Single-cell transcriptomics reveals maturation of transplanted stem cell-derived retinal pigment epithelial cells toward native state.

Transplantation of stem cell-derived retinal pigment epithelial (RPE) cells is considered a viable therapeutic option for age-related macular degeneration (AMD). Several landmark Phase I/II clinical trials have demonstrated safety and tolerability of RPE transplants in AMD patients, albeit with limited efficacy. Currently, there is limited understanding of how the recipient retina regulates the survival, maturation, and fate specification of transplanted RPE cells. To address this, we transplanted stem cell-derived RPE into the subretinal space of immunocompetent rabbits for 1 mo and conducted single-cell RNA sequencing analyses on the explanted RPE monolayers, compared to their age-matched in vitro counterparts. We observed an unequivocal retention of RPE identity, and a trajectory-inferred survival of all in vitro RPE populations after transplantation. Furthermore, there was a unidirectional maturation toward the native adult human RPE state in all transplanted RPE, regardless of stem cell resource. Gene regulatory network analysis suggests that tripartite transcription factors (FOS, JUND, and MAFF) may be specifically activated in posttransplanted RPE cells, to regulate canonical RPE signature gene expression crucial for supporting host photoreceptor function, and to regulate prosurvival genes required for transplanted RPE's adaptation to the host subretinal microenvironment. These findings shed insights into the transcriptional landscape of RPE cells after subretinal transplantation, with important implications for cell-based therapy for AMD.

What care do people with dementia receive at the end of life? Lessons from a retrospective clinical audit of deaths in hospital and other settings.

BACKGROUND: The need for better end-of-life care for people with dementia has been acknowledged. Existing literature suggests that people dying with dementia have less access to palliative care, yet little is known about the care provided to people with dementia at the end of life. This study aimed to establish evidence related to end-of-life care for people dying with dementia in hospital compared to other settings. METHODS: A retrospective clinical audit of people who had a diagnosis of dementia and had accessed services within a local health district, who died between 2015 and 2019, was conducted. A total of 705 people were identified, and a subset of 299 people randomly selected for manual audit. Chi-square p-values were used to compare the place of death, and a t-test or non-parametric test was used to assess the significance of the difference, as appropriate. Measures of functional decline within one month of death were assessed using mixed effects logistic regression models. RESULTS: The characteristics of people differed by place of death, with people who died in hospital more likely to be living at home and to not have a spouse. Less than 1 in 5 people had advance care directives or plans. Many were still being actively treated at the time of death: almost half of people who died in hospital had an investigation in their final 72 hours, less than half of people were coded as receiving palliative care at death, and more than 2 in 3 people did not get access to specialist palliative care. Declining function was associated with the terminal phase. CONCLUSION: This study provides novel insights for those providing end-of-life care for people with dementia. Healthcare professionals and policy makers should consider how demographic characteristics relate to the places people with dementia receive end-of-life care. The care provided to people with dementia in the last year of their life highlights the need for more support to prepare advance care documentation and timely consideration for palliative care. Changes in markers of nutritional status and function in people with advanced dementia may help with identification of terminal phases.

Patients' Acceptability and Satisfaction With Teleconsultation for Pelvic Floor Exercises for Stress Urinary Incontinence During COVID-19.

OBJECTIVES: This was the first urogynaecology specialty nurse teleconsultation offered by a public hospital during COVID-19 for learning pelvic floor exercises. This study assessed patients' perception, acceptance, and satisfaction using 2 validated questionnaires. METHODS: In total, 25 patients with stress urinary incontinence attended the teleconsultation via videoconferencing in April 2022, and completed the Telemedicine Perception Questionnaire (TMPQ) and Telemedicine Satisfaction Questionnaire (TSQ). The TMPQ was a 17-item, 5-point Likert scale questionnaire for assessing the acceptability of telemedicine. The TSQ was a 14-item, 5-point Likert scale questionnaire for assessing satisfaction with teleconsultation. The higher the score, the greater the acceptance and satisfaction. Information on demographics, symptom severity by Urogenital Distress Inventory-6 and Incontinence Impact Questionnaire-7, internet access, and transport arrangements were included. RESULTS: Participants had a mean age of 54.6 ± 7.37 years. Their mean Urogenital Distress Inventory-6 score was 40.60/100 (SD = 17.83) and Impact Questionnaire-7 was 27.90/100 (SD = 19.83). Pre-teleconsultation mean TMPQ score was 59.16 ± 5.78/85. Post-teleconsultation mean score was 64.92 ± 5.21/85, which was 3.64 higher (t = 3.642, df = 24, P = 0.001), indicating a significant increase in positive perception and acceptability. There were fewer concerns with the usage (P = 0.017) and reliability (P = 0.003) of technology, while there was increased agreement that teleconsultation is cost-saving for the health care system (P = 0.003) and offers easier access to health care providers (P = 0.006) after the teleconsultation. Mean TSQ score was 59.85 ± 9.46/70. CONCLUSION: Our pilot study demonstrated positive perception, high acceptability, and satisfaction from patients' first teleconsultation experience. Further multi-centre studies with the inclusion of a control group would help in understanding patients' needs and for service planning.

