Microbial extracellular vesicles contribute to antimicrobial resistance.

With the escalating global antimicrobial resistance crisis, there is an urgent need for innovative strategies against drug-resistant microbes. Accumulating evidence indicates microbial extracellular vesicles (EVs) contribute to antimicrobial resistance. Therefore, comprehensively elucidating the roles and mechanisms of microbial EVs in conferring resistance could provide new perspectives and avenues for novel antimicrobial approaches. In this review, we systematically examine current research on antimicrobial resistance involving bacterial, fungal, and parasitic EVs, delineating the mechanisms whereby microbial EVs promote resistance. Finally, we discuss the application of bacterial EVs in antimicrobial therapy.

Effectiveness of a self-determination theory-based smoking cessation intervention plus instant messaging via mobile application for smokers with cancer: Protocol for a pragmatic randomized controlled trial.

BACKGROUND AND AIMS: Despite evidence that patients living with cancer who continue to smoke after diagnosis are at higher risk for all-cause mortality and reduced treatment efficacy, many cancer patients continue to smoke. This protocol is for a study to test the effectiveness of a self-determination theory-based intervention (quit immediately or progressively) plus instant messaging (WhatsApp or WeChat) to help smokers with cancer to quit smoking. DESIGN: This will be a multi-centre, two-arm (1:1), single-blind, pragmatic, individually randomized controlled trial. SETTING: Taking part will be specialist outpatient clinics in five major hospitals in different location-based clusters in Hong Kong. PARTICIPANTS: The sample will include 1448 Chinese smokers living with cancer attending medical follow-ups at outpatient clinics. INTERVENTIONS: The intervention group will receive brief advice (approximately 5-8 minutes) from research nurses in the outpatient clinics and then be invited to choose their own quit schedules (immediate or progressive). During the first 6-month follow-up period they will receive instant messaging with smoking cessation advice once per week for the first 3 months, and thereafter approximately once per month. They will also receive four videos, and those opting to quit progressively will receive a smoking reduction leaflet. The control group will also receive brief advice but be advised to quit immediately, and instant messaging with general health advice during the first 6-month follow-up period using the same schedule as the intervention group. Participants in both groups will receive smoking cessation leaflets. MEASUREMENTS: The primary outcome is biochemically validated smoking abstinence at 6 months, as confirmed by saliva cotinine level and carbon monoxide level in expired air. Secondary outcomes include biochemically validated smoking abstinence at 12 months, self-reported 7-day point prevalence of smoking abstinence at 6 and 12 months, self-reported ≥ 50% reduction of cigarette consumption at 6 and 12 months and quality of life at 6 and 12 months. All time-points for outcomes measures are set after randomization. COMMENTS: The results could inform research, policymaking and health-care professionals regarding smoking cessation for patients living with cancer, and therefore have important implications for clinical practice and health enhancement.

Caregiver Employees' Mental Well-Being in Hong Kong.

BACKGROUND: The rapidly aging global population has increased the demand for caregivers. Many caregivers simultaneously engage in paid employment, and the dual role makes the needs of caregiver employees conceivably more remarkable. However, there is a gap in the literature about the specific needs of caregiver employees. METHOD: Caregiver employees (n = 1205) across Hong Kong caring for those ≥65 years were recruited for a cross-sectional face-to-face survey from December 2021 to January 2022, to evaluate mental well-being measured by the Short Warwick -Edinburgh Mental Well-being Scale. Univariate and multivariate analyses were conducted; significant variables (p < 0.05) were included in multiple linear regression, along with caregiver-friendly workplace policies' availability, to understand their association with their mental well-being. FINDINGS: The mean score of the Short Warwick-Edinburgh Mental Well-being Scale among caregiver employees in this study was 24.9, with 7.2% indicative of probable clinical depression and 10.0% possible mild depression. In addition, the current study showed that 30.2% of the caregiver employees felt distressed about the caregiving role. Among external factors, family support (measured by the Lubben Social Network Scale) and workplace culture (measured by the Marshall Supervision Subscale) positively correlated with mental well-being with regression coefficients of 0.252 (p < 0.001) and 0.482 (p < 0.001), respectively. In the fully adjusted model, a negative regression coefficient was observed for overall spillover (-0.050, p < 0.001) and Short Warwick-Edinburgh Mental Well-being Scale scores, while positive regression coefficients were observed for overall self-rate (0.041, p < 0.001), Lubben (0.124, p < 0.001), and corporate culture (0.365, p < 0.001). Better Short Warwick-Edinburgh Mental Well-being Scale scores were observed when caregiver-friendly workplace policies were clearly stated than when they were made on a case-by-case discretionary basis. CONCLUSIONS: Caregiver-friendly workplace policies may be critical to Hong Kong's sustainable future, both economically and socially, as they ensure a healthy and productive workforce to support an aging population.

