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  1. Lee ZY, Lew CCH, Berger MM, Hill A, Stoppe C
    Lancet Respir Med, 2023 Jul;11(7):e62-e63.
    PMID: 37244261 DOI: 10.1016/S2213-2600(23)00214-X
    Matched MeSH terms: Humans
  2. Wise SK, Damask C, Roland LT, Ebert C, Levy JM, Lin S, et al.
    Int Forum Allergy Rhinol, 2023 Apr;13(4):293-859.
    PMID: 36878860 DOI: 10.1002/alr.23090
    BACKGROUND: In the 5 years that have passed since the publication of the 2018 International Consensus Statement on Allergy and Rhinology: Allergic Rhinitis (ICAR-Allergic Rhinitis 2018), the literature has expanded substantially. The ICAR-Allergic Rhinitis 2023 update presents 144 individual topics on allergic rhinitis (AR), expanded by over 40 topics from the 2018 document. Originally presented topics from 2018 have also been reviewed and updated. The executive summary highlights key evidence-based findings and recommendation from the full document.

    METHODS: ICAR-Allergic Rhinitis 2023 employed established evidence-based review with recommendation (EBRR) methodology to individually evaluate each topic. Stepwise iterative peer review and consensus was performed for each topic. The final document was then collated and includes the results of this work.

    RESULTS: ICAR-Allergic Rhinitis 2023 includes 10 major content areas and 144 individual topics related to AR. For a substantial proportion of topics included, an aggregate grade of evidence is presented, which is determined by collating the levels of evidence for each available study identified in the literature. For topics in which a diagnostic or therapeutic intervention is considered, a recommendation summary is presented, which considers the aggregate grade of evidence, benefit, harm, and cost.

    CONCLUSION: The ICAR-Allergic Rhinitis 2023 update provides a comprehensive evaluation of AR and the currently available evidence. It is this evidence that contributes to our current knowledge base and recommendations for patient evaluation and treatment.

    Matched MeSH terms: Humans
  3. Schliemann D, Jamil ASA, Mohan D, Tan MM, Cardwell CR, Ismail R, et al.
    PLoS One, 2023;18(10):e0288437.
    PMID: 37796803 DOI: 10.1371/journal.pone.0288437
    INTRODUCTION: Breast cancer (BC) screening uptake in Malaysia is low and a high number of cases present at a late stage. Community navigation and mobile health (mHealth) may increase screening attendance, particularly by women from rural communities. This randomized controlled study evaluated an intervention that used mHealth and community health workers to educate women about BC screening and navigate them to clinical breast examination (CBE) services in the context of the COVID-19 pandemic.

    METHODS: Women aged 40-74 years, from Segamat, Malaysia, with a mobile phone number, who participated in the South East Asian Community Observatory health survey, (2018) were randomized to an intervention (IG) or comparison group (CG). The IG received a multi-component mHealth intervention, i.e. information about BC was provided through a website, and telephone calls and text messages from community health workers (CHWs) were used to raise BC awareness and navigate women to CBE services. The CG received no intervention other than the usual option to access opportunistic screening. Regression analyses were conducted to investigate between-group differences over time in uptake of screening and variable influences on CBE screening participation.

    RESULTS: We recruited 483 women in total; 122/225 from the IG and 144/258 from the CG completed the baseline and follow-up survey. Uptake of CBE by the IG was 45.8% (103/225) whilst 3.5% (5/144) of women from the CG who completed the follow-up survey reported that they attended a CBE during the study period (adjusted OR 37.21, 95% CI 14.13; 98.00, p<0.001). All IG women with a positive CBE attended a follow-up mammogram (11/11). Attendance by IG women was lower among women with a household income ≥RM 4,850 (adjusted OR 0.48, 95% CI 0.20; 0.95, p = 0.038) compared to participants with a household income

    Matched MeSH terms: Humans
  4. Sidonio RF, Thompson AA, Peyvandi F, Stasyshyn O, Yeoh SL, Sosothikul D, et al.
    Expert Rev Hematol, 2023;16(10):793-801.
    PMID: 37646148 DOI: 10.1080/17474086.2023.2247160
    AIM: To determine the immunogenicity, safety, and efficacy of rurioctocog alfa pegol in previously untreated patients (PUPs) with severe hemophilia A (HA).