Improving end-of-life care for people with dementia: a mixed-methods study.

BACKGROUND: Improving palliative and end-of-life care for people with dementia is a growing priority globally. This study aimed to integrate multiple perspectives on end-of-life care for people with dementia and carers, to identify clinically relevant areas for improvement. METHODS: The mixed-methods study involved surveys, interviews, and workshops with two participant groups: healthcare professionals and carers (individuals who provided care and support to a family member or friend). Healthcare professionals were invited to complete an online adapted version of the Australian Commission on Safety and Quality in Health Care, End-of-Life Care Toolkit: Clinician Survey Questions. Carers completed a hard copy or online adapted version of the Views of Informal Carers-Evaluation of Services (Short form) (VOICES-SF) questionnaire. Interview schedules were semi-structured, and workshops followed a co-design format. Findings were integrated narratively using a weaving approach. RESULTS: Five areas in which we can improve care for people with dementia at the end of life, were identified: 1) Timely recognition of end of life; 2) Conversations about palliative care and end of life; 3) Information and support for people with dementia and carers; 4) Person-and-carer-centred care; 5) Accessing quality, coordinated care. CONCLUSIONS: There are multiple areas where we can improve the quality of end-of-life care people with dementia receive. The findings demonstrate that the heterogeneous and challenging experiences of living with and caring for people with dementia necessitate a multidisciplinary, multifaceted approach to end-of-life care. The identified solutions, including care coordination, can guide local development of co-designed models of end-of-life care for people with dementia.

Iterative Design of Ionizable Lipids for Intramuscular mRNA Delivery.

Lipid nanoparticles (LNPs) are the most clinically advanced delivery vehicles for RNA and have enabled the development of RNA-based drugs such as the mRNA COVID-19 vaccines. Functional delivery of mRNA by an LNP greatly depends on the inclusion of an ionizable lipid, and small changes to these lipid structures can significantly improve delivery. However, the structure-function relationships between ionizable lipids and mRNA delivery are poorly understood, especially for LNPs administered intramuscularly. Here, we show that the iterative design of a novel series of ionizable lipids generates key structure-activity relationships and enables the optimization of chemically distinct lipids with efficacy that is on-par with the current state of the art. We find that the combination of ionizable lipids comprising an ethanolamine core and LNPs with an apparent pKa between 6.6 and 6.9 maximizes intramuscular mRNA delivery. Furthermore, we report a nonlinear relationship between the lipid-to-mRNA mass ratio and protein expression, suggesting that a critical mass ratio exists for LNPs and may depend on ionizable lipid structure. Our findings add to the mechanistic understanding of ionizable lipids and demonstrate that hydrogen bonding, ionization behavior, and lipid-to-mRNA mass ratio are key design parameters affecting intramuscular mRNA delivery. We validate these insights by applying them to the rational design of new ionizable lipids. Overall, our iterative design strategy efficiently generates potent ionizable lipids. This hypothesis-driven method reveals structure-activity relationships that lay the foundation for the optimization of ionizable lipids in future LNP-RNA drugs. We foresee that this design strategy can be extended to other optimization parameters beyond intramuscular expression.

Principles of dimer-specific gene regulation revealed by a comprehensive characterization of NF-κB family DNA binding.

The unique DNA-binding properties of distinct NF-κB dimers influence the selective regulation of NF-κB target genes. To more thoroughly investigate these dimer-specific differences, we combined protein-binding microarrays and surface plasmon resonance to evaluate DNA sites recognized by eight different NF-κB dimers. We observed three distinct binding-specificity classes and clarified mechanisms by which dimers might regulate distinct sets of genes. We identified many new nontraditional NF-κB binding site (κB site) sequences and highlight the plasticity of NF-κB dimers in recognizing κB sites with a single consensus half-site. This study provides a database that can be used in efforts to identify NF-κB target sites and uncover gene regulatory circuitry.