Phonological processing in Chinese word repetition: Dementia effect and age effect.

This paper examined phonological processing as reflected in Mandarin word and non-word repetition. Issues related to dementia effects, age effects, and linguistic variables are discussed. Forty-five speakers of Mandarin Chinese in Taiwan took part in this study. Fourteen seniors with Alzheimer's disease (AD), 14 healthy adults, and 17 healthy seniors individually completed a task of word repetition. Scores of accurate repetition were calculated, and error types as well as error frequency were analysed. Linguistic variables, including lexicality, frequency, non-word, and syllable length, were discussed. Major findings were indicative of a significant dementia effect, in which participants with AD were significantly impaired in repeating words with more syllables, specifically 5-syllable non-words of low frequency. Numerous significant age effects were noted. Theoretical implications and directions for future study are discussed.

Abortive reaction leads to selective adsorbate rotation.

Electron-induced dissociation of a fluorocarbon adsorbate CF3 (ad) at 4.6 K is shown by Scanning Tunnelling Microscopy (STM) to form directed energetic F-atom 'projectiles' on Cu(110). The outcome of a collision between these directed projectiles and stationary co-adsorbed allyl 'target' molecules was found through STM to give rotational excitation of the target allyl, clockwise or anti-clockwise, depending on the chosen collision geometry. Molecular dynamics computation linked the collisional excitation of the allyl target to an 'abortive chemical reaction', in which the approach of the F-projectile stretched an H-C bond lifting the allyl above the surface, facilitating isomerization from 'Across' to 'Along' a Cu row.

Exploring potential EQ-5D bolt-on dimensions with a qualitative approach: an interview study in Hong Kong SAR, China.

PURPOSE: The introduction of bolt-on dimensions in EQ-5D instruments is growing common, but most bolt-on studies have targeted the diseased population and obtained bolt-on from other existing Health-related Quality of Life (HRQoL) instruments. As the qualitative approach offers important evidence to support the consistency and design of the potential bolt-on items, this paper studies the Hong Kong SAR community's perception of the current EQ-5D-5 L instrument and identifies potential bolt-on via a qualitative approach. METHODS: A representative sample mix was recruited based on the age group, gender, and education level composition of the Hong Kong SAR community by quota sampling. Semi-structured interviews were conducted and the interviews were transcribed and coded to identify emergent and recurrent themes. RESULTS: Thirty interviews were conducted and the majority of the interviewees considered the EQ-5D-5 L insufficiently comprehensive to illustrate their HRQoL. While some key HRQoL aspects included in the EQ-5D matched with the community's HRQoL perception, respondents showed concern about the potential overlap of the existing HRQoL dimension, the optimal number or attributes, and the appropriateness of the EQ-VAS. Among the potential bolt-on dimensions that emerged, 'Sleep', 'Interpersonal Relationship', and 'Satisfaction' were the key potential bolt-on dimensions identified and emphasized in the interviews. CONCLUSIONS: The qualitative findings of the study illustrate the possible gap between EQ-5D-5 L measurements and community HRQoL perception, while the findings support the development of EQ-5D bolt-on dimensions in the target community with content and face validity.

Evaluating the impact of sugar-sweetened beverages tax on overweight, obesity, and type 2 diabetes in an affluent Asian setting: A willingness-to-pay survey and simulation analysis.

