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Problem Recent progress in vaccine availability and affordability has raised prospects for reducing death and disability from neurological infections in children. In many Asian countries, however, the epidemiology and public health burden of neurological diseases such as Japanese encephalitis and bacterial meningitis are poorly understood. Approach A sentinel surveillance system for Japanese encephalitis was developed and embedded within the routine meningoencephalitis syndromic surveillance system in Cambodia in 2006. The sentinel surveillance system was designed so surveillance and laboratory testing for other etiologies of neurological infection could be incorporated. Local setting The Communicable Disease Control department of the Ministry of Health in Cambodia worked with partners to establish the sentinel surveillance system. Relevant changes The sentinel surveillance system has provided important information on the disease burden of Japanese encephalitis in Cambodia and is now providing a platform for expansion to incorporate laboratory testing for other vaccine-preventable neurological infections in children. Lessons learned Sentinel surveillance systems, when linked to syndromic reporting systems, can characterize the epidemiology of meningoencephalitis and identify the proportion of hospital-based neurological infection in children that is vaccine preventable. Integrated systems enable consistency in data collection, analysis and information dissemination, and they enhance the capacity of public health managers to provide more credible and integrated information to policy-makers. This will assist decision-making about the potential role of immunization in reducing the incidence of childhood neurological infections. Copyright © 2009 World Health Organization [ABSTRACT FROM AUTHOR]

An initial challenge to apply relevant social psychological knowledge to the HIV/AIDS epidemic in Cambodia has grown, using a Lewinian 'action research' perspective, into a multi-sectoral research and health intervention programme. This addresses inequalities in literacy, employment, poverty and the risk of dying from HIV/AIDS. At the level of the individual, it seeks behavioural change to 100% condom use for women and men at risk. At the social level, a pyramidal 'peer educator' training program is initiated, while at the community, institutional and international levels, hiring policies of hotels and the health policies of globalised businesses are challenged to contribute proactively to the campaign against the spread of HIV/AIDS. While a grass-roots community (NGO) group works locally to improve the situation of married women and the 'beer girls' of Siem Reap, students in several countries are organising internet sites concerning the ethical and fair-trade practices of international beer companies profiting from the sales of these beer-girls, who are now 20% HIV positive. [ABSTRACT FROM AUTHOR]

Upper gastrointestinal (UGI) tumors, notably gastric cancer (GC) and esophageal cancer (EC), are significant global health concerns due to their high morbidity and mortality rates. However, only a limited number of metabolites have been identified as biomarkers for these cancers. To explore the association between metabolites and UGI tumors, the present study conducted a comprehensive two‑sample Mendelian randomization (MR) analysis using publicly available genetic data. In the present study, the causal relationships were examined between 1,400 metabolites and UGI cancer using methods such as inverse variance weighting and weighted medians, along with sensitivity analyses for heterogeneity and pleiotropy. Functional experiments were conducted to validate the MR results. The analysis identified 57 metabolites associated with EC and 58 with GC. Key metabolites included fructosyllysine [EC: Odds ratio (OR)=1.450, 95% confidence interval (CI)=1.087‑1.934, P=0.011; GC: OR=1.728, 95% CI=1.202‑2.483, P=0.003], 2'‑deoxyuridine to cytidine ratio (EC: OR=1.464, 95% CI=1.111‑1.929, P=0.007; GC: OR=1.464, 95% CI=1.094‑1.957, P=0.010) and carnitine to protonylcarnitine (C3) ratio (EC: OR=0.655, 95% CI=0.499‑0.861, P=0.002; GC: OR=0.664, 95% CI=0.486‑0.906, P=0.010). Notably, fructosyllysine levels and the 2'‑deoxyuridine to cytidine ratio were identified as risk factors for both EC and GC, while the C3 ratio served as a protective factor. Functional experiments demonstrated that fructosyllysine and the 2'‑deoxyuridine to cytidine ratio promoted the proliferation of EC and GC cells, whereas carnitine inhibited their proliferation. In conclusion, the present findings provide insights into the causal factors and biomarkers associated with UGI tumors, which may be instrumental in guiding targeted dietary and pharmacological interventions, thereby contributing to the prevention and treatment of UGI cancer.

