Eukaryotic translation initiation factor eIF4E-5 is required for spermiogenesis in Drosophila melanogaster.

Drosophila sperm development is characterized by extensive post-transcriptional regulation whereby thousands of transcripts are preserved for translation during later stages. A key step in translation initiation is the binding of eukaryotic initiation factor 4E (eIF4E) to the 5' mRNA cap. In addition to canonical eIF4E-1, Drosophila has multiple eIF4E paralogs, including four (eIF4E-3, -4, -5, and -7) that are highly expressed in the testis. Among these, only eIF4E-3 has been characterized genetically. Here, using CRISPR/Cas9 mutagenesis, we determined that eIF4E-5 is essential for male fertility. eIF4E-5 protein localizes to the distal ends of elongated spermatid cysts, and eIF4E-5 mutants exhibit defects during post-meiotic stages, including a mild defect in spermatid cyst polarization. eIF4E-5 mutants also have a fully penetrant defect in individualization, resulting in failure to produce mature sperm. Indeed, our data indicate that eIF4E-5 regulates non-apoptotic caspase activity during individualization by promoting local accumulation of the E3 ubiquitin ligase inhibitor Soti. Our results further extend the diversity of non-canonical eIF4Es that carry out distinct spatiotemporal roles during spermatogenesis.

Bacillus subtilis NrnB is expressed during sporulation and acts as a unique 3'-5' exonuclease.

All cells employ a combination of endo- and exoribonucleases to degrade long RNA polymers to fragments 2-5 nucleotides in length. These short RNA fragments are processed to monoribonucleotides by nanoRNases. Genetic depletion of nanoRNases has been shown to increase abundance of short RNAs. This deleteriously affects viability, virulence, and fitness, indicating that short RNAs are a metabolic burden. Previously, we provided evidence that NrnA is the housekeeping nanoRNase for Bacillus subtilis. Herein, we investigate the biological and biochemical functions of the evolutionarily related protein, B. subtilis NrnB (NrnBBs). These experiments show that NrnB is surprisingly different from NrnA. While NrnA acts at the 5' terminus of RNA substrates, NrnB acts at the 3' terminus. Additionally, NrnA is expressed constitutively under standard growth conditions, yet NrnB is selectively expressed during endospore formation. Furthermore, NrnA processes only short RNAs, while NrnB unexpectedly processes both short RNAs and longer RNAs. Indeed, inducible expression of NrnB can even complement the loss of the known global 3'-5' exoribonucleases, indicating that it acts as a general exonuclease. Together, these data demonstrate that NrnB proteins, which are widely found in Firmicutes, Epsilonproteobacteria and Archaea, are fundamentally different than NrnA proteins and may be used for specialized purposes.

Catheter-associated urinary tract infection by Pseudomonas aeruginosa progresses through acute and chronic phases of infection.

Healthcare-associated infections are major causes of complications that lead to extended hospital stays and significant medical costs. The use of medical devices, including catheters, increases the risk of bacterial colonization and infection through the presence of a foreign surface. Two outcomes are observed for catheterized patients: catheter-associated asymptomatic bacteriuria and catheter-associated urinary tract infection (CAUTI). However, the relationship between these two events remains unclear. To understand this relationship, we studied a murine model of Pseudomonas aeruginosa CAUTI. In this model, we also observe two outcomes in infected animals: acute symptoms that is associated with CAUTI and chronic colonization that is associated with asymptomatic bacteriuria. The timing of the acute outcome takes place in the first week of infection, whereas chronic colonization occurs in the second week of infection. We further showed that mutants lacking genes encoding type III secretion system (T3SS), T3SS effector proteins, T3SS injection pore, or T3SS transcriptional activation all fail to cause acute symptoms of CAUTI. Nonetheless, all mutants defective for T3SS colonized the catheter and bladders at levels similar to the parental strain. In contrast, through induction of the T3SS master regulator ExsA, all infected animals showed acute phenotypes with bacteremia. Our results demonstrated that the acute symptoms, which are analogous to CAUTI, and chronic colonization, which is analogous to asymptomatic bacteriuria, are independent events that require distinct bacterial virulence factors. Experimental delineation of asymptomatic bacteriuria and CAUTI informs different strategies for the treatment and intervention of device-associated infections.

