Functional and Molecular Characterization of New SPTLC1 Missense Variants in Patients with Hereditary Sensory and Autonomic Neuropathy Type 1 (HSAN1).

Hereditary sensory and autonomic neuropathy type 1 is an autosomal dominant neuropathy caused by the SPTLC1 or SPTLC2 variants. These variants modify the preferred substrate of serine palmitoyl transferase, responsible for the first step of de novo sphingolipids synthesis, leading to accumulation of cytotoxic deoxysphingolipids. Diagnosis of HSAN1 is based on clinical symptoms, mainly progressive loss of distal sensory keep, and genetic analysis. Aim: Identifying new SPTLC1 or SPTLC2 "gain-of-function" variants raises the question as to their pathogenicity. This work focused on characterizing six new SPTLC1 variants using in silico prediction tools, new meta-scores, 3D modeling, and functional testing to establish their pathogenicity. Methods: Variants from six patients with HSAN1 were studied. In silico, CADD and REVEL scores and the 3D modeling software MITZLI were used to characterize the pathogenic effect of the variants. Functional tests based on plasma sphingolipids quantification (total deoxysphinganine, ceramides, and dihydroceramides) were performed by tandem mass spectrometry. Results: In silico predictors did not provide very contrasting results when functional tests discriminated the different variants according to their impact on deoxysphinganine level or canonical sphingolipids synthesis. Two SPTLC1 variants were newly described as pathogenic: SPTLC1 NM_006415.4:c.998A>G and NM_006415.4:c.1015G>A. Discussion: The combination of the different tools provides arguments to establish the pathogenicity of these new variants. When available, functional testing remains the best option to establish the in vivo impact of a variant. Moreover, the comprehension of metabolic dysregulation offers opportunities to develop new therapeutic strategies for these genetic disorders.

Clinical Outcomes of 111 Patients with Early Onset Idiopathic Scoliosis (EOIS) Receiving Brace Treatment: A Longitudinal Retrospective Cohort Study.

Introduction: Bracing is one of the first-line treatment for early-onset idiopathic scoliosis (EOIS) to control curves from progression. This study aimed to explore the determinants that govern bracing effectiveness in EOIS. Methods: One hundred and eleven patients with EOIS (mean age of 8.6 ± 1.25 at diagnosis) received bracing treatment and had a final follow-up beyond skeletal maturity were identified from records between 1988 and 2021. Demographic data and clinical features of spinal curvature were obtained for correlation analyses to determine the associations between curve outcomes and clinical features. Results: Most patients were female (85.6%) and had a major curve on the left side (67%). The mean baseline Cobb angle of major curves was 21.73 ± 7.92°, with a mean Cobb angle progression of 18.05 ± 19.11°. The average bracing duration was 5.3 ± 1.9 years. Only 26 (23.4%) of them underwent surgery. The final Cobb angle and curve progression at the final follow-up with a Cobb angle of ≥50° were positively correlated with the initial Cobb angle (r = 0.206 and r = 0.313, respectively) and negatively correlated with maturity parameters. The lumbar curve type was found to correlate with a smaller final Cobb angle. Conclusions: The majority of patients had a final Cobb angle < 50°, which was considered a successful bracing outcome. The final Cobb angle correlated with the initial Cobb angle and curve types observed in EOIS.

Mitral annular disjunction on cardiac MRI: Prevalence and association with disease severity in Loeys-Dietz syndrome.