Rabies remains a global health threat despite being preventable with post-exposure prophylaxis (PEP). This study assessed one-year humoral and T cell immunity in PEP recipients of the Insitut Pasteur du Cambodge (IPC) regimen, recommended by WHO. We analyzed rabies virus (RABV) neutralizing antibodies (nAbs) and T cell responses at baseline, 7 and 14 days, 6 and 12 months after PEP. A total of 148 patients were included, with 78 bitten by confirmed RABV-positive dogs receiving PEP and equine rabies immunoglobulins (eRIG), and 70 bitten by RABV-negative dogs receiving only PEP. Fourteen days after PEP, all but two individuals seroconverted for nAbs ( ≥ 0.5 IU/mL) with 87% maintaining this response even after 12 months. Interleukin-4 (IL-4) and interferon-gamma (IFN-γ)-secreting T cells were significantly elevated after 14 days and sustained for one year. No differences were observed between the RABV-exposed and -unexposed groups. This study demonstrates robust one-year immunity after IPC PEP., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Objective: Upper gastrointestinal (UGI) cancers, including esophageal (EC) and gastric (GC) cancers, pose a significant global health challenge. Previous studies have indicated a fundamental correlation between basophil count and the risk of UGI cancer. However, confirming a causal relationship demands further investigation. Mendelian randomization (MR) provides a critical method for evaluating the possible causal connections between peripheral circulating blood cells (PCBCs) and UGI cancer., Method: Our study comprehensively employed a two-sample MR analysis. We used publicly available genetic data to survey the causal association between PCBC and UGI cancer. We used inverse variance weighting and weighted median for MR analyses and sensitivity analyses to assess heterogeneity and pleiotropy., Results: In terms of the association between PCBCs and UGI cancer, we found that basophils count (EC: OR = 1.416, 95% CI = 1.125-1.783, p = 0.003; GC: OR = 1.623, 95% CI = 1.052-2.505, p = 0.029) were all strongly correlated with both EC and GC. Interestingly, Basophil count was a risk factor for both EC and GC. However, no significant correlations were seen between eosinophil, monocyte, lymphocyte or white blood cell count and UGI cancer., Conclusion: The findings of this research corroborate the idea that basophils might serve as a fundamental risk factor for UGI cancer. Further exploration of the underlying mechanisms driving this relationship could provide crucial understanding helpful in creating prospective preventive and treatment methods for UGI cancer., Competing Interests: No competing interests., (© the authors; licensee ecancermedicalscience.)

