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Background: Sex differences in the pathogenesis of hypertension exist. While gut microbiota (GM) has been associated with hypertension, it is unclear whether there are sex-linked differences in the association between GM and hypertension. Methods: We conducted a cross-sectional study to investigate the sex differences in associations between GM characterized by shotgun sequencing, GM-derived short-chain fatty acids, and 24-hour ambulatory blood pressure in 241 Hong Kong Chinese (113 men and 128 women; mean age, 54±6 years). Results: The hypertensive group was associated with GM alterations; however, significant differences in β-diversity and GM composition in hypertensive versus normotensive groups were only observed in women and not in men under various statistical models adjusting for the following covariates: age, sex, body mass index, sodium intake estimated by spot urine analysis, blood glucose, triglycerides, low- and high-density lipoprotein cholesterol, smoking, menopause, and fatty liver status. Specifically, Ruminococcus gnavus , Clostridium bolteae , and Bacteroides ovatus were significantly more abundant in the hypertensive women, whereas Dorea formicigenerans was more abundant in the normotensive women. No bacterial species were found to be significantly associated with hypertension in men. Furthermore, total plasma short-chain fatty acids and propionic acid were independent predictors of systolic and diastolic blood pressure in women but not men. Conclusions: GM dysregulation was strongly associated with 24-hour ambulatory blood pressure in women but not men, which may be mediated through propionic acid. Our work suggests that sex differences may be an important consideration while assessing the role of GM in the development and treatment of hypertension.

Female genital melanomas are rare. At diagnosis, most affected patients have advanced disease. Surgery remains the primary treatment, and adjuvant therapy is largely ineffective. Recently, immune checkpoints and the mitogen-activated protein kinase pathway have been explored as treatment targets. However, evaluation of these biomarkers in genital melanomas is limited. We evaluated the clinicopathological features of 20 vulvar, 32 vaginal, and three cervical melanomas and assessed programmed cell death ligand 1 (PD-L1) expression, CD8 tumor-infiltrating lymphocyte density, mismatch repair proteins, VE1 immunohistochemistry, and KIT and BRAF mutations. The median age of the patients was 66 years, and median tumor sizes were 25, 30, and 20 mm for vulvar, vaginal, and cervical tumors, respectively. Mean mitotic figures were 18, 19, and 30 per mm2. Thirty-seven patients (67%) had operable tumors. After a median follow-up of 15 months, only nine patients (16%) were alive. Eight of the nine survivors did not have lymph node metastasis. Using 5% as the threshold, PD-L1 expression was observed in 55%, 50%, and 33% of vulvar, vaginal, and cervical tumors, respectively, when the Roche SP263 antibody was used and 20%, 53%, and 0%, respectively, when the Dako 28-8 antibody was used. The median CD8 tumor-infiltrating lymphocyte density was significantly higher in vulvar/vaginal than cervical melanomas and correlated with PD-L1 expression. No cases exhibited loss of mismatch repair proteins. Five cases harbored KIT mutations, three of which were hotspots. BRAF V600E mutation was not detected. Univariable analysis showed that tumor size greater than or equal to 33 mm, mitotic figures of greater than or equal to 10 per mm2, lymph node metastasis, and low CD8+ tumor-infiltrating lymphocyte density were adverse prognostic factors. Thus, patients with genital melanomas have a poor prognosis, and evaluation of multiple biomarkers is necessary to identify patients who may benefit from immunotherapy or targeted therapy.

Much research on children in high-risk environments has focused on the biological consequences of maltreatment, adversity, and trauma. Whether other early-life stress sources such as family financial hardship are implicated in the cellular mechanism of disease development remains unclear. This study investigated the long-term effect of childhood exposure to family financial pressure on telomere length. It involved two waves of data collection occurring when participants reached Grade 3 (W1) and 7 (W2), respectively. In W1, parents reported family demographics and perceived financial stressors and pressure. In W2, participants provided buccal swab samples for measurement of their telomere length. Data from 92 participants (Mage in W2 = 13.2 years; 56.5% male) were analyzed. The main type of stressors reported by parents who perceived high family financial pressure in W1 were child-level stressors including affordability of their medical and educational expenses. Participants exposed to high parent-perceived family financial pressure in W1 had shorter telomeres in W2 when compared to those exposed to low parent-perceived family financial pressure (β = −0.61, p = 0.042). Subgroup analyses revealed stronger associations in girls than boys. These findings reveal an important spillover effect between parental financial perceptions and stress and children’s health at the cellular level.