BACKGROUND: The purpose of this study was to evaluate mitral annular disjunction (MAD) on cardiac magnetic resonance imaging (MRI) in Loeys-Dietz Syndrome (LDS) and to explore its association with adverse outcomes. METHODS: In this retrospective cohort study, adult patients with LDS who underwent cardiac MRI were evaluated for MAD, aortic dimensions, and ventricular volumetry. Aortic events were defined as aortic surgery and/or dissection and severe arrhythmic events as cardiac arrest or sustained ventricular tachycardia (VT). RESULTS: Among 46 LDS patients (52% female, 37.2 ± 14.3 years), 17 had MAD (37%). MAD and no MAD groups were similar in age, sex, aortic dimensions and left ventricular parameters. After a clinical follow-up of 4.3 years (IQR 1.5-8.4), 3 in MAD and 4 in no MAD groups required aortic valve sparing root replacement (VSRR) and 1 in MAD developed type A dissection. Over a similar imaging follow-up period [4.1 years (IQR 2.7-9.1) vs. 3.2 years (IQR 1.0-9.0), p = 0.65], compared to baseline, increase in native aortic root size was significant only in MAD (39.4 ± 4.6 mm vs. 38.1 ± 5.3 mm, p = 0.02, 19.3 ± 2.4 mm/m2 vs. 18.7 ± 2.4 mm/m2, p = 0.01) compared to those without MAD. Patients with MAD were younger at first aortic event compared to those without (26.7 ± 11.5 years vs. 45.0 ± 14.9 years, p = 0.03). MAD distance correlated with need for VSRR, r = 0.57, p = 0.02. Two patients in the MAD group developed sustained VT. No cardiac arrest or death was observed. CONCLUSION: MAD is highly prevalent in LDS, associated with progressive aortic dilatation, and aortic events at younger age. MAD may be a marker of disease severity necessitating close surveillance.

Clinical characteristics of unvaccinated or incompletely vaccinated children with neurological manifestations due to SARS-CoV-2 Omicron infection.

Omicron generally causes milder disease than previous strains of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), especially in fully vaccinated individuals. However, incompletely vaccinated children may develop Omicron-related complications such as those affecting the central nervous system. To characterize the spectrum of clinical manifestations of neuro-COVID and to identify potential biomarkers associated with clinical outcomes, we recruited 15 children hospitalized for Omicron-related neurological manifestations in three hospitals in Hong Kong (9 boys and 6 girls aged 1-13 years). All were unvaccinated or incompletely vaccinated. Fourteen (93.3%) were admitted for convulsion, including benign febrile seizure (n = 7), complex febrile seizure (n = 2), seizure with fever (n = 3), and recurrent breakthrough seizure (n = 2), and the remaining nonconvulsive patient developed encephalopathic state with impaired consciousness. None of the seven children with benign febrile seizure and six of eight children with other neurological manifestations had residual deficits at 9-month follow-up. SARS-CoV-2 RNA was undetectable in the cerebrospinal fluid (CSF) specimens of seven patients who underwent lumbar puncture. Spike-and-wave/sharp waves affecting the frontal lobes were detected in four of seven (57.1%) patients who underwent electroencephalogram. Children with Omicron-related neurological manifestations had significantly higher blood levels of IL-6 (p < 0.001) and CHI3L1 (p = 0.022) than healthy controls, and higher CSF levels of IL-6 (p = 0.002) than children with non-COVID-19-related febrile illnesses. Higher CSF-to-blood ratios of IL-8 and CHI3L1 were associated with longer length of stay, whereas higher ratios of IL-6 and IL-8 were associated with higher blood tau level. The role of CSF:blood ratio of IL-6, IL-8, and CHI3L1 as prognostic markers for neuro-COVID should be further evaluated.

The Use of a Non-Invasive Biomarker for Colorectal Cancer Screening: A Comparative Cost-Effectiveness Modeling Study.

This study aimed to examine the cost-effectiveness of fecal biomarker M3 panel compared to fecal immunochemical test (FIT) and colonoscopy in an Asian population. In a hypothetical population of 100,000 persons aged 50 years who received FIT yearly, M3 biomarker yearly, or colonoscopy every 10 years until the age of 75 years. Participants with positive FOBT or a result of "high risk" identified using the M3 biomarker are offered colonoscopy. We assumed surveillance colonoscopy is repeated every 3 years, and examined the treatment cost. A comparison of various outcome measures was conducted using Markov modelling. The incremental cost-effectiveness ratio (ICER) of FIT, M3 biomarker, and colonoscopy was USD108,176, USD133,485 and USD159,596, respectively. Comparing with FIT, the use of M3 biomarker could lead to significantly smaller total loss of cancer-related life-years (2783 vs. 5279); a higher number of CRC cases prevented (1622 vs. 146), a higher proportion of CRC cases prevented (50.2% vs. 4.5%), more life-years saved (2852 vs. 339), and cheaper total costs per life-year saved (USD212,553 vs. 773,894). The total costs per life-year saved is more affordable than that achieved by colonoscopy as a primary screening tool (USD212,553 vs. USD236,909). The findings show that M3 biomarkers may be more cost-effective than colonoscopy.

