MRI features distinguishing pediatric Lyme arthritis from septic arthritis.

OBJECTIVE: This study aims to identify distinguishing MRI features of Lyme arthritis (LA), an increasingly prevalent cause of pediatric infectious arthritis in the USA, to enable rapid discrimination from septic arthritis (SA) and facilitate appropriate management. MATERIALS AND METHODS: A single-center, retrospective analysis was conducted on a convenience sample of pediatric patients with LA in an endemic area using EPIC electronic health record data between January 2010 and December 2020. Patients with positive serologic testing and concurrent MRI were selected. MRI scans were reviewed by a subspecialty-trained pediatric radiologist. Key MRI features analyzed include joint effusion, synovitis, myositis, soft tissue edema, and osseous edema and erosions. MRI features, demographics, and clinical data were compared using univariable and multivariable analyses. RESULTS: Fifty cases of knee LA and 13 cases of knee SA were included. Larger joint effusion (p = 0.0055, z = - 2.779) and abnormally thickened synovium (p = 0.0011, χ2 = 10.622) were more associated with LA. In contrast, increased myositis, subcutaneous edema, and osseous changes were more prevalent in SA. Abnormal bone marrow signal (p < 0.0001, χ2 = 36.893) and bone erosion (p < 0.0001, χ2 = 25.506) were observed in 84.6% (11/13) and 46.2% (6/13) of SA cases, respectively, while no bone erosion was found in LA. CONCLUSION: MRI can be a valuable tool in differentiating LA from SA. Abnormal synovium and increasing joint effusion favor LA, while increasing soft tissue edema and osseous changes favor SA. Notably, the presence of bone erosion effectively excluded LA from consideration.

Pericatheter Leak Associated With Earlier Peritoneal Dialysis Initiation Does Not Influence Long-Term Outcomes.

Introduction: Internationally, peritoneal dialysis (PD) is increasingly being commenced within 2 weeks of catheter insertion. Studies are warranted to evaluate outcomes of this strategy. Methods: This study examines outcomes of early-start PD (ESPD) and conventional-start PD (CSPD), commencing at ≤14 days and >14 days after catheter insertion, respectively. All adults with kidney failure within a large metropolitan PD unit initiating PD through a new catheter, inserted using laparoscopic or modified Seldinger technique, between August 2019 and August 2022, were included in this retrospective observational study. Demographic data and episodes of infectious and mechanical complications were collected using electronic medical records. Analysis was conducted using analysis of variance and Chi-square testing. A P-value < 0.05 was significant with Bonferroni correction performed where relevant. Kaplan-Meier and competing risks analyses were performed for time to PD-related peritonitis and transfer to hemodialysis. Results: A total of 297 patients (70% male, mean age 58.7 years) were included, with 130 (43.8%) patients undertaking ESPD. Most patients had laparoscopically inserted catheters (65.3%) and 65 patients (22.0%) received prior hemodialysis. When compared to CSPD, ESPD was associated with a higher number of pericatheter leaks (6.9% vs. 0.6%, P = 0.003), with otherwise similar complication episodes and no significant difference with respect to time to PD-related peritonitis or transfer to hemodialysis. Catheter insertion technique or prior hemodialysis treatment did not significantly influence outcomes. Conclusion: ESPD is associated with increased pericatheter leaks when compared to CSPD, with an otherwise similar complication profile.

Diribonuclease activity eliminates toxic diribonucleotide accumulation.

RNA degradation is a central process required for transcriptional regulation. Eventually, this process degrades diribonucleotides into mononucleotides by specific diribonucleases. In Escherichia coli, oligoribonuclease (Orn) serves this function and is unique as the only essential exoribonuclease. Yet, related organisms, such as Pseudomonas aeruginosa, display a growth defect but are viable without Orn, contesting its essentiality. Here, we take advantage of P. aeruginosa orn mutants to screen for suppressors that restore colony morphology and identified yciV. Purified YciV (RNase AM) exhibits diribonuclease activity. While RNase AM is present in all γ-proteobacteria, phylogenetic analysis reveals differences that map to the active site. RNase AMPa expression in E. coli eliminates the necessity of orn. Together, these results show that diribonuclease activity prevents toxic diribonucleotide accumulation in γ-proteobacteria, suggesting that diribonucleotides may be utilized to monitor RNA degradation efficacy. Because higher eukaryotes encode Orn, these observations indicate a conserved mechanism for monitoring RNA degradation.