    METHODS: This prospective, phase 3 study (NCT02615691) was conducted in PUPs, or patients with ≤2 exposure days (EDs) prior to screening, aged <6 years with severe HA. The primary endpoint was incidence of factor VIII (FVIII) inhibitor development. This protocol-specified interim analysis was conducted after 50 patients had completed ≥50 EDs without developing FVIII inhibitors or had developed a confirmed inhibitor at any time.

    RESULTS: Of the enrolled patients, 59/80 (73.8%) received ≥1 dose of rurioctocog alfa pegol; 54 received prophylaxis, and 35 on-demand treatment. Incidence of inhibitor development was 0.19 (10/52). Total annualized bleeding rate (95% CIs) was 3.2 (2.0-5.0) for patients receiving prophylaxis and 3.2 (1.6-6.3) for on-demand treatment. Hemostatic efficacy of most bleedings was rated as 'excellent' or 'good' after 24 hours (122/131 [93.1%]) and at resolution (161/170 [94.7%]). Five patients received ≥1 dose of rurioctocog alfa pegol for immune tolerance induction (ITI) and 1 patient was defined as having ITI success. Thirteen patients experienced 14 treatment-related adverse events, including 10 cases of FVIII inhibitor development.

    CONCLUSION: This is the first prospective study of rurioctocog alfa pegol for the treatment of PUPs with severe HA.

    TRIAL REGISTRATION: This trial is registered at ClinicalTrials.gov (CT.gov identifier: NCT02615691).