The cross-sectional and longitudinal relationship of diabetic retinopathy to cognitive impairment: a systematic review and meta-analysis.

OBJECTIVES: To establish a potential relationship between diabetic retinopathy (DR) and different stages of cognitive impairment METHODS: Literature searches were conducted on PubMed and EMBASE, with keywords "diabetic retinopathy" and "cognitive impairment". Inclusion criteria were original human studies, and English language. Quality of studies was assessed by the Newcastle-Ottawa Quality Assessment (NOSGEN). The register number of this study on the International Prospective Register of Systematic Reviews (PROSPERO) is CRD42021236747. The main outcome measures were odds ratios (OR) and risk ratios (RR) for cross-sectional and longitudinal studies, respectively. Meta-regression was performed to evaluate the effects of potential moderator variables, including, age, onset age of diabetes mellitus (DM), duration of DM, and HbA1c. RESULTS: Twenty-five studies (17 cross-sectional and 8 longitudinal studies) with a total of 1,963,914 subjects, were included. Among the cross-sectional studies, the pooled ORs of any cognitive impairment, early stage of cognitive impairment and dementia in subjects with DR (95% confidence interval) were 1.48 (1.08-2.02), 1.59 (1.01-2.51), and 1.13 (0.86-1.50), respectively. Among the longitudinal studies, the pooled RRs of any cognitive impairment, early stage of cognitive impairment, and dementia in subjects with DR (95% confidence interval) were 1.35 (1.12-1.65), 1.50 (1.06-2.12), and 1.31 (1.03-1.66), respectively. Meta-regression showed age, onset age of DM, duration of DM, and glycated hemoglobin (HbA1c) were not statistically associated with the outcomes. CONCLUSIONS: The presence of DR in DM patients indicates both higher odds of prevalent cognitive impairment and escalated risks of developing cognitive impairment in the future.

Association of Pectus Excavatum With Ventricular Remodelling and Mitral Valve Abnormalities in Marfan Syndrome.

Background: Marfan syndrome (MFS) is an inherited connective tissue disorder. Pectus excavatum (PEX) is common in MFS. The purpose was to evaluate the association of PEX with cardiovascular manifestations of MFS, biventricular size and function. Methods: MFS adults undergoing cardiac MRI were retrospectively evaluated. Exclusion criteria were incomplete cardiac MRI, significant artifacts, co-existent ischaemic or congenital heart disease. Haller Index (HI) ≥3.25 classified patients as PEX positive (PEX+) and PEX negative (PEX-). Cardiac MRI analysis included assessment of mitral valve prolapse (MVP), mitral annular disjunction (MAD), biventricular volumetry and aortic dimensions. Results: 212 MFS patients were included, 76 PEX+ and 136 PEX- (HI 8.3 ± 15.2 vs 2.3 ± 0.5, P < .001). PEX+ were younger (33.4 ± 12.0 vs 38.1 ± 14.3 years, P = .02) and similar in sex distribution (55% vs 63% male, P = .26) compared to PEX-. MVP and MAD were more frequent in PEX+ vs PEX- (43/76 [57%] vs 37/136 [27%], P < .001; 44/76 [58%] vs 50/136[37%], P = .003, respectively). PEX+ had higher right ventricular end-diastolic and end-systolic volumes (RVEDVi 92 ± 17mL/m2 vs 84 ± 22mL/m2, P = .04; RVESVi 44 ± 10 mL/m2 vs 39 ± 14 mL/m2, P = .02), lower RV ejection fraction (RVEF 52 ± 5% vs 55 ± 6%, P = .01) compared to PEX-. Left ventricular (LV) volumes, LVEF and aortic dimensions were similar. Conclusion: MFS adults with PEX have higher frequency of cardiac manifestations including MV abnormalities, increased RV volumes and lower RVEF compared to those without PEX. Awareness of this association is important for all radiologists who interpret aortic CT or MRI, where HI can be easily measured. PEX in MFS may suggest more severe disease expression necessitating careful screening for MV abnormalities and outcomes surveillance.

Alterations in the Choroidal Sublayers in Relationship to Severity and Progression of Diabetic Retinopathy: A Swept-Source OCT Study.