Long-term effect of increasing water intake on repeated self-assessed health-related quality of life (HRQoL) in autosomal dominant polycystic kidney disease.

Background: The aim of this study was to determine the long-term effect of increasing water intake in patients with autosomal dominant polycystic kidney disease (ADPKD) on longitudinal changes in health-related quality of life (HRQoL) in the setting of a clinical trial. Methods: Self-completed HRQoL (using the KDQoL-SF, v.1.3 questionnaire) was assessed annually in participants of a 3-year randomized controlled clinical trial (n = 187), allocated (1:1) either to increase water intake to reduce urine osmolality to ≤270 mosmol/kg (implemented by dietetic coaching, self-monitoring tools, text messaging) or continue usual water intake. Results: Overall, 96% and 81.8% of participants (n = 187) completed the questionnaire at the baseline and final study visits, respectively. At baseline, the physical component summary score (PCS) and mental component summary score (MCS) were similar in the two groups (P > 0.05) and the five dimensions with the lowest scores in both groups were: energy and fatigue; general and overall health; sleep; emotional well-being; and pain. Within each group, there were no longitudinal changes over time. At the final visit, the PCS was higher in the increased water intake group (51.3 ± 7.6, mean ± standard deviation) compared to the usual water intake group 48.8 ± 9.3; P = 0.037) whereas the MCS was numerically similar. The improvement in the PCS was due to higher sub-scale values for physical functioning and pain (both P < 0.05). By multivariate analysis, only baseline PCS and height-corrected total kidney volume were associated with the final PCS (P < 0.05). Conclusion: HRQoL scores remained stable over a 3 year period, and were not adversely affected by the intervention to increase water intake. Future studies should evaluate the clinical significance of the higher PCS in the increased water intake group.

Personalized neoantigen vaccines as early intervention in untreated patients with lymphoplasmacytic lymphoma: a non-randomized phase 1 trial.

Lymphoplasmacytic lymphoma (LPL) is an incurable low-grade lymphoma with no standard therapy. Nine asymptomatic patients treated with a first-in-human, neoantigen DNA vaccine experienced no dose limiting toxicities (primary endpoint, NCT01209871). All patients achieve stable disease or better, with one minor response, and median time to progression of 72+ months. Post-vaccine single-cell transcriptomics reveal dichotomous antitumor responses, with reduced tumor B-cells (tracked by unique B cell receptor) and their survival pathways, but no change in clonal plasma cells. Downregulation of human leukocyte antigen (HLA) class II molecules and paradoxical upregulation of insulin-like growth factor (IGF) by the latter suggest resistance mechanisms. Vaccine therapy activates and expands bone marrow T-cell clonotypes, and functional neoantigen-specific responses (secondary endpoint), but not co-inhibitory pathways or Treg, and reduces protumoral signaling by myeloid cells, suggesting favorable perturbation of the tumor immune microenvironment. Future strategies may require combinations of vaccines with agents targeting plasma cell subpopulations, or blockade of IGF-1 signaling or myeloid cell checkpoints.

The Incidental Finding of Trichilemmal Cyst in a Patient With Acute Kidney Injury.

This case highlights the importance of thorough clinical examinations from head to toe and the early diagnosis of trichilemmal cysts. We present a case of an incidentally discovered trichilemmal cyst in a 72-year-old patient who presented with acute kidney injury secondary to a urinary tract infection. In rare instances, these cysts can transform into malignant lesions. Therefore, clinicians should be aware of the potential for malignancy when diagnosing and managing trichilemmal cysts.

Lithium-Associated Kidney Failure: Predictors and Outcomes.