Characterization of the Entner-Doudoroff pathway in Pseudomonas aeruginosa catheter-associated urinary tract infections.

Pseudomonas aeruginosa is an opportunistic nosocomial pathogen responsible for a subset of catheter-associated urinary tract infections (CAUTI). In a murine model of P. aeruginosa CAUTI, we previously demonstrated that urea within urine suppresses quorum sensing and induces the Entner-Doudoroff (E-D) pathway. The E-D pathway consists of the genes zwf, pgl, edd, and eda. Zwf and Pgl convert glucose-6-phosphate into 6-phosphogluconate. Edd hydrolyzes 6-phosphogluconate to 2-keto-3-deoxy-6-phosphogluconate (KDPG). Finally, Eda cleaves KDPG to glyceraldehyde-3-phosphate and pyruvate, which enters the citric acid cycle. Here, we generated in-frame E-D mutants in the strain PA14 and assessed their growth phenotypes on chemically defined and complex media. These E-D mutants have a growth defect when grown on glucose or gluconate as the sole carbon source, which is similar to results previously reported for PAO1 mutants lacking E-D genes. RNA-sequencing following short exposure to urine revealed minimal gene regulation differences compared to the wild type. In a murine CAUTI model, virulence testing of E-D mutants revealed that two mutants lacking zwf and pgl showed minor fitness defects. Infection with the ∆pgl strain exhibited a 20% increase in host survival, and the ∆zwf strain displayed decreased colonization of the catheter and kidneys. Consequently, our findings suggest that the E-D pathway in P. aeruginosa is dispensable in this model of CAUTI. IMPORTANCE Prior studies have shown that the Entner-Doudoroff pathway is up-regulated when Pseudomonas aeruginosa is grown in urine. Pseudomonads use the Entner-Doudoroff (E-D) pathway to metabolize glucose instead of glycolysis, which led us to ask whether this pathway is required for urinary tract infection. Here, single-deletion mutants of each gene in the pathway were tested for growth on chemically defined media with single-carbon sources as well as complex media. The effect of each mutant on global gene expression in laboratory media and urine was characterized. The virulence of these mutants in a murine model of catheter-associated urinary tract infection revealed that these mutants had similar levels of colonization indicating that glucose is not the primary carbon source utilized in the urinary tract.

A summary of the 2023 Society of Obstetric Medicine of Australia and New Zealand (SOMANZ) hypertension in pregnancy guideline.

INTRODUCTION: Hypertensive disorders of pregnancy (HDP) affect up to 10% of all pregnancies annually and are associated with an increased risk of maternal and fetal morbidity and mortality. This guideline represents an update of the Society of Obstetric Medicine of Australia and New Zealand (SOMANZ) guidelines for the management of hypertensive disorders of pregnancy 2014 and has been approved by the National Health and Medical Research Council (NHMRC) under section 14A of the National Health and Medical Research Council Act 1992. In approving the guideline recommendations, NHMRC considers that the guideline meets NHMRC's standard for clinical practice guidelines. MAIN RECOMMENDATIONS: A total of 39 recommendations on screening, preventing, diagnosing and managing HDP, especially preeclampsia, are presented in this guideline. Recommendations are presented as either evidence-based recommendations or practice points. Evidence-based recommendations are presented with the strength of recommendation and quality of evidence. Practice points were generated where there was inadequate evidence to develop specific recommendations and are based on the expertise of the working group. CHANGES IN MANAGEMENT RESULTING FROM THE GUIDELINE: This version of the SOMANZ guideline was developed in an academically robust and rigorous manner and includes recommendations on the use of combined first trimester screening to identify women at risk of developing preeclampsia, 14 pharmacological and two non-pharmacological preventive interventions, clinical use of angiogenic biomarkers and the long term care of women who experience HDP. The guideline also includes six multilingual patient infographics which can be accessed through the main website of the guideline. All measures were taken to ensure that this guideline is applicable and relevant to clinicians and multicultural women in regional and metropolitan settings in Australia and New Zealand.

NrnA is a 5'-3' exonuclease that processes short RNA substrates in vivo and in vitro.