Purpose: To examine the association of baseline choroidal sublayers metrics with the risk of diabetic retinopathy (DR) progression over 2 years, with adjustment for confounding factors that affect choroidal measurements. Design: Prospective, observational cohort study. Participants: One hundred three eyes from 62 patients with diabetes mellitus (DM). Methods: Patients were followed up at 6-month intervals for at least 2 years. Choroidal metrics including choroidal area, choroidal thickness (CT), and choroidal vascularity index were measured for both (1) the choriocapillaris plus Sattler's layer and (2) the Haller's layer within the subfoveal and parafoveal region. Cox proportional models were constructed to estimate the relationship between baseline choroidal metrics and DR progression, adjusted for intereye correlation, established risk factors (i.e., duration of DM, glycated hemoglobin [HbA1c] level, body mass index [BMI], use of insulin, and mean arterial blood pressure [MABP]) and confounding factors of choroidal measurements (i.e., age and axial length). Additional predictive value of choroidal metrics was assessed using the C-statistic. Main Outcome Measures: Hazard ratios (HRs) calculated by Cox proportional hazards model to demonstrate the associations between baseline choroidal metrics and DR progression. Results: After adjusting for age, axial length, and intereye correlation, choroidal metrics in Haller's layer at baseline that were associated with a higher risk of DR progression included increases in subfoveal choroidal area (HR, 2.033; 95% confidence interval [CI], 1.179-3.505; P = 0.011), subfoveal plus parafoveal choroidal area (HR, 1.909; 95% CI, 1.096-3.326; P = 0.022), subfoveal CT (HR, 2.032; 95% CI, 1.181-3.498; P = 0.010), and subfoveal plus parafoveal CT (HR, 1.908; 95% CI, 1.097-3.319; P = 0.022). These associations remained statistically significant after additionally adjusting for duration of DM, HbA1c level, BMI, use of insulin, and MABP. Addition of these choroidal metrics significantly improved the discrimination for DR progression when compared with established risk factors alone (e.g., duration of DM and HbA1c; increase in C-statistic ranged from 8.08% to 9.67% [P < 0.05]). Conclusions: Eyes with a larger choroidal area and CT in Haller's layer at baseline were associated with a higher risk of DR progression over 2 years.

A deep learning model for detection of Alzheimer's disease based on retinal photographs: a retrospective, multicentre case-control study.

BACKGROUND: There is no simple model to screen for Alzheimer's disease, partly because the diagnosis of Alzheimer's disease itself is complex-typically involving expensive and sometimes invasive tests not commonly available outside highly specialised clinical settings. We aimed to develop a deep learning algorithm that could use retinal photographs alone, which is the most common method of non-invasive imaging the retina to detect Alzheimer's disease-dementia. METHODS: In this retrospective, multicentre case-control study, we trained, validated, and tested a deep learning algorithm to detect Alzheimer's disease-dementia from retinal photographs using retrospectively collected data from 11 studies that recruited patients with Alzheimer's disease-dementia and people without disease from different countries. Our main aim was to develop a bilateral model to detect Alzheimer's disease-dementia from retinal photographs alone. We designed and internally validated the bilateral deep learning model using retinal photographs from six studies. We used the EfficientNet-b2 network as the backbone of the model to extract features from the images. Integrated features from four retinal photographs (optic nerve head-centred and macula-centred fields from both eyes) for each individual were used to develop supervised deep learning models and equip the network with unsupervised domain adaptation technique, to address dataset discrepancy between the different studies. We tested the trained model using five other studies, three of which used PET as a biomarker of significant amyloid ß burden (testing the deep learning model between amyloid ß positive vs amyloid ß negative). FINDINGS: 12 949 retinal photographs from 648 patients with Alzheimer's disease and 3240 people without the disease were used to train, validate, and test the deep learning model. In the internal validation dataset, the deep learning model had 83·6% (SD 2·5) accuracy, 93·2% (SD 2·2) sensitivity, 82·0% (SD 3·1) specificity, and an area under the receiver operating characteristic curve (AUROC) of 0·93 (0·01) for detecting Alzheimer's disease-dementia. In the testing datasets, the bilateral deep learning model had accuracies ranging from 79·6% (SD 15·5) to 92·1% (11·4) and AUROCs ranging from 0·73 (SD 0·24) to 0·91 (0·10). In the datasets with data on PET, the model was able to differentiate between participants who were amyloid ß positive and those who were amyloid ß negative: accuracies ranged from 80·6 (SD 13·4%) to 89·3 (13·7%) and AUROC ranged from 0·68 (SD 0·24) to 0·86 (0·16). In subgroup analyses, the discriminative performance of the model was improved in patients with eye disease (accuracy 89·6% [SD 12·5%]) versus those without eye disease (71·7% [11·6%]) and patients with diabetes (81·9% [SD 20·3%]) versus those without the disease (72·4% [11·7%]). INTERPRETATION: A retinal photograph-based deep learning algorithm can detect Alzheimer's disease with good accuracy, showing its potential for screening Alzheimer's disease in a community setting. FUNDING: BrightFocus Foundation.

