Changes in nutritional status and the development of obesity and metabolic syndrome following pediatric heart transplantation.

BACKGROUND: Nutritional status in pediatric patients undergoing heart transplantation (HT) is frequently a focus of clinical management and requires high resource utilization. Pre-operative nutrition status has been shown to affect post-operative mortality but no studies have been performed to assess how nutritional status may change and the risk of developing nutritional comorbidities long-term in the post-transplant period. METHODS: A single-center retrospective chart review of patients ≥2 years of age who underwent heart transplantation between 1/1/2005 and 4/30/2020 was performed. Patient data were collected at listing, time of transplant, 1-year, and 3-year follow-up post-transplant. Nutrition status was classified based on body mass index (BMI) percentile in the primary analysis. Alternative nutritional indices, namely the nutrition risk index (NRI), prognostic nutrition index (PNI), and BMI z-score, were utilized in secondary analyses. RESULTS: Of the 63 patients included, the proportion of patients with overweight/obese status increased from 21% at listing to 41% at 3-year follow-up. No underweight patients at listing became overweight/obese at follow-up. Of patients who were overweight/obese at listing, 88% maintained that status at 3-year follow-up. Overweight/obese status at listing, 1-year, and 3-year post-transplantation were significantly associated with developing metabolic syndrome. In comparison to the alternative nutritional indices, BMI percentile best predicted post-transplant metabolic syndrome. CONCLUSIONS: The results suggest that pediatric patients who undergo heart transplantation are at risk of developing overweight/obesity and related nutritional sequelae (ie, metabolic syndrome). Improved surveillance and interventions targeted toward overweight/obese HT patients should be investigated to reduce the burden of associated comorbidities.

Identifying factors associated with post-hospital falls in older patients: a territory-wide cohort study.

OBJECTIVES: Post-hospital falls impose a substantial healthcare burden on older adults, yet contributing factors remain inadequately examined. This study aimed to investigate underinvestigated factors associated with post-hospital falls. STUDY DESIGN: Retrospective territory-wide cohort study. METHODS: We examined the electronic medical records of patients aged ≥65 who were discharged from public hospitals in Hong Kong (2007-2018). During the 12 months following discharge, participants were monitored to identify falls based on diagnosis codes or clinical notes from inpatient episodes, the emergency department (ED) visits, and death records. Falls were categorized into two groups: those only requiring ED visits and those requiring hospitalizations. Binary logistic and multinomial logistic regressions examined the associated factors for post-hospital falls and subcategories of falls, respectively. RESULTS: Among 606,392 older patients, 28,593 (4.71%; 95% CI = 4.66%-4.77%) experienced falls within 12 months after discharge. Of those, 8438 (29.5%) only required ED visits, and 20,147 (70.5%) required hospitalizations. Discharge from non-surgical wards, length of stay over two weeks, receiving the Geriatric Day Hospital and Rehabilitation Day Program, advancing age, being female, having more comorbidities, taking more fall risk increasing drugs, previous admission for falls, and living in Hong Kong Island were associated with increased fall risk. Receiving allied health service or nurse service was associated with reduced risk. The same factors were more associated with falls requiring hospitalizations rather than falls only requiring ED visits. CONCLUSIONS: Older patients with identified factors were particularly vulnerable to post-hospital falls leading to rehospitalizations. Fall risk assessment and tailored prevention should prioritize this group.

GABA receptor associated protein changes the electrostatic environment around the GABA type A receptor.

We have performed fully atomistic molecular dynamics simulations of the intracellular domain of a model of the GABAA receptor with and without the GABA receptor associated protein (GABARAP) bound. We have also calculated the electrostatic potential due to the receptor, in the absence and presence of GABARAP. We find that GABARAP binding changes the electrostatic properties around the GABAA receptor and could lead to increased conductivity of chloride ions through the receptor. We also find that ion motions that would result in conducting currents are observed nearly twice as often when GABARAP binds. These results are consistent with data from electrophysiological experiments.

