Displaying publications 41 - 60 of 113 in total

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  1. Archuleta S, Chia PY, Wei Y, Syed-Omar SF, Low JG, Oh HM, et al.
    Clin Infect Dis, 2020 07 11;71(2):383-389.
    PMID: 31626692 DOI: 10.1093/cid/ciz850
    BACKGROUND: Platelet transfusion is common in dengue patients with thrombocytopenia. We previously showed in a randomized clinical trial that prophylactic platelet transfusion did not reduce clinical bleeding. In this study, we aimed to characterize the predictors and clinical outcomes of poor platelet recovery in transfused and nontransfused participants.

    METHODS: We analyzed patients from the Adult Dengue Platelet Study with laboratory-confirmed dengue with ≤20 000 platelets/μL and without persistent mild bleeding or any severe bleeding in a post hoc analysis. Poor platelet recovery was defined as a platelet count of ≤20 000/μL on Day 2. We recruited 372 participants from 5 acute care hospitals located in Singapore and Malaysia between 29 April 2010 and 9 December 2014. Of these, 188 were randomly assigned to the transfusion group and 184 to the control group.

    RESULTS: Of 360 patients, 158 had poor platelet recovery. Age, white cell count, and day of illness at study enrollment were significant predictors of poor platelet recovery after adjustment for baseline characteristics and platelet transfusion. Patients with poor platelet recovery had longer hospitalizations but no significant difference in other clinical outcomes, regardless of transfusion. We found a significant interaction between platelet recovery and transfusion; patients with poor platelet recovery were more likely to bleed if given a prophylactic platelet transfusion (odds ratio 2.34, 95% confidence interval 1.18-4.63).

    CONCLUSIONS: Dengue patients with thrombocytopenia who were older or presented earlier and with lower white cell counts were more likely to have poor platelet recovery. In patients with poor platelet recovery, platelet transfusion does not improve outcomes and may actually increase the risk of bleeding. The mechanisms of poor platelet recovery need to be determined.

    CLINICAL TRIALS REGISTRATION: NCT01030211.