Chromohalobacter salixigens Uronate Dehydrogenase: Directed Evolution for Improved Thermal Stability and Mutant CsUDH-inc X-ray Crystal Structure.

Chromohalobacter salixigens contains a uronate dehydrogenase termed CsUDH that can convert uronic acids to their corresponding C1,C6-dicarboxy aldaric acids, an important enzyme reaction applicable for biotechnological use of sugar acids. To increase the thermal stability of this enzyme for biotechnological processes, directed evolution using gene family shuffling was applied, and the hits selected from 2-tier screening of a shuffled gene family library contained in total 16 mutations, only some of which when examined individually appreciably increased thermal stability. Most mutations, while having minimal or no effect on thermal stability when tested in isolation, were found to exhibit synergy when combined; CsUDH-inc containing all 16 mutations had ΔK t 0.5 +18 °C, such that k cat was unaffected by incubation for 1 hr at ~70 °C. X-ray crystal structure of CsUDH-inc showed tight packing of the mutated residue side-chains, and comparison of rescaled B-values showed no obvious differences between wild type and mutant structures. Activity of CsUDH-inc was severely depressed on glucuronic and galacturonic acids. Combining select combinations of only three mutations resulted in good or comparable activity on these uronic acids, while maintaining some improved thermostability with ΔK t 0.5 ~+ 10 °C, indicating potential to further thermally optimize CsUDH for hyperthermophilic reaction environments.

Identification of sleep fragmentation-induced gut microbiota alteration and prediction of functional impact in Sprague Dawley rats harboring microbiome derived from multiple human donors.

Objectives: Poor quality sleep, including sleep fragmentation (SF), can result in severe health consequences. Gut microbiota symbiotically coexist with the host, making essential contributions to overall well-being. In this study, the effects of both acute (6-day) and chronic (6-week) SF in a humanized rat model were examined to evaluate the impact of SF on this symbiotic relationship. Material and Methods: Human fecal material was transplanted into antibiotic-treated, microbially depleted, Sprague Dawley rats. Animals were subjected to either acute or chronic SF and shifts to gut microbiota were investigated using 16S rRNA sequencing and predictive functional profiles were constructed with PICRUSt. We also investigated SF-induced intestinal microbial adhesion and penetration or increased microbial invasion of selected tissues and organs; as well as changes in crypt/villi architecture. Results: Microbiota profiling indicated that chronic, but not acute, SF significantly decreased the richness of alpha-diversity of distal ileum microbiota, and altered cecum and distal ileum beta-diversity; although both acute and chronic SF significantly changed select populations of microbiota in all three regions. Neither acute nor chronic SF induced changes to microbial adhesion, penetration, or invasion into intestinal tissues or nearby organs. Additionally, we found that chronic SF caused a reduction in villus height in the proximal colon. Discussion: Our study suggests that acute SF alters the gut microbiota in this humanized rat model, while chronic SF produces more pronounced changes to microbiota populations. This study identified potential microbiota targets for the prevention and/or intervention of the adverse effects of S F.

Myocardial Injury Pattern at MRI in COVID-19 Vaccine-Associated Myocarditis.

