Nevin Manimala

Front Immunol. 2024 Dec 9;15:1455334. doi: 10.3389/fimmu.2024.1455334. eCollection 2024.

ABSTRACT

Age-associated differences in the effect of repetitive vaccination, particularly on memory T-cell and B-cell responses, remain unclear. While older adults (aged ≥65 years) exhibited enhanced IgG responses following COVID-19 mRNA booster vaccination, they produced fewer spike-specific circulating follicular helper T cells-1 than younger adults. Similarly, the cytotoxic CD8⁺ T-cell response remained diminished with reduced PD-1 expression even after booster vaccination compared with that in younger adults, suggesting impaired memory T-cell activation in older adults. In contrast, although B-cell responses in older adults were weaker than those in younger adults in the primary response, the responses were significantly enhanced upon booster vaccination, reaching levels comparable with that observed in younger adults. Therefore, while booster vaccination ameliorates impaired humoral immunity in older adults by efficiently stimulating memory B-cell responses, it may less effectively enhance T-cell-mediated cellular immunity. Our study provides insights for the development of effective therapeutic and vaccine strategies for the most vulnerable older population.

PMID:39717779 | PMC:PMC11663736 | DOI:10.3389/fimmu.2024.1455334

Front Immunol. 2024 Dec 9;15:1453703. doi: 10.3389/fimmu.2024.1453703. eCollection 2024.

ABSTRACT

BACKGROUND: Autoimmune diseases pose significant health challenges worldwide and affect millions. In recent years, there has been growing interest in exploring preventive strategies through nutritional interventions using vitamins, antioxidants, and micronutrients to reduce the risk of developing autoimmune diseases. However, excessive supplementation has also been associated with toxicity.

OBJECTIVE: We aim to assess how the intake of vitamins, antioxidants and micronutrients affect the risk of developing autoimmune diseases.

METHODS: This PRISMA-adherent systematic review involved a systematic search of PubMed, Embase and Cochrane for controlled studies that evaluated the risk of incident autoimmune diseases after supplementation. Random effects meta-analyses were used for primary analysis.

RESULTS: 18 studies were included. Overall meta-analyses observed that vitamin D did not influence the risk of autoimmune diseases (RR=0.99, 95%CI: 0.81-1.20). However, among the different vitamin D dosages, subgroup analysis demonstrated that those who were supplemented with 600-800IU/day may have a statistically significant reduction in risk (RR=0.55, 95%CI: 0.38; 0.82). Systematic review suggested that consumption of most vitamins, micronutrients and antioxidants may not have any effect on the risk of autoimmune diseases. Smoking, age, physical or outdoor activity and diet were significant confounding factors that affected the efficacy of such interventions.

CONCLUSION: We studied the effect of various vitamins, micronutrients and antioxidants on the risk of developing autoimmune diseases. Our study contributes to the evolving landscape of nutritional immunology, providing a foundation for future research to unravel more definite relationships with supplementation and the development of incident autoimmune diseases.

SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero/, identifier CRD42024504796.

PMID:39717776 | PMC:PMC11663920 | DOI:10.3389/fimmu.2024.1453703

Front Oncol. 2024 Dec 9;14:1465334. doi: 10.3389/fonc.2024.1465334. eCollection 2024.

ABSTRACT

INTRODUCTION: Acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) constitute myeloid malignancies, and allogeneic hematopoietic stem cell transplantation (allo-HSCT) is considered as a potentially optimal approach for achieving a long term cure. However, post-allo-HSCT relapse remains a leading cause of mortality and therapeutic failure.

METHODS: To evaluate the efficacy and safety of combining hypomethylating agents (HMAs) with Bcl-2 inhibitors in the treatment of AML/MDS relapse following allo-HSCT, we retrospectively collected data from 42 patients who experienced relapse between April 2012 and March 2022 at Peking University First Hospital. Among these patients, 21 underwent intensive chemotherapy (IC) alone, while the other 21 received treatment with HMAs after IC treatment, either alone or in combination with the Bcl-2 inhibitor venetoclax (VEN).