    Matched MeSH terms: Humans
  5. Umar M, Ahmad A, Sroufe R, Muhammad Z
    Environ Sci Pollut Res Int, 2024 Feb;31(10):15026-15038.
    PMID: 38285260 DOI: 10.1007/s11356-024-31952-8
    Enterprises across the globe are facing increasing pressure to effectively utilize resources and reduce costs through green supply chain practices. Emerging technology, such as blockchain technology which enables green practices, has become a contemporary industrial paradigm. However, enterprises need to build green intellectual capital to implement blockchain technology, which can be key to realizing green supply chain practices. This research examines the impact of green intellectual capital (GIC) on blockchain technology and its role in implementing green manufacturing to achieve sustainability. Partial least squares structural equation modeling was utilized for assessing the proposed hypotheses, and cross-sectional data was accumulated from manufacturing firms. As per the results, GIC, which includes green human capital, green structural capital, and green relational capital has a crucial role in the implementation of blockchain technology. The outcomes also indicated that the adoption of blockchain technology significantly influences green manufacturing. Moreover, green manufacturing (GM) has a substantial role in improving business sustainability. This empirical research provides a deeper understanding of how GIC and blockchain technology contribute to the implementation of GM. This research also provides guidelines that managers, policymakers, and producers can use to facilitate the incorporation of GM practice into business activities.
    Matched MeSH terms: Humans
  6. Qing H, Ibrahim R, Nies HW
    Sci Rep, 2024 Feb 26;14(1):4657.
    PMID: 38409430 DOI: 10.1038/s41598-024-54444-8
    The evolution of Internet technology has led to an increase in online users. This study focuses on the pivotal role of visual elements in web content conveyance and their impact on user browsing behavior. Therefore, the use of visual elements in web design based on big data has aroused widespread concern among web designers, they apply visual elements to their web design works to make the web more attractive. This study examines the composition and distribution characteristics of key visual elements identified through user behavior data in a big data environment and discusses the use of visual elements in web design in the era of network economy. In addition, this paper issued 200 questionnaires to investigate the degree of attention to visual elements in web pages for users of different occupations and different educational backgrounds. Our survey indicated that visual elements captured the attention of 41% of corporate employees, whereas a mere 1% of social welfare workers focused on web content; 36% of undergraduates pay attention to visual elements of web pages, but only 5% and 4% of postgraduates and doctoral degrees and above. Therefore, the visual elements of the designed web page need to conform to the user's cultural background and professional background.
    Matched MeSH terms: Humans
  7. Muro K, Lordick F, Tsushima T, Pentheroudakis G, Baba E, Lu Z, et al.
    Ann Oncol, 2019 Jan 01;30(1):34-43.
    PMID: 30475943 DOI: 10.1093/annonc/mdy498
    The most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of oesophageal cancer was published in 2016, and covered the management and treatment of local/locoregional disease, limited disease, locally advanced disease and the management of advanced/metastatic disease. At the ESMO Asia Meeting in November 2017 it was decided by both ESMO and the Japanese Society of Medical Oncology (JSMO) to convene a special guidelines meeting immediately after the JSMO Annual Meeting in 2018. The aim was to adapt the ESMO 2016 guidelines to take into account the ethnic differences associated with the treatment of metastatic oesophageal cancer in Asian patients. These guidelines represent the consensus opinions reached by experts in the treatment of patients with metastatic oesophageal cancer representing the oncological societies of Japan (JSMO), China (CSCO), Korea (KSMO), Malaysia (MOS), Singapore (SSO) and Taiwan (TOS). The voting was based on scientific evidence, and was independent of both the current treatment practices and the drug availability and reimbursement situations in the individual participating Asian countries.
    Matched MeSH terms: Humans
  8. Lanciano T, Alfeo F, Curci A, Marin C, D'Uggento AM, Decarolis D, et al.
    Memory, 2024 Feb;32(2):264-282.
    PMID: 38315731 DOI: 10.1080/09658211.2024.2310554
    Flashbulb memories (FBMs) refer to vivid and long-lasting autobiographical memories for the circumstances in which people learned of a shocking and consequential public event. A cross-national study across eleven countries aimed to investigate FBM formation following the first COVID-19 case news in each country and test the effect of pandemic-related variables on FBM. Participants had detailed memories of the date and others present when they heard the news, and had partially detailed memories of the place, activity, and news source. China had the highest FBM specificity. All countries considered the COVID-19 emergency as highly significant at both the individual and global level. The Classification and Regression Tree Analysis revealed that FBM specificity might be influenced by participants' age, subjective severity (assessment of COVID-19 impact in each country and relative to others), residing in an area with stringent COVID-19 protection measures, and expecting the pandemic effects. Hierarchical regression models demonstrated that age and subjective severity negatively predicted FBM specificity, whereas sex, pandemic impact expectedness, and rehearsal showed positive associations in the total sample. Subjective severity negatively affected FBM specificity in Turkey, whereas pandemic impact expectedness positively influenced FBM specificity in China and negatively in Denmark.
    Matched MeSH terms: Humans
  9. Abdul-Halim MAZ, Baharudin N, Abdul-Hamid H, Mohamed-Yassin MS, Daud MH, Badlishah-Sham SF, et al.
    BMC Prim Care, 2024 Feb 03;25(1):51.
    PMID: 38310212 DOI: 10.1186/s12875-024-02281-z
    BACKGROUND: Self-management support has been recognized as one of the most essential elements of the Chronic Care Model (CCM). Inspired by the CCM, the EMPOWER-SUSTAIN Global Cardiovascular Risks Self-Management Booklet© was developed to aid and sustain self-management among patients with metabolic syndrome (MetS) in primary care to prevent cardiovascular complications. However, the usability of this booklet among these patients is not known. Therefore, this study aimed to evaluate the usability of this self-management booklet and identify the factors associated with its usability among patients with MetS in primary care.

    METHODS: This cross-sectional study was conducted among patients with MetS attending a university primary care clinic in Selangor, Malaysia. The usability score was measured using a previously translated and validated EMPOWER-SUSTAIN Usability Questionnaire (E-SUQ) with a score of > 68 indicating good usability. Multiple logistic regressions determined the factors associated with its usability.

    RESULTS: A total of 391 patients participated in this study. More than half (61.4%) had a good usability score of > 68, with a mean (± SD) usability score of 72.8 (± 16.1). Participants with high education levels [secondary education (AOR 2.46, 95% CI 1.04, 5.83) and tertiary education (AOR 2.49, 95% CI 1.04, 5.96)], those who used the booklet at home weekly (AOR 2.94, 95% CI 1.63, 5.33) or daily (AOR 2.73, 95% CI 1.09, 6.85), and those who had social support to use the booklet (AOR 1.64, 95% CI 1.02, 2.64) were significantly associated with good usability of the booklet.

    CONCLUSIONS: The usability of the EMPOWER-SUSTAIN Global Cardiovascular Risks Self-Management Booklet© was good among patients with MetS in this primary care clinic, which supports its widespread use as a patient empowerment tool. The findings of this study also suggest that it is vital to encourage daily or weekly use of this booklet at home, with the support of family members. The focus should also be given to those with lower education to improve the usability of this booklet for this group of patients.