Introduction: Despite the widespread use of lithium for bipolar disorders and depression, little is known about the characteristics of patients with lithium-associated kidney failure receiving kidney replacement therapy (KRT). Methods: We conducted a retrospective study using the Australian and New Zealand Dialysis and Transplant Registry (ANZDATA) to investigate the predictors and outcomes of patients with lithium-associated kidney failure receiving KRT. Results: A total of 437 patients with lithium-associated kidney failure were compared to 1280 ANZDATA allocated controls of patients with kidney failure not associated with lithium. Patients with lithium-associated kidney failure commenced KRT at significantly older age (62 ± 10 vs. 58 ± 15 years; P < 0.001) and were more likely to be European (93% vs. 68%, P < 0.001), to be female (63% vs. 40%, P < 0.001), and to live in a postcode with a higher socioeconomic status (SES) (P < 0.001). In patients with lithium-associated kidney failure, there were lower rates of coronary artery disease (17% vs. 37%, P < 0.001), peripheral vascular disease (7% vs. 25%, P < 0.001), cerebrovascular disease (8% vs. 14%, P = 0.004) and diabetes mellitus (16% vs. 47%, P < 0.001). There were no differences between first KRT modality, although kidney transplantation and retransplantation rates were lower (21% vs. 27%, P = 0.008; 0.2% vs 3%, P = 0.001) with shorter wait-times to first transplantation (20 months vs. 29 months, P = 0.02) in the patients with lithium-associated kidney failure. Rates of at least 1 rejection episode was comparable (21% vs. 22%, P = 0.85) between the 2 groups. In addition, there were no survival differences regardless of KRT modality between the 2 groups. Conclusion: Lithium-associated kidney failure represents a unique cohort which is predominantly older, female, European, with a higher SES and less comorbidities. Despite this, there are no differences in survival. Given the lower rate of transplantation, barriers to transplantation need further exploration.

Quantitative Magnetic Resonance Cerebral Spinal Fluid Flow Properties and Executive Function Cognitive Outcomes in Congenital Heart Disease.

Cerebrospinal fluid (CSF) circulation has recently been shown to be important in nutrient distribution, waste removal, and neurogenesis. Increased CSF volumes are frequently observed in congenital heart disease (CHD) and are associated with neurodevelopmental deficits. This suggests prolonged perturbation to the CSF system and possible interference to its homeostatic function, which may contribute to the neurodevelopmental deficits in CHD. CSF flow has yet to be studied in CHD patients, but the pulsatile flow of CSF throughout the brain is driven mainly by cardiopulmonary circulation. Given the underlying heart defects in CHD, the cardiopulmonary circulatory mechanisms in CHD might be impaired with resultant perturbation on the CSF circulation. In this study, we determine whether CSF flow, using MRI measurements of static and dynamic pulsatile flow, is abnormal in youths with CHD compared to healthy controls in relation to executive cognitive function. CSF flow measurements were obtained on a total of 58 child and young adult participants (CHD=20, healthy controls = 38). The CSF flow was measured across the lumen of the Aqueduct of Sylvius using cardiac-gated phase-contrast MRI at 3.0T. Static pulsatility was characterized as anterograde and retrograde peak velocities, mean velocity, velocity variance measurements, and dynamic pulsatility calculated as each participant's CSF flow deviation from the study cohort's consensus flow measured with root mean squared deviation (RMSD) were obtained. The participants had neurocognitive assessments for executive function with focus on inhibition, cognitive flexibility, and working memory domains. The CHD group demonstrated greater dynamic pulsatility (higher overall flow RMSD over the entire CSF flow cycle) compared to controls (p=0.0353), with no difference detected in static pulsatility measures. However, lower static CSF flow pulsatility (anterograde peak velocity: p=0.0323) and lower dynamic CSF flow pulsatility (RMSD: p=0.0181) predicted poor inhibitory executive function outcome. Taken together, while the whole CHD group exhibited higher dynamic CSF flow pulsatility compared to controls, the subset of CHD subjects with relatively reduced static and dynamic CSF flow pulsatility had the worst executive functioning, specifically the inhibition domain. These findings suggest that altered CSF flow pulsatility may be central to not only brain compensatory mechanisms but can also drive cognitive impairment in CHD. Further studies are needed to investigate possible mechanistic etiologies of aberrant CSF pulsatility (i.e. primary cardiac hemodynamic disturbances, intrinsic brain vascular stiffness, altered visco-elastic properties of tissue, or glial-lymphatic disturbances), which can result in acquired small vessel brain injury (including microbleeds and white matter hyperintensities).

