A novel splicing variant in ABCA1 in the first reported Hong Kong Chinese patient with high-density lipoprotein deficiency.

Summary: Low high-density lipoprotein cholesterol (HDL-C) is a risk factor for cardiovascular disease. Very low HDL-C levels (less than 20 mg/dL), however, were uncommonly seen and can be due to genetic defects involving the metabolic pathway of high-density lipoprotein (HDL). We encountered a 50-year-old Chinese man who was only noticed to have extremely low HDL-C levels after surviving recurrent episodes of myocardial infarction. Further workup revealed the undetectable level of apolipoprotein A-I, the absence of HDL on gel electrophoresis, and a novel heterozygous splicing variant in the ABCA1 gene, which was predicted to be pathogenic by in silico analysis. To the best of our knowledge, this is the first reported Hong Kong Chinese with ABCA1 deficiency and probable Tangier disease. The association of ABCA1 deficiency/Tangier disease and accelerated atherosclerosis is discussed. Learning points: Clinicians should be aware of the differential diagnoses of very low HDL-C, which could be divided into genetic and acquired causes. Genetic low HDL syndromes include apoA-I deficiency, Tangier disease, and familial LCAT deficiency, each of which has characteristic clinical features and can be differentiated from the other further by apoA-I measurement, lipoprotein analysis, and genetic testing. Patients with ABCA1 deficiency and Tangier disease are at risk of premature coronary artery disease and should be aggressively screened and treated for cardiovascular risk factors and established cardiovascular diseases. Revascularization strategy and indications for coronary artery bypass grafting in patients with Tangier disease and coronary artery disease follow that as for patients without Tangier disease.

Force-induced tail-autotomy mitochondrial fission and biogenesis of matrix-excluded mitochondrial-derived vesicles for quality control.

Mitochondria constantly fuse and divide for mitochondrial inheritance and functions. Here, we identified a distinct type of naturally occurring fission, tail-autotomy fission, wherein a tail-like thin tubule protrudes from the mitochondrial body and disconnects, resembling autotomy. Next, utilizing an optogenetic mitochondria-specific mechanostimulator, we revealed that mechanical tensile force drives tail-autotomy fission. This force-induced fission involves DRP1/MFF and endoplasmic reticulum tubule wrapping. It redistributes mitochondrial DNA, producing mitochondrial fragments with or without mitochondrial DNA for different fates. Moreover, tensile force can decouple outer and inner mitochondrial membranes, pulling out matrix-excluded tubule segments. Subsequent tail-autotomy fission separates the matrix-excluded tubule segments into matrix-excluded mitochondrial-derived vesicles (MDVs) which recruit Parkin and LC3B, indicating the unique role of tail-autotomy fission in segregating only outer membrane components for mitophagy. Sustained force promotes fission and MDV biogenesis more effectively than transient one. Our results uncover a mechanistically and functionally distinct type of fission and unveil the role of tensile forces in modulating fission and MDV biogenesis for quality control, underscoring the heterogeneity of fission and mechanoregulation of mitochondrial dynamics.

Cardiovascular risk factors and complications in patients with systemic lupus erythematosus with and without nephritis: a systematic review and meta-analysis.

INTRODUCTION: It remains unclear how the presence of renal involvement will affect the cardiovascular (CV) risk factors and complications in patients with SLE. METHODS: We conducted a systematic review and meta-analysis using PubMed, EMBASE, MEDLINE and Scopus to identify studies published between 1947 and 2022 that evaluate the CV risk factors and complications in patients with SLE with or without lupus nephritis (LN). RESULTS: 58 studies were evaluated, with 22 two-arm studies (n=8675) included in two-arm meta-analysis and 45 studies (n=385 315) included in proportional meta-analysis. Patients with SLE with LN showed significantly higher risk of hypertension (HT) (OR=4.93, 95% CI=3.17 to 7.65, p<0.00001, I2=56%), hyperlipidaemia (OR=11.03, 95% CI=4.20 to 28.95, p<0.00001, I2=0%) and diabetes mellitus (DM) (OR=1.88, 95% CI=1.09 to 3.25, p=0.02, I2=32%) compared with those without LN. Patients with LN showed numerically higher prevalence of myocardial infarction (OR=1.35, 95% CI=0.53 to 3.45, p=0.52, I2=78%) and cerebrovascular accident (OR=1.64, 95% CI=0.79 to 3.39, p=0.27, I2=23%) than general patients with SLE. The incidence rates of CV mortality are also increased in patients with SLE with LN compared with those without LN (11.7/1000 patient-years vs 3.6/1000 patient-years). CONCLUSION: Patients with SLE with LN show increased risk of CV risk factors including DM, HT and hyperlipidaemia. Early identification and optimal control of these CV risk factors may reduce the risk of CV disease and other non-CV complications. PROSPERO REGISTRATION NUMBER: CRD42022314682.

