METHODS: This cross-sectional seroprevalence study with a two-stage stratified random cluster sampling design included 5,131 representative community dwellers in Malaysia aged ≥1 year. Data collection lasted from 7 August to 11 October 2020 involving venous blood sampling and interviews for history of COVID-19 symptoms and diagnosis. Previous SARS-CoV-2 infection was defined as screened positive using the Wantai SARS-CoV-2 Total Antibody enzyme-linked immunosorbent assay and confirmed positive using the GenScript SARS-CoV-2 surrogate Virus Neutralization Test. We performed a complex sampling design analysis, calculating sample weights considering probabilities of selection, non-response rate and post-stratification weight.
RESULTS: The overall weighted prevalence of SARS-CoV-2 infection was 0.49% (95%CI 0.28-0.85) (N = 150,857). Among the estimated population with past infection, around 84.1% (95%CI 58.84-95.12) (N = 126 826) were asymptomatic, and 90.1% (95%CI 67.06-97.58) (N = 135 866) were undiagnosed.
CONCLUSIONS: Our study revealed a low pre-variant and pre-vaccination seroprevalence of SARS-CoV-2 infection in Malaysia up to mid-October 2020, with a considerable proportion of asymptomatic and undiagnosed cases. This led to subsequent adoption of SARS-CoV-2 antigen rapid test kits to increase case detection rate and to reduce time to results and infection control measures.
METHOD: Data was collected on 1085 CI recipients of as part of a prospective, longitudinal, observational, international, multi-centre, paediatric registry, initiated by Cochlear Ltd (Sydney, NSW, Australia). Outcome data from children (≤10 years old) implanted in routine practice was voluntarily entered into a central, externally hosted, e-platform. Collection occurred prior to initial device activation (baseline) and at six monthly follow-up intervals up to 24 months and then at 3 years post activation. Clinician reported baseline and follow up questionnaires and Categories of Auditory Performance version II (CAP-II) outcomes were collated. Self-reported evaluation forms and patient information were provided by the parent/caregiver/patient via the implant recipient baseline and follow up, Children Using Hearing Implants Quality of Life (CuHIQoL) and Speech Spatial Qualities (SSQ-P) Parents Version questionnaires.
RESULTS: Children were mainly bilaterally profoundly deaf, unilaterally implanted and used a contralateral hearing aid. Prior to implant 60% used signing or total communication as their main mode of communication. Mean age at implant was 3.2 ± 2.2 years (range 0-10 years). At baseline 8.6% were in mainstream education with no additional support and 82% had not yet entered school. After three years of implant use, 52% had entered mainstream education with no additional support and 38% had not yet entered school. In the sub-group of 141 children who were implanted at or after three years of age and were thus old enough to be in mainstream school at the three-year follow up, an even higher proportion (73%) were in mainstream education with no support. Quality of life scores for the child improved statistically significantly post implant compared to baseline and continued to improve significantly at each interval up to 3 years (p
SUMMARY ANSWER: Age, ethnicity, obesity (BMI ≥ 30 kg/m2), and polycystic ovarian syndrome (PCOS) significantly impacted serum AMH levels, with the rate of decrease accelerating as age increased; a concentration of 4.0 ng/ml was the optimal cut-off for diagnosis of PCOS.
WHAT IS KNOWN ALREADY: There are significant differences in ovarian reserve among women from different races and ethnicities, and Asian women often have poorer reproductive outcomes during assisted reproductive treatment cycles.
STUDY DESIGN, SIZE, DURATION: A population-based multi-nation, multi-centre, multi-ethnicity prospective cohort study of 4613 women was conducted from January 2020 to May 2021. Infertile women of 20-43 years of age were enrolled. The exclusion criteria included: age <20 or >43, non-Asian ethnicity, and missing critical data.
PARTICIPANTS/MATERIALS, SETTING, METHODS: Participants were Asian women of Chinese, Japanese, Korean, Thai, Vietnamese, Malay, Indian, and Indonesian ethnicities from 12 IVF centres across Asia. These women were all naïve to ovarian stimulation cycles and attended IVF centres for fertility assessment. The AMH measurement was performed using an AMH automated assay on a clinically validated platform.
MAIN RESULTS AND THE ROLE OF CHANCE: A total of 4556 infertile Asian women were included in the final analyses. The mean ± SD for serum AMH concentrations (ng/ml) across specific age groups were: overall, 3.44 ± 2.93; age <30, 4.58 ± 3.16; 30-31, 4.23 ± 3.23; 32-33, 3.90 ± 3.06; 34-35, 3.21 ± 2.65; 36-37, 2.74 ± 2.44; 38-39, 2.30 ± 1.91; 40 and above, 1.67 ± 2.00. The rate of AMH decrease was ∼0.13 ng/ml/year in patients aged 25-33 and 0.31 ng/ml/year in women aged 33-43. The highest rates of PCOS were found in Indians (18.6%), Malays (18.9%), and Vietnamese (17.7%). Age (P S): This study was technically supported by Ferring Pharmaceuticals and received no specific grant from any funding agency. All authors have no competing interests to disclose.