Pre-conditioning modifies the TME to enhance solid tumor CAR T cell efficacy and endogenous protective immunity.

Chimeric antigen receptor (CAR) T cell therapy has led to impressive clinical responses in patients with hematological malignancies; however, its effectiveness in patients with solid tumors has been limited. While CAR T cells for the treatment of advanced prostate and pancreas cancer, including those targeting prostate stem cell antigen (PSCA), are being clinically evaluated and are anticipated to show bioactivity, their safety and the impact of the immunosuppressive tumor microenvironment (TME) have not been faithfully explored preclinically. Using a novel human PSCA knockin (hPSCA-KI) immunocompetent mouse model, we evaluated the safety and therapeutic efficacy of PSCA-CAR T cells. We demonstrated that cyclophosphamide (Cy) pre-conditioning significantly modified the immunosuppressive TME and was required to uncover the efficacy of PSCA-CAR T cells in metastatic prostate and pancreas cancer models, with no observed toxicities in normal tissues with endogenous expression of PSCA. This combination dampened the immunosuppressive TME, generated pro-inflammatory myeloid and T cell signatures in tumors, and enhanced the recruitment of antigen-presenting cells, as well as endogenous and adoptively transferred T cells, resulting in long-term anti-tumor immunity.

Coordinate expression loss of GKN1 and GKN2 in gastric cancer via impairment of a glucocorticoid-responsive enhancer.

Gastrokines (GKNs) are anti-inflammatory proteins secreted by gastric epithelial (surface mucous and pit) cells, with their aberrant loss of expression causally linked to premalignant inflammation and gastric cancer (GC). Transcriptional mechanisms accounting for GKN expression loss have not been elucidated. Using human clinical cohorts, mouse transgenics, bioinformatics, and transfection/reporter assays, we report a novel mechanism of GKN gene transcriptional regulation and its impairment in GC. GKN1/GKN2 loss is highly coordinated, with both genes showing parallel downregulation during human and mouse GC development, suggesting joint transcriptional control. In BAC transgenic studies, we defined a 152-kb genomic region surrounding the human GKN1/GKN2 genes sufficient to direct their tissue- and lineage-restricted expression. A screen of the 152-kb region for candidate regulatory elements identified a DNase I hypersensitive site (CR2) located 4 kb upstream of the GKN1 gene. CR2 showed overlapping enrichment of enhancer-related histone marks (H3K27Ac), a consensus binding site (GRE) for the glucocorticoid receptor (GR), strong GR occupancy in ChIP-seq data sets and, critically, exhibited dexamethasone-sensitive enhancer activity in reporter assays. Strikingly, GR showed progressive expression loss, paralleling that of GKN1/2, in human and mouse GC, suggesting desensitized glucocorticoid signaling as a mechanism underlying GKN loss. Finally, mouse adrenalectomy studies revealed a critical role for endogenous glucocorticoids in sustaining correct expression (and anti-inflammatory restraint) of GKNs in vivo. Together, these data link the coordinate expression of GKNs to a glucocorticoid-responsive and likely shared transcriptional enhancer mechanism, with its compromised activation contributing to dual GKN loss during GC progression.NEW & NOTEWORTHY Gastrokine 2 (GKN2) is an anti-inflammatory protein produced by the gastric epithelium. GKN2 expression is progressively lost during gastric cancer (GC), which is believed to play a casual role in GC development. Here, we use bacterial artificial chromosome transgenic studies to identify a glucocorticoid-responsive enhancer element that likely governs expression of GKN1/GKN2, which, via parallel expression loss of the anti-inflammatory glucocorticoid receptor, reveals a novel mechanism to explain the loss of GKN2 during GC pathogenesis.

Effect of couple-based cognitive behavioural intervention on prevention of postnatal depression: multisite randomised controlled trial.