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.

Postnatal Brain Trajectories and Maternal Intelligence Predict Childhood Outcomes in Complex CHD.

Objective: To determine whether early structural brain trajectories predict early childhood neurodevelopmental deficits in complex CHD patients and to assess relative cumulative risk profiles of clinical, genetic, and demographic risk factors across early development. Study Design: Term neonates with complex CHDs were recruited at Texas Children's Hospital from 2005-2011. Ninety-five participants underwent three structural MRI scans and three neurodevelopmental assessments. Brain region volumes and white matter tract fractional anisotropy and radial diffusivity were used to calculate trajectories: perioperative, postsurgical, and overall. Gross cognitive, language, and visuo-motor outcomes were assessed with the Bayley Scales of Infant and Toddler Development and with the Wechsler Preschool and Primary Scale of Intelligence and Beery-Buktenica Developmental Test of Visual-Motor Integration. Multi-variable models incorporated risk factors. Results: Reduced overall period volumetric trajectories predicted poor language outcomes: brainstem ((ß, 95% CI) 0.0977, 0.0382-0.1571; p = 0.0022) and white matter (0.0023, 0.0001-0.0046; p = 0.0397) at 5 years; brainstem (0.0711, 0.0157-0.1265; p = 0.0134) and deep grey matter (0.0085, 0.0011-0.0160; p = 0.0258) at 3 years. Maternal IQ was the strongest contributor to language variance, increasing from 37% at 1 year, 62% at 3 years, and 81% at 5 years. Genetic abnormality's contribution to variance decreased from 41% at 1 year to 25% at 3 years and was insignificant at 5 years. Conclusion: Reduced postnatal subcortical-cerebral white matter trajectories predicted poor early childhood neurodevelopmental outcomes, despite high contribution of maternal IQ. Maternal IQ was cumulative over time, exceeding the influence of known cardiac and genetic factors in complex CHD, underscoring the importance of heritable and parent-based environmental factors.

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.

Early Infant Prefrontal Cortical Microstructure Predicts Present and Future Emotionality.

BACKGROUND: High levels of infant negative emotionality (NE) and low positive emotionality (PE) predict future emotional and behavioral problems. The prefrontal cortex (PFC) supports emotional regulation, with each PFC subregion specializing in specific emotional processes. Neurite orientation dispersion and density imaging estimates microstructural integrity and myelination via the neurite density index (NDI) and dispersion via the orientation dispersion index (ODI), with potential to more accurately evaluate microstructural alterations in the developing brain. Yet, no study has used these indices to examine associations between PFC microstructure and concurrent or developing infant emotionality. METHODS: We modeled PFC subregional NDI and ODI at 3 months with caregiver-reported infant NE and PE at 3 months (n = 61) and at 9 months (n = 50), using multivariable and subsequent bivariate regression models. RESULTS: The most robust statistically significant findings were positive associations among 3-month rostral anterior cingulate cortex (ACC) ODI and caudal ACC NDI and concurrent NE, a positive association between 3-month lateral orbitofrontal cortex ODI and prospective NE, and a negative association between 3-month dorsolateral PFC ODI and concurrent PE. Multivariate models also revealed that other PFC subregional microstructure measures, as well as infant and caregiver sociodemographic and clinical factors, predicted infant 3- and 9-month NE and PE. CONCLUSIONS: Greater NDI and ODI, reflecting greater microstructural complexity, in PFC regions supporting salience perception (rostral ACC), decision making (lateral orbitofrontal cortex), action selection (caudal ACC), and attentional processes (dorsolateral PFC) might result in greater integration of these subregions with other neural networks and greater attention to salient negative external cues, thus higher NE and/or lower PE. These findings provide potential infant cortical markers of future psychopathology risk.

