Adolescents' attitudes to the COVID-19 vaccination.

Vaccines against COVID-19 are now available for adolescents in Hong Kong but vaccine hesitancy is a major barrier to herd immunity. This survey study explores Hong Kong adolescents' attitudes towards the COVID-19 vaccination. 2609 adolescents from across Hong Kong completed an online survey focused on the intent to vaccinate and the reasons for their choice. 39% of adolescents intended to take the COVID-19 vaccination and significant factors for this decision include: having at least one parent vaccinated, knowing somebody diagnosed with COVID-19 and receiving the influenza vaccine. Adolescents' major concerns were either the safety and efficacy of the vaccine or the risk of infection. This study has proved that even in adolescents the vaccine hesitancy model is prominent with adolescents' intentions highly related to confidence in the vaccine and perception of disease risk. Future interventions should target these specific concerns to ensure adolescents are well educated to overcome vaccine hesitancy.

Personalized prediction of transcranial magnetic stimulation clinical response in patients with treatment-refractory depression using neuroimaging biomarkers and machine learning.

BACKGROUND: Functional connectivity between the left dorsolateral prefrontal cortex (DLPFC) and subgenual cingulate (sgACC) may serve as a biomarker for transcranial magnetic stimulation (rTMS) treatment response. The first aim was to establish whether this finding is veridical or artifactually induced by the pre-processing method. Furthermore, alternative biomarkers were identified and the clinical utility for personalized medicine was examined. METHODS: Resting-state fMRI data were collected in medication-refractory depressed patients (n = 70, 16 males) before undergoing neuronavigated left DLPFC rTMS. Seed-based analyses were performed with and without global signal regression pre-processing to identify biomarkers of short-term and long-term treatment response. Receiver Operating Characteristic curve and supervised machine learning analyses were applied to assess the clinical utility of these biomarkers for the classification of categorical rTMS response. RESULTS: Regardless of the pre-processing method, DLPFC-sgACC connectivity was not associated with treatment outcome. Instead, poorer connectivity between the sgACC and three clusters (peak locations: frontal pole, superior parietal lobule, occipital cortex) and DLPFC-central opercular cortex were observed in long-term nonresponders. The identified connections could serve as acceptable to excellent markers. Combining the features using supervised machine learning reached accuracy rates of 95.35% (CI=82.94-100.00) and 88.89% (CI=63.96-100.00) in the cross-validation and test dataset, respectively. LIMITATIONS: The sample size was moderate, and features for machine learning were based on group differences. CONCLUSIONS: Long-term nonresponders showed greater disrupted connectivity in regions involving the central executive network. Our findings may aid the development of personalized medicine for medication-refractory depression.

Psychometric Properties of the Traditional Chinese Version of the Child and Adolescent Needs and Strengths-Trauma Comprehensive.

OBJECTIVE: To determine the internal consistency, construct validity, and scaling properties of the traditional Chinese version of the Child and Adolescent Needs and Strengths-Trauma Comprehensive (TC-CANS-Trauma). METHODS: 66 male and 62 female children, adolescents, and young adults aged 3 to 22 years who were referred to trauma treatment service were selected by convenience sampling. The original English version of the CANS-Trauma was translated to traditional Chinese by a medical professional, back-translated to English by a clinical psychologist, and then cross-checked by another psychologist to ensure consistency. Chinese wordings were adjusted to maintain the conceptual rather than literal meaning. Participants were assessed using the TC-CANS-Trauma as well as the traditional Chinese version of the Life Events Checklist (LEC), the Children's Impact of Event Scale-Revised (CHIES-R), the Strengths and Difficulties Questionnaire-Impact Component (SDQ-Impact), and the Parenting Sense of Competence (PSOC). Internal consistency of eight primary domains of the TC-CANS-Trauma was evaluated by Cronbach's alpha. Construct (convergent and divergent) validity of five of these domains with the LEC, the CHIES-R, the SDQ-Impact, and the PSOC was assessed. Rasch modelling was used to evaluate the scaling properties of the eight primary domains of the TC-CANS-Trauma. RESULTS: Internal consistency of the eight primary domains of the TC-CANS-Trauma was satisfactory, with Cronbach's alpha ranging from 0.63 to 0.90. Construct (convergent and divergent) validity of five of these domains with the LEC, the CHIES-R, the SDQ-Impact, and the PSOC was good. In Rasch modelling, most TC-CANS-Trauma domains showed good item separation values. Infit and outfit statistics of most domain items were <2 indicating good item fitness in their respective domains. For person separation, all domains of the TC-CANS-Trauma did not have a sufficient discriminability to identify high and low performers. CONCLUSIONS: The TC-CANS-Trauma is valid for comprehensive assessment of trauma-related domains among Hong Kong children and adolescents. Its ratings can be used to guide the levels of clinical intervention required. Clinicians are recommended to implement the TC-CANS-Trauma to facilitate trauma-informed practice in Hong Kong.