The phylogeny and evolutionary ecology of hoverflies (Diptera: Syrphidae) inferred from mitochondrial genomes.

Hoverflies (Diptera: Syrphidae) are a diverse group of pollinators and a major research focus in ecology, but their phylogenetic relationships remain incompletely known. Using a genome skimming approach we generated mitochondrial genomes for 91 species, capturing a wide taxonomic diversity of the family. To reduce the required amount of input DNA and overall cost of the library construction, sequencing and assembly was conducted on mixtures of specimens, which raises the problem of chimera formation of mitogenomes. We present a novel chimera detection test based on gene tree incongruence, but identified only a single mitogenome of chimeric origin. Together with existing data for a final set of 127 taxa, phylogenetic analysis on nucleotide and amino acid sequences using Maximum Likelihood and Bayesian Inference revealed a basal split of Microdontinae from all other syrphids. The remainder consists of several deep clades assigned to the subfamily Eristalinae in the current classification, including a clade comprising the subfamily Syrphinae (plus Pipizinae). These findings call for a re-definition of subfamilies, but basal nodes had insufficient support to fully justify such action. Molecular-clock dating placed the origin of the Syrphidae crown group in the mid-Cretaceous while the Eristalinae-Syrphinae clade likely originated near the K/Pg boundary. Transformation of larval life history characters on the tree suggests that Syrphidae initially had sap feeding larvae, which diversified greatly in diet and habitat association during the Eocene and Oligocene, coinciding with the diversification of angiosperms and the evolution of various insect groups used as larval host, prey, or mimicry models. Mitogenomes proved to be a powerful phylogenetic marker for studies of Syrphidae at subfamily and tribe levels, allowing dense taxon sampling that provided insight into the great ecological diversity and rapid evolution of larval life history traits of the hoverflies.

A PSGL-1 glycomimetic reduces thrombus burden without affecting hemostasis.

Events mediated by the P-selectin/PSGL-1 pathway play a critical role in the initiation and propagation of venous thrombosis by facilitating the accumulation of leukocytes and platelets within the growing thrombus. Activated platelets and endothelium express P-selectin, which binds P-selectin glycoprotein ligand-1 (PSGL-1) that is expressed on the surface of all leukocytes. We developed a pegylated glycomimetic of the N terminus of PSGL-1, PEG40-GSnP-6 (P-G6), which proved to be a highly potent P-selectin inhibitor with a favorable pharmacokinetic profile for clinical translation. P-G6 inhibits human and mouse platelet-monocyte and platelet-neutrophil aggregation in vitro and blocks microcirculatory platelet-leukocyte interactions in vivo. Administration of P-G6 reduces thrombus formation in a nonocclusive model of deep vein thrombosis with a commensurate reduction in leukocyte accumulation, but without disruption of hemostasis. P-G6 potently inhibits the P-selectin/PSGL-1 pathway and represents a promising drug candidate for the prevention of venous thrombosis without increased bleeding risk.

Towards an integrative hope-dysfunctional beliefs perspective to personal recovery in schizophrenia: a path analysis.

BACKGROUND: Evidence shows that negative symptoms of schizophrenia and underlying dysfunctional cognition are related to persistently low functioning and quality of life. However, despite the abundance of existing recovery programs for people with schizophrenia, few have examined whether and how the widely-adopted hope-motivation recovery pathway and the deficit-oriented cognitive pathway might converge to influence functioning and quality of life. METHODS: A cross-sectional, quantative survey recruited a convenient sample of adult outpatients with DSM-5 schizophrenia spectrum disorders and low social functioning (n = 124). Self-reported measurements included personal recovery (30-item Mental Health Recovery Measure), social functioning (8-item Social Functioning Questionnaire), hope (12-item Hope Scale), quality of life (28-item World Health Organization Quality of Life Scale-Abbreviated Version-Hong Kong), defeatist beliefs (15-item extracted from Dysfunctional Attitude Scale), and asocial beliefs (15-item extracted from Revised Social Anhedonia Scale). Correlation analysis and structural equation modelling was applied to investigate how the two pathways intertwined to predict social functioning and quality of life. RESULTS: Asocial beliefs and hope separately mediated two partial mediation pathways from defeatist beliefs to recovery outcomes (social functioning and personal recovery). Meanwhile, defeatist beliefs, social functioning, and personal recovery further predicted quality of life. CONCLUSIONS: This is one of the very few studies that provides empirical evidence of a deficit-strength linkage in the recovery from schizophrenia. Remediation of dysfunctional beliefs and the injection of hope and successful experiences should be undertaken concurrently in recovery as they are associated with differential effects on enhancing social functioning and personal recovery, which then converge and contribute to a better quality of life.