Comparison of prediction models for cardiovascular and mortality risk in people with type 2 diabetes: An external validation in 23 685 adults included in the UK Biobank.

AIMS: To validate cardiovascular risk prediction models for individuals with diabetes using the UK Biobank in order to assess their applicability. METHODS: We externally validated 19 cardiovascular risk scores from seven risk prediction models (Chang et al., Framingham, University of Hong Kong-Singapore [HKU-SG], Li et al, RECODe [risk equations for complications of type 2 diabetes], SCORE [Systematic Coronary Risk Evaluation] and the UK Prospective Diabetes Study Outcomes Model 2 [UKPDS OM2]), identified from systematic reviews, using UK Biobank data from 2006 to 2021 (n = 23 685; participant age 40-71 years, 63.5% male). We evaluated performance by assessing the discrimination and calibration of the models for the endpoints of mortality, cardiovascular mortality, congestive heart failure, myocardial infarction, stroke, and ischaemic heart disease. RESULTS: Over a total of 269 430 person-years of follow-up (median 11.89 years), the models showed low-to-moderate discrimination performance on external validation (concordance indices [c-indices] 0.50-0.71). Most models had low calibration with overprediction of the observed risk. RECODe outperformed other models across four comparable endpoints for discrimination: all-cause mortality (c-index 0.67, 95% confidence interval [CI] 0.65-0.69), congestive heart failure (c-index 0.71, 95% CI 0.69-0.72), myocardial infarction (c-index 0.67, 95% CI 0.65-0.68); and stroke (c-index 0.65, 95% CI 0.62-0.68), and for calibration (except for all-cause mortality). The UKPDS OM2 had comparable performance to RECODe for all-cause mortality (c-index 0.67, 95% CI 0.66-0.69) and cardiovascular mortality (c-index 0.71, 95% CI 0.70-0.73), but worse performance for other outcomes. The models performed better for younger participants and somewhat better for non-White ethnicities. Models developed from non-Western datasets showed worse performance in our UK-based validation set. CONCLUSIONS: The RECODe model led to better risk estimations in this predominantly White European population. Further validation is needed in non-Western populations to assess generalizability to other populations.

Sortilin-Driven Cancer Secretome Enhances Tumorigenic Properties of Hepatocellular Carcinoma via de Novo Lipogenesis.

A growing body of evidence suggests de novo lipogenesis as a key metabolic pathway adopted by cancers to fuel tumorigenic processes. While increased de novo lipogenesis has also been reported in hepatocellular carcinoma (HCC), understanding on molecular mechanisms driving de novo lipogenesis remains limited. In the present study, the functional role of sortilin, a member of the vacuolar protein sorting 10 protein receptor family, in HCC was investigated. Sortilin was overexpressed in HCC and was associated with poorer survival outcome. In functional studies, sortilin-overexpressing cells conferred tumorigenic phenotypes, namely, self-renewal and metastatic potential, of HCC cells via the cancer secretome. Proteomic profiling highlighted fatty acid metabolism as a potential molecular pathway associated with sortilin-driven cancer secretome. This finding was validated by the increased lipid content and expression of fatty acid synthase (FASN) in HCC cells treated with conditioned medium collected from sortilin-overexpressing cells. The enhanced tumorigenic properties endowed by sortilin-driven cancer secretome were partly abrogated by co-administration of FASN inhibitor C75. Further mechanistic dissection suggested protein stabilization by post-translational modification with O-GlcNAcylation as a major mechanism leading to augmented FASN expression. In conclusion, the present study uncovered the role of sortilin in hepatocarcinogenesis via modulation of the cancer secretome and deregulated lipid metabolism.