Bacterial RNases process RNAs until only short oligomers (2-5 nucleotides) remain, which are then processed by one or more specialized enzymes until only nucleoside monophosphates remain. Oligoribonuclease (Orn) is an essential enzyme that acts in this capacity. However, many bacteria do not encode for Orn and instead encode for NanoRNase A (NrnA). Yet, the catalytic mechanism, cellular roles and physiologically relevant substrates have not been fully resolved for NrnA proteins. We herein utilized a common set of reaction assays to directly compare substrate preferences exhibited by NrnA-like proteins from Bacillus subtilis, Enterococcus faecalis, Streptococcus pyogenes and Mycobacterium tuberculosis. While the M. tuberculosis protein specifically cleaved cyclic di-adenosine monophosphate, the B. subtilis, E. faecalis and S. pyogenes NrnA-like proteins uniformly exhibited striking preference for short RNAs between 2-4 nucleotides in length, all of which were processed from their 5' terminus. Correspondingly, deletion of B. subtilis nrnA led to accumulation of RNAs between 2 and 4 nucleotides in length in cellular extracts. Together, these data suggest that many Firmicutes NrnA-like proteins are likely to resemble B. subtilis NrnA to act as a housekeeping enzyme for processing of RNAs between 2 and 4 nucleotides in length.

The nucleotide messenger (p)ppGpp is an anti-inducer of the purine synthesis transcription regulator PurR in Bacillus.

The nucleotide messenger (p)ppGpp allows bacteria to adapt to fluctuating environments by reprogramming the transcriptome. Despite its well-recognized role in gene regulation, (p)ppGpp is only known to directly affect transcription in Proteobacteria by binding to the RNA polymerase. Here, we reveal a different mechanism of gene regulation by (p)ppGpp in Firmicutes: (p)ppGpp directly binds to the transcription factor PurR to downregulate purine biosynthesis gene expression upon amino acid starvation. We first identified PurR as a receptor of (p)ppGpp in Bacillus anthracis. A co-structure with Bacillus subtilis PurR reveals that (p)ppGpp binds to a PurR pocket reminiscent of the active site of phosphoribosyltransferase enzymes that has been repurposed to serve a purely regulatory role, where the effectors (p)ppGpp and PRPP compete to allosterically control transcription. PRPP inhibits PurR DNA binding to induce transcription of purine synthesis genes, whereas (p)ppGpp antagonizes PRPP to enhance PurR DNA binding and repress transcription. A (p)ppGpp-refractory purR mutant in B. subtilis fails to downregulate purine synthesis genes upon amino acid starvation. Our work establishes the precedent of (p)ppGpp as an effector of a classical transcription repressor and reveals the key function of (p)ppGpp in regulating nucleotide synthesis through gene regulation, from soil bacteria to pathogens.

The use of sodium MRI in the diagnosis of an anaplastic astrocytoma during immunotherapy: a case report.

Gliomas in the pediatric population are targeted with immune-modulating therapies. The gold standard imaging modality for diagnosis and monitoring treatment response is magnetic resonance imaging (MRI); however, the complex post-therapy-induced changes can make treatment response assessment difficult. These include radiation necrosis, pseudoresponse, and pseudoprogression, as well as more complex responses in the setting of immunotherapy. We report a case of an 11-year-old male with a supratentorial astrocytoma (WHO grade 3) that underwent treatment with immunotherapy. There was a clinical concern for progression due to increased fluid-attenuated inversion recovery (FLAIR) hyperintensity at the site of the primary neoplasm during immunotherapy. However, the Sodium (23Na) MRI continued demonstrating decreased total sodium concentrations, supporting pseudoprogression over true progression, which was confirmed clinicaly. This case reports the capability of 23Na MRI to differentiate between progression, recurrence, and other posttreatment changes.

Laser Tracker and Terrestrial Laser Scanner Range Error Evaluation by Stitching.

Laser trackers (LTs) are dimensional measurement instruments commonly employed in the manufacture and assembly of large structures. Terrestrial laser scanners (TLSs) are a related class of dimensional measurement instruments more commonly employed in surveying, reverse engineering, and forensics. Commercially available LTs typically have measurement ranges of up to 80 m. The measurement ranges of TLSs vary from about 50 m to several hundred meters, with some extending as far as several kilometers. It is difficult, if not impossible, to construct long reference lengths to evaluate the ranging performances of these instruments over that distance. In this context, we explore the use of stitching errors (i.e., stacking errors in adjoining or overlapping short lengths) and stitching lengths (i.e., constructing long reference lengths from multiple positions of a reference instrument by registration) to evaluate these instruments. Through experimental data and a discussion on uncertainty, we show that stitching is indeed a viable option to evaluate the ranging performances of LTs and TLSs.