The novel SARS-CoV-2 Omicron variant may increase the risk of re-infection and vaccine breakthrough infections as it possesses key mutations in the spike protein that affect neutralizing antibody response. Most studies on neutralization susceptibility were conducted using specimens from adult COVID-19 patients or vaccine recipients. However, since the paediatric population has an antibody response to SARS-CoV-2 infection that is distinct from the adult population, it is critical to assess the neutralization susceptibility of pediatric serum specimens. This study compared the neutralization susceptibility of serum specimens collected from 49 individuals of

Background Antimicrobial resistance is an increasingly important issue in public health as antibiotics are overused. Resistance to antimicrobial agents can pose significant challenges to infection treatment. Objectives To evaluate risk factors associated with carriage of antimicrobial-resistant (AMR) bacteria in children in the Asia-Pacific region to consolidate evidence for future implementation of antibiotic prescribing practice. Methods Three electronic databases—PubMed, EMBASE and Cochrane Library—were searched. Observational studies that investigated the risk factors for carriage of MRSA, penicillin-resistant Streptococcus pneumoniae, ESBL-producing Escherichia coli and Klebsiella pneumoniae among the paediatric population in community settings in the Asia-Pacific region were considered eligible. Summary statistics from the identified studies were pooled using meta-analyses. Results From the 4145 search results, 25 papers were included in this review. Sixteen papers were included in the meta-analysis based on reported risk factors. Young age of 2–6 months compared with children aged 7–60 months (OR 2.74, 95% CI: 1.75–4.29), antibiotic use within the past 3 months (OR 2.65, 95% CI: 1.70–4.12), daycare attendance (OR 1.49, 95% CI: 1.17–1.91) and hospital admission within the past 3 months (OR 3.43, 95% CI: 2.13–5.51) were found to be significant risk factors for AMR bacterial carriage, whilst breastfeeding (OR 0.69, 95% CI: 0.60–0.81) and concurrent colonization of S. pneumoniae (OR 0.59, 95% CI: 0.38–0.91) are protective factors. Conclusions The findings support that there are a number of significant risk factors associated with carriage of AMR bacteria in the Asia-Pacific paediatric population. To combat antimicrobial resistance in the future, these risk factors should be considered, and measures taken to mitigate associated carriage.

Background Age-specific incidence of acute myocarditis/pericarditis in adolescents following Comirnaty vaccination in Asia is lacking. This study aimed to study the clinical characteristics and incidence of acute myocarditis/pericarditis among Hong Kong adolescents following Comirnaty vaccination. Methods This is a population cohort study in Hong Kong that monitored adverse events following immunization through a pharmacovigilance system for coronavirus disease 2019 (COVID-19) vaccines. All adolescents aged between 12 and 17 years following Comirnaty vaccination were monitored under the COVID-19 vaccine adverse event response and evaluation program. The clinical characteristics and overall incidence of acute myocarditis/pericarditis in adolescents following Comirnaty vaccination were analyzed. Results Between 14 June 2021 and 4 September 2021, 33 Chinese adolescents who developed acute myocarditis/pericarditis following Comirnaty vaccination were identified. In total, 29 (87.88%) were male and 4 (12.12%) were female, with a median age of 15.25 years. And 27 (81.82%) and 6 (18.18%) cases developed acute myocarditis/pericarditis after receiving the second and first dose, respectively. All cases are mild and required only conservative management. The overall incidence of acute myocarditis/pericarditis was 18.52 (95% confidence interval [CI], 11.67–29.01) per 100 000 persons vaccinated. The incidence after the first and second doses were 3.37 (95% CI, 1.12–9.51) and 21.22 (95% CI, 13.78–32.28 per 100 000 persons vaccinated, respectively. Among male adolescents, the incidence after the first and second doses were 5.57 (95% CI, 2.38–12.53) and 37.32 (95% CI, 26.98–51.25) per 100 000 persons vaccinated. Conclusions There is a significant increase in the risk of acute myocarditis/pericarditis following Comirnaty vaccination among Chinese male adolescents, especially after the second dose.