RESULTS: The median overall survival (OS) was 9 ± 2.153 months, and the one-year OS rate was 41.5%. The overall response rate (ORR) in the chemotherapy group and the IC+HMAs ± VEN group was 52.38% (11/21) and 76.19% (16/21), respectively, with no significant difference found (P=0.107). Kaplan-Meier analysis revealed a significant difference in OS between the chemotherapy group and the IC+HMAs ± VEN group in our retrospective cohort study (P=0.041, χ2= 4.016). Additionally, a significant difference in overall survival (OS) rates was observed between the two groups for patients categorized as intermediate/high risk (P=0.008). The secondary relapse rate was 45.45% (5/11) in the IC cohort and 25% (4/16) in the IC+HMAs ± VEN group, respectively, with no significant difference identified between the two cohorts (P=0.268). Furthermore, upon assessing the risk of graft-versus-host disease (GvHD), infection, and agranulocytosis, no notable differences were observed with the use of HMAs, suggesting that HMAs did not increase the risk. In the IC+HMAs ± VEN group, 7 patients received VEN in addition to HMAs, and no significant statistical difference was found in OS when comparing patients who received HMAs alone and those who received HMA+VEN (P=0.183), also, a statistically significant difference in OS was noted between the two groups whenaccounting for competing risks (P=0.028).

CONCLUSIONS: This retrospective study highlights the efficacy of IC+HMAs ± VEN in treating AML/MDS patients experiencing relapse post allo-HSCT, improving survival rates, especially for those classified as intermediate/high risk, with favorable tolerability.

PMID:39717745 | PMC:PMC11663890 | DOI:10.3389/fonc.2024.1465334

Ther Adv Musculoskelet Dis. 2024 Dec 22;16:1759720X241295920. doi: 10.1177/1759720X241295920. eCollection 2024.

ABSTRACT

BACKGROUND: Psoriatic arthritis (PsA) is a chronic inflammatory condition that can affect individuals of all ages. Patients may experience a range of physical and psychological issues.

OBJECTIVE: To examine the impact of PsA on an individual’s quality of life (QoL) and physical function.

DESIGN: A systematic review of the literature.

DATA SOURCES AND METHODS: A comprehensive search was conducted across seven electronic databases (Cochrane Central Register of Controlled Trials (CENTRAL), CINAHL, AMED, EMBASE, Global Health, MEDLINE and PsycINFO) to retrieve articles related to QoL and lifestyle in adults with PsA. The inclusion criteria were studies published between 2010 and 2021 that used outcomes validated in patients with PsA. The methodological quality was assessed using Joanna Briggs Institute Critical Appraisal Tools. Our primary outcomes were patient-reported outcomes (PROs) measuring QoL and the impact of disease on physical function. The secondary outcomes were assessments of fatigue, anxiety, depression, sleep, work productivity and employment.

RESULTS: The study included 37 comprehensive studies that examined the impact of PsA on QoL and physical function. The findings revealed that the impact of PsA extends to various aspects of life, including activities of daily living, physical, and emotional aspects, such as fatigue, sleep disturbance, anxiety and depression. Notably, people with PsA experience reduced health-related quality of life (HRQoL), particularly in emotional, social and mental health aspects. The severity of pain and/or fatigue is directly linked to decreased HRQoL. Importantly, those who fail to achieve minimal disease activity face challenges in work productivity and employment status.

CONCLUSION: To conclude, our review underscores the significant impact of PsA on patients’ HRQoL beyond joint disease. The emotional, social, and mental aspects of PsA require compassionate and holistic management.

TRIAL REGISTRATION: The PROSPERO international prospective register of systematic reviews – CRD42021257395.

PMID:39717741 | PMC:PMC11664531 | DOI:10.1177/1759720X241295920

Front Plant Sci. 2024 Dec 9;15:1486564. doi: 10.3389/fpls.2024.1486564. eCollection 2024.

ABSTRACT

BACKGROUND: Alfalfa, scientifically identified as Medicago sativa, is repeatedly referred to as the “king of forages”. Because of its tight relationship to winter hardiness, the alfalfa’s root crown plays a significant role as a storage organ over the winter. At present, it is still unknown what molecular process makes the alfalfa root crown resistant to cold. This study was aimed to study these knowledge gaps. Using RNA sequencing (RNA-Seq) technology, significant genes associated with cold hardiness were found.

METHODS: According to the random block design, Longmu 806 alfalfa and Sardi alfalfa were planted in regional experiments. Under the condition of low-temperature treatment in winter, the differentially expressed genes (DEGs), winter survival rate (WSR), and physiological characteristics were, in turn, calculated by RNA-Seq, chemical analysis, and field investigation.