  2. Pardhi DM, Şen Karaman D, Timonen J, Wu W, Zhang Q, Satija S, et al.
    Int J Pharm, 2020 Aug 30;586:119531.
    PMID: 32540348 DOI: 10.1016/j.ijpharm.2020.119531
    This review details the antimicrobial applications of inorganic nanomaterials of mostly metallic form, and the augmentation of activity by surface conjugation of peptide ligands. The review is subdivided into three main sections, of which the first describes the antimicrobial activity of inorganic nanomaterials against gram-positive, gram-negative and multidrug-resistant bacterial strains. The second section highlights the range of antimicrobial peptides and the drug resistance strategies employed by bacterial species to counter lethality. The final part discusses the role of antimicrobial peptide-decorated inorganic nanomaterials in the fight against bacterial strains that show resistance. General strategies for the preparation of antimicrobial peptides and their conjugation to nanomaterials are discussed, emphasizing the use of elemental and metallic oxide nanomaterials. Importantly, the permeation of antimicrobial peptides through the bacterial membrane is shown to aid the delivery of nanomaterials into bacterial cells. By judicious use of targeting ligands, the nanomaterial becomes able to differentiate between bacterial and mammalian cells and, thus, reduce side effects. Moreover, peptide conjugation to the surface of a nanomaterial will alter surface chemistry in ways that lead to reduction in toxicity and improvements in biocompatibility.
  3. Lye DC, Archuleta S, Syed-Omar SF, Low JG, Oh HM, Wei Y, et al.
    Lancet, 2017 Apr 22;389(10079):1611-1618.
    PMID: 28283286 DOI: 10.1016/S0140-6736(17)30269-6
    BACKGROUND: Dengue is the commonest vector-borne infection worldwide. It is often associated with thrombocytopenia, and prophylactic platelet transfusion is widely used despite the dearth of robust evidence. We aimed to assess the efficacy and safety of prophylactic platelet transfusion in the prevention of bleeding in adults with dengue and thrombocytopenia.
    METHODS: We did an open-label, randomised, superiority trial in five hospitals in Singapore and Malaysia. We recruited patients aged at least 21 years who had laboratory-confirmed dengue (confirmed or probable) and thrombocytopenia (≤20 000 platelets per μL), without persistent mild bleeding or any severe bleeding. Patients were assigned (1:1), with randomly permuted block sizes of four or six and stratified by centre, to receive prophylactic platelet transfusion in addition to supportive care (transfusion group) or supportive care alone (control group). In the transfusion group, 4 units of pooled platelets were given each day when platelet count was 20 000 per μL or lower; supportive care consisted of bed rest, fluid therapy, and fever and pain medications. The primary endpoint was clinical bleeding (excluding petechiae) by study day 7 or hospital discharge (whichever was earlier), analysed by intention to treat. Safety outcomes were analysed according to the actual treatment received. This study was registered with ClinicalTrials.gov, number NCT01030211, and is completed.
    FINDINGS: Between April 29, 2010, and Dec 9, 2014, we randomly assigned 372 patients to the transfusion group (n=188) or the control group (n=184). The intention-to-treat analysis included 187 patients in the transfusion group (one patient was withdrawn immediately) and 182 in the control group (one was withdrawn immediately and one did not have confirmed or probable dengue). Clinical bleeding by day 7 or hospital discharge occurred in 40 (21%) patients in the transfusion group and 48 (26%) patients in the control group (risk difference -4·98% [95% CI -15·08 to 5·34]; relative risk 0·81 [95% CI 0·56 to 1·17]; p=0·16). 13 adverse events occurred in the transfusion group and two occurred in the control group (5·81% [-4·42 to 16·01]; 6·26 [1·43 to 27·34]; p=0·0064). Adverse events that were possibly, probably, or definitely related to transfusion included three cases of urticaria, one maculopapular rash, one pruritus, and one chest pain, as well as one case each of anaphylaxis, transfusion-related acute lung injury, and fluid overload that resulted in serious adverse events. No death was reported.
    INTERPRETATION: In adult patients with dengue and thrombocytopenia, prophylactic platelet transfusion was not superior to supportive care in preventing bleeding, and might be associated with adverse events.
    FUNDING: National Medical Research Council, Singapore.
    Study site: Hospitals, Singapore; University Malaya Medical Centre (UMMC). Kuala Lumpur, Malaysia
    Study protocol: https://clinicaltrials.gov/ct2/show/NCT01030211
  4. Smedley CJ, Stanley PA, Qazzaz ME, Prota AE, Olieric N, Collins H, et al.
    Sci Rep, 2018 Jul 13;8(1):10617.
    PMID: 30006510 DOI: 10.1038/s41598-018-28880-2
    The jerantinine family of Aspidosperma indole alkaloids from Tabernaemontana corymbosa are potent microtubule-targeting agents with broad spectrum anticancer activity. The natural supply of these precious metabolites has been significantly disrupted due to the inclusion of T. corymbosa on the endangered list of threatened species by the International Union for Conservation of Nature. This report describes the asymmetric syntheses of (-)-jerantinines A and E from sustainably sourced (-)-tabersonine, using a straight-forward and robust biomimetic approach. Biological investigations of synthetic (-)-jerantinine A, along with molecular modelling and X-ray crystallography studies of the tubulin-(-)-jerantinine B acetate complex, advocate an anticancer mode of action of the jerantinines operating via microtubule disruption resulting from binding at the colchicine site. This work lays the foundation for accessing useful quantities of enantiomerically pure jerantinine alkaloids for future development.
  5. Khaled YS, Khot MI, Aiyappa-Maudsley R, Maisey T, Pramanik A, Tiernan J, et al.