    Matched MeSH terms: Humans
  10. Boufkhed S, Thorogood N, Ariti C, Durand MA
    BMJ Glob Health, 2024 Feb 05;9(2).
    PMID: 38316464 DOI: 10.1136/bmjgh-2023-013521
    BACKGROUND: The exploitation of migrant workers ranks high on global political agendas including the Sustainable Development Goals. Research on exploited workers, using assessment tools where exploitation is defined by professional experts, indicates serious health concerns and needs. Yet, migrant workers are rarely asked about their understanding of a phenomenon they may experience. Our study aimed to conceptualise 'labour exploitation' from the perspective of migrant workers employed in manual low-skilled jobs.

    METHODS: Twenty-seven Latin Americans working in London (UK) participated in Group Concept Mapping; a participatory mixed-method where qualitative data are collected to define a concept's content and then analysed using quantitative methods to generate a structured conceptual framework. Participants generated statements describing the concept content during brainstorming sessions, and structured them during sorting-rating exercises. Multi-Dimensional Scaling and Cluster Analysis were performed, generating a conceptual framework that clarified the dimensions, subdimensions and constituent statements of the concept of labour exploitation from migrant workers' perspectives.

    RESULTS: Three key dimensions were identified: 'poor employment conditions and lack of protection', covering contractual arrangements and employment relations; 'disposability and abuse of power' (or 'dehumanisation') covering mechanisms or means which make migrant workers feel disposable and abused; and 'health and safety and psychosocial hazards' encompassing issues from physical and psychosocial hazards to a lack of health and social protection. 'Dehumanisation' has not been included in mainstream tools assessing exploitation, despite its importance for study participants who also described harsh situations at work including sexual, physical and verbal abuse.

    CONCLUSION: Our study provides a conceptual framework of labour exploitation that gives voice to migrant workers and can be operationalised into a measure of migrant labour exploitation. It also calls for the dimension 'dehumanisation' and structural forms of coercion to be integrated into mainstream conceptualisations, and their workplace hazards to be urgently addressed.