BACKGROUND: The potential health effects of taxing sugar-sweetened beverages (SSBs) has been insufficiently examined in Asian contexts. This study aimed to assess the impact of SSB taxation on the prevalence of obesity/overweight and type 2 diabetes mellitus (T2DM) in Hong Kong using a willingness-to-pay (WTP) survey and simulation analysis. METHODS: A random telephone survey was conducted with 1000 adults from May to June 2020. We used a contingent valuation approach to assess individuals' WTP for SSBs under four tax payment scenarios (5%, 10%, 40%, and 50% of the current market price). Based on the WTP, a simulation analysis was conducted to project changes in SSB purchase and associated reductions in the prevalence of obesity/overweight and T2DM over a 10-year simulation period. FINDINGS: When 5% and 10% taxation rates were introduced, approximately one-third of the population were unwilling to maintain their SSB purchase. Our simulation demonstrated a gradual decline in the prevalence of obesity/overweight and diabetes with a more pronounced decrease when higher taxation rates were introduced. 10% taxation resulted in a mean reduction of 1532.7 cases of overweight/obesity per 100 thousand population at the sixth year, while T2DM prevalence decreased by 267.1 (0.3%). CONCLUSIONS: This study underscores the effects of an SSB tax on purchase behaviors and health outcomes in an affluent Asia setting, with a more pronounced influence on adult population. These findings are expected to inform policymakers in making decisions regarding an effective and equitable tax rate on SSBs.

Fabrication of nanocrystal forms of á´ -cycloserine and their application for transdermal and enteric drug delivery systems.

ᴅ-cycloserine (DCS), an FDA-approved medicine for the treatment of tuberculosis, is also a partial agonist at the glycine recognition site of N-methyl-ᴅ-aspartate (NMDA) receptor and has shown significant treatment efficacy for central nervous system (CNS) disorders including depression, schizophrenia, Alzheimer's disease, and post-traumatic stress disorder. The physicochemical properties of DCS, however, limit the options of formulation and medicinal applications of DCS, and warrants further investigation for the development of CNS therapeutics. Nanocrystals play an important role in pharmaceutic design and development. The properties of nanocrystals are remarkably different from their bulk material counterpart, attributed to the large surface-area-to-volume ratio which can improve the bioavailability. In this study, for the first time, DCS, a highly water-soluble compound, has formed nanocrystals and this was confirmed by scanning electronic microscopy and X-ray powder diffraction. Furthermore, DCS nanocrystals were applied to several formulations to test their stability and then to the in vitro Franz diffusion test with reservoir patch formulation as well as in vivo pharmacokinetics study with enteric capsules. We tested these formulations regarding their nanocrystal physical properties, size effect, and dissolution rate, respectively. We found that DCS nanocrystals showed good performance in the Franz diffusion test and rodent pharmacokinetic studies due to the nanoparticle size and faster dissolution as compared with the commercial DCS powder. These DCS nanocrystal formulations could offer a new approach for the development of an advanced drug delivery system for the treatment of CNS disorders.

Enhancing cutaneous wound healing: A study on the beneficial effects of nano-gelatin scaffold in rat models.

The challenges in achieving optimal outcomes for wound healing have persisted for decades, prompting ongoing exploration of interventions and management strategies. This study focuses on assessing the potential benefits of implementing a nano-gelatin scaffold for wound healing. Using a rat skin defect model, full-thickness incisional wounds were created on each side of the thoracic-lumbar regions after anesthesia. The wounds were left un-sutured, with one side covered by a gelatin nano-fibrous membrane and the other left uncovered. Wound size changes were measured on days 1, 4, 7, and 14, and on day 14, rats were sacrificed for tissue sample excision, examined with hematoxylin and eosin, and Masson's trichrome stain. Statistical comparisons were performed. The gelatin nanofibers exhibited a smooth surface with a fiber diameter of 260 ± 40 nm and porous structures with proper interconnectivity. Throughout the 14-day experimental period, significant differences in the percentage of wound closure were observed between the groups. Histological scores were higher in the experiment group, indicating less inflammation but dense and well-aligned collagen fiber formation. A preliminary clinical trial on diabetic ulcers also demonstrated promising results. This study highlights the potential of the nano-collagen fibrous membrane to reduce inflammatory infiltration and enhance fibroblast differentiation into myofibroblasts during the early stages of cutaneous wound healing. The nano-fibrous collagen membrane emerges as a promising candidate for promoting wound healing, with considerable potential for future therapeutic applications.

Social Support, Resilience, and Mental Health Among Three High-Risk Groups in Hong Kong: A Mediation Analysis.

