV) infection during pregnancy. Hyperimmune globulin products such as VARIZIG and WinRho are FDA-approved to treat conditions during pregnancy such as Varicella Zoster virus infection and Rh-incompatibility. We administered ZIKV-specific human immune globulin as a treatment in pregnant rhesus macaques one day after subcutaneous ZIKV infection. All animals controlled ZIKV viremia following the treatment and generated robust levels of anti-Zika virus antibodies in their blood. No adverse fetal or infant outcomes were identified in the treated animals, yet the placebo control treated animals also did not have signs related to congenital Zika syndrome (CZS). Human immune globulin may be a viable prophylaxis and treatment option for ZIKV infection during pregnancy, however, more studies are required to fully assess the impact of this treatment to prevent CZS.
Journal Article
Assessment of Pathological Complete Response Using Vacuum-Assisted Biopsy in Breast Cancer Patients Who Have Clinical and Radiological Complete Response After Neo-Adjuvant Chemotherapy
2023
Background:
Any treatment protocol that leads to complete elimination of surgery may lead to a better patient acceptance of breast cancer treatments.
Objectives:
We conducted this study to assess the feasibility of preoperative vacuum-assisted biopsies in identifying pathological complete response (pCR) and its accuracy in correlation to final histopathology report (HPR), in an Indian setting.
Methods:
This was a prospective study conducted between October 1, 2019, and March 31, 2021. Patients with early breast cancer, estrogen and progesterone receptors negative and either Her2 positive or negative, and who were fit to undergo marker placement at the centre of the tumour and to receive third-generation chemotherapy (4 cycles of 3 weekly doxorubicin and cyclophosphamide followed by 4 cycles of 3 weekly docetaxel) were included in the study. Following the enrolment, a tissue marker was placed at the centre of the tumour and appropriate chemotherapy was started. Patients who achieved clinical complete response were subjected to ultrasound-guided vacuum-assisted biopsy (VAB) from the tumour bed before surgery. Pathology results of the VAB and resected specimen were then compared. Descriptive statistics were used in the study.
Results:
Eighteen patients were enrolled in the study, with a mean age of 43.6 ± 9.8 years. However, only 10 were eligible for VAB procedure, and sensitivity and specificity were calculated based on the results of these 10 patients only. Vacuum-assisted biopsy showed sensitivity of 50% and specificity of 100% in identifying pCR. Combination of mammography, ultrasonography, and VAB showed sensitivity of 77.8% and specificity of 66.7% in identifying pCR.
Conclusion:
Vacuum-assisted biopsy of tumour bed may not be sensitive enough to eliminate surgery even in patients who have had exceptional response to neo-adjuvant chemotherapy.
Journal Article
Dynamics of cytokine and antibody responses in community versus hospital SARS-CoV-2 infections
2024
Dysregulated host cytokine responses to SARS-CoV-2 infection are a primary cause of progression to severe disease, whereas early neutralizing antibody responses are considered protective. However, there are gaps in understanding the early temporal dynamics of these immune responses, and the profile of productive immune responses generated by non-hospitalized people with mild infections in the community.
Here we conducted a prospective cohort study of people with suspected infections/exposures in the US state of North Carolina, before vaccine availability. We recruited participants not only in hospitals/clinics, but also in their homes. With serial sampling, we compared virologic and immunologic factors in 258 community cases versus 114 hospital cases of COVID-19 to define factors associated with severity.
We found that high early neutralizing antibodies were associated with lower nasal viral load, but not protection from hospitalization. Cytokine responses were evaluated in 125 cases, with subsets at first versus second week of illness to assess for time-dependent trajectories. The hospital group demonstrated a higher magnitude of serum IL-6, IL-1R antagonist, IP-10, and MIG; prolonged upregulation of IL-17; and lesser downregulation of GROα, IL-1R antagonist, and MCP1, in comparison to the community group suggesting that these factors may contribute to immunopathology. In the second week of illness, 2-fold increases in IL-6, IL-1R antagonist, and IP-10 were associated with 2.2, 1.8, and 10-fold higher odds of hospitalization respectively, whereas a 2-fold increase in IL-10 was associated with 63% reduction in odds of hospitalization (p<0.05). Moreover, antibody responses at 3-6 months post mild SARS-CoV-2 infections in the community revealed long-lasting antiviral IgM and IgA antibodies as well as a stable set point of neutralizing antibodies that were not waning.
Our data provide valuable temporal cytokine benchmarks to track the progression of immunopathology in COVID-19 patients and guide improvements in immunotherapies.
Journal Article
Frequency of dengue virus-specific T cells is related to infection outcome in endemic settings
by
Balmaseda, Ángel
,
Gálvez, Rosa Isela
,
Weiskopf, Daniela
in
Adolescent
,
CD4 antigen
,
CD4-Positive T-Lymphocytes - immunology
2025
Dengue is widespread in tropical and subtropical regions globally and imposes a considerable disease burden. Annually, dengue virus (DENV) causes up to 400 million infections, of which approximately 25% present with clinical manifestations ranging from mild to fatal. Despite its significance as a growing public health concern, developing effective DENV vaccines has been challenging. One reason is the lack of comprehensive understanding of the influence exerted by prior DENV infections and immune responses with cross-reactive properties. To investigate this, we collected samples from a pediatric cohort study in dengue-endemic Managua, Nicaragua. We characterized T cell responses in 71 healthy children who had previously experienced 1 or more natural DENV infections and who, within 1 year after sample collection, had a subsequent DENV infection that was either symptomatic or inapparent. Our study investigated the effect of preexisting DENV-specific T cell responses on clinical outcomes of subsequent DENV infection. We assessed DENV-specific T cell responses using an activation-induced marker assay. Children with only 1 prior DENV infection displayed heterogeneous DENV-specific CD4+ and CD8+ T cell frequencies. In contrast, children with 2 or more prior DENV infections showed significantly higher DENV-specific CD4+ and CD8+ T cell frequencies associated with inapparent rather than symptomatic outcomes in subsequent infection. These findings demonstrate the protective role of DENV-specific T cells against symptomatic DENV infection and advance efforts to identify protective immune correlates against dengue.
Journal Article