    Nanoscale, 2024 Apr 04;16(14):7185-7199.
    PMID: 38506227 DOI: 10.1039/d3nr04118b
    Theranostic nanoparticles hold promise for simultaneous imaging and therapy in colorectal cancer. Carcinoembryonic antigen can be used as a target for these nanoparticles because it is overexpressed in most colorectal cancers. Affimer reagents are synthetic proteins capable of binding specific targets, with additional advantages over antibodies for targeting. We fabricated silica nanoparticles using a water-in-oil microemulsion technique, loaded them with the photosensitiser Foslip, and functionalised the surface with anti-CEA Affimers to facilitate fluorescence imaging and photodynamic therapy of colorectal cancer. CEA-specific fluorescence imaging and phototoxicity were quantified in colorectal cancer cell lines and a LS174T murine xenograft colorectal cancer model. Anti-CEA targeted nanoparticles exhibited CEA-specific fluorescence in the LoVo, LS174T and HCT116 cell lines when compared to control particles (p < 0.0001). No toxicity was observed in LS174T cancer mouse xenografts or other organs. Following photo-irradiation, the anti-CEA targeted particles caused significant cell death in LoVo (60%), LS174T (90%) and HCT116 (70%) compared to controls (p < 0.0001). Photodynamic therapy (PDT) at 24 h in vivo showed a 4-fold reduction in tumour volume compared to control mouse xenografts (p < 0.0001). This study demonstrates the efficacy of targeted fluorescence imaging and PDT using Foslip nanoparticles conjugated to anti-CEA Affimer nanoparticles in in vitro and in vivo colorectal cancer models.
  6. Harcourt BH, Lowe L, Tamin A, Liu X, Bankamp B, Bowden N, et al.
    Emerg Infect Dis, 2005 Oct;11(10):1594-7.
    PMID: 16318702
    Until 2004, identification of Nipah virus (NV)-like outbreaks in Bangladesh was based on serology. We describe the genetic characterization of a new strain of NV isolated during outbreaks in Bangladesh (NV-B) in 2004, which confirms that NV was the etiologic agent responsible for these outbreaks.
  7. Elsmani MI, Fatima N, Torres I, Fernández S, Jallorina MPA, Chelvanathan P, et al.
    Materials (Basel), 2022 Jul 19;15(14).
    PMID: 35888490 DOI: 10.3390/ma15145024
    The silicon heterojunction solar cell (SHJ) is considered the dominant state-of-the-art silicon solar cell technology due to its excellent passivation quality and high efficiency. However, SHJ's light management performance is limited by its narrow optical absorption in long-wave near-infrared (NIR) due to the front, and back tin-doped indium oxide (ITO) layer's free carrier absorption and reflection losses. Despite the light-trapping efficiency (LTE) schemes adopted by SHJ in terms of back surface texturing, the previous investigations highlighted the ITO layer as a reason for an essential long-wavelength light loss mechanism in SHJ solar cells. In this study, we propose the use of Molybdenum disulfide (MoS2) as a way of improving back-reflection in SHJ. The text presents simulations of the optical response in the backside of the SHJ applying the Monte-Carlo raytracing method with a web-based Sunsolve high-precision raytracing tool. The solar cells' electrical parameters were also resolved using the standard electrical equivalent circuit model provided by Sunsolve. The proposed structure geometry slightly improved the SHJ cell optical current density by ~0.37% (rel.), and hence efficiency (η) by about 0.4% (rel.). The SHJ cell efficiency improved by 21.68% after applying thinner back ITO of about 30 nm overlayed on ~1 nm MoS2. The efficiency improvement following the application of MoS2 is tentatively attributed to the increased NIR absorption in the silicon bulk due to the light constructive interface with the backside components, namely silver (Ag) and ITO. Study outcomes showed that improved SHJ efficiency could be further optimized by addressing front cell components, mainly front ITO and MoS2 contact engineering.
  8. Paul A, Nath TK, Mahanta J, Sultana NN, Kayes ASMI, Noon SJ, et al.
    Asia Pac J Public Health, 2021 01;33(1):100-108.
    PMID: 33289393 DOI: 10.1177/1010539520977304
    The objective of this research is to understand the psychological and livelihood-related impacts of coronavirus disease 2019 (COVID-19) on Bangladeshi lower income group people who depend on daily earnings for their living. Following the convenience sampling method, 576 respondents were interviewed for quantitative data and 30 in-depth interviews for qualitative information in several districts of Bangladesh. To 94.1% respondents, livelihood has been affected by the COVID-19 outbreak with an overall score of 3.20 ± 0.77 on a 4-point Likert-type scale. In comparison to unemployed respondents, daily workers have been hardly affected by the COVID-19 outbreak (odds ratio [OR] = 7.957; P < .01), and so they are going outside more frequently in search of jobs (OR = 9.984, P < .01). Due to fear of COVID-19 infection and lack of livelihood means, respondents (76.6%) have been stressed out (overall score 3.19 ± 0.81 on a 4-point Likert-type scale), and those working in industries (OR = 5.818, P < .01), farmers (OR = 3.029, P < .05), and day laborers (OR = 2.651, P < .05) have been highly stressed.
  9. Paul A, Sikdar D, Hossain MM, Amin MR, Deeba F, Mahanta J, et al.
    PLoS One, 2020;15(9):e0238492.
    PMID: 32877449 DOI: 10.1371/journal.pone.0238492