    Matched MeSH terms: Humans
  11. Muro K, Van Cutsem E, Narita Y, Pentheroudakis G, Baba E, Li J, et al.
    Ann Oncol, 2019 Jan 01;30(1):19-33.
    PMID: 30475956 DOI: 10.1093/annonc/mdy502
    The most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of gastric cancer (GC) was published in 2016, and covered the management and treatment of local, locoregional, locally advanced and metastatic disease. At the ESMO Asia Meeting in November 2017 it was decided by both ESMO and The Japanese Society of Medical Oncology (JSMO) to convene a special guidelines meeting immediately after the JSMO Annual Meeting in 2018. The aim was to adapt the ESMO 2016 guidelines to take into account the ethnic differences associated with the treatment of metastatic GC in Asian patients. These guidelines represent the consensus opinions reached by experts in the treatment of patients with metastatic GC representing the oncological societies of Japan (JSMO), China (CSCO), Korea (KSMO), Malaysia (MOS), Singapore (SSO) and Taiwan (TOS). The voting was based on scientific evidence and was independent of both the current treatment practices and the drug availability and reimbursement situations in the individual participating Asian countries.
    Matched MeSH terms: Humans
  12. Ong MLY, Green CG, Bongiovanni T, Heaney LM
    Benef Microbes, 2023 Dec 12;14(6):565-590.
    PMID: 38350483 DOI: 10.1163/18762891-20230069
    The gut microbiome is known to play an important role in the day-to-day physiology and health of the human host. It is, therefore, not surprising that there is interest surrounding the gut microbiome and its potential to benefit athletic health and performance. This has, in part, been driven by the consideration that gut bacterial by-products (i.e. metabolic waste) could be harnessed by the host and utilised for a beneficial outcome. The concept of harnessing bacterial metabolites as beneficial health modulators has developed the theory of leveraging short-chain fatty acids (SCFAs) as novel supplements for enhancing athletic performance. This review discusses the current literature investigating SCFA administration in cellular, animal, and human models, with the aim of linking the demonstrated physiological/biochemical mechanisms to potential exercise/athletic benefit. In addition, practical implications and factors relating to SCFA-supplementation in athletic populations are considered. The literature demonstrates a tangible rationale that SCFAs can have a positive impact on human physiology to afford benefits to the athletic population. These advantages include the capacity to improve respiratory immunity to combat elevated levels/severity of upper respiratory tract infections often reported in athletes; the blunting of pro-inflammatory and pro-fibrotic pathways to aid in exercise recovery; and the role of SCFAs as usable energy sources and metabolism modulators to fuel exercise and improve performance and/or endurance capacity. However, there is currently minimal research completed in human participants and thus further investigations into the direct benefit of SCFAs in exercise performance and/or recovery-based studies are required.
    Matched MeSH terms: Humans
  13. Selvavinayagam ST, Suvaithenamudhan S, Yong YK, Hemashree K, Rajeshkumar M, Kumaresan A, et al.
    J Med Virol, 2024 Feb;96(2):e29456.
    PMID: 38329187 DOI: 10.1002/jmv.29456
    A state-wide prospective longitudinal investigation of the genomic surveillance of the omicron B.1.1.529 SARS-CoV-2 variant and its sublineages in Tamil Nadu, India, was conducted between December 2021 and March 2023. The study aimed to elucidate their mutational patterns and their genetic interrelationship in the Indian population. The study identified several unique mutations at different time-points, which likely could attribute to the changing disease characteristics, transmission, and pathogenicity attributes of omicron variants. The study found that the omicron variant is highly competent in its mutating potentials, and that it continues to evolve in the general population, likely escaping from natural as well as vaccine-induced immune responses. Our findings suggest that continuous surveillance of viral variants at the global scenario is warranted to undertake intervention measures against potentially precarious SARS-CoV-2 variants and their evolution.
    Matched MeSH terms: Humans
  14. Fox L, Santaolalla A, Handford J, Sullivan R, Torode J, Vanderpuye V, et al.
    JCO Glob Oncol, 2023 Aug;9:e2300111.
    PMID: 37561978 DOI: 10.1200/GO.23.00111
    PURPOSE: The post-COVID-19 funding landscape for cancer research globally has become increasingly challenging, particularly in resource-challenged regions (RCRs) lacking strong research ecosystems. We aimed to produce a list of priority areas for cancer research in countries with limited resources, informed by researchers and patients.

    METHODS: Cancer experts in lower-resource health care systems (as defined by the World Bank as low- and middle-income countries; N = 151) were contacted to participate in a modified consensus-seeking Delphi survey, comprising two rounds. In round 1, participants (n = 69) rated predetermined areas of potential research priority (ARPs) for importance and suggested missing ARPs. In round 2, the same participants (n = 49) rated an integrated list of predetermined and suggested ARPs from round 1, then undertook a forced choice priority ranking exercise. Composite voting scores (T-scores) were used to rank the ARPs. Importance ratings were summarized descriptively. Findings were discussed with international patient advocacy organization representatives.

    RESULTS: The top ARP was research into strategies adapting guidelines or treatment strategies in line with available resources (particularly systemic therapy) (T = 83). Others included cancer registries (T = 62); prevention (T = 52); end-of-life care (T = 53); and value-based and affordable care (T = 51). The top COVID-19/cancer ARP was strategies to incorporate what has been learned during the pandemic that can be maintained posteriorly (T = 36). Others included treatment schedule interruption (T = 24); cost-effective reduction of COVID-19 morbidity/mortality (T = 19); and pandemic preparedness (T = 18).

    CONCLUSION: Areas of strategic priority favored by cancer researchers in RCRs are related to adaptive treatment guidelines; sustainable implementation of cancer registries; prevention strategies; value-based and affordable cancer care; investments in research capacity building; epidemiologic work on local risk factors for cancer; and combatting inequities of prevention and care access.

    Matched MeSH terms: Humans
  15. Lee YL, Nasir FFWA, Selveindran NM, Zaini AA, Lim PG, Jalaludin MY
    Diabetes Res Clin Pract, 2023 Nov;205:110981.
    PMID: 37890700 DOI: 10.1016/j.diabres.2023.110981
    AIMS: Despite emerging evidence of increased paediatric diabetes mellitus (DM) and diabetic ketoacidosis (DKA) worldwide following the COVID-19 pandemic, studies in Asia are lacking. We aimed to determine the frequency, demographics, and clinical characteristics of new onset type 1 DM (T1DM) during the pandemic in Malaysia.