RESULTS: The WSR of the Longmu 806 alfalfa was 3.68-fold greater than that of the Sardi alfalfa. The jasmonic acid (JA), soluble sugar (SS), proline (Pro), and glutathione (GSH) concentration in the roots of Longmu 806 alfalfa was more than the same amount in Sardi alfalfa in other words P is less than 0.05. An entire set of 878 DEGs related to winter hardiness was found by statistical analysis. Among them, 463 DEGs showed an increase in expression, whereas 415 DEGs showed a decrease in expression. The metabolic pathways’ examination presented that the DEGs (MsERF1, MsCHIB, MsJAZ, MsAOC, MsGST, MsINV, MsTPS, and MsOAT) were linked to the pathways of “plant hormone signaling transduction”, “Amino sugar and nucleotide sugar metabolism”, and “glutathione metabolism”. Furthermore, the physiological changes in JA, SS, Pro content, and GSH were influenced by the dynamic transcription profile of LT (low- temperature) resistance-related genes.

PMID:39717732 | PMC:PMC11663680 | DOI:10.3389/fpls.2024.1486564

Virus Evol. 2024 Nov 22;10(1):veae100. doi: 10.1093/ve/veae100. eCollection 2024.

ABSTRACT

Interest in phage therapy-the use of bacterial viruses to treat infections-has increased recently because of the rise of infections with antibiotic-resistant bacteria and the failure to develop new antibiotics to treat those infections. Phages have shown therapeutic promise in recent work, and successful treatment minimally requires giving the patient a phage that will grow on their infecting bacterium. Although nature offers a bountiful and diverse supply of phages, there have been a surprising number of patient infections that could not be treated with phages because no suitable phage was found to kill the patient’s bacterium. Here, we develop computational models to analyze an alternative approach to obtaining phages with new host ranges-directed evolution via laboratory propagation of phages to select mutants that can grow on a new host. The models separately explore alternative directed evolution protocols for phage variants that overcome three types of bacterial blocks to phage growth: a block in adsorption, temperate phage immunity to superinfection, and abortive infection. Protocols assume serial transfer to amplify pre-existing, small-effect mutants that are initially rare. Best protocols are sensitive to the nature of the block, and the models provide several insights for enhancing success specific to each case. A common result is that low dilution rates between transfers are beneficial in reducing the mutant growth rate needed to ascend. Selection to overcome an adsorption block is insensitive to many protocol variations but benefits from long selection times between transfers. A temperate phage selected to grow on its lysogens can evolve in any of three phenotypes, but a common protocol favors the desired changes in all three. Abortive infection appears to be the least amenable to evolving phage growth because it is prone to select phages that avoid infection.

PMID:39717707 | PMC:PMC11665826 | DOI:10.1093/ve/veae100

J Ethnobiol Ethnomed. 2024 Dec 23;20(1):108. doi: 10.1186/s13002-024-00749-x.

ABSTRACT

BACKGROUND: Ethnobotanical knowledge about plant roles in fisheries is crucial for sustainable resource management. Local ecological knowledge helps understand dynamics of the lake ecosystem. Fishers use plants based on availability and characteristics while adapting to the changes in the environment. Studying fishery related uses of plants and algae and the challenges interconnected with them from local perspectives can provide insights into their beneficial uses and impacts to the ecosystem.

METHODS: The study investigates the botanical knowledge of three fishing villages in Laguna Lake or Laguna de Bay (LB), Philippines, including Buhangin, Sampiruhan, and Mabato-Azufre, each with varying degrees of industrialization. The ethnobotanical study, which gathered 27 interviews between June 2022 and July 2024, included plant collection with the help of local collaborators, including local fishers as research guides.

RESULTS: Fishers in LB highlighted positive and negative plant-fishing interactions. The most frequently mentioned plant applications were fish habitat and fish hiding places. Fish food, spawning sites, conservation, and a number of challenges such as navigational concerns and aquaculture fish deaths had been previously reported in local use reports. The remaining observations provide new insights into plant-fishing interactions, including indicators of food quality and food sources for fish, the decrease in the action of waves, and how plants help in improving the quality of the water.

CONCLUSION: These results highlight that the knowledge of fishers regarding the ecosystem in which they conduct their fishing activities provides baseline information about the positive and negative relationships between plants and fishing activities in the region, which is vital for further understanding its biodiversity and ecosystem interactions. It is crucial to consider fisher knowledge and involve them as equal partners in conservation efforts of LB.