Objectives: To compare the prevalence of anxiety/depression, resilience, and social support among nurses, foreign domestic helpers (FDHs), and residents living in subdivided units (SDUs), and to examine their associations in these high-risk groups in Hong Kong during Omicron waves. Methods: We recruited 1,014 nurses, 621 FDHs, and 651 SDU residents from December 2021 to May 2022 in this cross-sectional survey. The depression, anxiety, social support, and resilience levels were measured by the validated scales. The multivariate binary logistic regression and causal mediation analysis were applied to examine the associations. Results: We observed a prevalence of 17.7% in anxiety and 21.6% in depression which were the highest in SDU residents, followed by FDHs, and lowest in nurses. Social support was associated with increased resilience levels and decreased risks of anxiety/depression. The association of social support with mental disorders was partly mediated by resilience, accounting for 30.9% and 20.9% of the total effect of social support on anxiety and depression, respectively. Conclusion: Public health strategies should target improving social support and providing resilience-promoting interventions to help reduce mental disorders in vulnerable groups.

The Development of a Regulator of Human Serine Racemase for N-Methyl-D-aspartate Function.

It is crucial to regulate N-methyl-D-aspartate (NMDA) function bivalently depending on the central nervous system (CNS) conditions. CNS disorders with NMDA hyperfunction are involved in the pathogenesis of neurotoxic and/or neurodegenerative disorders with elevated D-serine, one of the NMDA receptor co-agonists. On the contrary, NMDA-enhancing agents have been demonstrated to improve psychotic symptoms and cognition in CNS disorders with NMDA hypofunction. Serine racemase (SR), the enzyme regulating both D- and L-serine levels through both racemization (catalysis from L-serine to D-serine) and ß-elimination (degradation of both D- and L-serine), emerges as a promising target for bidirectional regulation of NMDA function. In this study, we explored using dimethyl malonate (DMM), a pro-drug of the SR inhibitor malonate, to modulate NMDA activity in C57BL/6J male mice via intravenous administration. Unexpectedly, 400 mg/kg DMM significantly elevated, rather than decreased (as a racemization inhibitor), D-serine levels in the cerebral cortex and plasma. This outcome prompted us to investigate the regulatory effects of dodecagalloyl-α-D-xylose (α12G), a synthesized tannic acid analog, on SR activity. Our findings showed that α12G enhanced the racemization activity of human SR by about 8-fold. The simulated and fluorescent assay of binding affinity suggested a noncooperative binding close to the catalytic residues, Lys56 and Ser84. Moreover, α12G treatment can improve behaviors associated with major CNS disorders with NMDA hypofunction including hyperactivity, prepulse inhibition deficit, and memory impairment in animal models of positive symptoms and cognitive impairment of psychosis. In sum, our findings suggested α12G is a potential therapeutic for treating CNS disorders with NMDA hypofunction.

Beyond the brain: General intensive care considerations in pediatric neurocritical care.

Managing children with critical neurological conditions requires a comprehensive understanding of several principles of critical care. Providing a holistic approach that addresses not only the acute interactions between the brain and different organ systems, but also critical illness-associated complications and recovery is essential for improving outcomes in these patients. The brain reacts to an insult with autonomic responses designed to optimize cardiac output and perfusion, which can paradoxically be detrimental. Managing neuro-cardiac interactions therefore requires balancing adequate cerebral perfusion and minimizing complications. The need for intubation and airway protection in patients with acute encephalopathy should be individualized following careful risk/benefit deliberations. Ventilatory strategies can have profound impact on cerebral perfusion. Therefore, understanding neuro-pulmonary interactions is vital to optimize ventilation and oxygenation to support a healing brain. Gastrointestinal dysfunction is common and often complicates the care of patients with critical neurological conditions. Kidney function, along with fluid status and electrolyte derangements, should also be carefully managed in the acutely injured brain. While in the pediatric intensive care unit, prevention of critical illness-associated complications such as healthcare-associated infections and deep vein thrombosis is vital in improving outcomes. As the brain emerges from the acute injury, rehabilitation and management of delirium and paroxysmal sympathetic hyperactivity is paramount for optimal recovery. All these considerations provide a foundation for the care of pediatric patients with critical neurological conditions in the intensive care unit.

Toosendanin inhibits T-cell proliferation through the P38 MAPK signalling pathway.