Are we facing an increasing surgical demand for high myopic traction maculopathies? A 12-year study from Hong Kong.

PURPOSE: We aimed to investigate the longitudinal change in the number of surgically operated myopic traction maculopathies (MTM) cases at a tertiary eye centre. METHODS: A retrospective study of all consecutive cases of surgically operated MTM over 12 years (2009-2020) was conducted in a myopia prevalent region. We compared outcomes among three groups: (1) myopic macular hole (MH), (2) myopic macular hole with retinal detachment (MHRD), and (3) myopic foveoschisis with retinal detachment (MFRD). RESULTS: Fifty-one cases were included in the study (8 cases of MH, 33 cases of MHRD and 10 cases of MFRD). The overall mean age was 63.8 +/- 8.7 with a female preponderance (2:1). The mean age of the MH group (58.6) was significantly younger than the MHRD group (64.2) and MFRD group (66.6) (p = 0.02). Subgroup analysis using ATN classification did not show its correlation with both visual improvement and anatomical success. When comparing the first 6-year period (2009-2014) with the second 6-year period (2015-2020), there was a significant increase in the number of cases (p = 0.01). CONCLUSION: We observe an increase in the number of surgically operated MTM. This follows the trend of the global rise in the prevalence of myopia and baby boomers entering retirement.

Dose-Intensified Infliximab Rescue Therapy for Severe Ulcerative Colitis Does Not Reduce Short-term Colectomy Rates or Increase Postoperative Complications.