Cognitive Behaviour Therapy (CBT) for Depersonalization Derealization Disorder (DDD): a self-controlled cross-over study of waiting list vs. active treatment.

Depersonalisation-Derealisation Disorder (DDD) has a prevalence of around 1% but is under-recognised and often does not respond to medical intervention. We report on a clinical audit of 36 participants with a diagnosis of chronic DDD who were sequentially recruited from a specialist DDD National Health Service clinic in London, United Kingdom, and who completed Cognitive Behavioural Therapy specifically adapted for DDD. The sample population had a mean age of 38.7 years (s.d. = 13.4), 61% were male and 69% were of White ethnicity. Three outcomes were assessed (Cambridge Depersonalisation Scale [CDS], Beck Depression Inventory [BDI], and the Beck Anxiety Inventory [BAI]) at three time points in a naturalistic, self-controlled, cross-over design. Hierarchical longitudinal analyses for outcome response clustered by patient were performed using scores from baseline, beginning, and end of therapy. All scores showed improvement during the treatment period, with medium effect sizes. CBT may be an effective treatment for DDD. However, treatment was not randomly assigned, and the sample was small. More research is needed, including the use of randomisation to assess the efficacy of CBT for DDD.

Feasibility and safety of left distal trans-radial approach for coronary angiogram and percutaneous coronary intervention in a center in Hong Kong.

INTRODUCTION: The left distal trans-radial approach is not only more convenient for the operator than the conventional left forearm radial approach, it is also more comfortable for right-hand patients during the peri-procedural period. Comparing with conventional approach, it has lower bleeding risk, less pain and lower risk of radial artery occlusion. The aim of this study was to determine the feasibility and the safety of left distal trans-radial approach for coronary angiogram and percutaneous coronary intervention in Hong Kong Chinese who had smaller body built and therefore smaller radial arterial size. METHOD: In this single-center prospective study, 72 patients undergoing elective coronary angiography and/or percutaneous coronary intervention were recruited from August to October 2018. All right-handed patients aged 18 or above undergoing elective procedures during the period were recruited. Exclusion criteria were non-palpable radial arteries, pregnancies, incapability to consent, abnormal Allen's test, and emergency procedures. Sixty patients (42 males, age ranging from 45 to 86 years old) were recruited and underwent the procedures via left distal radial approach. The measurements during access establishment, the procedure details, complications, patients' satisfaction, and arterial occlusion rate were studied. RESULTS: The procedures with left distal radial approach were successful in 51 patients (85%). Crossover rate to conventional right radial approach was 15% (nine patients). Among successful cases, the mean patients' satisfaction was 8.32/10 and the mean pain score was 1.6/10. Post-procedural radial artery occlusion was not encountered. CONCLUSION: Left distal radial approach is a feasible alternative for patients undergoing coronary angiography and/or percutaneous coronary intervention in Hong Kong Chinese patients. It provides good comfortability with minimal pain in right-handed patients. The risk of radial artery occlusion is minimal.

IPSC-Derived Sensory Neurons Directing Fate Commitment of Human BMSC-Derived Schwann Cells: Applications in Traumatic Neural Injuries.

The in vitro derivation of Schwann cells from human bone marrow stromal cells (hBMSCs) opens avenues for autologous transplantation to achieve remyelination therapy for post-traumatic neural regeneration. Towards this end, we exploited human induced pluripotent stem-cell-derived sensory neurons to direct Schwann-cell-like cells derived from among the hBMSC-neurosphere cells into lineage-committed Schwann cells (hBMSC-dSCs). These cells were seeded into synthetic conduits for bridging critical gaps in a rat model of sciatic nerve injury. With improvement in gait by 12-week post-bridging, evoked signals were also detectable across the bridged nerve. Confocal microscopy revealed axially aligned axons in association with MBP-positive myelin layers across the bridge in contrast to null in non-seeded controls. Myelinating hBMSC-dSCs within the conduit were positive for both MBP and human nucleus marker HuN. We then implanted hBMSC-dSCs into the contused thoracic cord of rats. By 12-week post-implantation, significant improvement in hindlimb motor function was detectable if chondroitinase ABC was co-delivered to the injured site; such cord segments showed axons myelinated by hBMSC-dSCs. Results support translation into a protocol by which lineage-committed hBMSC-dSCs become available for motor function recovery after traumatic injury to both peripheral and central nervous systems.