OBJECTIVE: To compare a couple-based cognitive behavioural intervention (CBI) for postnatal depression with CBI delivered to women alone and control (standard perinatal care). DESIGN: Multisite randomised controlled trial. SETTING: Antenatal clinics at three regional public hospitals in Hong Kong. SAMPLE: 388 low-risk childbearing couples. METHODS: Childbearing couples were randomly allocated to couple-based CBI (n = 134), women-alone CBI (n = 124) or control (n = 130). The CBI consists of a 3-hour antenatal group session and two 30-minute postnatal telephone follow-up sessions. MAIN OUTCOME MEASURES: The primary outcome was depressive symptoms, measured on the Edinburgh Postnatal Depression Scale (EPDS). Assessments were collected at baseline (during pregnancy), 6 weeks, 6 months, and 12 months postpartum. RESULTS: Depressive symptoms were significantly more improved at 6 weeks postpartum for mothers in couple-based CBI than in women-alone CBI (difference 1.46, 95% CI 0.11-2.81) or control groups (difference 1.71, 95% CI 0.29-3.13). The proportion of mothers with postnatal depression (EPDS score ≥ 10) was significantly lower at 6 weeks postpartum in couple-based CBI than in control (difference 17.8%, 95% CI 3.6-32.0). However, the treatment effect was not maintained at 6 and 12 months. There was no significant intervention effect among fathers. CONCLUSIONS: Couple-based CBI is more effective than CBI delivered to mothers alone and standard perinatal care in reducing the incidence of postnatal depression among Chinese mothers in the early postpartum period. TWEETABLE ABSTRACT: Couple-based cognitive behavioural intervention is effective in reducing postnatal depression among Chinese mothers in the early postpartum period.

Functional movements of the GABA type A receptor.

We have performed a parallel tempering crankshaft motion Monte Carlo simulation on a model of the GABA type A receptor with the aim of exploring a wide variety of local conformational space. We develop a novel method to analyse the protein movements in terms of a correlation tensor and use this to explore the gating process, that is, how agonist binding could cause ion channel opening. We find that simulated binding impulses to varying clusters of GABA binding site residues produce channel opening, and that equivalent impulses to single GABA sites produce partial opening.

Rapid Estimate of Inadequate Health Literacy (REIHL): development and validation of a practitioner-friendly health literacy screening tool for older adults.

INTRODUCTION: This study aimed to develop and validate a brief practitioner-friendly health literacy screening tool, called Rapid Estimate of Inadequate Health Literacy (REIHL), that estimates patients' health literacy inadequacy in demanding clinical settings. METHODS: This is a methodological study of 304 community-dwelling older adults recruited from one community health centre and five district elderly community centres. Logistic regression models were used to identify the coefficients of the REIHL score's significant factors. Receiver operating characteristic (ROC) curve analysis was then used to assess the REIHL's sensitivity and specificity. Path analysis was employed to examine the REIHL's criterion validity with the Chinese Health Literacy Scale for Chronic Care and concurrent validity with self-rated health scale and the Geriatric Depression Scale-15. RESULTS: The REIHL has scores ranging from 0 to 23. It had 76.9% agreement with the Chinese Health Literacy Scale for Chronic Care. The area under the ROC curve for predicting health literacy inadequacy was 0.82 (95% confidence interval=0.78-0.87, P<0.001). The ROC curve of the REIHL showed that scores ≥11 had a sensitivity of 77.8% and specificity of 75.6% for predicting health literacy inadequacy. The path analysis model showed excellent fit (Chi squared [2, 304] 0.16, P=0.92, comparative fit index 1.00, root mean square error of approximation <0.001, 90% confidence interval=0.00-0.04), indicating that the REIHL has good criterion and concurrent validity. CONCLUSION: The newly developed REIHL is a practical tool for estimating older adults' inadequate health literacy in clinical care settings.

Improving the monitoring of suicide incidence by estimating the probability of news reporting.