New Service Model for Common Mental Disorders in Hong Kong: a Retrospective Outcome Study.

OBJECTIVE: To review the first 8-month outcome of the Common Mental Disorder Clinic model in Hong Kong in terms of patient exit status and improvement in depressive and anxiety symptoms. METHODS: During the first appointment, patients were interviewed by a multidisciplinary team comprising a psychiatrist, a psychiatric nurse, and an occupational therapist. A multidisciplinary case conference was conducted to discuss clinical observations, diagnosis, issues of concern, and the optimal individualised treatment plan. Low-intensity interventions by nurses and/or occupational therapists were provided, as were optional, time-limited, protocol-based interventions by clinical psychologists for those with mild to moderate depressive and anxiety symptoms. Pharmacological intervention may be used when indicated. Upon completion of the treatment plan, patients were reassessed by the treating psychiatrist. Discharge options included discharge without psychiatric follow-up, step-up to psychiatric outpatient clinics, and step-down services. The self-administered Patient Health Questionnaire-9 (PHQ-9) and Generalised Anxiety Disorder 7-item scale (GAD-7) were used to assess the past 2 weeks' depressive and anxiety symptoms, respectively, at baseline and at each session. RESULTS: From July 2015 to February 2016, 1325 Chinese patients received the new service. Of them, 170 men and 363 women (mean age, 52.6 years) completed the treatment plan. After treatment, their mean PHQ-9 score decreased from 11.06 to 7.55 (p < 0.001), and the mean GAD-7 score decreased from 9.94 to 6.54 (p < 0.001). After treatment, 42.4% and 48.2% of the patients were within the normal range of PHQ-9 and GAD-7 scores, respectively, compared with 16.9% and 20.8% before treatment. The mean time to implementation of the individualised treatment plan was 82.33 days. Of the patients, 54.4% were discharged without any need for medical or psychiatric follow-up; 28% were stepped up to psychiatric outpatient clinics; and 17.3% were stepped down. The predictors of exit status were whether psychiatric medication was prescribed during initial intake (p = 0.011), whether psychiatric medication was prescribed at last follow-up (p < 0.001), the service period (p = 0.010), and the GAD-7 final score (p = 0.005). CONCLUSIONS: The first 8-month outcome of the new service model was encouraging, with shortened waiting time, reduced severity of symptoms, and better exit status (high recovery and step-down rates).

A "Stone in the Pond" Approach to Contact Tracing: Responding to a Large-Scale, Nosocomial Tuberculosis Exposure in a Moderate TB-Burden Setting.

A "stone in the pond" strategy is a practical approach to investigating large-scale nosocomial tuberculosis (TB) exposures. Here, we describe such a risk-stratified approach to contact tracing after a TB exposure that occurred over 5 months in a pediatric inpatient ward in a country with a moderate TB burden. Infect Control Hosp Epidemiol 2017;38:1509-1511.