Development of a novel diagnostic assay for insulin receptor autoantibodies based on a patient with autoimmune hypoglycaemia.

Differential diagnosis of hypoglycaemia can at times be challenging for patients who appear to be well. Here we identify the case of a 66-year-old Chinese man presenting with recurrent episodes of fasting hypoglycaemia and confusion without any other manifestations. He had no personal or family history of diabetes, nor was he on any hypoglycaemic drugs. The fasting insulin levels were elevated while the C-peptide and pro-insulin levels were slightly low or normal. Antibodies against insulin were negative and levels of insulin-like growth factors were normal. A series of imaging diagnosis excluded the presence of insulinoma or ectopic insulin-secreting neuroendocrine tumor. Ultimately, insulin receptor autoantibodies (IRAb) were detected by both immunoprecipitation assay and enzyme-linked immunosorbent assay (ELISA) developed in house. In a cell study, the immunoglobulins isolated from this patient exerted insulin-like effects on stimulation of post-insulin receptor signaling and glucose uptake as well as inhibited 125I-insulin binding with insulin receptors. Collectively, this patient was diagnosed with IRAb-induced autoimmune hypoglycaemia. Although this patient had no obvious immune disorders, several autoantibodies were identified in his plasma samples, suggesting the patient might have mild aberrant autoimmunity and therefore generated IRAb. IRAb-related disease is uncommon and possibly underdiagnosed or missed due to the lack of simple detection methods for IRAb. Our in-house user-friendly ELISA kit provides a valuable tool for diagnosis of this disease.

Spontaneous rectus sheath hematoma associated with apixaban in an elderly gentleman with chronic obstructive airway disease - a case report.

BACKGROUND: Rectus sheath hematoma (RSH) is a relatively uncommon cause of acute abdominal pain and can be mistaken as other surgical causes of acute abdomen. A diagnosis requires high index of suspicion especially in susceptible patients, for example, in patients on anticoagulation. While anticoagulation is the commonest risk factor for RSH, direct-acting oral anticoagulants have only been very recently implicated as a potential cause with fewer than ten cases reported in the literature. CASE PRESENTATION: An 82-year-old Chinese man with chronic obstructive airway disease, ischemic heart disease, heart failure and atrial fibrillation on apixaban presenting with acute onset of lower abdominal pain. Physical examination showed peritoneal signs with tenderness and guarding over the lower quadrants with hypotension. Computed tomography (CT) of the abdomen confirmed a large rectus sheath hematoma (RSH) without active extravasation. He was given fluid resuscitation and was managed successfully with supportive treatment and cessation of apixaban. A follow-up CT two months later showed resolving hematoma and aspirin was resumed primarily for ischemic heart disease. The patient tolerated anti-platelet therapy without recurrence of RSH. The risk factors, treatment options, prognosis and issue related to anticoagulation resumption after an episode of RSH are discussed. Reported cases of RSH associated with direct-acting oral anticoagulants are reviewed. CONCLUSIONS: Direct-acting oral anticoagulant-associated rectus sheath hematoma is rare. With increasing use of direct-acting oral anticoagulants in multiple clinical settings, clinicians should remain vigilant of this potentially life-threatening bleeding complication when a patient presents with acute abdominal pain. Conservative treatment with cessation of anti-coagulant and supportive transfusion remains the mainstay of treatment.

Was It an Adrenocortical Adenoma or an Adrenocortical Carcinoma? Limitation of the Weiss Scoring System in Determining the Malignant Potential of Adrenocortical Tumor: Report on Two Cases.