A timely estimate of suicide incidence is important for surveillance and monitoring but always difficult if not possible. The delay in reporting suicide cases between the time of occurrence of the deaths and them being registered is unavoidable. There is at least one year if not more of the delay time in the latest WHO website reporting the suicide statistics of most countries. Based on the daily newspaper reporting on suicide incidence, this study proposes a method to estimate the unknown incidence in a timely manner. It is shown that demographic characteristics such as age, suicide methods, and the districts of the deceased were significantly associated with the probability of the newspapers reporting the suicides. By incorporating this information on the daily suicide news reports into estimating the probability of the newspapers reporting the suicides, the daily number of suicide cases can be estimated. The proposed method is applied to estimate the number of suicides in Hong Kong where there is the Coroner's Court to investigate into suicide deaths, but it takes at least six months to deliver a verdict. The present method can generate timely and accurate estimations on the daily count of suicide deaths with only a one day lag. In a threefold nested cross-validation, the proposed approach has achieved an average RMSE of 1.38, MAE of 1.10, and R2 of 0.24. It can also serve as a surveillance system in providing estimations of temporal clusters of suicides with certain characteristics timelessly and accurately.

Prediction of GABARAP interaction with the GABA type A receptor.

We have performed docking simulations on GABARAP interacting with the GABA type A receptor using SwarmDock. We have also used a novel method to study hydration sites on the surface of these two proteins; this method identifies regions around proteins where desolvation is relatively easy, and these are possible locations where proteins can bind each other. There is a high degree of consistency between the predictions of these two methods. Moreover, we have also identified binding sites on GABARAP for other proteins, and listed possible binding sites for as yet unknown proteins on both GABARAP and the GABA type A receptor intracellular domain.

Type 2 diabetes is associated with higher trabecular bone density but lower cortical bone density: the Vietnam Osteoporosis Study.

It is not clear why type 2 diabetes (T2D) has an increased risk of fracture despite higher areal bone mineral density. This study showed that compared with controls, T2D patients had higher trabecular bone density but lower cortical bone density, resulting in a lower bone strength. INTRODUCTION: To define the association between type 2 diabetes and bone architecture and measures of bone strength. METHODS: The study was part of the Vietnam Osteoporosis Study, in which 1115 women and 614 men aged ≥ 30 were randomly recruited from Ho Chi Minh City. HbA1c levels were measured with analyzers ADAMS™ A1c HA-8160 (Arkray, Kyoto, Japan). The diagnosis of T2D was made if HbA1c was ≥ 6.5%. Trabecular and cortical volumetric bone density (vBMD) was measured in the forearm and leg by a pQCT XCT2000 (Stratec, Germany). Polar stress strain index (pSSI) was derived from the pQCT measurements. Difference in bone parameters between T2D and non-diabetic individuals was assessed by the number of standard deviations (effect size [ES]) by the propensity score analysis. RESULTS: The prevalence of T2D was ~ 8%. The results of propensity score matching for age, sex, and body mass index in 137 pairs of diabetic and non-diabetic individuals showed that T2D patients had significantly higher distal radius trabecular vBMD (ES 0.26; 95% CI, 0.02 to 0.50), but lower cortical vBMD (ES - 0.22; - 0.46 to 0.00) and reduced pSSI (ES - 0.23; - 0.47 to - 0.02) compared with non-diabetic individuals. Multiple linear regression analysis based on the entire sample confirmed the results of the propensity score analysis. CONCLUSION: Compared with non-diabetic individuals, patients with T2D have greater trabecular but lower cortical vBMD which leads to lower bone strength.

Process of medical simulator development: An approach based on personal experience.

With increasing demand for simulators from the healthcare community and increasingly sophisticated technology being used in the manufacture of medical simulators, the manufacture of healthcare simulators has become a multifaceted undertaking. Based on our experience in the field and our diverse backgrounds, we explore the processes and issues related to the development of these simulators and suggest ways for the developing teams to collaborate and coordinate with each other to achieve a successful outcome.

Use of fluoroquinolones is the single most important risk factor for the high bacterial load in patients with nasal and gastrointestinal colonization by multidrug-resistant Acinetobacter baumannii.