TRIAL REGISTRATION NUMBER: NCT04203355.
DISCUSSION: We present a summary of the current and novel TPT regimens, including current evidence of use with antiretroviral regimens (ART). We review challenges and opportunities to scale-up TB prevention within HIV programmes, including the use of differentiated care approaches and demand creation for effective TB/HIV services delivery. TB preventive vaccines and diagnostics, including optimal algorithms, while important topics, are outside of the focus of this commentary.
CONCLUSIONS: A number of new tools and strategies to make TPT a standard of care in HIV programmes have become available. The new TPT regimens are safe and effective and can be used with current ART, with attention being paid to potential drug-drug interactions between rifamycins and some classes of antiretrovirals. More research and development is needed to optimize TPT for small children, pregnant women and drug-resistant TB (DR-TB). Effective programmatic scale-up can be supported through context-adapted demand creation strategies and the inclusion of TPT in client-centred services, such as differentiated service delivery (DSD) models. Robust collaboration between the HIV and TB programmes represents a unique opportunity to ensure that TB, a preventable and curable condition, is no longer the number one cause of death in PLHIV.
METHODOLOGY: A retrospective analysis of a methanol poisoning outbreak in September 2018 was performed, describing patients who presented to a major tertiary referral centre.
RESULT: A total of 31 patients were received over the period of 9 days. Thirty of them were males with a mean age of 32 years old. They were mostly foreigners. From the 31 patients, 19.3% were dead on arrival, 3.2% died in the emergency department and 38.7% survived and discharged. The overall mortality rate was 61.3%. Out of the 12 patients who survived, two patients had toxic optic neuropathy, and one patient had uveitis. The rest of the survivors did not have any long-term complications. Osmolar gap and lactate had strong correlations with patient's mortality. Serum pH, bicarbonate, lactate, potassium, anion gap, osmolar gap and measured serum osmolarity between the alive and dead patients were significant. Post-mortem findings of the brain were unremarkable.
CONCLUSION: The mortality rate was higher, and the morbidity includes permanent visual impairment and severe neurological sequelae. Language barrier, severity of illness, late presentation, unavailability of intravenous ethanol and fomipezole and delayed dialysis may have been the contributing factors. Patient was managed based on clinical presentation. Laboratory parameters showed difference in median between group that survived and succumbed for pH, serum bicarbonate, lactate, potassium and osmolar and anion gap. Management of methanol toxicity outbreak in resource-limited area will benefit from a well-designed guideline that is adaptable to the locality.
AREAS COVERED: We intend to discuss the pathogenesis, diagnosis, and treatment modalities directed toward EBV-associated LPD in patients with distinct IEIs.
EXPERT OPINION: EBV-driven lymphoproliferation in IEIs presents a diagnostic and therapeutic problem that necessitates a comprehensive understanding of host-pathogen interactions, immune dysregulation, and personalized treatment approaches. A multidisciplinary approach involving immunologists, hematologists, infectious disease specialists, and geneticists is paramount to addressing the diagnostic and therapeutic challenges posed by this intriguing yet formidable clinical entity.
RECENT FINDINGS: Several F-box containing proteins have been characterized either as tumor suppressors (FBXW8, FBXL3, FBXW8, FBXL3, FBXO1, FBXO4, and FBXO18) or as oncogenes (FBXO5, FBXO9, and SKP2). Besides, F-box members like βTrcP1 and βTrcP2, the ones with context-dependent functionality, have also been studied and reported. FBXW7 is a well-studied F-box protein and is a tumor suppressor. FBXW7 regulates the activity of a range of substrates, such as c-Myc, cyclin E, mTOR, c-Jun, NOTCH, myeloid cell leukemia sequence-1 (MCL1), AURKA, NOTCH through the well-known ubiquitin-proteasome system (UPS)-mediated degradation pathway. NOTCH signaling is a primitive pathway that plays a crucial role in maintaining normal tissue homeostasis. FBXW7 regulates NOTCH protein activity by controlling its half-life, thereby maintaining optimum protein levels in tissue. However, aberrations in the FBXW7 or NOTCH expression levels can lead to poor prognosis and detrimental outcomes in patients. Therefore, the FBXW7-NOTCH axis has been a subject of intense study and research over the years, especially around the interactome's role in driving cancer development and progression. Several studies have reported the effect of FBXW7 and NOTCH mutations on normal tissue behavior. The current review attempts to critically analyze these mutations prognostic value in a wide range of tumors. Furthermore, the review summarizes the recent findings pertaining to the FBXW7 and NOTCH interactome and its involvement in phosphorylation-related events, cell cycle, proliferation, apoptosis, and metastasis.
CONCLUSION: The review concludes by positioning FBXW7 as an effective diagnostic marker in tumors and by listing out recent advancements made in cancer therapeutics in identifying protocols targeting the FBXW7-NOTCH aberrations in tumors.