Background There are limited data on the pattern and severity of myocardial injury in patients with COVID-19 vaccination-associated myocarditis. Purpose To describe myocardial injury following COVID-19 vaccination and to compare these findings to other causes of myocarditis. Materials and Methods In this retrospective cohort study, consecutive adult patients with myocarditis with at least one T1-based and at least one T2-based abnormality at cardiac MRI performed at a tertiary referral hospital from December 2019 to November 2021 were included. Patients were classified into one of three groups: myocarditis following COVID-19 vaccination, myocarditis following COVID-19 illness, and other myocarditis not associated with COVID-19 vaccination or illness. Results Of the 92 included patients, 21 (23%) had myocarditis following COVID-19 vaccination (mean age, 31 years ± 14 [SD]; 17 men; messenger RNA-1273 in 12 [57%] and BNT162b2 in nine [43%]). Ten of 92 (11%) patients had myocarditis following COVID-19 illness (mean age, 51 years ± 14; three men) and 61 of 92 (66%) patients had other myocarditis (mean age, 44 years ± 18; 36 men). MRI findings in the 21 patients with vaccine-associated myocarditis included late gadolinium enhancement (LGE) in 17 patients (81%) and left ventricular dysfunction in six (29%). Compared with other causes of myocarditis, patients with vaccine-associated myocarditis had a higher left ventricular ejection fraction and less extensive LGE, even after controlling for age, sex, and time from symptom onset to MRI. The most frequent location of LGE in all groups was subepicardial at the basal inferolateral wall, although septal involvement was less common in vaccine-associated myocarditis. At short-term follow-up (median, 22 days [IQR, 7-48 days]), all patients with vaccine-associated myocarditis were asymptomatic with no adverse events. Conclusion Cardiac MRI demonstrated a similar pattern of myocardial injury in vaccine-associated myocarditis compared with other causes, although abnormalities were less severe, with less frequent septal involvement and no adverse events over the short-term follow-up. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Raman and Neubauer in this issue.

TRPV1 Contributes to Modulate the Nitric Oxide Pathway and Oxidative Stress in the Isolated and Perfused Rat Heart during Ischemia and Reperfusion.

The transient vanilloid receptor potential type 1 (TRPV1) regulates neuronal and vascular functions mediated by nitric oxide (NO) and by the calcitonin gene-related peptide (CGRP). Here, we study the participation of TRPV1 in the regulation of myocardial injury caused by ischemia-reperfusion and in the control of NO, tetrahydrobiopterin (BH4), the cGMP pathway, CGRP, total antioxidant capacity (TAC), malondialdehyde (MDA) and phosphodiesterase-3 (PDE-3). Isolated hearts of Wistar rats perfused according to the Langendorff technique were used to study the effects of an agonist of TRPV1, capsaicin (CS), an antagonist, capsazepine (CZ), and their combination CZ+CS. The hearts were subjected to three conditions: (1) control, (2) ischemia and (3) ischemia-reperfusion. We determined cardiac mechanical activity and the levels of NO, cGMP, BH4, CGRP, TAC, MDA and PDE-3 in ventricular tissue after administration of CS, CZ and CZ+CS. Western blots were used to study the expressions of eNOS, iNOS and phosphorylated NOS (pNOS). Structural changes were determined by histological evaluation. CS prevented damage caused by ischemia-reperfusion by improving cardiac mechanical activity and elevating the levels of NO, cGMP, BH4, TAC and CGRP. TRPV1 and iNOS expression were increased under ischemic conditions, while eNOS and pNOS were not modified. We conclude that the activation of TRPV1 constitutes a therapeutic possibility to counteract the damage caused by ischemia and reperfusion by regulating the NO pathway through CGRP.

The role of machine learning in the primary prevention of work-related musculoskeletal disorders: A scoping review.

To determine the applications of machine learning (ML) techniques used for the primary prevention of work-related musculoskeletal disorders (WMSDs), a scoping review was conducted using seven literature databases. Of the 4,639 initial results, 130 primary research studies were deemed relevant for inclusion. Studies were reviewed and classified as a contribution to one of six steps within the primary WMSD prevention research framework by van der Beek et al. (2017). ML techniques provided the greatest contributions to the development of interventions (48 studies), followed by risk factor identification (33 studies), underlying mechanisms (29 studies), incidence of WMSDs (14 studies), evaluation of interventions (6 studies), and implementation of effective interventions (0 studies). Nearly a quarter (23.8%) of all included studies were published in 2020. These findings provide insight into the breadth of ML techniques used for primary WMSD prevention and can help identify areas for future research and development.

A comparison of augmented feedback and didactic training approaches to reduce spine motion during occupational lifting tasks.