Gastrointestinal colonization by carbapenem-resistant Acinetobacter baumannii (CRAB) and multidrug-resistant Acinetobacter baumannii (MRAB) provides an important reservoir for clinical infections and hospital outbreaks. We conducted a 7-month study in a 3200-bed healthcare network to investigate the prevalence of gastrointestinal colonization of CRAB and MRAB in Hong Kong. Between 1 June and 31 December 2014, a total of 17,760 fecal specimens from 9469 patients were screened. Testing showed that 340 (1.9%) specimens from 224 (2.6%) patients were CRAB-positive, which included 70 (0.39%) MRAB-positive specimens from 54 (0.57%) patients. The presence of wound or ulcer, use of broad-spectrum antibiotics in the preceding 6 months, and residence in elderly homes are independent risk factors for gastrointestinal colonization of CRAB. Quantitative bacterial counts in various body sites (rectal, nasal, axilla, wound, catheterized urine, if available) were performed in 33 (61.1%) of 54 MRAB patients. Ten (30.3%) and 8 (24.2%) patients had high bacterial load (defined as over 3 log10) in rectal and nasal swabs, with a median of 5.04 log10 cfu/ml of rectal swab and 4.89 log10 cfu/ml of nasal swab in saline diluent, respectively. Nine (81.8%) of 11 patients with wounds had high bacterial load in wound swabs, with a median of 5.62 log10 cfu/ml. Use of fluoroquinolones 6 months before admission was the only significant factor associated with high bacterial load in nasal and rectal swabs. With the implementation of directly observed hand hygiene before meals and medications to all conscious hospitalized patients, no hospital outbreaks were observed during our study period.

Control of hospital endemicity of multiple-drug-resistant Acinetobacter baumannii ST457 with directly observed hand hygiene.

An increasing endemicity of multiple-drug-resistant Acinetobacter baumannii (MRAB) ST457 was noted in Hong Kong. The epidemiology, risk factors, and infection control measures to prevent nosocomial transmission of this epidemic clone were analyzed. A total of 5,058 patients cultured positive with A. baumannii between 1 January 2004 and 30 June 2014 were included, of which 297 (5.9 %) had bacteremia. The first case of MRAB bacteremia emerged in 2009, with an incidence that increased from 0.27 (one case) in 2009 to 1.86 (14 cases) per 100,000 patient-days in 2013 (p < 0.001). With the implementation of strict contact precautions and directly observed hand hygiene in conscious patients immediately before receiving meals and medications in July 2013, the incidence of MRAB bacteremia reduced from its peak to 0.77 (one case) per 100,000 patient-days in the first 6 months of 2014 (p < 0.001). Patients from long-term care facilities for the elderly [odds ratio (OR) 18.6, confidence interval (CI) 2.1-162.4, p = 0.008] and history of carbapenem (OR 7.0, CI 1.7-28.0, p = 0.006) and beta-lactam/beta-lactamase use (OR 5.6, CI 1.1-28.7, p = 0.038) 90 days prior to admission were independent risk factors for MRAB bacteremia by logistic regression when compared with carbapenem-susceptible A. baumannii bacteremia.

Containment of Clostridium difficile infection without reduction in antimicrobial use in Hong Kong.