A Preliminary Longitudinal Analysis of Symptom Management, Post-traumatic Stress, and Depressive Symptoms in Chinese Adults with Dissociative Symptoms.

People with dissociative symptoms are generally poly-symptomatic and require high levels of healthcare resources. Post-traumatic stress disorder (PTSD) and depressive symptoms are two major disabling comorbid symptoms in people with dissociative symptoms. While the sense of control over symptoms may be associated with PTSD and dissociative symptoms, the interplay among these factors over time remains unexplored. This study examined the predictors of PTSD and depressive symptoms in people with dissociative symptoms. Longitudinal data from 61 participants with dissociative symptoms were analyzed. Participants completed self-report measures of dissociative, depressive, and PTSD symptoms and the sense of control over symptoms two times (T1 & T2) with an interval of over one month. PTSD and depressive symptoms were not transient or time-specific, but they persisted over time in our sample. Hierarchical multiple regression analyses revealed that, after controlling for age, treatment usage and baseline symptom severity, T1 symptom management scores (ß = -.264, p = .006) negatively predicted T2 PTSD symptoms, while T1 PTSD symptoms (ß = .268, p = .017) positively predicted T2 depressive symptoms. T1 depressive symptoms (ß = -.087, p = .339) did not predict T2 PTSD symptoms. The findings highlight the importance of improving symptom management skills and treating comorbid PTSD symptoms when working with people with dissociative symptoms.

Trauma, Emotional Regulation, and Coping Styles in Individuals with and without Probable Dissociative Disorders in Hong Kong.

Previous studies showed that dissociation and dissociative disorders (DDs) are prevalent and are associated with considerable individual and social consequences. There are ongoing debates regarding whether dissociation is a response to betrayal trauma across cultures and whether dissociation can be explained by maladaptive coping. Additionally, little is known about the clinical features of individuals with DDs in the Chinese context. This study aimed to investigate the relationship between trauma, emotional regulation, coping, and dissociation. We analyzed baseline data from a randomized controlled trial (N = 101). Participants with dissociative symptoms in Hong Kong completed self-report assessments. Structured interviews were also conducted subsequently. Participants with probable DDs reported more traumatic events (p = .009 to .017) and exhibited significantly higher levels of dysfunctional coping (p < .001) compared to those who reported dissociative symptoms but did not have a DD. Dissociative symptoms were more strongly associated with betrayal trauma than with non-betrayal trauma. Among different emotion regulation and coping strategies, dysfunctional coping was the only significant factor associated with dissociative symptoms (ß = .309, p = .003). Dysfunctional coping was a statistically significant mediator that may explain the relationship between betrayal trauma and dissociative symptoms. Although other mediation paths are also possible and further longitudinal studies are required, our findings highlight the strong link between dysfunctional coping and dissociative symptoms and suggest that coping skills training should be incorporated into interventions for betrayal trauma survivors with dissociative symptoms. Additionally, this study provides evidence for the cross-cultural validity of the betrayal trauma theory. Further studies, however, are required.

COULD FAMILY WELL-BEING MODERATE THE RELATIONSHIP BETWEEN ADVERSE CHILDHOOD EXPERIENCES AND SOMATOFORM DISSOCIATION? A PRELIMINARY INVESTIGATION.

The impacts of adverse childhood experiences (ACEs) have been well documented. One possible consequence of ACEs is dissociation, which is a major feature of post-traumatic psychopathology and is also associated with considerable impairment and health care costs. Although ACEs are known to be associated with both psychoform and somatoform dissociation, much less is known about the mechanisms behind this relationship. Little is known about whether social and interpersonal factors such as family environments would moderate the relationship between ACEs and somatoform dissociation. This paper discusses the importance of having a positive and healthy family environment in trauma recovery. We then report the findings of a preliminary study in which we examined whether the association between ACEs and somatoform dissociation would be moderated by family well-being in a convenience sample of Hong Kong adults (N = 359). The number of ACEs was positively associated with somatoform dissociative symptoms, but this association was moderated by the level of family well-being. The number of ACEs was associated with somatoform dissociation only when the family well-being scores were low. These moderating effects were medium. The findings point to the potential importance of using family education and intervention programs to prevent and treat trauma-related dissociative symptoms, but further investigation is needed.