BACKGROUND: Dose-intensified rescue therapy with infliximab for hospitalized patients with ulcerative colitis has become increasingly popular in recent years. However, there is ongoing debate about both the efficacy of these regimens to reduce the rate of colectomy and the associated risks of increased infliximab exposure. OBJECTIVE: The purpose of this study was to compare the colectomy and postoperative complication rates in hospitalized patients with severe ulcerative colitis receiving standard infliximab induction therapy (3 doses of 5 mg/kg at weeks 0, 2, and 6) and dose-intensified regimens including a higher weight-based dosing or more rapid interval. DESIGN: This was a retrospective cohort study. SETTINGS: This study was conducted at an academic tertiary care hospital. PATIENTS: A total of 145 adult patients received inpatient rescue infliximab therapy for the treatment of ulcerative colitis between 2008 and 2020. MAIN OUTCOME MEASURES: The primary outcome was colectomy rate within 3 months of rescue therapy. Secondary outcomes include mid-term colectomy rates, as well as perioperative complications in patients receiving colectomy within 3 months of rescue infliximab initiation. RESULTS: The proportion of dose-intensified regimens increased over time. Unadjusted 3-month colectomy rates were 14% in patients who received standard rescue infliximab dosing, 16% in patients given a single dose-escalated dose, and 24% in patients given multiple inpatient dose-escalated doses. These rates were not statistically significantly different. Of the patients requiring colectomy within 3 months of infliximab rescue, those who received multiple inpatient doses of dose-escalated therapy had a higher percentage of colectomy during the initial hospitalization but a lower rate of perioperative complications. LIMITATIONS: This study was limited by the use of retrospective data and the limited power to account for the heterogeneity of disease. CONCLUSIONS: No significant difference was found in colectomy rates between patients receiving standard or dose-intensified regimens. However, dose-intensified regimens, including multiple inpatient doses given to patients with more severe disease, were not associated with a greater risk of perioperative complications. See Video Abstract at http://links.lww.com/DCR/B864 . LA TERAPIA DE RESCATE CON DOSIS INTENSIFICADA DE INFLIXIMAB EN COLITIS ULCEROSA GRAVE NO REDUCE LAS TASAS DE COLECTOMA A CORTO PLAZO NI AUMENTA LAS COMPLICACIONES POSOPERATORIAS: ANTECEDENTES:La terapia de rescate de dosis intensificada con infliximab para pacientes hospitalizados con colitis ulcerosa se ha vuelto cada vez más popular en los últimos años. Sin embargo, existe un debate en curso sobre la eficacia de estos regímenes para reducir la tasa de colectomía y los riesgos asociados a una mayor exposición al infliximab.OBJETIVO:El propósito de este estudio fue comparar las tasas de colectomía y complicaciones posoperatorias en pacientes hospitalizados con colitis ulcerosa grave que recibieron terapia estándar de inducción de infliximab (3 dosis de 5 mg/kg en las semanas 0, 2, 6) y regímenes de dosis intensificada que incluyen una dosificación más alta basada en el peso o intervalo más rápido.DISEÑO:Fue un estudio de cohorte retrospectivo.ENTORNO CLÍNICO:Este estudio se realizó en un hospital académico de tercer nivel.PACIENTES:Un total de 145 pacientes adultos que recibieron terapia de rescate con infliximab para el tratamiento de la colitis ulcerosa entre 2008 y 2020.PRINCIPALES MEDIDAS DE VALORACIÓN:El resultado principal fue la tasa de colectomía dentro de los 3 meses posteriores a la terapia de rescate. Los resultados secundarios incluyen tasas de colectomía a mediano plazo, así como las complicaciones perioperatorias en pacientes que reciben colectomía dentro de los 3 meses posteriores al inicio de infliximab de rescate.RESULTADOS:La proporción de regímenes de dosis intensificada aumentó con el tiempo. Las tasas de colectomía de 3 meses no ajustadas fueron del 14% en los pacientes que recibieron dosis estándar de infliximab de rescate, del 16% en los pacientes que recibieron una dosis única escalonada y del 24% en los pacientes que recibieron múltiples dosis hospitalarias escalonadas. Estas tasas no fueron estadísticamente significativas. De los pacientes que requirieron colectomía dentro de los 3 meses posteriores al rescate de infliximab, aquellos que recibieron terapia de múltiples dosis hospitalarias escalonadas tuvieron un mayor porcentaje de colectomía durante la hospitalización inicial pero una menor tasa de complicaciones perioperatorias.LIMITACIONES:Datos retrospectivos y poder limitado para explicar la heterogeneidad de la enfermedad.CONCLUSIONES:No se encontraron diferencias significativas en las tasas de colectomía entre los pacientes que recibieron regímenes estándar o de dosis intensificada. Sin embargo, los regímenes de dosis intensificadas, incluidas múltiples dosis hospitalarias administradas a pacientes con enfermedad más grave, no se asociaron con un mayor riesgo de complicaciones perioperatorias. Consulte Video Resumen en http://links.lww.com/DCR/B864 . (Traducción-Dr. Ingrid Melo ).

Patient's compliance is a contributor to failure of extended antithrombotic prophylaxis in colorectal surgery: prospective cohort study.

BACKGROUND: Venous thromboembolic events (VTE) continue to be a major source of morbidity following colorectal surgery. Selective extended VTE prophylaxis for high-risk patients is recommended; however, provider compliance is low. The purpose of this study is to evaluate whether the "global" extended use of enoxaparin in all colorectal patients is feasible and safe. METHODS: This is a prospective study conducted at a tertiary care center. All Patients undergoing elective colorectal procedures from November 1, 2017 to October 31, 2018 were discharged on 30 days of enoxaparin. Safety of use and patient compliance were examined. RESULTS: Total of 270 patients received extended prophylaxis during the study period (100% of intended patients) with five VTE recorded (1.85%). There was no significant difference in rates of VTE or complications when compared to years of selective prophylaxis (1.26% for 2016, 2.32% for 2017). Only 64% of patients reported full compliance. CONCLUSION: Global use of extended enoxaparin prophylaxis is safe, but does not decrease rates of VTE when compared to selective use. Patient's non-adherence is likely a significant contributing factor.

Very long-term follow-up of autologous pubovaginal fascia slings in women with stress urinary incontinence.