Objective: Hepatocellular carcinoma (HCC) is a complex and multifaceted disease that is increasingly prevalent globally. The involvement of immune cells in the tumour microenvironment has been linked to the progression of HCC, but the exact cause-and-effect relationship is not yet clear. In this study, we utilise Mendelian randomization (MR) to investigate the potential causal links between immune factors and the development of HCC., Method: We executed a comprehensive MR study, leveraging publicly accessible genetic datasets to explore the potential causal links between 731 types of immune cells and HCC. Our analysis primarily applied inverse variance weighting and weighted median methods. To evaluate the robustness of our findings and probe for the presence of heterogeneity and pleiotropy, we also conducted thorough sensitivity analyses., Results: We found 36 immune cells were associated with HCC, CD64 on CD14- CD16+ monocytes (OR = 1.328, 95% CI = 1.116- 1.581, p = 0.001), CD3- lymphocyte %lymphocytes (OR = 1.341, 95% CI = 1.027- 1.750, p = 0.031), HLA DR on CD14+ monocytes (OR = 1.256, 95% CI = 1.089- 1.448, p = 0.002), CD19 on CD19 on Plasma Blast-Plasma Cell (OR = 1.224, 95% CI = 1.073- 1.396, p = 0.003), CCR2 on monocytes (OR = 1.204, 95% CI = 1.073- 1.351, p = 0.002) and Naive CD4+ T cell Absolute Count (OR = 0.797, 95% CI = 0.655- 0.969, p = 0.023) were the most strongly associated with HCC. Among them, CD64 on CD14- CD16+ monocytes, CD3 - lymphocyte %lymphocytes, HLA DR on CD14+ monocytes and CD19 on Plasma Blast-Plasma Cells are the risk factors, while Naive CD4+ T cell Absolute Count are protective factors for HCC., Conclusion: Our MR analysis of the role of immune cells and HCC provides a framework for knowledge of circulating immune status. Systematic assays of infiltrating immune cells in HCC can help dissect the immune status of HCC, assess the current use of checkpoint blockers, and most importantly, aid in the development of innovative immunotherapies. Further research is necessary to validate these findings and explore the underlying mechanisms that influence the immune response to HCC., Competing Interests: The authors declare that they have no competing interests., (© the authors; licensee ecancermedicalscience.)

Objective: Upper gastrointestinal (UGI) cancers, particularly esophageal cancer (EC) and gastric cancer (GC) represent a significant health burden with complex etiologies. Metabolic alterations are known to play a crucial role in cancer development and progression. Identifying key metabolic biomarkers may offer insights into the pathophysiology of UGI cancers and potential therapeutic targets. This study aimed to investigate the causal associations between 1,400 types of metabolites, specifically phosphate-to-alanine and bilirubin-to-androsterone glucuronide, and the risk of developing UGI cancers using Mendelian randomisation (MR) analysis., Method: We conducted a two-sample MR study utilising genetic instruments identified from large-scale genome-wide association studies (GWASs) for metabolic traits. The outcomes were derived from GWAS datasets of UGI cancer patients, including EC and GC. Several MR methods were employed to ensure the robustness of the findings, including inverse variance weighted (IVW), MR-Egger and weighted median approaches., Results: Our analysis found a total of 44 metabolites associated with EC and 15 metabolites associated with GC. The MR analyses revealed a significant causal relationship between the phosphate-to-alanine ratio (EC: OR = 1.002,95% CI = 1.00034-1.0037, p = 0.0037; GC: OR = 1.24,95% CI = 1.046-1.476, p = 0.01) and increased risk of UGI cancers. In contrast, the bilirubin-to-androsterone glucuronide ratio (EC: OR = 0.998,95% CI = 0.997-0.999, p = 0.03; GC: OR = 0.80,95% CI = 0.656-0.991, p = 0.04) was inversely associated with the risk, suggesting a potential protective effect., Conclusion: Our findings suggest that the phosphate-to-alanine ratio and bilirubin-to-androsterone glucuronide ratio are key hub metabolites in the etiology of UGI cancers. These metabolic ratios could serve as potential biomarkers for early detection or targets for therapeutic intervention. Further research is warranted to elucidate the underlying biological mechanisms and to validate the clinical utility of these associations., Competing Interests: The authors declare no competing interests., (© the authors; licensee ecancermedicalscience.)