    The current novel coronavirus (nCoV) pandemic, COVID-19, was first reported in December 2019 in Wuhan, China, and has spread globally, causing startling loss of life, stalling the global economy, and disrupting social life. One of the challenges to contain COVID-19 is convincing people to adopt personal hygiene, social distancing, and self-quarantine practices that are related to knowledge, attitudes, and practices (KAP) of the residents of respective countries. Bangladesh, a densely populated country with a fast-growing economy and moderate literacy rate, has shown many hiccups in its efforts to implement COVID-19 policies. Understanding KAP may help policy makers produce informed decisions. This study assessed KAP in relation to COVID-19 in Bangladesh. An online survey using a pre-tested questionnaire conducted in late March 2020 attained 1,837 responses across Bangladesh. Ultimately, 1,589 completed responses were included in a statistical analysis to calculate KAP scores and their interrelations with sociodemographic variables. The overall KAP was poor, with only 33% of the participants demonstrating good knowledge, whereas 52.4% and 44.8% of the subjects showed good attitudes and practices, respectively. Sociodemographic factors had strong bearings on the KAP scores. Significantly higher KAP scores were evident in females over males, among aged 45 years and older over younger participants, and among retired workers and homemakers over students and public service employees. This study indicated a panic fuelled by poor understanding of COVID-19 associated facts and the need for the government to ensure more granular and targeted awareness campaigns in a transparent and factual manner to foster public confidence and ensure more meaningful public participation in mitigation measures. This study provides a KAP baseline regarding COVID-19 among Bangladeshis.
  10. Paul A, Sikdar D, Mahanta J, Ghosh S, Jabed MA, Paul S, et al.
    PLoS One, 2021;16(8):e0256493.
    PMID: 34415969 DOI: 10.1371/journal.pone.0256493
    In order to eliminate COVID-19, many countries provided vaccinations. However, success depends on peoples' knowledge levels and rates of acceptance. But, previous research on this topic is currently lacking in Bangladesh. This cross-sectional study aimed at to investigate Bangladeshi peoples' knowledge, acceptance, and perception of challenges regarding COVID-19 vaccines. Quantitative data were collected using an online survey (n = 1975) and face-to-face interviews (n = 2200) with a pre-tested structured questionnaire. In addition, seven open-ended interviews were conducted with health experts regarding challenges of vaccination. Binary logistic regression analyses were conducted to assess the association between explanatory and dependent variables. Effect size was estimated to understand the magnitude of relationship between two variables. Of 4175 respondents, 92.6% knew about COVID-19 vaccines, while only 37.4% believed vaccines to be effective in controlling COVID-19. Nearly 46% of respondents believed that COVID-19 vaccines have side-effects, and 16.4% of respondents believed that side-effects could be life-threatening. Only 60.5% of respondents indicated that they would receive the COVID-19 vaccine. Out of 1650 respondents (39.5%) who did not intend to receive the vaccine, 948 (57.4%) believed that they would be naturally protected. Regressions results indicated that men had higher rates of knowledge regarding the vaccine. In addition, rural respondents demonstrated lower knowledge regarding the vaccine. Furthermore, education had a significant association with knowledge of COVID-19 vaccines. Respondents with university education had more knowledge regarding the vaccine (Odds ratio, OR = 29.99; 95% confidence interval, CI 11.40-78.90, effect size 1.88; p = 0.01) and correct dosage (OR 27.34; 95% CI 15.25-49.00, effect size 1.83; p = 0.01). However, women (OR 1.16; 95% CI 0.96-1.40, effect size 0.08) and rural (OR 1.24; 95% CI 1.07-1.44, effect size 0.12; p = 0.01) respondents were more enthusiastic regarding receiving the COVID-19 vaccine. Higher educated respondents showed higher probability of receiving the vaccine. Those who believed in the effectiveness of the COVID-19 vaccine were 11.57 times more interested (OR 11.57; 95% CI 8.92-15.01, effect size 1.35; p = 0.01) in receiving the vaccine. Open-ended interviews identified several challenges toward successful COVID-19 vaccination. Mass awareness creation, uninterrupted supply, equitable distribution, and sectoral coordination were suggested to achieve at least 70% immunization across the country.
  11. Hasan A, Nurunnabi M, Morshed M, Paul A, Polini A, Kuila T, et al.
    Biomed Res Int, 2014;2014:307519.
    PMID: 25165697 DOI: 10.1155/2014/307519
    Biosensors research is a fast growing field in which tens of thousands of papers have been published over the years, and the industry is now worth billions of dollars. The biosensor products have found their applications in numerous industries including food and beverages, agricultural, environmental, medical diagnostics, and pharmaceutical industries and many more. Even though numerous biosensors have been developed for detection of proteins, peptides, enzymes, and numerous other biomolecules for diverse applications, their applications in tissue engineering have remained limited. In recent years, there has been a growing interest in application of novel biosensors in cell culture and tissue engineering, for example, real-time detection of small molecules such as glucose, lactose, and H2O2 as well as serum proteins of large molecular size, such as albumin and alpha-fetoprotein, and inflammatory cytokines, such as IFN-g and TNF-α. In this review, we provide an overview of the recent advancements in biosensors for tissue engineering applications.
  12. Nath TK, Paul A, Sikdar D, Mahanta J, Paul S, Amin MR, et al.
    BMC Health Serv Res, 2021 Oct 11;21(1):1079.
    PMID: 34635110 DOI: 10.1186/s12913-021-07071-2
    BACKGROUND: The safety of health care workers (HCWs) in Bangladesh and the factors associated with getting COVID-19 have been infrequently studied. The aim of this study was to address this gap by assessing the capacity development and safety measures of HCWs in Bangladesh who have been exposed to COVID-19 and by identifying the factors associated with respondents' self-reported participation in capacity development trainings and their safety practices.