INTRODUCTION AND HYPOTHESIS: The objective was to report on the very long-term outcome of a published series of autologous pubovaginal slings (PVS) in women with stress urinary incontinence (SUI). METHODS: Following institutional review board approval, a cohort of well characterized, non-neurogenic women who underwent an autologous PVS (primary [PVS1] and secondary [PVS2]) for SUI was re-evaluated for their very long-term outcome status. Data collected included demographics, validated questionnaires (Urogenital Distress Inventory - short form [UDI-6], Incontinence Impact Questionnaire - short form 7, quality of life), SUI retreatment/operations, and subjective patient-reported SUI improvement (%) and symptom recurrence. The primary outcome was success defined as UDI-6 question 3 (SUI) ≤ 1 and no SUI retreatment/operation. Patients not seen in clinic for 2 years were contacted via a standardized phone interview. RESULTS: From 83 patients with 7-year intermediate follow-up data, 34 (PVS1 = 18, PVS2 = 16) had very long-term follow-up based on clinic visit (7) or phone interviews (27). Those lost to follow-up (49), including 5 deceased, did not differ in demographics and intermediate outcomes from the followed cohort, but lived further away (>75 miles). At a mean age of 74 years, and with a median follow-up of 14.5 years, 53% met the success criteria (PVS1 = 44%, PVS2 = 63%). Mean postoperative questionnaire scores did not differ significantly between intermediate and very long-term follow-ups, and long-term outcomes between PVS1 and PVS2 remained similar. CONCLUSIONS: A majority of women with long-term follow-up after PVS for primary and secondary SUI remained successful more than 14 years after their surgery. Both groups, PVS1 and PVS2, fared equally well, confirming the durability of PVS as a treatment alternative for SUI.

Conserved L464 in p97 D1-D2 linker is critical for p97 cofactor regulated ATPase activity.

p97 protein is a highly conserved, abundant, functionally diverse, structurally dynamic homohexameric AAA enzyme-containing N, D1, and D2 domains. A truncated p97 protein containing the N and D1 domains and the D1-D2 linker (ND1L) exhibits 79% of wild-type (WT) ATPase activity whereas the ND1 domain alone without the linker only has 2% of WT activity. To investigate the relationship between the D1-D2 linker and the D1 domain, we produced p97 ND1L mutants and demonstrated that this 22-residue linker region is essential for D1 ATPase activity. The conserved amino acid leucine 464 (L464) is critical for regulating D1 and D2 ATPase activity by p97 cofactors p37, p47, and Npl4-Ufd1 (NU). Changing leucine to alanine, proline, or glutamate increased the maximum rate of ATP turnover (kcat) of p47-regulated ATPase activities for these mutants, but not for WT. p37 and p47 increased the kcat of the proline substituted linker, suggesting that they induced linker conformations facilitating ATP hydrolysis. NU inhibited D1 ATPase activities of WT and mutant ND1L proteins, but activated D2 ATPase activity of full-length p97. To further understand the mutant mechanism, we used single-particle cryo-EM to visualize the full-length p97L464P and revealed the conformational change of the D1-D2 linker, resulting in a movement of the helix-turn-helix motif (543-569). Taken together with the biochemical and structural results we conclude that the linker helps maintain D1 in a competent conformation and relays the communication to/from the N-domain to the D1 and D2 ATPase domains, which are ∼50 Šaway.

Risk and protective factors of Internet gaming disorder among Chinese people: A meta-analysis.

OBJECTIVES: Effective prevention and intervention of Internet gaming disorder require the identification of risk and protective factors. This study aims to exhaustively review the risk and protective factors of Internet gaming disorder among Chinese people. METHOD: We searched for articles published from database inception to February 2020 in MEDLINE, PsycINFO, Embase, PubMed, Web of Science and two Chinese databases, CNKI and Wanfang Data. Studies were included in the meta-analysis if they addressed Internet gaming disorder, sampled people in China, presented correlational factors of Internet gaming disorder and reported the effect sizes for correlations. Reviewers independently selected the studies, assessed their validity and extracted the data. Pooled Pearson's correlations were calculated using the random effects model. RESULT: In the meta-analysis, 153 studies covering 115,975 subjects were included. We identified 56 risk factors and 28 protective factors. Most risk factors strongly correlated with Internet gaming disorder fell into the category of maladaptive cognitions and motivations. Other factors that showed high effect sizes fell into various categories, including psychopathological characteristics, personality traits, cognition emotion regulation style and gaming-related factors. The only protective factor strongly correlated with Internet gaming disorder was self-control. We found that the factors related to the 'environments' show modest effect sizes compared to those related to the individual. The pooled effect sizes for most factors were not influenced by outliers and publication bias. CONCLUSION: Factors strongly correlated with Internet gaming disorder, especially maladaptive cognitions and motivations, are more likely to be proximal correlates of Internet gaming disorder and may be considered the focus of interventions. We encourage further empirical and experimental studies to examine the causal pathway and the treatment efficacy.