Multi-Domains Lifestyle Interventions Reduces Depressive Symptoms among Frail and Pre-Frail Older Persons: Randomized Controlled Trial.

BACKGROUND: We investigated the effect of multi-domain lifestyle (physical, nutritional, cognitive) interventions among frail and pre-frail community-living older persons on reducing depressive symptoms. METHOD: Participants aged 65 and above were randomly allocated to 24 weeks duration interventions with nutritional supplementation (N=49), physical training (N=48), cognitive training (N=50), combination intervention (N=49) and usual care control (N=50). Depressive symptoms were assessed by the Geriatric Depression Scale (GDS-15) at baseline (0M), 3 month (3M), 6 month (6M) and 12 month (12M). RESULTS: Mean GDS scores in the control group increased from 0.52 (0M) and 0.54 (3M) to 0.74 (6M), and 0.83 (12M). Compared to the control group, interventions showed significant differences (∆=change) at 6M for cognitive versus control (∆=-0.39, p=0.021, group*time interaction p=0.14); physical versus control (∆ =-0.37, p=0.026, group*time interaction p=0.13), and at 12M for nutrition versus control (∆ =-0.46, p=0.016, group*time interaction p=0.15). The effect for combination versus control was significant at 6M (∆ =-0.43, p=0.020) and 12M (∆ =-0.51, p=0.005, group*time interaction p=0.026). Estimated 12-month cumulative incidence of depressive symptoms (GDS≥2) relative to control were OR=0.38, p=0.037 (nutrition); OR=0.71, p=0.40 (cognitive); OR=0.39, p=0.042 (physical training) and OR=0.38, p=0.037 (combination). Changes in gait speed and energy level were significantly associated with changes in GDS scores over time. CONCLUSION: Multi-domain interventions that reverse frailty among community-living older persons also reduce depressive symptomatology. Public health education and programmatic measures combining nutritional, physical and cognitive interventions for at-risk frail older people may likely benefit psychological wellbeing.

Coronavirus infections in horses in Saudi Arabia and Oman.

Equine coronaviruses (ECoV) are the only coronavirus known to infect horses. So far, data on ECoV infection in horses remain limited to the USA, France and Japan and its geographic distribution is not well understood. We carried out RT-PCR on 306 nasal and 315 rectal swabs and tested 243 sera for antibodies to detect coronavirus infections in apparently healthy horses in Saudi Arabia and Oman. We document evidence of infection with ECoV and HKU23 coronavirus by RT-PCR. There was no conclusive evidence of Middle East respiratory syndrome coronavirus infection in horses. Serological data suggest that lineage A betacoronavirus infections are commonly infecting horses in Saudi Arabia and Oman but antibody cross-reactivities between these viruses do not permit us to use serological data alone to identify which coronaviruses are causing these infections.

Biological and clinical consequences of NPM1 mutations in AML.

Acute myeloid leukemia (AML) is characterized by accumulation of myeloid cells in the bone marrow because of impaired differentiation and proliferation, resulting in hematopoietic insufficiency. NPM1 is one of the most commonly mutated genes in AML, present in 20-30% of cases. Mutations in NPM1 represent a distinct entity in the World Health Organization (WHO) classification and commonly indicate a better risk prognosis. In this review, we discuss the many functions of NPM1, the consequence of mutations in NPM1 and possible mechanisms through which mutations lead to leukemogenesis. We also discuss clinical consequences of mutations, associated gene expression patterns and the role of NPM1 mutations in informing prognosis and therapeutic decisions and predicting relapse in AML.

Isocitrate dehydrogenase mutations in myeloid malignancies.