Attenuation of renal injury by depleting cDC1 and by repurposing Flt3 inhibitor in anti-GBM disease.

Previous studies found cDC1s to be protective in early stage anti-GBM disease through Tregs, but pathogenic in late stage Adriamycin nephropathy through CD8+ T cells. Flt3 ligand is a growth factor essential for cDC1 development and Flt3 inhibitors are currently used for cancer treatment. We conducted this study to clarify the role and mechanisms of effects of cDC1s at different time points in anti-GBM disease. In addition, we aimed to utilize drug repurposing of Flt3 inhibitors to target cDC1s as a treatment of anti-GBM disease. We found that in human anti-GBM disease, the number of cDC1s increased significantly, proportionally more than cDC2s. The number of CD8+ T cells also increased significantly and their number correlated with cDC1 number. In XCR1-DTR mice, late (day 12-21) but not early (day 3-12) depletion of cDC1s attenuated kidney injury in mice with anti-GBM disease. cDC1s separated from kidneys of anti-GBM disease mice were found to have a pro-inflammatory phenotype (i.e. express high level of IL-6, IL-12 and IL-23) in late but not early stage. In the late depletion model, the number of CD8+ T cells was also reduced, but not Tregs. CD8+ T cells separated from kidneys of anti-GBM disease mice expressed high levels of cytotoxic molecules (granzyme B and perforin) and inflammatory cytokines (TNF-α and IFN-γ), and their expression reduced significantly after cDC1 depletion with diphtheria toxin. These findings were reproduced using a Flt3 inhibitor in wild type mice. Therefore, cDC1s are pathogenic in anti-GBM disease through activation of CD8+ T cells. Flt3 inhibition successfully attenuated kidney injury through depletion of cDC1s. Repurposing Flt3 inhibitors has potential as a novel therapeutic strategy for anti-GBM disease.

Exposure to Violence in Social Unrest, Resilience, and Mental Health of Older People in Hong Kong.

OBJECTIVE: Older adults are prone to the negative effects of exposure to violence on their mental health. This study aimed to examine the impact of exposure to violence during social unrest and the role of resilience in the mental health of older people. DESIGN: A total of 1,203 people aged 65 years or older were randomly selected for a telephone survey using the random digit dialing numbering method in Hong Kong. MEASUREMENTS: A 13-item scale was developed to measure exposure to violence. The Chinese versions of the Connor-Davidson Resilience Scale and the Startle, Physiological Arousal, Anger, and Numbness scales for measuring mental health status were adopted in the survey. RESULTS: The results showed that the more frequently older people were exposed to information, the more negative mental health status they had. However, exposure to witnessing and experiencing violence was not significantly associated with mental health status. Older adults' level of resilience had a moderating effect between exposure to information and mental health, whereas the effect of exposure to information on mental health was stronger for respondents with lower resilience. CONCLUSION: This study showed that emotional problems caused by exposure to related information among older people should be properly addressed during massive social unrest and conflict. Their resilience capacity is an important moderating factor. Future interventions and support services should focus on enhancing the resilience of older people to better equip them with overcoming problems related to macro-social issues.

Trends in elder abuse and age discrimination during the COVID-19 pandemic in Hong Kong: Findings from a two-wave representative telephone survey study.

OBJECTIVES: Empirical evidence about the heightened risks of elder abuse and age discrimination during the COVID-19 pandemic is scarce. This study aimed to track the changes in rates of both, and investigated their associated factors in the community-dwelling older population in Hong Kong. METHODS: In this two-wave, cross-sectional telephone survey, we interviewed a population-based sample of individuals (≥55 years), and captured the situation of elder abuse and age discrimination before the COVID-19 outbreak (n = 1209, Wave 1: October-December 2019) and during the pandemic (n = 891, Wave 2: December 2020-January 2021). Participants reported their experiences of different types of abuse and discrimination, financial health, subjective well-being, satisfaction with environment, health and social services, and resilience. RESULTS: Abuse was reported by 20.2% of the sample before the outbreak and 17.8% during the pandemic; while discrimination was reported by 24.6% and 29.8% at the two time points, respectively. A drop in physical abuse was observed, but it was accompanied by a rise in discrimination in the form of harassment or refusal of services. Findings of logistic regression analysis show that abuse during the pandemic was associated with younger age, poorer subjective well-being, and lower resilience; while discrimination was associated with female gender, being married, and poorer subjective well-being. CONCLUSIONS: Elder abuse and discrimination were prevalent across time points. The pandemic has highlighted the marginalization of older persons in our communities. There is an urgent need for development of effective interventions to end abuse and discrimination.