Manual handling training may be improved if it relied on the provision of individualized, augmented feedback about key movement features. The purpose of this study was to compare the reduction in sagittal spine motion during manual lifting tasks following two training approaches: didactic (DID) and augmented feedback (AUG). Untrained participants (n = 26) completed lifting tests (box, medication bag, and paramedic backboard) and a randomly-assigned intervention involving 50 practice box lifts. Lifting tests were performed immediately before and after training, and one-week after interventions. Both groups exhibited reductions in spine motions immediately and one-week after the interventions. However, the AUG intervention group elicited significantly greater reductions in 5 of 12 between-group comparisons (3 tasks × 4 spine motion variables). The results of the current study support the use of augmented feedback-based approaches to manual handling training over education-based approaches.

Chemical Characterization and Evaluation of the Antihyperglycemic Effect of Lychee (Litchi chinensis Sonn.) cv. Brewster.

Lychee is a fruit of Asian origin with an exquisite flavor and an attractive reddish color. However, according to recent reports, the consumption of this fruit reduces the levels of blood glucose with adverse effects on human health such as encephalopathy and hypoglycemic. The objective of this work was to determine if the peel, pulp, and seed of "Brewster" lychee fruits harvested at two stages of maturity had antihyperglycemic effect. This effect was determined by an oral glucose tolerance test using Wistar rats. In addition, ultraviolet-visible spectrophotometry and high-resolution liquid chromatography were used to quantify phenolic compounds, flavonoids, organic acids (OAs), sugars, and antioxidant activity. Results indicated that stage I pulp (immature fruits) and stage II peel and seed (export mature fruits) reduced blood glucose levels, and the effects of the former two were synergistic with metformin. The pulp of mature fruits (stage II), however, lacked a hypoglycemic effect. Additionally, the peel and the seeds of these fruits presented a high antioxidant activity (as determined by DPPH [2,2-diphenyl-2-picryl-hydracyl] and ABTS+ [2,2-azino-bis-(3-ethylbenzothiazoline)-6-sulfonic acid] methods), which correlated well with the total content of phenolic compounds. The highest content of polyphenolics, flavonoids, and OAs was found in the extracts of the peel and seeds of both stages of maturity. It was therefore concluded that "Brewster" mature lychees are safe for human consumption, and both the seed and the peel can be useful sources for obtaining new compounds with antihyperglycemic activity.

Epidemiology of Acute Myocarditis/Pericarditis in Hong Kong Adolescents Following Comirnaty Vaccination.

BACKGROUND: Age-specific incidence of acute myocarditis/pericarditis in adolescents following Comirnaty vaccination in Asia is lacking. This study aimed to study the clinical characteristics and incidence of acute myocarditis/pericarditis among Hong Kong adolescents following Comirnaty vaccination. METHODS: This is a population cohort study in Hong Kong that monitored adverse events following immunization through a pharmacovigilance system for coronavirus disease 2019 (COVID-19) vaccines. All adolescents aged between 12 and 17 years following Comirnaty vaccination were monitored under the COVID-19 vaccine adverse event response and evaluation program. The clinical characteristics and overall incidence of acute myocarditis/pericarditis in adolescents following Comirnaty vaccination were analyzed. RESULTS: Between 14 June 2021 and 4 September 2021, 33 Chinese adolescents who developed acute myocarditis/pericarditis following Comirnaty vaccination were identified. In total, 29 (87.88%) were male and 4 (12.12%) were female, with a median age of 15.25 years. And 27 (81.82%) and 6 (18.18%) cases developed acute myocarditis/pericarditis after receiving the second and first dose, respectively. All cases are mild and required only conservative management. The overall incidence of acute myocarditis/pericarditis was 18.52 (95% confidence interval [CI], 11.67-29.01) per 100 000 persons vaccinated. The incidence after the first and second doses were 3.37 (95% CI, 1.12-9.51) and 21.22 (95% CI, 13.78-32.28 per 100 000 persons vaccinated, respectively. Among male adolescents, the incidence after the first and second doses were 5.57 (95% CI, 2.38-12.53) and 37.32 (95% CI, 26.98-51.25) per 100 000 persons vaccinated. CONCLUSIONS: There is a significant increase in the risk of acute myocarditis/pericarditis following Comirnaty vaccination among Chinese male adolescents, especially after the second dose.