In recent years, immunosuppressants have shown significant success in the treatment of autoimmune diseases. Therefore, there is an urgent need to develop additional immunosuppressants that offer more options for patients. Toosendanin has been shown to have immunosuppressive activity in vitro as well as effects on autoimmune hepatitis (AIH) in vivo. Toosendanin did not induce apoptosis in activated T-cells and affect the survival rate of naive T-cells. Toosendanin did not affect the expression of CD25 or secretion of IL-2 by activated T-cells, and not affect the expression of IL-4 and INF-γ. Toosendanin did not affect the phosphorylation of STAT5, ERK, AKT, P70S6K. However, toosendanin inhibited proliferation of anti-CD3/anti-CD28 mAbs-activated T-cells with IC50 of (10 ± 2.02) nM. Toosendanin arrested the cell cycle in the G0/G1 phase, significantly inhibited IL-6 and IL-17A secretion, promoted IL-10 expression, and inhibited the P38 MAPK pathway. Finally, toosendanin significantly alleviated ConA-induced AIH in mice. In Summary, toosendanin exhibited immunosuppressive activity in vivo and in vitro. Toosendanin inhibits the proliferation of activated T-cells through the P38 MAPK signalling pathway, significantly suppresses the expression of inflammatory factors, enhances the expression of anti-inflammatory factors, and effectively alleviates ConA-induced AIH in mice, suggesting that toosendanin may be a lead compound for the development of novel immunomodulatory agents with improved efficacy and reduced toxicity.

Association of minor electrocardiographic (ECG) abnormalities with epilepsy duration in children: A manifestation of the epileptic heart?

PURPOSE: Cardiac abnormalities resulting from chronic epilepsy ("the epileptic heart") constitute a well-recognized comorbidity. However, the association of cardiac alterations with epilepsy duration remains understudied. We sought to evaluate this association using electrocardiogram (ECG). METHODS: We prospectively enrolled children between 1 months and 18 years of age without known cardiac conditions or ion channelopathies during routine clinic visits. ECGs were categorized as abnormal if there were alterations in rhythm; PR, QRS, or corrected QT interval; QRS axis or morphology; ST segment or T wave. An independent association between ECG abnormalities and epilepsy duration was evaluated using multivariable logistic regression modeling. RESULTS: 213 children were enrolled. 100 ECGs (47%) exhibited at least one alteration; most commonly in the ST segment (37, 17%) and T wave (29, 11%). Children with normal ECGs had shorter epilepsy duration as compared to those with ECG abnormalities (46 [18-91] months vs. 73 [32-128 months], p = 0.004). A multivariable logistic regression model demonstrated that increasing epilepsy duration was independently associated with the presence of ECG abnormalities (OR=1.09, 95% CI=1.02-1.16, p = 0.008), adjusted for seizure frequency, generalized tonic-clonic/focal to bilateral tonic-clonic seizures as the predominant seizure type, and number of channel-modifying anti-seizure medications. Increasing epilepsy duration was also independently associated with the presence of ST/T wave abnormalities (OR=1.09, 95% CI=1.01-1.16, p = 0.017), adjusted for the same covariates. SIGNIFICANCE: Increasing epilepsy duration is independently associated with the presence of minor ECG abnormalities. Additional studies are needed to evaluate whether this finding may represent a manifestation of the "epileptic heart".

Nervogenic Acid Derivatives and Phenanthrenes from Liparis nervosa and Their Antimicrobial and Immunosuppressive Activities.

Two new nervogenic acid derivatives liparisnervosides Q (1) and R (5), as well as five known nervogenic acid derivatives (2-4, 6, 7) and four phenanthrenes (8-11) were isolated from the whole plant of Liparis nervosa (Thunb. ex A. Murray) Lindl.. Their structures were detremined using extensive spectroscopic techniques, including 1D, 2D NMR, and HR-ESI-MS, and acid hydrolysis. Furthermore, their antimicrobial and immunosuppressive activities were evaluated. Nervosine VII (3) exhibited antimicrobial activity against Staphylococcus aureus with an MIC of 62.5 µg/mL and inhibited the proliferation of human T cells with an IC50 value of 9.67±0.96 µM. These findings contribute to our understanding of the potential pharmacological properties of these compounds.