Telemedicine in urogynaecology during COVID-19 in Hong Kong: An assessment of Chinese patients' acceptability using a validated questionnaire.

AIMS: There is no urogynaecology teleconsultation services available in Hong Kong's public health system. This cross-sectional study aimed to assess Chinese womens' acceptance of teleconsultations during the COVID-19 pandemic using the validated Telemedicine Perception Questionnaire (TMPQ). MATERIALS AND METHODS: One hundred and fifty-one patients attending our urogynaecology clinic between February and March 2021 were recruited for an in-person interview. Patients who could not comprehend the questionnaire due to neurological or psychiatric conditions were excluded. TMPQ is a 17-item, five-point Likert scale questionnaire developed to assess the acceptability of telemedicine. Scores range from 17 to 85; a higher score reflects a more positive overall perception of telemedicine. Additional questions on demographics, medical history, Internet access and transport arrangements were included. RESULTS: Mean age was 67.5 ± 11.3 years. Mean TMPQ score was 53.93 ± 8.49. Younger age, higher education, employment, prior telecommunication platform usage, lower travelling costs and interest in telemedicine were associated with a higher TMPQ score (P < 0.05). Multiple linear regression analysis found age (ß = -0.132, 95% CI (confidence interval): -0.225 to -0.04), interest in telemedicine (ß = 10.169, 95% CI: 8.073-12.266) and post-operative status (ß = 4.743, 95% CI: 1.172-8.314) significantly predicted TMPQ score (adjusted R2  = 0.427). CONCLUSIONS: Our study found that the acceptability of telemedicine in Hong Kong was weak and identified patient groups that showed favourable attitudes. Future research directions would be to perform pilot studies to assess any change in perception after using telemedicine so that this service can be provided to patient groups who would benefit most, ensuring effective use of public resources.

Family functioning under COVID-19: An ecological perspective of family resilience of Hong Kong Chinese families.

This study tested an ecological model of resilience that illustrated the influence of COVID-19-related stressors (i.e., social and health stressors) and various socio-ecological factors at microsystem (i.e., parent-child conflicts and couple relationship) and exo-system levels (i.e., the utilization of community resources) on family functioning among Chinese families during COVID-19. An anonymous telephone survey was conducted using random sampling method. The sample contained 322 respondents who were co-habiting with their child(ren) and their partner. Hierarchical regression analysis and structural equation modelling were used to examine the differential impacts of various levels of factors and the model that were proposed. Results showed that 13.2% of the households were categorized as at-risk of poorer family functioning. Couple relationship and stressors significantly accounted for much of the variance in family functioning. While stressors had a significant direct effect on family functioning, couple relationship, but not parent-child conflicts or utilization of community resources, significantly mediated and moderated the impact of stressors on family functioning. The findings highlighted the impacts of both individual and ecological factors on family functioning under COVID-19. Importantly, cultural and contextual factors should be considered when adopting ecological model of resilience to examine family functioning in diverse cultural groups.

Real-World Application of Pre-Orchiectomy miR-371a-3p Test in Testicular Germ Cell Tumor Management.

PURPOSE: Current serum tumor markers for testicular germ cell tumor are limited by low sensitivity. Growing evidence supports the use of circulating miR-371a-3p as a superior marker for malignant (viable) germ cell tumor management. We evaluated the real-world application of serum miR-371a-3p levels in detecting viable germ cell tumor among patients undergoing partial or radical orchiectomy. MATERIALS AND METHODS: Serum samples were collected from 69 consecutive patients before orchiectomy. Performance characteristics of serum miR-371a-3p were compared with conventional serum tumor markers (⍺-fetoprotein/ß-human chorionic gonadotropin/lactate dehydrogenase) between patients with viable germ cell tumor and those without viable germ cell tumor on orchiectomy pathology. Relative miR-371a-3p levels were correlated with clinical course. The Kruskal-Wallis test and linear and ordinal regression models were used for analysis. RESULTS: For detecting viable germ cell tumor, combined conventional serum tumor markers had a specificity of 100%, sensitivity of 58% and AUC of 0.79. The miR-371a-3p test showed a specificity of 100%, sensitivity of 93% and AUC of 0.978. Median relative expression of miR-371a-3p in viable germ cell tumor cases was more than 6,800-fold higher than in those lacking viable germ cell tumor. miR-371a-3p levels correlated with composite stage (p=0.006) and, among composite stage I cases, independently associated with embryonal carcinoma percentage (p=0.0012) and tumor diameter (p <0.0001). Six patients underwent orchiectomy after chemotherapy and were correctly predicted to have presence or absence of viable germ cell tumor by the miR-371a-3p test. CONCLUSIONS: If validated, the miR-371a-3p test can be used in conjunction with conventional serum tumor markers to aid clinical decision making. A positive miR-371a-3p test in patients after preoperative chemotherapy or with solitary testes could potentially guide subsequent orchiectomy or observation.