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.

Enhancing digital health services: A machine learning approach to personalized exercise goal setting.

Background: The utilization of digital health has increased recently, and these services provide extensive guidance to encourage users to exercise frequently by setting daily exercise goals to promote a healthy lifestyle. These comprehensive guides evolved from the consideration of various personalized behavioral factors. Nevertheless, existing approaches frequently neglect the users' dynamic behavior and the changing in their health conditions. Objective: This study aims to fill this gap by developing a machine learning algorithm that dynamically updates auto-suggestion exercise goals using retrospective data and realistic behavior trajectory. Methods: We conducted a methodological study by designing a deep reinforcement learning algorithm to evaluate exercise performance, considering fitness-fatigue effects. The deep reinforcement learning algorithm combines deep learning techniques to analyze time series data and infer user's exercise behavior. In addition, we use the asynchronous advantage actor-critic algorithm for reinforcement learning to determine the optimal exercise intensity through exploration and exploitation. The personalized exercise data and biometric data used in this study were collected from publicly available datasets, encompassing walking, sports logs, and running. Results: In our study, we conducted the statistical analyses/inferential tests to compare the effectiveness of machine learning approach in exercise goal setting across different exercise goal-setting strategies. The 95% confidence intervals demonstrated the robustness of these findings, emphasizing the superior outcomes of the machine learning approach. Conclusions: Our study demonstrates the adaptability of machine learning algorithm to users' exercise preferences and behaviors in exercise goal setting, emphasizing the substantial influence of goal design on service effectiveness.

Systematic Review on Treatment and Outcomes of Tuberculous Peritonitis in Patients on Peritoneal Dialysis.

Introduction: Peritoneal dialysis (PD)-associated peritonitis due to tuberculosis (TB) is associated with poor outcomes and optimal treatment strategies for this condition remain unknown. Our study aimed to: (i) systematically review the published literature on peritonitis caused by Mycobacterium tuberculosis in patients on PD and (ii) review cases of peritonitis due to M tuberculosis in patients on PD reported in Australia and New Zealand to determine the epidemiology, management strategies, and outcomes of this condition. Methods: A literature search of Medline, Scopus, Embase, ClinicalTrials.gov, Cochrane CENTRAL Register of Controlled Trials and Google Scholar for articles published from inception date to June 2022 was conducted. To be eligible, articles had to describe patient characteristics, initial anti-TB therapy, and treatment outcomes in all patients on PD with peritonitis caused by M tuberculosis. Data from the Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry of patients on PD who developed peritonitis due to M tuberculosis between September 2001 and December 2020 were included and analyzed. Results: The systematic literature review identified 70 case studies (151 patients) and 8 cohort studies (97 patients), whereas the ANZDATA Registry identified 17 cases of peritonitis due to M tuberculosis. Overall, in patients diagnosed with peritonitis due to M tuberculosis, the rates of PD catheter removal and permanent transfer to hemodialysis (HD) were numerically higher in the ANZDATA Registry cases (82%) than in the case studies (23%) and cohort studies (20%). Observed all-cause mortality rates were also higher as observed in the case studies (33%) and cohort studies (26%) than in the ANZDATA Registry cases (6%). Conclusion: Tuberculous peritonitis is uncommon in patients on PD and is associated with poor outcomes. Prospective studies are warranted to study the effect of retaining PD catheters after M tuberculosis infection on patient outcomes.

Long-term efficacy and safety of a treatment strategy for HIV infection using protease inhibitor monotherapy: 8-year routine clinical care follow-up from a randomised, controlled, open-label pragmatic trial (PIVOT).