Women's experience of perinatal support in a high migrant Australian population during the COVID-19 pandemic: a mixed methods study.

BACKGROUND: As a COVID-19 risk mitigation measure, Australia closed its international borders for two years with significant socioeconomic disruption including impacting approximately 30% of the Australian population who are migrants. Migrant populations during the peripartum often rely on overseas relatives visiting for social support. High quality social support is known to lead to improved health outcomes with disruption to support a recognised health risk. AIM: To explore women's experience of peripartum social support during the COVID-19 pandemic in a high migrant population. To quantify type and frequency of support to identify characteristics of vulnerable perinatal populations for future pandemic preparedness. METHODS: A mixed methods study with semi-structured interviews and a quantitative survey was conducted from October 2020 to April 2021. A thematic approach was used for analysis. RESULTS: There were 24 participants interviewed both antenatally and postnatally (22 antenatal; 18 postnatal). Fourteen women were migrants and 10 Australian born. Main themes included; 'Significant disruption and loss of peripartum support during the COVID-19 pandemic and ongoing impact for migrant women'; 'Husbands/partners filling the support gap' and 'Holding on by a virtual thread'. Half of the participants felt unsupported antenatally. For Australian born women, this dissipated postnatally, but migrants continued to feel unsupported. Migrant women discussed partners stepped into traditional roles and duties of absent mothers and mothers-in-law who were only available virtually. CONCLUSION: This study identified disrupted social support for migrant women during the pandemic, providing further evidence that the pandemic has disproportionately impacted migrant populations. However, the benefits identified in this study included high use of virtual support, which could be leveraged for improving clinical care in the present and in future pandemics. The COVID-19 pandemic impacted most women's peripartum social support with migrant families having ongoing disruption. Gains in the pandemic included greater gender equity for domestic work as husbands/partners increased their contribution to domestic work and childcare.

Cigarette smoking and adverse health outcomes in patients treated with maintenance dialysis.

BACKGROUND: The association of smoking with new-onset cardiovascular disease, chronic lung disease, malignancy and mortality in dialysis is well-known. The smoking prevalence and its association with clinical outcome was assessed. METHODS: Multicentre cohort study using 'ANZDATA' Registry, 57 838 adults who commenced dialysis (>3 months) between 1990 and 2016 were included. Patients' demographics, initial dialysis modality, presence of comorbidities and smoking history are predictors. The primary outcome was all-cause mortality. Secondary outcomes were smoking prevalence, cause-specific mortality, non-skin cancers, cardiovascular and chronic lung diseases. RESULTS: Of the 57 838 patients, 56 512 (mean age of 58.9 ± 15.1 years, 40.1% female, 43% diabetic), had data on smoking history with 13.6% current, 40.7% former and 45.6% never smokers. Former and current smokers had 10% (HR 1.10; 95% CI: 1.08, 1.13) and 22%(HR 1.22; 95% CI: 1.18, 1.26) higher risk of all-cause mortality. They were 13% (HR 1.13; 95% CI: 1.09, 1.18) and 23% (HR 1.23; 95% CI: 1.17, 1.29) for CVD mortality. Smoking was associated with higher mortality from respiratory failure (HR 1.59; 95% CI: 1.13, 2.23, p = .073 and HR 1.33; 95% CI: 1.01, 1.74, p = .042) for current and former smokers. Current and former smokers had higher risk for non-skin cancer (HR 1.30; 95% CI: 1.19, 1.42 and HR 1.24; 95% CI: 1.17, 1.32). Smoking was associated with a higher rate of death from cancer (HR 1.26; 95% CI 1.19-1.33) and chronic lung disease (HR 1.48; 95% CI 1.15-1.92). Former and current smokers had a higher adjusted risk for de novo vascular disease (PVD, CVD), CAD (adjusted RR 1.1; 95% Cl: 1.09-1.12). CONCLUSIONS: In dialysis patients, smoking was associated with higher rates of all-cause mortality, cardiovascular mortality, respiratory failure, chronic lung disease and malignancy along with higher risks of non-skin cancers, de novo vascular disease and chronic lung disease.