    METHODS: This cross-sectional study was based on an online survey of 811 HCWs working at 39 dedicated COVID-19 hospitals in Bangladesh. A pretested structured questionnaire consisting of questions related to respondents' characteristics, capacity development trainings and safety measures was administered. Binary logistic regressions were run to assess the association between explanatory and dependent variables.

    RESULTS: Among the respondents, 58.1% had been engaged for at least 2 months in COVID-19 care, with 56.5% of them attending capacity development training on the use of personal protective equipment (PPE), 44.1% attending training on hand hygiene, and 35% attending training on respiratory hygiene and cough etiquette. Only 18.1% reported having read COVID-19-related guidelines. Approximately 50% of the respondents claimed that there was an inadequate supply of PPE for hospitals and HCWs. Almost 60% of the respondents feared a high possibility of becoming COVID-19-positive. Compared to physicians, support staff [odds ratio (OR) 4.37, 95% confidence interval (CI) 2.25-8.51] and medical technologists (OR 8.77, 95% CI 3.14-24.47) were more exhausted from working in COVID-19 care. Respondents with longer duty rosters were more exhausted, and those who were still receiving infection prevention and control (IPC) trainings were less exhausted (OR 0.54, 95% CI 0.34-0.86). Those who read COVID-19 guidelines perceived a lower risk of being infected by COVID-19 (OR 0.44, 95% CI 0.29-0.67). Compared to the respondents who strongly agreed that hospitals had a sufficient supply of PPE, others who disagreed (OR 2.68, 95% CI 1.31-5.51) and strongly disagreed (OR 5.05, 95% CI 2.15-11.89) had a higher apprehension of infection by COVID-19.