    METHODS: This is a retrospective multicenter study involving new onset T1DM paediatric patients in Klang Valley, Malaysia during two time periods ie 18th September 2017-17th March 2020 (pre-pandemic) and 18th March 2020-17th September 2022 (pandemic).

    RESULTS: There was a total of 180 patients with new onset T1DM during the 5-year study period (71 pre-pandemic, 109 pandemic). An increase in frequency of T1DM was observed during the pandemic (52 in 2021, 38 in 2020, 27 in 2019 and 30 in 2018). A significantly greater proportion of patients presented with DKA (79.8 % vs 64.8 %), especially severe DKA (46.8 % vs 28.2 %) during the pandemic. Serum glucose was significantly higher (28.2 mmol vs 25.9 mmol/L) with lower venous pH (7.10 vs 7.16), but HbA1c was unchanged.

    CONCLUSIONS: New onset T1DM increased during the pandemic, with a greater proportion having severe DKA. Further studies are required to evaluate the mechanism leading to this rise to guide intervention measures.

    Matched MeSH terms: Humans
  16. Wilcox N, Dumont M, González-Neira A, Carvalho S, Joly Beauparlant C, Crotti M, et al.
    Nat Genet, 2023 Sep;55(9):1435-1439.
    PMID: 37592023 DOI: 10.1038/s41588-023-01466-z
    Linkage and candidate gene studies have identified several breast cancer susceptibility genes, but the overall contribution of coding variation to breast cancer is unclear. To evaluate the role of rare coding variants more comprehensively, we performed a meta-analysis across three large whole-exome sequencing datasets, containing 26,368 female cases and 217,673 female controls. Burden tests were performed for protein-truncating and rare missense variants in 15,616 and 18,601 genes, respectively. Associations between protein-truncating variants and breast cancer were identified for the following six genes at exome-wide significance (P 
    Matched MeSH terms: Humans
  17. Byrne I, William T, Chua TH, Patterson C, Hall T, Tan M, et al.
    Sci Rep, 2023 Aug 10;13(1):12998.
    PMID: 37563178 DOI: 10.1038/s41598-023-39670-w
    Malaysia has reported no indigenous cases of P. falciparum and P. vivax for over 3 years. When transmission reaches such low levels, it is important to understand the individuals and locations where exposure risks are high, as they may be at greater risk in the case of a resurgence of transmission. Serology is a useful tool in low transmission settings, providing insight into exposure over longer durations than PCR or RDT. We ran blood samples from a 2015 population-based survey in northern Sabah, Malaysian Borneo on a multiplex bead assay. Using supervised machine learning methods, we characterised recent and historic exposure to Plasmodium falciparum and P. vivax and found recent exposure to P. falciparum to be very low, with exposure to both species increasing with age. We performed a risk-factor assessment on environmental, behavioural, demographic and household factors, and identified forest activity and longer travel times to healthcare as common risk-factors for exposure to P. falciparum and P. vivax. In addition, we used remote-sensing derived data and geostatistical models to assess environmental and spatial associations with exposure. We created predictive maps of exposure to recent P. falciparum in the study area and showed 3 clear foci of exposure. This study provides useful insight into the environmental, spatial and demographic risk factors for P. falciparum and P. vivax at a period of low transmission in Malaysian Borneo. The findings would be valuable in the case of resurgence of human malarias in the region.
    Matched MeSH terms: Humans
  18. Phoon WH, Bell-Sakyi L, AbuBakar S, Chang LY
    Trop Biomed, 2023 Mar 01;40(1):29-36.
    PMID: 37356001 DOI: 10.47665/tb.40.1.009
    Nipah virus (NiV), a highly pathogenic henipavirus of the family Paramyxoviridae, which causes fatal encephalitis in 40-70% of affected patients, was first reported in Malaysia over 20 years ago. Pteropid bats are the natural hosts of henipaviruses, and ticks have been proposed as a possible link between bats and mammalian hosts. To investigate this hypothesis, infection of the tick cell line IDE8 with NiV was examined. Presence of viral RNA and antigen in the NiV-infected tick cells was confirmed. Infectious virions were recovered from NiV-infected tick cells and ultrastructural features of NiV were observed by electron microscopy. These results suggest that ticks could support NiV infection, potentially playing a role in transmission.