Background: Adrenocortical carcinoma (ACC) is a rare endocrine malignancy. An accurate diagnosis of ACC is of paramount importance as it greatly impacts the management and prognosis of a patient. However, the differentiation between early stage, low-grade ACC and adrenocortical adenoma (ACA) may not always be straightforward. The recommended classification system, namely, the Weiss scoring system, is not without flaws. We herein report two cases of ACC which were initially diagnosed as ACA according to the Weiss scoring system but developed distant metastases in subsequent years. Case Presentation. Case 1: A 60-year-old Chinese woman presented with a recent onset of worsening of blood pressure control and clinical features of Cushing's syndrome. Investigations confirmed ACTH-independent endogenous hypercortisolism, and a CT abdomen showed a 6 cm right adrenal mass. Twenty-four-hour urine steroid profiling revealed co-secretion of adrenal androgens and atypical steroid metabolites. Laparoscopic right adrenalectomy was performed, and pathology of the tumor was classified as an ACA by the Weiss scoring system. Four years later, the patient presented with an abrupt onset of severe hypercortisolism and was found to have a metastatic recurrence in the liver and peritoneum. The patient received a combination of mitotane, systemic chemotherapy, and palliative debulking surgery and succumbed 8.5 years after the initial presentation due to respiratory failure with extensive pulmonary metastases. Case 2: A 68-year-old Chinese woman presented with acute bilateral pulmonary embolism and was found to have a 3 cm left adrenal mass. Hormonal workup confirmed ACTH-independent endogenous hypercortisolism, and laparoscopic left adrenalectomy revealed an ACA according to the Weiss scoring system. Five years later, she presented with recurrent hypercortisolism due to hepatic and peritoneal metastases. The patient had progressive disease despite mitotane therapy and succumbed 7 years after initial presentation. Conclusions: Although the Weiss scoring system is recommended as the reference pathological classification system to diagnose adrenocortical carcinoma, there remain tumors of borderline malignant potential which may escape accurate classification. Various alternative classification systems and algorithms exist but none are proven to be perfect. Clinicians should recognize the potential limitation of these histological criteria and scoring systems and incorporate other clinical parameters, such as the pattern of hormonal secretion, urinary steroid profiling, and radiographic features, to improve the prognostication and surveillance strategy of these tumors.

Sex-specific analysis of microRNA profiles in HBV-associated cirrhosis by small RNA-sequencing.

Liver cirrhosis represents an advanced stage of chronic liver disease and is associated with significant morbidity, mortality, and risk of cancer development. While sex disparity of liver diseases has been observed, understanding at a genetic level awaits more thorough investigation. In this study, we performed a sex-specific analysis of the microRNA (miR) profiles in hepatitis B virus (HBV)-associated cirrhosis by small RNA-sequencing using clinical tissue samples. Potential associated signaling pathways, downstream gene targets, and upstream regulators were highlighted by computational prediction analyses based on the differentially expressed miRs (DEmiRs). From our results, deregulation of miRs in cirrhosis showed a marked difference between males and females by the degree and pattern. Sixty-five (64 up-regulated, 1 down-regulated) and 12 (6 up-regulated, 6 down-regulated) DEmiRs were found in males and females, respectively, when compared with their respective control group. A number of DEmiRs were only observed in one sex but not the other. In addition, 26 DEmiRs were identified between cirrhosis female and cirrhosis male groups. Fatty acid biosynthesis pathway, extracellular matrix-receptor interaction, p53 signaling, Hippo signaling, tumor necrosis factor signaling, the forkhead box O signaling, as well as gene targets ribosomal protein S27 like, methyl CpG binding protein 2, and estrogen receptor 1, may contribute to the pathogenesis and biological behavior of cirrhosis in a sex-specific manner. Analysis of the Cancer Genome Atlas data set suggested a role of sex-specific DEmiRs in multistep hepatocarcinogenesis. Conclusion: Our findings illustrate that miR profiles in HBV-associated cirrhosis are distinct between the males and females and suggest a potential role of sex-specific biomarkers and molecular mechanisms in disease development and progression.

Genome of the ramshorn snail Biomphalaria straminea-an obligate intermediate host of schistosomiasis.