Background: Treatment-simplification strategies are important tools for patient-centred management. We evaluated long-term outcomes from a PI monotherapy switch strategy. Methods: Eligible participants attending 43 UK treatment centres had a viral load (VL) below 50 copies/ml for at least 24 weeks on combination ART. Participants were randomised to maintain ongoing triple therapy (OT) or switch to a strategy of physician-selected PI monotherapy (PI-mono) with prompt return to combination therapy if VL rebounded. The primary outcome, previously reported, was loss of future drug options after 3 years, defined as new intermediate/high level resistance to at least one drug to which the participant's virus was considered sensitive at trial entry. Here we report resistance and disease outcomes after further extended follow-up in routine care. The study was registered as ISRCTN04857074. Findings: We randomised 587 participants to OT (291) or PI-mono (296) between Nov 4, 2008, and July 28, 2010 and followed them for a median of more than 8 years (100 months) until 2018. At the end of this follow-up time, one or more future drug options had been lost in 7 participants in the OT group and 6 in the PI-mono group; estimated cumulative risk by 8 years of 2.7% and 2.1% respectively (difference -0.6%, 95% CI -3.2% to 2.0%). Only one PI-mono participant developed resistance to the protease inhibitor they were taking (atazanavir). Serious clinical events (death, serious AIDS, and serious non-AIDS) were infrequent; reported in a total of 12 (4.1%) participants in the OT group and 23 (7.8%) in the PI-mono group (P = 0.08) over the entire follow-up period. Interpretation: A strategy of PI monotherapy, with regular VL monitoring and prompt reintroduction of combination treatment following rebound, preserved future treatment options. Findings confirm the high genetic barrier to resistance of the PI drug class that makes them well suited for creative, patient-centred, treatment-simplification approaches. The possibility of a small excess risk of serious clinical events with the PI monotherapy strategy cannot be excluded. Funding: The National Institute for Health Research Health Technology Assessment programme.

Personal Competence or Environmental Characteristics? Factors Influencing Happiness among Ageing Adults in Hong Kong Around the Period of COVID-19 Pandemic.

Drawing upon person-environment fit perspective, this study examines the joint and interactive influences of personal competence and environmental characteristics on the happiness of ageing adults around the period of COVID-19 pandemic. Data was collected in two rounds, before and during the pandemic, with 2,028 participants aged 55 years and older in Hong Kong. Personal competence encompassed financial status, physical health, and mental capital, while environmental characteristics included experiences of ageism, perceived social conditions, and age-friendly policies. Ordinary least squares regression was used to examine personal and environmental influences on happiness. Results indicated a significant decline in happiness following the onset of COVID-19 pandemic. Mental capital was found to have the strongest positive influence on happiness, followed by physical health, financial status, and social conditions. Mental capital mitigated the negative relationship between experiences of ageism and happiness. Practical interventions are informed to improve the well-being of ageing adults during pandemic.

Rehabilitation after Hypoxic and Metabolic Brain Injury in a Mountain Climber.

A patient in her 50s presented with altered mental status and shortness of breath at 4600 m elevation. After descent to the base of the mountain, the patient became comatose. She was found to have bilateral pulmonary infiltrates and a serum sodium of 102 mEq/L. She was rapidly corrected to 131 mEq/L in 1 day. Initial MRI showed intensities in bilateral hippocampi, temporal cortex and insula. A repeat MRI 17 days post injury showed worsened intensities in the bilateral occipital lobes. On admission to acute rehabilitation, the patient presented with blindness, agitation, hallucinations and an inability to follow commands. Midway through her rehabilitation course, antioxidant supplementations were started with significant improvement in function. Rapid correction of hyponatraemia may cause central pontine myelinolysis or extrapontine myelinolysis (EPM). In some cases of hypoxic brain injury, delayed post-hypoxic leucoencephalopathy (DPHL) may occur. Treatment options for both disorders are generally supportive. This report represents the only documented interdisciplinary approach to treatment of a patient with DPHL and EPM. Antioxidant supplementation may be beneficial as a treatment option for both EPM and DPHL.

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.

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.