    CONCLUSION: The findings indicated a need for necessary support, including continuous training, a reasonable duty roster, timely diagnosis of patients, and an adequate supply of quality PPE.

  13. Bakshi HA, Zoubi MSA, Hakkim FL, Aljabali AAA, Rabi FA, Hafiz AA, et al.
    Nutrients, 2020 06 26;12(6).
    PMID: 32604971 DOI: 10.3390/nu12061901
    Pancreatic cancer is one of the fatal causes of global cancer-related deaths. Although surgery and chemotherapy are standard treatment options, post-treatment outcomes often end in a poor prognosis. In the present study, we investigated anti-pancreatic cancer and amelioration of radiation-induced oxidative damage by crocin. Crocin is a carotenoid isolated from the dietary herb saffron, a prospect for novel leads as an anti-cancer agent. Crocin significantly reduced cell viability of BXPC3 and Capan-2 by triggering caspase signaling via the downregulation of Bcl-2. It modulated the expression of cell cycle signaling proteins P53, P21, P27, CDK2, c-MYC, Cyt-c and P38. Concomitantly, crocin treatment-induced apoptosis by inducing the release of cytochrome c from mitochondria to cytosol. Microarray analysis of the expression signature of genes induced by crocin showed a substantial number of genes involved in cell signaling pathways and checkpoints (723) are significantly affected by crocin. In mice bearing pancreatic tumors, crocin significantly reduced tumor burden without a change in body weight. Additionally, it showed significant protection against radiation-induced hepatic oxidative damage, reduced the levels of hepatic toxicity and preserved liver morphology. These findings indicate that crocin has a potential role in the treatment, prevention and management of pancreatic cancer.
  14. El Rassi E, Adappa ND, Battaglia P, Castelnuovo P, Dallan I, Freitag SK, et al.
    Int Forum Allergy Rhinol, 2019 07;9(7):804-812.
    PMID: 30809970 DOI: 10.1002/alr.22316
    BACKGROUND: Orbital cavernous hemangiomas (OCH) are the most common adult orbital tumor and represent an ideal index lesion for endonasal orbital tumor surgery. In order to standardize outcomes reporting, an anatomic-based staging system was developed.

    METHODS: An international, multidisciplinary panel of 23 experts in orbital tumor surgery was formed. A modified Delphi method was used to develop the cavernous hemangioma exclusively endonasal resection (CHEER) staging system with a total of 2 rounds being completed.

    RESULTS: Tumors medial to a plane along the long axis of the optic nerve may be considered amenable for an exclusively endonasal resection. In select cases, tumors may extend inferolaterally if the tumor remains below a plane from the contralateral naris through the long axis of the optic nerve (ie, plane of resectability [POR]). This definition reached consensus with 91.3% of panelists in agreement. Five stages were designed based on increasing technical resection difficulty and potential for morbidity. Stages were based on the relationship of the tumor to the extraocular muscles, the inferomedial muscular trunk of the ophthalmic artery (IMT), and orbital foramina. Staging by anatomic location also reached consensus with 87.0% of panelists in agreement. Size was not included in the staging system due to the lack of agreement on the contribution of size to resection difficulty.

    CONCLUSION: Endoscopic orbital tumor surgery is a nascent field with a growing, yet heterogeneous, body of literature. The CHEER staging system is designed to facilitate international, high-quality, standardized studies establishing the safety, efficacy, and outcomes of endonasal resection of OCH.

  15. Senin A, Noordin NM, Sani JAM, Mahat D, Donadel M, Scobie HM, et al.
    PLoS One, 2024;19(3):e0298730.
    PMID: 38483868 DOI: 10.1371/journal.pone.0298730
    INTRODUCTION: A lateral flow rapid diagnostic test (RDT) enables detection of measles specific immunoglobulin M (IgM) antibody in serum, capillary blood, and oral fluid with accuracy consistent with enzyme immunoassay (EIA). The objectives of the study were: 1) to assess measles RDT inter-reader agreement between two clinic staff; 2) to assess the sensitivity and specificity of the measles RDT relative to standard surveillance testing in a low transmission setting; 3) to evaluate the knowledge, attitudes, and practices of staff in clinics using the RDT; and 4) to assess the impact of RDT testing on the measles public health response in Malaysia.