Alterations to genes involved in cellular metabolism and epigenetic regulation are implicated in the pathogenesis of myeloid malignancies. Recurring mutations in isocitrate dehydrogenase (IDH) genes are detected in approximately 20% of adult patients with acute myeloid leukemia (AML) and 5% of adults with myelodysplastic syndromes (MDS). IDH proteins are homodimeric enzymes involved in diverse cellular processes, including adaptation to hypoxia, histone demethylation and DNA modification. The IDH2 protein is localized in the mitochondria and is a critical component of the tricarboxylic acid (also called the 'citric acid' or Krebs) cycle. Both IDH2 and IDH1 (localized in the cytoplasm) proteins catalyze the oxidative decarboxylation of isocitrate to α-ketoglutarate (α-KG). Mutant IDH enzymes have neomorphic activity and catalyze reduction of α-KG to the (R) enantiomer of 2-hydroxyglutarate, which is associated with DNA and histone hypermethylation, altered gene expression and blocked differentiation of hematopoietic progenitor cells. The prognostic significance of mutant IDH (mIDH) is controversial but appears to be influenced by co-mutational status and the specific location of the mutation (IDH1-R132, IDH2-R140, IDH2-R172). Treatments specifically or indirectly targeted to mIDH are currently under clinical investigation; these therapies have been generally well tolerated and, when used as single agents, have shown promise for inducing responses in some mIDH patients when used as first-line treatment or in relapsed or refractory AML or MDS. Use of mIDH inhibitors in combination with drugs with non-overlapping mechanisms of action is especially promising, as such regimens may address the clonal heterogeneity and the multifactorial pathogenic processes involved in mIDH myeloid malignancies. Advances in mutational analysis have made testing more rapid and convenient, and less expensive; such testing should become part of routine diagnostic workup and repeated at relapse to identify patients who may benefit from treatments that target mIDH.

Role of cysteine 288 in nucleophosmin cytoplasmic mutations: sensitization to toxicity induced by arsenic trioxide and bortezomib.

Mutations in exon 12 of the nucleophosmin (NPM1) gene (NPMc+ (NPM1 COOH terminal mutations)) define a distinct subset of acute myelogenous leukemias (AMLs), in which the NPMc+ protein localizes aberrantly to the leukemic cell cytoplasm. We have found that introduction of the most common NPMc+ variant into K562 and 32D cells sensitizes these cells to apoptosis induced by drugs such as bortezomib and arsenic trioxide (ATO) that induce reactive oxygen species (ROS) formation, and that cytotoxicity is prevented in the presence of N-acetyl-L-cysteine (NAC), an ROS scavenger. The substitution of tryptophan 288 (W288) by cysteine occurs in the great majority of NPM1c+ mutations. Mutagenesis of cysteine 288 to alanine re-localizes NPMc+ from the cytoplasm to the nucleolus and attenuates the sensitivity of cells expressing this mutation to bortezomib and ATO. Primary AML cells expressing NPMc+ are also significantly more sensitive than other AML cells to apoptosis induced by both drugs at pharmacologically achievable doses. We conclude that the presence of a cysteine moiety at position 288 results in the cytoplasmic localization of NPM1c+ and the increased sensitivity to bortezomib and ATO. These data suggest that bortezomib and ATO may have increased therapeutic efficacy in NPM1c+ leukemias.

Laparoscopic Heller's cardiomyotomy achieved lesser recurrent dysphagia with better quality of life when compared with endoscopic balloon dilatation for treatment of achalasia.

Achalasia is a rare primary motility disorder of esophagus; treatments include endoscopic balloon dilatation (EBD) and laparoscopic Heller's cardiomyotomy (LC). This study compared EBD versus LC for treatment of achalasia with focus on quality of life (QoL) and prevalence of post-treatment gastroesophageal reflux disease. This was a retrospective cohort study of all patients diagnosed with achalasia older than 16 treated with either EBD or LC from January 1998 to April 2008. Patients' demographic data, comorbidities, postintervention GERD symptoms, QoL, recurrence of dysphagia, reintervention rate, hospital stay, and time to resumption of diet were collected. Sixty-eight patients were recruited into the study (EBD n= 50; LC n= 18). A significant improvement in QoL was found in patients undergoing LC (0.917 vs. 0.807, P= 0.006). A higher proportion of patients treated with EBD developed post-treatment gastroesophageal reflux symptoms (60.5% vs. 43.8%) when compared with LC, although statistically insignificant (P= 0.34). Patients treated with balloon dilatation had a greater percentage of recurrence of dysphagia (55.1% vs. 26.7%; P= 0.235) and need of reintervention (42.1% vs. 9.1%; P= 0.045). However, these patients had a shorter median hospital stay (1d [range 0-4]) and earlier resumption of diet (0d [range 0-3]). Although EBD is associated with a quicker perioperative recovery, LC accomplished a better QoL, lower incidence of recurrence of dysphagia, and need of reintervention after treatment for achalasia.