Knowledge, perception and expectation of management of hepatitis B infection among pregnant hepatitis B carriers in Hong Kong.

Lack of awareness regarding the risk of hepatitis B virus (HBV) infection and the interventions available during pregnancy among the pregnant carriers may influence their willingness and adherence to the management. This study assessed the knowledge, perception and expectation of HBV infection among pregnant HBV carriers in Hong Kong. A prospective multicentre cross-sectional questionnaire study was carried out between August 2019 and April 2021. The general knowledge on HBV, perception and expectation, and interventions to reduce vertical transmission were questioned. Obtaining ≥70% correct answers was defined as having sufficient knowledge. 422 (82.7%) were known carriers. Only 18.4% of women had sufficient overall knowledge. The correct answer rates and percentage of sufficient knowledge were statistically lower for HBV knowledge specific to pregnancy compared with general knowledge (42.5% vs. 58.5%, p < 0.001; 8.8% vs. 30.2%, p < 0.001 respectively). Multiple logistic regression showed higher education and receiving HBV medical care within a year prior to pregnancy were associated with sufficient overall (OR 3.46; 95% CI 2.05-5.83 and OR 2.76; 95% CI 1.62-4.7, p < 0.001), and general knowledge (OR 2.86; 95% CI 1.81-4.51 and OR 2.14; 95% CI 1.33-3.44, p < 0.05). 298 (58.4%), 357 (70.0%) and 150 (29.4%) women believed they should receive care by obstetrician, hepatologist or general practitioner respectively. 46.9% did not want to initiate antiviral treatment due to the cost, perceived teratogenicity and maternal side effects. The knowledge of HBV among pregnant carriers in Hong Kong was poor despite the majority of them being aware of their carrier status prior to the pregnancy.

Chromosomal imbalances detected in NTRK-rearranged sarcomas by the use of comparative genomic hybridisation.

AIMS: NTRK-rearranged sarcomas are emerging as a distinct class of sarcomas of particular importance in the era of targeted therapy. The aim of this study was to use array comparative genomic hybridisation (aCGH) to explore the cytogenetic profile of six adult soft tissue sarcomas harbouring NTRK gene fusions. METHODS AND RESULTS: aCGH was performed on six adult soft tissue sarcomas with proven NTRK rearrangements [NTRK1, n = 1 (TPM3-NTRK1); NTRK2, n = 1 (MTMR2-NTRK2); NTRK3, n = 4 (two ETV6-NTRK3; two with unknown partners). The morphological patterns of these cases included inflammatory myofibroblastic tumour-like, fibrosarcoma/malignant peripheral nerve sheath tumour-like, and Ewing sarcoma-like. On the basis of the number of chromosomal copy number variations (CNVs), ranging from two to 15 per sample, NTRK-associated sarcomas could be subdivided into two groups: one with a relatively simple karyotype (n = 2; median of three genomic alterations), and those with a more complex karyotype (n = 4; median of 11 genomic imbalances). Recurrent chromosomal CNVs included gains at chromosomes 6p, 1q, 7 (whole chromosome), and 12p, and losses at chromosomes 10q, 13q, 19q, and 9p. CONCLUSIONS: NTRK-rearranged sarcomas constitute a heterogeneous group of tumours that can show a relatively simple or a complex karyotype. Although there were some, but inconsistent, associations between karyotype complexity and morphology, our study showed that a more complex karyotype in this group of tumours appeared to correlate with more aggressive clinical behaviour. Gains at chromosome 6p and 1q were the most common recurrent genomic alterations, being present in 67% of the samples (4/6), followed by gains at chromosome 7, which were present in 50% of the samples (3/6).