All World Health Organization (WHO) pre-qualified rabies vaccines for humans are inactivated tissue culture rabies virus formulations produced for intramuscular (IM) administration. Due to costs and vaccine shortage, dose-saving intradermal (ID) administration of rabies post-exposure prophylaxis (PEP) is encouraged by WHO. This study compared the immunogenicity of the ID 2-site, 3-visit Institut Pasteur Cambodge (IPC) PEP regimen to the IM 1-site, 4-visit 4-dose Essen regimen using Verorab vaccine (Sanofi). The development of neutralizing antibodies (nAbs) and T cell response was assessed in 210 patients with a category II or III animal exposure in a rabies-endemic country. At day 28, all participants developed nAbs (≥0.5 IU/mL), irrespective of PEP scheme, age, or administration of rabies immunoglobulin. T cell response and nAb titers were similar for both PEP schemes. This study demonstrated that the 1-week ID IPC regimen is as effective as the 2-week IM 4-dose Essen regimen in inducing an anti-rabies immune response under real-life PEP., Competing Interests: Potential conflicts of interest. V. B. C., C. A., and C. P. are employees of Sanofi, have received travel support, and may hold shares and/or stock options in the company. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: In the last decade, nursing education has begun to reform to competency-based education worldwide, including in low-and middle-income countries. Case-Based Learning (CBL), an approach to delivering competency-based education, contributes to acquiring critical thinking competency, problem-solving, higher knowledge, professional value and attitude. However, it needs to be taught in a culturally appropriate manner. In Cambodia, CBL was initiated in a classroom and clinical practicum by faculty and preceptors who graduated from the upgrading course. This study examined the factors associated with the competency level of nursing students, explored the practice and perceptions of teaching-learning activities among students, faculty members and preceptors and assessed the coherence of qualitative and quantitative findings., Methods: This was a convergent, mixed methods study. Data were collected from eight educational institutions for quantitative and qualitative studies and seven hospitals for qualitative studies. From June to September 2019, a cross-sectional survey of nursing students in the third year of the three-year programme (n = 719), eight focus group discussions (FGDs; n = 55) with 6-8 members and 15 FGDs with faculty (n = 38) and clinical preceptors (n = 37) with 4-7 members were conducted to elicit the teaching-learning experience and perceptions. Multiple linear regression was performed to investigate the factors associated with student competency. Moreover, the study conducted thematic content analysis on the qualitative data. The integrated analysis was presented as side-by-side joint displays., Results: First, the quantitative and qualitative findings confirmed each other 's CBL learning experiences. Students had higher levels of nursing competencies if they had CBL experiences, both in the classroom and clinical practicum, both in a group manner. Next, the quantitative and qualitative findings complemented students' academic satisfaction with the teaching by faculty members and preceptors. Finally, the quantitative and qualitative findings were expanded to explain students' academic satisfaction with the programme., Conclusions: The finding of CBL experiences in a group and students' satisfaction with faculty members' and preceptors' teaching improved nursing students' competency development. Meanwhile, students' satisfaction with the design and delivery of the educational programme provides implications for policy level to narrow the theory and practice gaps in low- and middle-income countries., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Objectives: Gut microbiota is a key component in obesity and type 2 diabetes, yet mechanisms and metabolites central to this interaction remain unclear. We examined the human gut microbiome's functional composition in healthy metabolic state and the most severe states of obesity and type 2 diabetes within the MetaCardis cohort. We focused on the role of B vitamins and B7/B8 biotin for regulation of host metabolic state, as these vitamins influence both microbial function and host metabolism and inflammation., Design: We performed metagenomic analyses in 1545 subjects from the MetaCardis cohorts and different murine experiments, including germ-free and antibiotic treated animals, faecal microbiota transfer, bariatric surgery and supplementation with biotin and prebiotics in mice., Results: Severe obesity is associated with an absolute deficiency in bacterial biotin producers and transporters, whose abundances correlate with host metabolic and inflammatory phenotypes. We found suboptimal circulating biotin levels in severe obesity and altered expression of biotin-associated genes in human adipose tissue. In mice, the absence or depletion of gut microbiota by antibiotics confirmed the microbial contribution to host biotin levels. Bariatric surgery, which improves metabolism and inflammation, associates with increased bacterial biotin producers and improved host systemic biotin in humans and mice. Finally, supplementing high-fat diet-fed mice with fructo-oligosaccharides and biotin