PMID:39716198 | DOI:10.1186/s13002-024-00749-x

Parasit Vectors. 2024 Dec 23;17(1):535. doi: 10.1186/s13071-024-06569-y.

ABSTRACT

BACKGROUND: Strongyloidiasis is a chronic parasitic disease that results in relevant human morbidity, caused by the nematode Strongyloides stercoralis. This nematode has a unique and complex life-cycle. There is so far no perfect test for this helminthiasis. Rapid immunochromatographic tests (RDTs) are of interest, specifically due to their feasibility for use in the field, where public health control of strongyloidiasis is recommended. The aim of this study was to evaluate two novel RDTs, one detecting immunoglobulin (Ig) G and the other detecting IgG4, based on a combination of recombinant antigens. The primary objective was to estimate the sensitivity and specificity of these RDTs, and the secondary objective was to assess ease of interpretation.

METHODS: Serum samples stored in our biobank with available matched results for at least one fecal (i.e. agar plate culture or PCR) and one serology test (i.e. enzyme-linked immunosorbent assay [ELISA] or indirect immunofluorescent antibody test [IFAT]) for S. stercoralis, were selected for this study. Those with at least one positive result for the fecal test were considered to be true positives (irrespective of the serology), while true negatives were those with negative results for both the fecal and serology tests. The results of the RDTs were read independently by two laboratory technicians. When disagreement over the results occurred, a third reader was involved, and the final result for each test was based on consistent results from two readers. Estimates were reported along with the 95% confidence intervals (CI). Regarding the secondary objective, agreement between two independent readers was calculated with Cohen’s kappa statistic (κ).

RESULTS: A total of 90 serum samples were tested. Sensitivity of the IgG- and the IgG4-RDTs was 91.1% (95% CI 78.8-97.5) and 77.3% (95% CI 62.2-88.5), respectively. Specificity was 91.1% (95% CI 78.8-97.5) for the IgG-RDT and 100% (95% CI 92.1-100) for the IgG4-RDT. Agreement between readers was excellent (Cohen’s κ = 0.96, 95% CI 0.86-1.08%).

CONCLUSIONS: The IgG-RDT demonstrated higher sensitivity and could hence be preferred for individual diagnosis, whereas the excellent specificity of the IgG4-RDT could be preferred for prevalence surveys in endemic areas. The results of both RDTs were easy to interpret based on excellent agreement between readers. Large prospective studies should follow to confirm these findings and to validate the use of either RDT for specific purposes/contexts.

PMID:39716196 | DOI:10.1186/s13071-024-06569-y

BMC Public Health. 2024 Dec 23;24(1):3567. doi: 10.1186/s12889-024-21129-w.

ABSTRACT

BACKGROUND: Community acceptance of Traditional birth attendants (TBAs) as professional birth attendant was reported as one of the bottlenecks that has been hindering facility childbirth care service use. Hence, the World Health Organization (WHO) recommended that all childbirths needed to be attended by professional skilled attendants who at least possessed midwifery skill through the safe motherhood initiative. However, many births in developing countries have been being attended by Traditional birth attendants (TBAs) mainly due to pregnant women and community acceptance for TBAs as sole birth attendants. Therefore, measuring pregnant women’s perceived community acceptance towards TBAs assisted childbirth care and identifying factors could be imperative. This provides evidence for policy makers, health program managers and health care practitioners in their effort to escalate skilled and facility childbirth care there by improving maternal and newborn health outcome.

METHODS: This study had used the cross-sectional baseline data from Performance and monitoring for action Ethiopia (PMA_Et) cohort one survey which enrolled and collected data from currently pregnant women and recently postpartum women. The baseline survey collected real time data on various sexual, reproductive, maternal and new born nationwide priority indicators using customized Open Data Kit Mobile application. These data were collected using standard pretested questionnaire prepared in three local languages (Amharic, Afan Oromo and Tigrigna) by well experienced resident enumerators. The final sample size was 2,186 women who were pregnant by the time of the survey and who provided response for the perceived community acceptance for TBAs assisted childbirth care question item. Frequencies were computed to describe the study participant’s characteristics. Multinomial logistics regression statistical model building process was employed to identify associated factors of perceived community acceptance for childbirths to be attended by TBAs. Results were presented in the form percentages and odds ratio with 95% Confidence Intervals. Candidate variables were selected using p-value of 0.25. Statistical significance was declared at p-value of 0.05.