Shyness in late childhood: relations with attributional styles and self-esteem.

BACKGROUND: Shyness in late childhood is related to social and psychological problems. The present study examined the relations among shyness, attributional styles and self-esteem. It was hypothesized that self-esteem mediated the effects of attributional styles on shyness. METHODS: Self-reported data on degree of shyness, attributional styles and self-esteem were obtained from 326 Chinese children with mean age of 10.85 years. RESULTS: It was found that positive attributional styles predicted shyness in the negative direction and the effects were fully mediated by self-esteem, and negative attributional styles predicted shyness in the positive direction both directly and through self-esteem. CONCLUSION: The results imply that how children attribute positive and negative outcomes affect both self-esteem and shyness. It is suggested that practitioners should conduct attribution-retraining workshops for shy children and help teachers and parents learn how to mitigate negative attributional style and foster positive attributional styles in children.

Tribological altruism: A sacrificial layer mechanism of synovial joint lubrication in articular cartilage.

Boundary lubrication is characterized by sliding surfaces separated by a molecularly thin film that reduces friction and wear of the underlying substrate when fluid lubrication cannot be established. In this study, the wear and replenishment rates of articular cartilage were examined in the context of friction coefficient changes, protein loss, and direct imaging of the surface ultrastructure, to determine the efficiency of the boundary lubricant (BL) layer. Depletion of cartilage lubricity occurred with the concomitant loss of surface proteoglycans. Restoration of lubrication by incubation with synovial fluid was much faster than incubation with culture media and isolated superficial zone protein. The replenishment action of the BL layer in articular cartilage was rapid, with the rate of formation exceeding the rate of depletion of the BL layer to effectively protect the tissue from mechanical wear. The obtained results indicate that boundary lubrication in articular cartilage depends in part on a sacrificial layer mechanism. The present study provides insight into the natural mechanisms that minimize wear and resist tissue degeneration over the lifetime of an organism.

Cutaneous lymphocyte antigen and α4ß7 T-lymphocyte responses are associated with peanut allergy and tolerance in children.

BACKGROUND: It is unclear whether the initial route of allergen exposure in early life could influence the subsequent development of allergy, with cutaneous sensitization leading to peanut allergy (PA), and tolerance induced by oral exposure. The skin- and gastrointestinal (GI)-homing markers, cutaneous lymphocyte antigen (CLA) and α4ß7 integrin, are used to determine whether the state of PA correlates with peanut-specific CLA responses, with tolerance associated with predominant α4ß7 responses. METHODS: CLA+ and α4ß7+ memory T cells were isolated and cultured with peanut extract to assess their proliferation. Stimulation indices were compared in peanut allergic and non-allergic (NA) groups, and peanut-specific cytokine production was measured. RESULTS: In peanut allergic patients, peanut-specific proliferation predominates in the skin-homing CLA+ subset, whilst peanut-tolerant groups have a mixed CLA/α4ß7 response (P = 0.008). Comparison with a control food antigen (ovalbumin) showed that these differences are allergen specific. Cytokine responses showed trends towards Th1 skewing in the GI-homing α4ß7+ cells of peanut-tolerant groups and Th2 skewing in the skin-homing CLA+ cells of peanut allergic patients. CONCLUSION: The predominance of the CLA+ response to peanut in peanut allergic patients is consistent with the hypothesis that allergic sensitization occurs through the skin. The predominant α4ß7+ response in peanut-tolerant groups suggests that allergen exposure through the GI tract induces tolerance.