BACKGROUND: Schistosomiasis, or bilharzia, is a parasitic disease caused by trematode flatworms of the genus Schistosoma. Infection by Schistosoma mansoni in humans results when cercariae emerge into water from freshwater snails in the genus Biomphalaria and seek out and penetrate human skin. The snail Biomphalaria straminea is native to South America and is now also present in Central America and China, and represents a potential vector host for spreading schistosomiasis. To date, genomic information for the genus is restricted to the neotropical species Biomphalaria glabrata. This limits understanding of the biology and management of other schistosomiasis vectors, such as B. straminea. FINDINGS: Using a combination of Illumina short-read, 10X Genomics linked-read, and Hi-C sequencing data, our 1.005 Gb B. straminea genome assembly is of high contiguity, with a scaffold N50 of 25.3 Mb. Transcriptomes from adults were also obtained. Developmental homeobox genes, hormonal genes, and stress-response genes were identified, and repeat content was annotated (40.68% of genomic content). Comparisons with other mollusc genomes (including Gastropoda, Bivalvia, and Cephalopoda) revealed syntenic conservation, patterns of homeobox gene linkage indicative of evolutionary changes to gene clusters, expansion of heat shock protein genes, and the presence of sesquiterpenoid and cholesterol metabolic pathway genes in Gastropoda. In addition, hormone treatment together with RT-qPCR assay reveal a sesquiterpenoid hormone responsive system in B. straminea, illustrating that this renowned insect hormonal system is also present in the lophotrochozoan lineage. CONCLUSION: This study provides the first genome assembly for the snail B. straminea and offers an unprecedented opportunity to address a variety of phenomena related to snail vectors of schistosomiasis, as well as evolutionary and genomics questions related to molluscs more widely.

Efficacy and Safety of Intravascular Lithotripsy in Lower Extremity Peripheral Artery Disease: A Systematic Review and Meta-Analysis.

OBJECTIVE: Intravascular lithotripsy (IVL) is a novel technique for plaque modification during endovascular revascularisation for peripheral artery disease (PAD) with severe calcification. The aim of this paper was to perform a systematic review and meta-analysis of contemporary data to elucidate the efficacy and safety of IVL in lower extremity PAD. DATA SOURCES: A systematic literature search with pre-defined search terms was performed using PubMed, Web of Sciences, OvidSP, and EMBASE. REVIEW METHODS: A meta-analysis was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Patient characteristics, lesion calcification, pre-IVL and post-IVL diameter stenosis, complications, and stent rates were evaluated. RESULTS: Nine studies were included, encompassing a total of 681 patients (769 lesions) with IVL performed for PAD, of which 75.53% (95% confidence interval [CI] 66.08% - 83.03%) of the lesions were reported to have severe calcification. Comparison between pre-IVL and post-IVL diameter stenosis demonstrated a diameter stenosis reduction of 59.3% (95% CI 53.30% - 65.31%). Vascular complications were rare, with flow limiting or type D/E/F dissection occurring in only 1.25% (95% CI 0.60% - 2.61%) of cases. The overall pooled event rate for stent placement was 15.89% (95% CI 5.22% - 39.34%). CONCLUSION: This meta-analysis supports IVL as an effective and safe approach for calcified plaque modification in lower extremity PAD, achieving a diameter stenosis reduction of 59.3% (95% CI 53.30% - 65.31%) with minimal vascular complications. Routine use of this device is not recommended; further high quality evidence is required to elucidate the efficacy of IVL with respect to different clinical characteristics such as lesion location and length, and in comparison with other treatment modalities such as atherectomy.

Sex differences in symptom severity, cognition and psychosocial functioning among individuals with at-risk mental state for psychosis.