improves not only the microbiome diversity, but also the potential of bacterial production of biotin and B vitamins, while limiting weight gain and glycaemic deterioration., Conclusion: Strategies combining biotin and prebiotic supplementation could help prevent the deterioration of metabolic states in severe obesity., Trial Registration Number: NCT02059538., Competing Interests: Competing interests: KC is a consultant for Danone Research, Ysopia and CONFO therapeutics for work not associated with this study. KC held a collaborative research contract with Danone Research in the context of MetaCardis project. FB is a shareholder of Implexion pharma AB. MB received lecture and/or consultancy fees from AstraZeneca, Boehringer-Ingelheim, Lilly, Novo Nordisk, Novartis and Sanofi., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Continuous professional development is important for improving professional competencies, such as cognitive knowledge, technical skills, behaviors, and attitudes. Trainees who complete training programs can have a positive influence on their workplaces. However, it is challenging to establish a process that can facilitate individual learning and help achieve training outcomes in educational and clinical workplaces. In Cambodia, a tumultuous history has played a part in the deficit of adequately prepared nursing faculty. Since the faculty development is vital to ensuring the quality of education, the application of upgraded nursing programs has started in 2011. After the completion of upgraded program, an immediate post-training study was conducted in 2014. Results showed that some faculty members did not accept trainees because they lacked an understanding about nursing concepts. The current study aimed to evaluate the medium-term outcomes of an established program that can improve nursing education and to identify relevant factors in light of the institutional development of educational and clinical facilities in Cambodia. A qualitative study incorporating focus group discussions, key-informant interviews, and teaching document reviews was performed with a thematic analysis using the four-level training evaluation model of Kirkpatrick. Finally, factors influencing outcomes were assessed based on the Bronfenbrenner's ecological system theory. Five themes for behavior and three themes for results were identified as medium-term outcomes from an institutional development aspect. The major enabling factors for the above-mentioned themes were the support of institutional managers, continuous networking among trainees, and supportive national policy. Compared with the immediate post-training study findings, the perceived medium-term outcomes became more strategically focused. Then, the impact of training at a considerably broader scale within the workplace was discussed. The findings highlighted the importance of medium-term program delivery and monitoring if one understands the role played in stimulating outcomes. Moreover, the importance of contextual factors including the influence of managers and policy environment were emphasized., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

In response to immune pressure, influenza viruses evolve, producing drifted variants capable of escaping immune recognition. One strategy for inducing a broad-spectrum immune response capable of recognizing multiple antigenically diverse strains is to target conserved proteins or protein domains. To that end, we assessed the efficacy and immunogenicity of mRNA vaccines encoding either the conserved stem domain of a group 1 hemagglutinin (HA), a group 2 nucleoprotein (NP), or a combination of the two antigens in mice, as well as evaluated immunogenicity in naïve and influenza seropositive nonhuman primates (NHPs). HA stem-immunized animals developed a robust anti-stem antibody binding titer, and serum antibodies recognized antigenically distinct group 1 HA proteins. These antibodies showed little to no neutralizing activity in vitro but were active in an assay measuring induction of antibody-dependent cellular cytotoxicity. HA-directed cell-mediated immunity was weak following HA stem mRNA vaccination; however, robust CD4 and CD8 T cell responses were detected in both mice and NHPs after immunization with mRNA vaccines encoding NP. Both HA stem and NP mRNA vaccines partially protected mice from morbidity following lethal influenza virus challenge, and superior efficacy against two different H1N1 strains was observed when the antigens were combined. In vivo T cell depletion suggested that anti-NP cell-mediated immunity contributed to protection in the mouse model. Taken together, these data show that mRNA vaccines encoding conserved influenza antigens, like HA stem and NP in combination, induce broadly reactive humoral responses as well as cell-mediated immunity in mice and NHPs, providing protection against homologous and heterologous influenza infection in mice., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Giuseppe Ciaramella, Jessica Anne Flynn, and Lan Zhang has patent BROAD SPECTRUM INFLUENZA VIRUS VACCINE pending to Moderna TX, Inc., Cambridge , MA (US)., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Abundance of Faecalibacterium prausnitzii, a dominant bacterium of the human microbiota that exhibits antiinflammatory effects, is decreased in patients with inflammatory bowel diseases (IBD). In