    MATERIALS AND METHODS: The clinic-based prospective evaluation included all suspected measles cases captured by routine measles surveillance at 34 purposely selected clinics in 15 health districts in Malaysia between September 2019 and June 2020, following day-long regional trainings on RDT use. Following informed consent, four specimens were collected from each suspected case, including those routinely collected for standard surveillance [serum for EIA and throat swabs for quantitative reverse transcriptase polymerase chain reaction (RT-qPCR)] together with capillary blood and oral fluid tested with RDTs during the study. RDT impact was evaluated by comparing the rapidity of measles public health response between the pre-RDT implementation (December 2018 to August 2019) and RDT implementation periods (September 2019 to June 2020). To assess knowledge, attitudes, and practices of RDT use, staff involved in the public health management of measles at the selected sites were surveyed.

    RESULTS: Among the 436 suspect cases, agreement of direct visual readings of measles RDT devices between two health clinic staff was 99% for capillary blood (k = 0.94) and 97% for oral fluid (k = 0.90) specimens. Of the total, 45 (10%) were positive by measles IgM EIA (n = 44, including five also positive by RT-qPCR) or RT-qPCR only (n = 1), and 38 were positive by RDT (using either capillary blood or oral fluid). Using measles IgM EIA or RT-qPCR as reference, RDT sensitivity using capillary blood was 43% (95% CI: 30%-58%) and specificity was 98% (95% CI: 96%-99%); using oral fluid, sensitivity (26%, 95% CI: 15%-40%) and specificity (97%, 95% CI: 94%-98%) were lower. Nine months after training, RDT knowledge was high among staff involved with the public health management of measles (average quiz score of 80%) and was highest among those who received formal training (88%), followed by those trained during supervisory visits (83%). During the RDT implementation period, the number of days from case confirmation until initiation of public response decreased by about 5 days.

    CONCLUSION: The measles IgM RDT shows >95% inter-reader agreement, high retention of RDT knowledge, and a more rapid public health response. However, despite ≥95% RDT specificity using capillary blood or oral fluid, RDT sensitivity was <45%. Higher-powered studies using highly specific IgM assays and systematic RT-qPCR for case confirmation are needed to establish the role of RDT in measles elimination settings.

  16. Dejonckheere E, Rhee JJ, Baguma PK, Barry O, Becker M, Bilewicz M, et al.
    Sci Rep, 2022 02 17;12(1):1514.
    PMID: 35177625 DOI: 10.1038/s41598-021-04262-z
    Happiness is a valuable experience, and societies want their citizens to be happy. Although this societal commitment seems laudable, overly emphasizing positivity (versus negativity) may create an unattainable emotion norm that ironically compromises individual well-being. In this multi-national study (40 countries; 7443 participants), we investigate how societal pressure to be happy and not sad predicts emotional, cognitive and clinical indicators of well-being around the world, and examine how these relations differ as a function of countries' national happiness levels (collected from the World Happiness Report). Although detrimental well-being associations manifest for an average country, the strength of these relations varies across countries. People's felt societal pressure to be happy and not sad is particularly linked to poor well-being in countries with a higher World Happiness Index. Although the cross-sectional nature of our work prohibits causal conclusions, our findings highlight the correlational link between social emotion valuation and individual well-being, and suggest that high national happiness levels may have downsides for some.
  17. Jafari A, Adappa ND, Anagnos VJ, Campbell RG, Castelnuovo P, Chalian A, et al.
    Int Forum Allergy Rhinol, 2023 Oct;13(10):1852-1863.
    PMID: 36808854 DOI: 10.1002/alr.23141
    BACKGROUND: The Cavernous Hemangioma Exclusively Endonasal Resection (CHEER) staging system has become the gold standard for outcomes reporting in endoscopic orbital surgery for orbital cavernous hemangiomas (OCHs). A recent systematic review demonstrated similar outcomes between OCHs and other primary benign orbital tumors (PBOTs). Therefore, we hypothesized that a simplified and more comprehensive classification system could be developed to predict surgical outcomes of other PBOTs.