AIM: Sex differences are well documented in schizophrenia, but have been much less studied in at-risk mental state (ARMS) for psychosis. We aimed to examine sex differences in symptomatology, cognition, social and role functioning in individuals with ARMS, with specific focus on clarifying relationships between sex, negative symptoms and functioning. METHODS: One hundred and seventy-seven Chinese participants aged 15-40 years with ARMS were recruited from a specialized early intervention service in Hong Kong. ARMS status was verified by Comprehensive Assessment of At-Risk Mental State. Assessments encompassing symptom profiles, a brief battery of cognitive tests and social and role functioning were conducted. Brief Negative Symptom Scale was adapted to measure negative symptoms at the level of five core domains. RESULTS: Males with ARMS exhibited significantly poorer social functioning and more severe asociality of negative symptoms than female counterparts. Mediation analysis revealed that sex difference in social functioning became statistically insignificant when asocality was included in the model, indicating that asociality mediated the relationship between sex and social functioning. No sex differences were observed in other core domains of negative symptoms, other symptom dimensions, cognitive measures and role functioning. CONCLUSIONS: This study suggests that sex differences in ARMS may be less pronounced that those observed in established psychotic disorders. Our findings of differential pattern of asociality between sexes and its mediating role on sex difference in social functioning underscore the importance in investigating negative symptoms at a separable domain-level. Further research is required to identify sex-specific predictors of longitudinal outcomes in at-risk populations.

Distance education for anatomy and surgical training - A systematic review.

Rapid development of COVID-19 has resulted in a massive shift from traditional to online teaching. This review aims to evaluate the effectiveness of distance learning on anatomy and surgical training. This systematic review was conducted in line with the PRISMA statement and current methodological literature. The databases CINAHL, Cochrane, EMBASE and Pubmed were searched using the search terms "Distant learning" OR "Distance learning" AND "Anatomy OR Surgery". 182 non-duplicate studies were identified. 20 studies were included for qualitative analysis. 10 studies evaluated students' performance with distance learning. 3 studies suggested that students' learning motivation improved with distance learning pedagogy. 5 studies found improved student performance with distance learning (performance or task completion time) when compared to conventional physical method. While 2 other studies found non-inferior student performance. 10 studies evaluated students' feedback on distance learning. Most feedbacks were positive, with flexibility, efficiency, increased motivation and better viewing angles as the most-liked features of distance teaching. 4 studies pointed out some limitations of distance learning, including the lack of personal contact with tutor, poor network and reduced student concentration. 7 studies evaluated tutors' feedback on distance learning. Tutors generally liked online platforms for the ease of tracking silent students, monitoring performance and updating fast-changing knowledge. Yet the lack of hands-on experience for students, technical issues and high costs are the main concerns for tutors. In conclusion, distance learning is a feasible alternative for anatomy and surgical teaching.

GmDNJ1, a type-I heat shock protein 40 (HSP40), is responsible for both Growth and heat tolerance in soybean.

Global warming poses severe threats to agricultural production, including soybean. One of the major mechanisms for organisms to combat heat stress is through heat shock proteins (HSPs) that stabilize protein structures at above-optimum temperatures, by assisting in the folding of nascent, misfolded, or unfolded proteins. The HSP40 subgroups, or the J-domain proteins, functions as co-chaperones. They capture proteins that require folding or refolding and pass them on to HSP70 for processing. In this study, we have identified a type-I HSP40 gene in soybean, GmDNJ1, with high basal expression under normal growth conditions and also highly inducible under abiotic stresses, especially heat. Gmdnj1-knockout mutants had diminished growth in normal conditions, and when under heat stress, exhibited more severe browning, reduced chlorophyll contents, higher reactive oxygen species (ROS) contents, and higher induction of heat stress-responsive transcription factors and ROS-scavenging enzyme-encoding genes. Under both normal and heat-stress conditions, the mutant lines accumulated more aggregated proteins involved in protein catabolism, sugar metabolism, and membrane transportation, in both roots and leaves. In summary, GmDNJ1 plays crucial roles in the overall plant growth and heat tolerance in soybean, probably through the surveillance of misfolded proteins for refolding to maintain the full capacity of cellular functions.