humans, colonic lamina propria contains IL-10-secreting, Foxp3- Tregs characterized by a double expression of CD4 and CD8α (DP8α) and a specificity for F. prausnitzii. This Treg subset is decreased in IBD. The in vivo effect of DP8α cells has not been evaluated yet to our knowledge. Here, using a humanized model of a NSG immunodeficient mouse strain that expresses the HLA D-related allele HLA-DR*0401 but not murine class II (NSG-Ab° DR4) molecules, we demonstrated a protective effect of a HLA-DR*0401-restricted DP8α Treg clone combined with F. prausnitzii administration in a colitis model. In a cohort of patients with IBD, we showed an independent association between the frequency of circulating DP8α cells and disease activity. Finally, we pointed out a positive correlation between F. prausnitzii-specific DP8α Tregs and the amount of F. prausnitzii in fecal microbiota in healthy individuals and patients with ileal Crohn's disease.

Respiratory syncytial virus (RSV) infection is a major cause of respiratory illness in infants and the elderly. Although several vaccines have been developed, none have succeeded in part due to our incomplete understanding of the correlates of immune protection. While both T cells and antibodies play a role, emerging data suggest that antibody-mediated mechanisms alone may be sufficient to provide protection. Therefore, to map the humoral correlates of immunity against RSV, antibody responses across six different vaccines were profiled in a highly controlled nonhuman primate-challenge model. Viral loads were monitored in both the upper and lower respiratory tracts, and machine learning was used to determine the vaccine platform-agnostic antibody features associated with protection. Upper respiratory control was associated with virus-specific IgA levels, neutralization, and complement activity, whereas lower respiratory control was associated with Fc-mediated effector mechanisms. These findings provide critical compartment-specific insights toward the rational development of future vaccines., Competing Interests: Declaration of interests Galit Alter is a founder of SeromYx Systems., (Copyright © 2021. Published by Elsevier Inc.)

Gut interleukin-17A (IL-17)-producing γδ T cells are tissue-resident cells that are involved in both host defense and regulation of intestinal inflammation. However, factors that regulate their functions are poorly understood. In this study, we find that the gut microbiota represses IL-17 production by cecal γδ T cells. Treatment with vancomycin, a Gram-positive bacterium-targeting antibiotic, leads to decreased production of short-chain fatty acids (SCFAs) by the gut microbiota. Our data reveal that these microbiota-derived metabolites, particularly propionate, reduce IL-17 and IL-22 production by intestinal γδ T cells. Propionate acts directly on γδ T cells to inhibit their production of IL-17 in a histone deacetylase-dependent manner. Moreover, the production of IL-17 by human IL-17-producing γδ T cells from patients with inflammatory bowel disease (IBD) is regulated by propionate. These data contribute to a better understanding of the mechanisms regulating gut γδ T cell functions and offer therapeutic perspectives of these cells., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Microbiome community typing analyses have recently identified the Bacteroides2 (Bact2) enterotype, an intestinal microbiota configuration that is associated with systemic inflammation and has a high prevalence in loose stools in humans 1,2 . Bact2 is characterized by a high proportion of Bacteroides, a low proportion of Faecalibacterium and low microbial cell densities 1,2 , and its prevalence varies from 13% in a general population cohort to as high as 78% in patients with inflammatory bowel disease 2 . Reported changes in stool consistency 3 and inflammation status 4 during the progression towards obesity and metabolic comorbidities led us to propose that these developments might similarly correlate with an increased prevalence of the potentially dysbiotic Bact2 enterotype. Here, by exploring obesity-associated microbiota alterations in the quantitative faecal metagenomes of the cross-sectional MetaCardis Body Mass Index Spectrum cohort (n = 888), we identify statin therapy as a key covariate of microbiome diversification. By focusing on a subcohort of participants that are not medicated with statins, we find that the prevalence of Bact2 correlates with body mass index, increasing from 3.90% in lean or overweight participants to 17.73% in obese participants. Systemic inflammation levels in Bact2-enterotyped individuals are higher than predicted on the basis of their obesity status, indicative of Bact2 as a dysbiotic microbiome constellation. We also observe that obesity-associated microbiota dysbiosis is negatively associated with statin treatment, resulting in a lower Bact2 prevalence of 5.88% in statin-medicated obese participants. This finding is validated in both the accompanying MetaCardis cardiovascular disease dataset (n = 282) and the independent Flemish Gut Flora Project population cohort (n = 2,345). The potential benefits of statins in this context will require further evaluation in a prospective clinical trial to ascertain whether the effect is reproducible in a randomized population and before considering their application as microbiota-modulating therapeutics.