RESULTS: The overall proportion of perceived community acceptance for TBAs assisted childbirth care was found to be 58.63% (95%CI: 56.47%, 60.76%). Attending primary education was found to increase the likelihood of pregnant women perceived community acceptance by most people in their community for TBAs assisted childbirth care. Women having intentions to have another child were found to have higher likelihood perceived community acceptance by few people in their community for TBAs assisted childbirth care. On the contrary, religion, residing in the well to do households, residing in the Southern nations, nationalities and Peoples Region (SNNPR) and Addis Ababa had lowered pregnant women’s perceived community acceptance by most, few and some pleople in their community for TBAs assisted childbirth care.

CONCLUSIONS: The overall substantially greater proportion of pregnant perceived community acceptance for TBAs assisted childbirth care calls up on tremendous work to be done to avert such high level pregnant women perceived community acceptance for childbirths to be assisted by TBAs. Activities targeting in improving women economic status and empowerment; increasing women enrollment to secondary and higher education; using religious leaders and institutions to promote skilled delivery and childbirth care service use could likely aid in mitigating such huge surge of misconceptions towards childbirth care attendants. This significant perceived community acceptance substantially impact maternal and newborn health outcomes negatively which calls for awareness creation through community campaign to reverse this skewed perception. The activities and interventions need to be region specific. The finding also underscores the relevance of birth preparedness and complication readiness. The implication of the study is that the Health Minister and relevant actors need to design and implement region specific programs and strategies on women reproductive health empowerment and skilled childbirth care service use improvement. The other key implication of the finding was serving as one source of evidence to follow the WHO’s recommendation aimed at reducing maternal mortality through skilled delivery and childbirth care service provision. It also served to track the status of the new role of TBAs to serve as a liaison between the pregnant women and the modern health care system to escalate skilled childbirth care services.

PMID:39716195 | DOI:10.1186/s12889-024-21129-w

Harm Reduct J. 2024 Dec 23;21(1):227. doi: 10.1186/s12954-024-01141-4.

ABSTRACT

BACKGROUND: The assessment of potential health effects of switching from cigarette smoking to non-combustible tobacco products has important implications for public health and regulatory decisions. Robust epidemiological evidence requires long-term follow-up of a large number of individuals. Real-world evidence derived from health records has the potential to help fill the gap in the interim. To our knowledge, this is the first study using individual-level healthcare claims data to assess the potential impact of transitioning from cigarette smoking to smokeless tobacco on short-term direct healthcare costs.

METHODS: We conducted a retrospective cohort study of adult male patients with COPD who smoked cigarettes at baseline using the MarketScan^® Databases. We compared changes in direct healthcare costs between the 12-month periods before (baseline) and after the index date (follow-up) across three cohorts: continued smoking (CS), quit all tobacco (QT), or switched to smokeless tobacco (SW), using a non-linear difference-in-differences model with average marginal effects.

RESULTS: A total of 23,427 COPD patients were included (CS: 11,167; QT: 12,013; SW: 247). At baseline, the QT cohort had the highest total average healthcare costs ($43,771), followed by SW ($38,419), and CS ($27,149). The unadjusted difference-in-differences model revealed no statistically significant differences in total healthcare cost changes when comparing the QT or SW cohorts to the CS cohort (-$1,532 [95% CI: -$3,671, $608] for the QT cohort, and -$452 [95% CI: -$15,415, $14,511] for the SW cohort). After adjusting for Deyo-Charlson Comorbidity Index and COPD exacerbation, assuming patients had two comorbidities and exacerbations, the QT cohort had greater reduction in total healthcare costs compared to the CS cohort (-$2,910 dollars [95% CI: -$4,485, $-1,335]). The same trend was observed for the SW cohort, although the estimate was not statistically significant (-$5,312 [95%CI: -$11,067, $442], p = 0.08).

CONCLUSIONS: This study demonstrated the feasibility of using administrative claims to conduct real-world evidence studies on the harm-reduction potential of non-combustible tobacco products and found evidence suggesting reductions in direct healthcare costs after quitting tobacco or switching to smokeless tobacco among patients with COPD. Based on the learnings and limitations identified during the study, we propose concrete recommendations to improve future observational studies by integrating additional real-world healthcare data from multiple data sources.

PMID:39716190 | DOI:10.1186/s12954-024-01141-4