Atopic diseases can impose a significant burden on children and adolescents. Telomere length is a cellular marker of aging reflecting the impact of cumulative stress exposure on individual health. Since elevated oxidative stress and inflammation burden induced by chronic atopy and snoring may impact telomere length, this study aimed to investigate whether snoring would moderate the relationship between atopic diseases and telomere length in early adolescence. We surveyed 354 adolescents and their parents. Parents reported the adolescents’ history of atopic diseases, recent snoring history as well as other family sociodemographic characteristics. Buccal swab samples were also collected from the adolescents for telomere length determination. Independent and combined effects of atopic diseases and snoring on telomere length were examined. Among the surveyed adolescents, 174 were reported by parents to have atopic diseases (20 had asthma, 145 had allergic rhinitis, 53 had eczema, and 25 had food allergy). Shorter TL was found in participants with a history of snoring and atopic diseases (β = −0.34, p = 0.002) particularly for asthma (β = −0.21, p = 0.007) and allergic rhinitis (β = −0.22, p = 0.023). Our findings suggest that snoring in atopic patients has important implications for accelerated telomere shortening. Proper management of atopic symptoms at an early age is important for the alleviation of long-term health consequences at the cellular level.

Recent evidence suggests that breastfeeding may increase the risk of vitamin D deficiency in offspring. However, it is unclear whether increased risk results from breastfeeding alone, or whether it is associated together with other risk factors. This study surveyed 208 infant–mother dyads recruited by stratified random sampling in different districts of Hong Kong. Mothers were asked to complete a questionnaire on their demographics, history of risk behavior, and feeding practices. Peripheral blood samples were collected from infants to determine their vitamin D status. Among all infant participants, 70 were vitamin D insufficient or deficient. Being breastfed, being a girl, having a multiparous mother, and the use of sun cream were found to be the strongest risk factors for vitamin D insufficiency during infancy (all p &lt, 0.05), after mutual adjustment. The cumulative risk model displayed a dose–response pattern between the number of risk factors and the risk of vitamin D insufficiency during this period. Our findings indicate the risk profile of infants with insufficient vitamin D. Guidelines and recommendations on healthy diet and lifestyle should be provided to mothers during the early stage of pregnancy to increase the likelihood of adequate levels of vitamin D in their offspring.

Background: During the coronavirus disease 2019 (COVID-19) pandemic, the implementation of social distancing and home confinement measures may elevate the risk of vitamin D deficiency particularly for infants. This study aimed to quantify changes in vitamin D level among infants and toddlers in Hong Kong after the COVID-19 outbreak. Methods: We recruited 303 infants and toddlers aged 2–24 months by stratified random sampling from 1 June 2019 to November 30, 2020. Regression models were used to estimate the effect of time on infants’ serum 25-hydroxyvitamin D (25(OH)D) level overall and by age groups before and after the outbreak. Interrupted time series (ITS) analysis was performed to examine the sustained effect of COVID-19 on their serum 25(OH)D level. Results: The ITS results showed no immediate reduction in serum 25(OH)D level among infants, but a decreasing trend was observed in the subsequent months post-outbreak at a monthly decline rate of −6.32 nmol/L. When analyzed by age group, the magnitude of post-outbreak reduction in 25(OH)D was stronger among younger infants (aged 2–6 months). Conclusion: Guidelines and recommendations should be given to pregnant women and mothers to ensure sufficient vitamin D level in their infants during the COVID-19 period.

Background. Exposure to suboptimal intrauterine environment might induce structural and functional changes that can affect neonatal health. Telomere length as an important indicator of cellular health has been associated with increased risk for disease development. Objectives. This study was aimed to examine the independent and combined effects of maternal, obstetric, and foetal factors on cord blood telomere length (TL). Methods. Pregnant women at the gestational age of 20th to 24th week who attended the antenatal clinic of a major local hospital in Hong Kong were recruited. Participants were asked to complete a questionnaire on demographics, health-related quality of life, and history of risk behaviors. Medical history including pregnancy complications and neonatal outcomes was obtained from electronic medical records of both mother and neonate. Umbilical cord blood was collected at delivery for TL determination. Results. A total of 753 pregnant women (average age: 32.18 ± 4.51 years) were recruited. The prevalence of maternal infection, anaemia, and hypertension during pregnancy was 30.8%, 30.0%, and 6.0%, respectively. The adjusted regression model displayed that maternal infection was negatively associated with cord blood TL ( β = − 0.18 , p = 0.026 ). This association became even stronger in the presence of antenatal anaemia, hypertension, delivery complications, or neonatal jaundice ( β = − 0.25 to −0.45). Conclusions. This study consolidates evidence on the impact of adverse intrauterine environment at the cellular level. Maternal infection was significantly associated with shorter cord blood TL in a unique manner such that its presence may critically determine the susceptibility of telomere to other factors.