Interpersonal stress mediates the relationship between childhood trauma and depressive symptoms: Findings from two culturally different samples.

OBJECTIVE: Childhood trauma is associated with adulthood depressive symptoms, but very few studies explored potential social and interpersonal mediators behind this association. This study made the first attempt to test the potential mediating effects of interpersonal stress in the associations between childhood betrayal and non-betrayal trauma and depressive symptoms. METHOD: We analyzed data in a sample of English-speaking adults from diverse backgrounds (from 19 different countries, mainly from Western countries) (N = 468). We then replicated and compared the results with those in another convenience sample of Chinese-speaking younger adults with different cultural backgrounds and mental health status (N = 205). RESULTS: The results in both samples indicated that (1) childhood betrayal trauma had a stronger relationship with depressive symptoms than childhood non-betrayal trauma and that (2) interpersonal stress was a significant mediator in the relationship between childhood betrayal trauma and depressive symptoms, even when childhood non-betrayal trauma was included as a covariate. The indirect effect of childhood non-betrayal trauma on depressive symptoms through interpersonal stress was not consistent in two samples. CONCLUSIONS: Our findings point to the importance of taking social and interpersonal contexts into account when investigating, preventing and managing depression in trauma-exposed populations. Early social interventions such as family interventions, interpersonal skills training and building social resources may have the potential to change the trajectory of the development of mental health problems in trauma survivors.

Establishing community mental health facilities: a comparative review of Hong Kong and international jurisdictions.

BACKGROUND: The establishment of mental health facilities in the community has been hindered by opposition from local residents in Hong Kong. Through a comparative review, this study aimed to compare the issues related to the process of establishment of community-based mental health facilities between Hong Kong and selected overseas countries and regions. It will better inform the strategies and best practices that can be adopted for the establishment of mental health facilities in Hong Kong. METHODS: Three electronic databases (PubMed, Scopus, and PsycINFO) were used to examine literature on nine jurisdictions in Asia and western societies from 2005 to 2019. In addition, we conducted a number of in-depth interviews with overseas experts to gain in-depth insights and clarify information that was unavailable or unclear. A total of 19,248 articles were identified through the initial search. 71 of them met the inclusion criteria. In addition, 20 articles about the establishment of other types of community facilities or sensitive facilities were identified from supplementary sources. RESULTS: Most Western countries and Singapore have adopted regulations or laws to reduce public discrimination against particular groups, giving them corresponding human rights and legislating to demarcate the use of land in the community. Regions close to Hong Kong emphasize communication with community leaders to obtain support for sensitive services or facilities. CONCLUSIONS: Hong Kong may consider strengthening the land zoning ordinance in relation to community sensitive facilities, as well as increasing communication with the community and considering the possibility of locating facilities in government buildings.

c-di-GMP inhibits LonA-dependent proteolysis of TfoY in Vibrio cholerae.

The LonA (or Lon) protease is a central post-translational regulator in diverse bacterial species. In Vibrio cholerae, LonA regulates a broad range of behaviors including cell division, biofilm formation, flagellar motility, c-di-GMP levels, the type VI secretion system (T6SS), virulence gene expression, and host colonization. Despite LonA's role in cellular processes critical for V. cholerae's aquatic and infectious life cycles, relatively few LonA substrates have been identified. LonA protease substrates were therefore identified through comparison of the proteomes of wild-type and ΔlonA strains following translational inhibition. The most significantly enriched LonA-dependent protein was TfoY, a known regulator of motility and the T6SS in V. cholerae. Experiments showed that TfoY was required for LonA-mediated repression of motility and T6SS-dependent killing. In addition, TfoY was stabilized under high c-di-GMP conditions and biochemical analysis determined direct binding of c-di-GMP to LonA results in inhibition of its protease activity. The work presented here adds to the list of LonA substrates, identifies LonA as a c-di-GMP receptor, demonstrates that c-di-GMP regulates LonA activity and TfoY protein stability, and helps elucidate the mechanisms by which LonA controls important V. cholerae behaviors.