Anti-tumour effects of PIM kinase inhibition on progression and chemoresistance of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a biologically aggressive cancer. Targeted therapy is in need to tackle challenges in the treatment perspective. A growing body of evidence suggests a promising role of pharmacological inhibition of PIM (proviral integration site for Moloney murine leukaemia virus) kinase in some human haematological and solid cancers. Yet to date, the potential application of PIM inhibitors in HCC is still largely unexplored. In the present study we investigated the pre-clinical efficacy of PIM inhibition as a therapeutic approach in HCC. Effects of PIM inhibitors on cell proliferation, migration, invasion, chemosensitivity, and self-renewal were examined in vitro. The effects of PIM inhibitors on tumour growth and chemoresistance in vivo were studied using xenograft mouse models. Potential downstream molecular mechanisms were elucidated by RNA sequencing (RNA-seq) of tumour tissues harvested from animal models. Our findings demonstrate that PIM inhibitors SGI-1776 and PIM447 reduced HCC proliferation, metastatic potential, and self-renewal in vitro. Results from in vivo experiments supported the role of PIM inhibition in suppressing of tumour growth and increasing chemosensitivity of HCC toward cisplatin and doxorubicin, the two commonly used chemotherapeutic agents in trans-arterial chemoembolisation (TACE) for HCC. RNA-seq analysis revealed downregulation of the MAPK/ERK pathway upon PIM inhibition in HCC cells. In addition, LOXL2 and ICAM1 were identified as potential downstream effectors. Taken together, PIM inhibitors demonstrated remarkable anti-tumourigenic effects in HCC in vitro and in vivo. PIM kinase inhibition is a potential approach to be exploited in formulating adjuvant therapy for HCC patients of different disease stages. © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Impacts of Typhoon Mangkhut in 2018 on the deposition of marine debris and microplastics on beaches in Hong Kong.

Storm surge and waves associated with tropical cyclones carry significant amounts of pollutants into the marine environment. This study evaluated the effects of Typhoon Mangkhut (7-18 September 2018) on marine debris pollution including macro-debris (>2.5 cm) and microplastics (5 µm-5 mm) in Hong Kong. Sampling was repeated on four beaches, two each from protected and exposed coastal areas, spanning from the eastern to western waters before and after the cyclone. For macro-debris, an average density of 0.047 items m-2 and 0.54 items m-2 was obtained before and after the cyclone, respectively or an 11.4-fold increase, with plastic being the most dominant type (61.9-93.3% and 80.7-92.4% before and after the cyclone, respectively) among total beached debris in all four beaches. Likewise, higher mean microplastic abundances were found in the post-cyclone period (335 items kg-1 sediment) when compared with the pre-cyclone period (188 items kg-1 sediment). The depositional dynamics for both macro-debris and microplastic were site-specific due to factors such as wind direction and the associated storm surge, topography and orientation of the site, and proximity to urban areas. This study has demonstrated the role cyclone induced overwash plays on introducing plastic pollution to beach environments. Considering an increase in both the intensity and frequency of cyclone in the future due to global warming, and a tremendous increase in marine plastic debris, more research effort should be spent on this understudied problem.

In the transition from fibrinolysis to primary PCI, the HERO trials help refine STEMI ECG interpretation and Q wave analysis potentially alters future management.

Electrocardiogram sub-studies from the Hirulog Early Reperfusion/Occlusion 1 and 2 trials, which tested bivalirudin as an adjunctive anticoagulant to fibrinolysis in ST-elevation myocardial infarction, have contributed to the literature. The concept of using the presence of infarct lead Q waves to determine reperfusion benefit has subsequently been explored in multiple primary percutaneous coronary intervention studies. The angiographic findings before percutaneous coronary intervention combine with the baseline electrocardiogram to accurately diagnose ST-elevation myocardial infarction and evaluate its potential territory. This review discusses the relative merits of the presence of infarct lead Q waves versus time duration from symptom onset using observational data from cohorts of patients from multiple clinical trials. The presence of infarct lead Q waves at presentation has been repeatedly shown to be superior to time duration from symptom onset in determining prognosis, despite that continuous variable (time duration) statistically should be more powerful than dichotomous variable (Q wave). If quantitative or semi-quantitative measurement of Q waves correlates well with irreversible myocardial injury in vivo (a research goal of many cardiac magnetic resonance imaging studies), Q waves measurements by mirroring ST-elevation myocardial infarction evolution better than the current metric of time duration of symptoms will impact future ST-elevation myocardial infarction reperfusion management. Newer methodology will more quickly capture and transmit electrocardiogram information including infarct lead Q waves potentially before first medical contact, and help differentiate new evolving Q waves of the ongoing ST-elevation myocardial infarction from old changes. Q waves as the new metric in ST-elevation myocardial infarction reperfusion should be tested in upcoming trials.