Female genital melanomas are rare. At diagnosis, most affected patients have advanced disease. Surgery remains the primary treatment, and adjuvant therapy is largely ineffective. Recently, immune checkpoints and the mitogen-activated protein kinase pathway have been explored as treatment targets. However, evaluation of these biomarkers in genital melanomas is limited. We evaluated the clinicopathological features of 20 vulvar, 32 vaginal, and three cervical melanomas and assessed programmed cell death ligand 1 (PD-L1) expression, CD8 tumor-infiltrating lymphocyte density, mismatch repair proteins, VE1 immunohistochemistry, and KIT and BRAF mutations. The median age of the patients was 66 years, and median tumor sizes were 25, 30, and 20 mm for vulvar, vaginal, and cervical tumors, respectively. Mean mitotic figures were 18, 19, and 30 per mm

Beta amyloid protein (Abeta) and acetylcholinesterase (AChE) have been shown to be closely implicated in the pathogenesis of Alzheimer's disease. In the current study, we investigated the effects of bis(7)-tacrine, a novel dimeric AChE inhibitor, on Abeta-induced neurotoxicity in primary cortical neurons. Bis(7)-tacrine, but not other AChE inhibitors, elicited a marked reduction of both fibrillar and soluble oligomeric forms of Abeta-induced apoptosis as evidenced by chromatin condensation and DNA specific fragmentation. Both nicotinic and muscarinic receptor antagonists failed to block the effects of bis(7)-tacrine. Instead, nimodipine, a blocker of L-type voltage-dependent Ca2+ channels (VDCCs), attenuated Abeta neurotoxicity, whereas N-, P/Q- or R-type VDCCs blockers and ionotropic glutamate receptor antagonists did not. Fluorescence Ca2+ imaging assay revealed that, similar to nimodipine, bis(7)-tacrine reversed Abeta-triggered intracellular Ca2+ increase, which was mainly contributed by the extracellular Ca2+ instead of endoplasmic reticulum and mitochondria Ca2+. Concurrently, using whole cell patch-clamping technique, it was found that bis(7)-tacrine significantly reduced the augmentation of high voltage-activated inward calcium currents induced by Abeta. These results suggest that bis(7)-tacrine attenuates Abeta-induced neuronal apoptosis by regulating L-type VDCCs, offers a novel modality as to how the agent exerts neuroprotective effects.

The neuroprotective properties of bis(7)-tacrine, a novel dimeric acetylcholinesterase (AChE) inhibitor, on glutamate-induced excitotoxicity were investigated in primary cultured cerebellar granule neurons (CGNs). Exposure of CGNs to 75 mum glutamate resulted in neuronal apoptosis as demonstrated by Hoechst staining, TUNEL, and DNA fragmentation assays. The bis(7)-tacrine treatment (0.01-1 mum) on CGNs markedly reduced glutamate-induced apoptosis in dose- and time-dependent manners. However, donepezil and other AChE inhibitors, even at concentrations of inhibiting AChE to the similar extents as 1 mum bis(7)-tacrine, failed to prevent glutamate-induced excitotoxicity in CGNs; moreover, both atropine and dihydro-beta-erythroidine, the cholinoreceptor antagonists, did not affect the anti-apoptotic properties of bis(7)-tacrine, suggesting that the neuroprotection of bis(7)-tacrine appears to be independent of inhibiting AChE and cholinergic transmission. In addition, ERK1/2 and p38 pathways, downstream signals of N-methyl-d-aspartate (NMDA) receptors, were rapidly activated after the exposure of glutamate to CGNs. Bis(7)-tacrine inhibited the apoptosis and the activation of these two signals with the same efficacy as the coapplication of PD98059 and SB203580. Furthermore, using fluorescence Ca(2+) imaging, patch clamp, and receptor-ligand binding techniques, bis(7)-tacrine was found effectively to buffer the intracellular Ca(2+) increase triggered by glutamate, to reduce NMDA-activated currents and to compete with [(3)H]MK-801 with an IC(50) value of 0.763 mum in rat cerebellar cortex membranes. These findings strongly suggest that bis(7)-tacrine prevents glutamate-induced neuronal apoptosis through directly blocking NMDA receptors at the MK-801-binding site, which offers a new and clinically significant modality as to how the agent exerts neuroprotective effects.