The role of lubricant entrapment at biological interfaces: reduction of friction and adhesion in articular cartilage.

Friction and adhesion of articular cartilage from high- and low-load-bearing regions of bovine knee joints were examined with a tribometer under various loads and equilibration times. The effect of trapped lubricants was investigated by briefly unloading the cartilage sample before friction testing, to allow fluid to reflow into the contact interface and boundary lubricants to rearrange. Friction and adhesion of high-load-bearing joint regions were consistently lower than those of low-load-bearing regions. This investigation is the first to demonstrate the regional variation in the friction and adhesion properties of articular cartilage. Friction coefficient decreased with increasing contact pressure and decreasing equilibration time. Briefly unloading cartilage before the onset of sliding resulted in significantly lower friction and adhesion and a loss of the friction dependence on contact pressure, suggesting an enhancement of the cartilage tribological properties by trapped lubricants. The results of this study reveal significant differences in the friction and adhesion properties between high- and low-load-bearing joint regions and elucidate the role of trapped lubricants in cartilage tribology.

The clinical significance of in-depth pathological assessment of extraprostatic extension and margin status in radical prostatectomies for prostate cancer.

Despite recent Level 1 evidence on the benefits of adjuvant radiotherapy for locally advanced prostate cancer (PCa), the timing and decision to administer adjuvant radiotherapy post-radical prostatectomy (post-RP) remains debatable, particularly for patients with focal extraprostatic extension (EPE) and/or focal positive surgical margins (PSMs). In this study, we assess the utility of detailed pathological assessment of EPE and PSM, as this may influence the criteria for instituting adjuvant radiotherapy. A total of 148 RP cases (1993-2001) were identified retrospectively as having EPE and/or PSM. All slides were re-reviewed, incorporating recent proposals by the Collage of American Pathologists (CAP) for the reporting of EPE and PSM, and correlated with clinical data. Both EPE and PSM were found to be independent predictors of biochemical failure (BCF); however, only EPE was associated with metastasis and death. BCF was also more likely to be associated with cases that had non-focal EPE than focal EPE. Similarly, non-focal PSM cases had a significantly higher risk of BCF than focal cases. Our study confirms the value of detailed pathological assessment of EPE and PSM post-RP. The results support the concept of selective adjuvant radiotherapy in patients with EPE and PSM, based on focality and extent.

Social competence of elementary-school children: relationships to maternal authoritativeness, supportive maternal responses and children's coping strategies.

BACKGROUND: Although the influences of parenting on children's development of social competence have been well established, research on the underlying mechanisms of this link is relatively limited. The present study examined children's coping strategies as a mediator of the effects of maternal authoritativeness and maternal inductive responses on their social competence. METHOD: The mothers of 183 Hong Kong Chinese children aged 6 to 8 years (89 girls and 94 boys) reported on their adoption of authoritative parenting and their responses to their children's expressions of emotion, and rated their children's adoption of constructive coping strategies. The children's teachers reported on the children's prosocial behaviour, and rated their level of peer acceptance at school. RESULTS: A model of maternal authoritativeness and supportive maternal responses affecting children's social competence is presented. The study results show that the effects of authoritative parenting on children's adoption of constructive coping strategies were mediated by supportive maternal responses to children's expression of emotion, and that the effects of maternal authoritativeness and maternal responses on children's social competence were mediated by children's coping strategies. These results suggest that school personnel should organize training programmes on emotion-coping strategies for both parents and children. CONCLUSION: The findings imply that positive parenting facilitates children's acquisition of constructive emotion-coping strategies. Programmes on emotion-coping strategies should be introduced for both parents and school children.