    Matched MeSH terms: Humans
  19. Sieghart W, Chiou LC, Ernst M, Fabjan J, M Savić M, Lee MT
    Pharmacol Rev, 2022 Jan;74(1):238-270.
    PMID: 35017178 DOI: 10.1124/pharmrev.121.000293
    GABAA receptors containing the α6 subunit are highly expressed in cerebellar granule cells and less abundantly in many other neuronal and peripheral tissues. Here, we for the first time summarize their importance for the functions of the cerebellum and the nervous system. The cerebellum is not only involved in motor control but also in cognitive, emotional, and social behaviors. α6βγ2 GABAA receptors located at cerebellar Golgi cell/granule cell synapses enhance the precision of inputs required for cerebellar timing of motor activity and are thus involved in cognitive processing and adequate responses to our environment. Extrasynaptic α6βδ GABAA receptors regulate the amount of information entering the cerebellum by their tonic inhibition of granule cells, and their optimal functioning enhances input filtering or contrast. The complex roles of the cerebellum in multiple brain functions can be compromised by genetic or neurodevelopmental causes that lead to a hypofunction of cerebellar α6-containing GABAA receptors. Animal models mimicking neuropsychiatric phenotypes suggest that compounds selectively activating or positively modulating cerebellar α6-containing GABAA receptors can alleviate essential tremor and motor disturbances in Angelman and Down syndrome as well as impaired prepulse inhibition in neuropsychiatric disorders and reduce migraine and trigeminal-related pain via α6-containing GABAA receptors in trigeminal ganglia. Genetic studies in humans suggest an association of the human GABAA receptor α6 subunit gene with stress-associated disorders. Animal studies support this conclusion. Neuroimaging and post-mortem studies in humans further support an involvement of α6-containing GABAA receptors in various neuropsychiatric disorders, pointing to a broad therapeutic potential of drugs modulating α6-containing GABAA receptors. SIGNIFICANCE STATEMENT: α6-Containing GABAA receptors are abundantly expressed in cerebellar granule cells, but their pathophysiological roles are widely unknown, and they are thus out of the mainstream of GABAA receptor research. Anatomical and electrophysiological evidence indicates that these receptors have a crucial function in neuronal circuits of the cerebellum and the nervous system, and experimental, genetic, post-mortem, and pharmacological studies indicate that selective modulation of these receptors offers therapeutic prospects for a variety of neuropsychiatric disorders and for stress and its consequences.
    Matched MeSH terms: Humans
  20. Tweed CD, Wills GH, Crook AM, Amukoye E, Balanag V, Ban AYL, et al.
    Int J Tuberc Lung Dis, 2021 Apr 01;25(4):305-314.
    PMID: 33762075 DOI: 10.5588/ijtld.20.0513
    BACKGROUND: Treatment for TB is lengthy and toxic, and new regimens are needed.METHODS: Participants with pulmonary drug-susceptible TB (DS-TB) were randomised to receive: 200 mg pretomanid (Pa, PMD) daily, 400 mg moxifloxacin (M) and 1500 mg pyrazinamide (Z) for 6 months (6Pa200MZ) or 4 months (4Pa200MZ); 100 mg pretomanid daily for 4 months in the same combination (4Pa100MZ); or standard DS-TB treatment for 6 months. The primary outcome was treatment failure or relapse at 12 months post-randomisation. The non-inferiority margin for between-group differences was 12.0%. Recruitment was paused following three deaths and not resumed.RESULTS: Respectively 4/47 (8.5%), 11/57 (19.3%), 14/52 (26.9%) and 1/53 (1.9%) DS-TB outcomes were unfavourable in patients on 6Pa200MZ, 4Pa200MZ, 4Pa100MZ and controls. There was a 6.6% (95% CI -2.2% to 15.4%) difference per protocol and 9.9% (95%CI -4.1% to 23.9%) modified intention-to-treat difference in unfavourable responses between the control and 6Pa200MZ arms. Grade 3+ adverse events affected 68/203 (33.5%) receiving experimental regimens, and 19/68 (27.9%) on control. Ten of 203 (4.9%) participants on experimental arms and 2/68 (2.9%) controls died.CONCLUSION: PaMZ regimens did not achieve non-inferiority in this under-powered trial. An ongoing evaluation of PMD remains a priority.
    Matched MeSH terms: Humans
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