The RSV Fusion (F) protein is a target for neutralizing antibody responses and is a focus for vaccine discovery; however, the process of RSV entry requires F to adopt a metastable prefusion form and transition to a more stable postfusion form, which displays less potent neutralizing epitopes. mRNA vaccines encode antigens that are translated by host cells following vaccination, which may allow conformational transitions similar to those observed during natural infection to occur. Here we evaluate a panel of chemically modified mRNA vaccines expressing different forms of the RSV F protein, including secreted, membrane associated, prefusion-stabilized, and non-stabilized structures, for conformation, immunogenicity, protection, and safety in rodent models. Vaccination with mRNA encoding native RSV F elicited antibody responses to both prefusion- and postfusion-specific epitopes, suggesting that this antigen may adopt both conformations in vivo. Incorporating prefusion stabilizing mutations further shifts the immune response toward prefusion-specific epitopes, but does not impact neutralizing antibody titer. mRNA vaccine candidates expressing either prefusion stabilized or native forms of RSV F protein elicit robust neutralizing antibody responses in both mice and cotton rats, similar to levels observed with a comparable dose of adjuvanted prefusion stabilized RSV F protein. In contrast to the protein subunit vaccine, mRNA-based vaccines elicited robust CD4+ and CD8+ T-cell responses in mice, highlighting a potential advantage of the technology for vaccines requiring a cellular immune response for efficacy., Competing Interests: Competing interestsA.S.E., P.J.C., M.P.C., D.W., D.J.D., C.C., G.O., J.G., R.S., S.T., Z.W., J.A., L.Z., J.A.F., K.S.C., D.C.F., K.V., A.H.L., J.S.S., M.E.G., D.H., A.J.B. are all employees and/or stockholders of Merck & Co., Inc., Kenilworth, NJ, USA. C.A.S., K.B., and G.C. are employees and/or stockholders of Moderna Inc., Cambridge, MA, USA. G.C., K.B., A.S.E., D.W. and A.J.B. are co-inventors on a patent application related to this work.40, (© The Author(s) 2020.)

Objective: To determine the cost-effectiveness of cochlear implantation (CI) with mainstream education and deaf education with sign language for treatment of children with profound sensorineural hearing loss in low- and lower-middle income countries in Asia., Study Design: Cost-effectiveness analysis., Setting: Bangladesh, Cambodia, India, Indonesia, Nepal, Pakistan, Philippines, and Sri Lanka participated in the study., Subjects and Methods: Costs were obtained from experts in each country with known costs and published data, with estimation when necessary. A disability-adjusted life-years model was applied with 3% discounting and 10-year length of analysis. A sensitivity analysis was performed to evaluate the effect of device cost, professional salaries, annual number of implants, and probability of device failure. Cost-effectiveness was determined with the World Health Organization standard of cost-effectiveness ratio per gross domestic product (CER/GDP) per capita <3., Results: Deaf education was cost-effective in all countries except Nepal (CER/GDP, 3.59). CI was cost-effective in all countries except Nepal (CER/GDP, 6.38) and Pakistan (CER/GDP, 3.14)-the latter of which reached borderline cost-effectiveness in the sensitivity analysis (minimum, maximum: 2.94, 3.39)., Conclusion: Deaf education and CI are largely cost-effective in participating Asian countries. Variation in CI maintenance and education-related costs may contribute to the range of cost-effectiveness ratios observed in this study.