Clostridium difficile ribotype 002 with hypersporulating capacity has been increasingly identified in Hong Kong. Proactive infection control measures are important to prevent the establishment of endemicity of C. difficile ribotype 002. A total of 329 patients with healthcare-associated C. difficile infection (CDI) were recruited in our healthcare network between 1 January 2008 and 30 June 2012 in this study. The incidence rates of healthcare-associated CDI per 10,000 admissions and 10,000 patient-days increased significantly by 15.3 and 17.0%, respectively, per quarter (p < 0.001) from 2008 1Q to 2010 1Q by segmented Poisson regression. With the full implementation of enhanced infection control interventions, there was an immediate significant reduction in both healthcare-associated CDI rates per 10,000 admissions and per 10,000 patient-days by 47% (p < 0.001) in 2010 2Q, followed by a further decline of CDI per 10,000 admissions and CDI per 10,000 patient-days by -19.4 and -19.8% from 2010 2Q to 2012 2Q, respectively (p < 0.001), despite a replacement of hand washing with soap and water by alcohol-based hand rub in the healthcare network. The proportion of C. difficile ribotype 002 was not statistically different (34/177, 19.2% vs. 25/152, 16.4%, p = 0.515), and the consumption of broad-spectrum antibiotics presented as divided daily dose per 1,000 acute bed-day occupancy per quarter remained unchanged (140.9 vs. 152.3) before and after infection control interventions. Our results suggested that the reduction of healthcare-associated CDI was attributable to infection control interventions instead of replacement of ribotypes or reduction in antimicrobial selective pressure.

Interconnected, inhabited and insecure: why bodies should not be property.

This article argues against the case for regarding bodies and parts of bodies to be property. It claims that doing so assumes an individualistic conception of the body.  It fails to acknowledge that our bodies are made up of non-human material; are unbounded; constantly changing and deeply interconnected with other bodies. It also argues that holding that our bodies are property does not recognise the fact that we have different attitudes towards different parts of our removed bodies and the contexts of their removal.  The appropriate legal reform should, therefore, be to produce a statute which can provide a balance between the competing personal, social and interpersonal interests in different body parts.

Relational bodies.

This article argues that debates over the legal status of bodies reveal a much deeper dispute over the nature of the self. In these discussions lawyers and ethicists have much to learn from a more profound understanding of the biological nature of the body. Far from being a static entity, the body is constantly recreating itself. It contains parts that are organisms in their own right. Bodies are dependent upon other bodies and the external environment for survival. The complex biological picture reflects a philosophical truth that bodies are interdependent and "leaky". We should not, therefore, expect a single legal regime, such as property to capture the biological and ethical values that are at stake in relation to every part of the body. A more complex statutory regime is required to recognise the complexity of the interests in, and nature of, different body parts.

Psychometric Properties of Vietnamese Versions of the Clinician-Rated and Self-Reported Quick Inventory of Depressive Symptomatology and the Patient Health Questionnaire.

OBJECTIVE: Major depressive disorder (MDD) is the second-most prevalent mental health condition in Vietnam. This study aims to validate the Vietnamese versions of the self-reported and clinician-rated Quick Inventory of Depressive Symptomatology (QIDS-SR and QIDS-C, respectively) and the Patient Health Questionnaire (PHQ-9), and to assess the correlations between the QIDS-SR, QIDS-C, and PHQ-9. METHODS: 506 participants with MDD (mean age, 46.3 years; 55.5% women) were assessed using the Structured Clinical Interview for DSM-5. The internal consistency, diagnostic efficiency, and concurrent validity of the Vietnamese versions of QIDS-SR, QIDS-C, and PHQ-9 were determined using the Cronbach's alpha, receiver operating characteristic curve, and Pearson correlation coefficient, respectively. RESULTS: The Vietnamese versions of QIDS-SR, QIDS-C, and PHQ-9 demonstrated acceptable validity, with an area under the receiver operating characteristic curve of 0.901, 0.967, and 0.864, respectively. Sensitivity and specificity, respectively, were 87.8% and 77.8% for QIDS-SR and 97.6% and 86.2% for QIDS-C at the cut-off score of 6, and were 82.9% and 70.1% for PHQ-9 at the cut-off score of 4. Cronbach's alphas for QIDS-SR, QIDS-C, and PHQ-9 were 0.709, 0.813, and 0.745, respectively. The PHQ-9 highly correlated with the QIDS-SR (r = 0.77, p < 0.001) and the QIDS-C (r = 0.75, p < 0.001). CONCLUSION: The Vietnamese versions of the QIDS-SR, QIDS-C, and PHQ-9 are valid and reliable tools for screening of MDD in primary healthcare settings.