    METHODS: Patient and tumor characteristics as well as surgical outcomes from 11 international centers were recorded. All tumors were retrospectively assigned an Orbital Resection by Intranasal Technique (ORBIT) class and stratified based on surgical approach as either exclusively endoscopic or combined (endoscopic and open). Outcomes based on approach were compared using chi-squared or Fisher's exact tests. The Cochrane-Armitage test for trend was used to analyze outcomes by class.

    RESULTS: Findings from 110 PBOTs from 110 patients (age 49.0 ± 15.0 years, 51.9% female) were included in the analysis. Higher ORBIT class was associated with a lower likelihood of gross total resection (GTR). GTR was more likely to be achieved when an exclusively endoscopic approach was utilized (p 

  18. Erker C, Mynarek M, Bailey S, Mazewski CM, Baroni L, Massimino M, et al.
    J Clin Oncol, 2023 Apr 01;41(10):1921-1932.
    PMID: 36548930 DOI: 10.1200/JCO.21.02968
    PURPOSE: Infant and young childhood medulloblastoma (iMB) is usually treated without craniospinal irradiation (CSI) to avoid neurocognitive late effects. Unfortunately, many children relapse. The purpose of this study was to assess salvage strategies and prognostic features of patients with iMB who relapse after CSI-sparing therapy.

    METHODS: We assembled a large international cohort of 380 patients with relapsed iMB, age younger than 6 years, and initially treated without CSI. Univariable and multivariable Cox models of postrelapse survival (PRS) were conducted for those treated with curative intent using propensity score analyses to account for confounding factors.

    RESULTS: The 3-year PRS, for 294 patients treated with curative intent, was 52.4% (95% CI, 46.4 to 58.3) with a median time to relapse from diagnosis of 11 months. Molecular subgrouping was available for 150 patients treated with curative intent, and 3-year PRS for sonic hedgehog (SHH), group 4, and group 3 were 60%, 84%, and 18% (P = .0187), respectively. In multivariable analysis, localized relapse (P = .0073), SHH molecular subgroup (P = .0103), CSI use after relapse (P = .0161), and age ≥ 36 months at initial diagnosis (P = .0494) were associated with improved survival. Most patients (73%) received salvage CSI, and although salvage chemotherapy was not significant in multivariable analysis, its use might be beneficial for a subset of children receiving salvage CSI < 35 Gy (P = .007).

    CONCLUSION: A substantial proportion of patients with relapsed iMB are salvaged after initial CSI-sparing approaches. Patients with SHH subgroup, localized relapse, older age at initial diagnosis, and those receiving salvage CSI show improved PRS. Future prospective studies should investigate optimal CSI doses and the role of salvage chemotherapy in this population.

  19. Thomassen M, Mesman RLS, Hansen TVO, Menendez M, Rossing M, Esteban-Sánchez A, et al.
    Hum Mutat, 2022 Dec;43(12):1921-1944.
    PMID: 35979650 DOI: 10.1002/humu.24449
    Skipping of BRCA2 exon 3 (∆E3) is a naturally occurring splicing event, complicating clinical classification of variants that may alter ∆E3 expression. This study used multiple evidence types to assess pathogenicity of 85 variants in/near BRCA2 exon 3. Bioinformatically predicted spliceogenic variants underwent mRNA splicing analysis using minigenes and/or patient samples. ∆E3 was measured using quantitative analysis. A mouse embryonic stem cell (mESC) based assay was used to determine the impact of 18 variants on mRNA splicing and protein function. For each variant, population frequency, bioinformatic predictions, clinical data, and existing mRNA splicing and functional results were collated. Variant class was assigned using a gene-specific adaptation of ACMG/AMP guidelines, following a recently proposed points-based system. mRNA and mESC analysis combined identified six variants with transcript and/or functional profiles interpreted as loss of function. Cryptic splice site use for acceptor site variants generated a transcript encoding a shorter protein that retains activity. Overall, 69/85 (81%) variants were classified using the points-based approach. Our analysis shows the value of applying gene-specific ACMG/AMP guidelines using a points-based approach and highlights the consideration of cryptic splice site usage to appropriately assign PVS1 code strength.
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