Background: Symptom assessment and quality of life (QoL) are considered two of the most important factors in the overall care of cancer patients. Although cancer is one of the leading causes of death after communicable disease in Cambodia, the QoL of Cambodian cancer patients has not been examined previously. This study aimed to describe the QoL of cancer patients in Cambodia., Methods: A cross-sectional study was conducted with cancer patients who visited Khmer-Soviet Friendship Hospital in Phnom Penh. Two hundred patients participated in this study. The inventory comprised two previously validated scales: the Center for Epidemiological Studies Depression Scale-10 (CESD-10) and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30. Descriptive analyses, independent samples t-tests, and Pearson's correlation analysis were performed to examine the differences and relationship between study variables., Results: The mean global health score was 51.62, and 58.5% of the participants had depressive symptom. The global health score was statistically significantly lower in depressive patients. The QoL was negatively correlated with depression, but positively and significant correlated with physical function, role function, emotional function, cognitive function, and social function., Conclusion: This study is the first to describe the QoL of Cambodian cancer patients. Our findings suggest that more attention should be paid to psychological concerns and symptom management in Cambodian cancer patients. Appropriate management could be effective in improving the QoL of cancer patients., (© 2019 John Wiley & Sons, Ltd.)

Respiratory syncytial virus (RSV) infection is the leading cause of hospitalization and infant mortality under six months of age worldwide; therefore, the prevention of RSV infection in all infants represents a significant unmet medical need. Here we report the isolation of a potent and broadly neutralizing RSV monoclonal antibody derived from a human memory B-cell. This antibody, RB1, is equipotent on RSV A and B subtypes, potently neutralizes a diverse panel of clinical isolates in vitro and demonstrates in vivo protection. It binds to a highly conserved epitope in antigenic site IV of the RSV fusion glycoprotein. RB1 is the parental antibody to MK-1654 which is currently in clinical development for the prevention of RSV infection in infants.

Purpose: Research shows that smoking during pregnancy is related to mental health diagnoses. The purpose of this study was to assess whether current general mental health status is related to current smoking status in pregnant women after controlling for other factors related to both mental health and tobacco use during pregnancy., Methods: This cross-sectional analysis used 2017 Behavioral Risk Factor Surveillance Survey (BRFSS) data for 621 pregnant women aged 18-38 from Florida (N=136), Kansas (N=116), Minnesota (N=105), Nebraska (N=90), New York (N=78), and Utah (N=96). Multiple logistic regression analysis was used to assess the relationship between current mental health status and current tobacco use, while controlling for state, depression diagnosis, routine checkup, healthcare plan, age, marital status, ethnicity/race, education level, income level, and employment status., Results: Overall, very few participants reported current smoking (6%) and about one-third reported low or moderate mental health status in the past 30 days. Adjusted results indicated that those who reported high mental health status were about 3 times less likely (OR=0.29, 95% CI=0.09, 0.88) to report current smoking status compared to those who reported low mental health status., Conclusions: Overall, current mental health status was highly related to current smoking status in pregnant women. Clinicians in obstetrics may expect a very low proportion of pregnant women to report smoking and up to one-third to report low or moderate current general mental health status. Given that current mental health issues and current tobacco use may harm both mother and child, be highly related in pregnant women, and change throughout the pregnancy, pregnant women should be screened automatically for both at each visit.