Dynamics of childhood obesity in Hong Kong throughout the COVID-19 pandemic before and after the school closures: a 3-year longitudinal study.

OBJECTIVE: This study is to evaluate if there is any difference in the balance between incidence of and remission from overweight/obesity in Hong Kong school-age children before and during the COVID-19 pandemic over three years. METHODS: This is a retrospective longitudinal study that involved children aged 6-16 years from a database of the School Physical Fitness Award Scheme. RESULTS: 2765 students were longitudinally followed up for two years. The prevalence of childhood overweight/obesity was increased between the 2019 and 2021 academic years (P < 0.001). During the COVID-19 pandemic, the rate of obesity remission significantly reduced by 7.9 % (P = 0.003), at a background of a plateau of obesity among children and adolescents. CONCLUSIONS: Our study provides evidence on the impact of school closure and home confinement as a standard infection control measure for the prevention of COVID-19, which are likely to break the balance between incidence of and remission from childhood obesity.

Cataract risk of neuro-interventional procedures: a nationwide population-based matched-cohort study.

AIM: To demonstrate the risk of cataract associated with radiation exposure from neuro-interventional procedures. MATERIALS AND METHODS: This was a nationwide population-based, matched-cohort study. The exposed group (group E) comprised patients diagnosed with an aneurysm, cerebrovascular system anomaly, or subarachnoid haemorrhage who underwent a neuro-interventional procedure, such as brain digital subtraction angiography or endovascular embolisation. The comparison group (group C) included subjects who were never exposed to radiation from neuro-interventional procedures and were propensity score-matched by the date of enrolment, age, sex, and associated comorbidities. Multiple Cox proportional hazard regression analysis was used to estimate the hazard ratio (HR) of cataract risk due to radiation exposure while adjusting for potential confounding factors. RESULTS: There were 838 patients and 3,352 matched subjects in groups E and C, respectively. The incidence of cataracts was significantly greater among subjects in group E (adjusted HR [aHR] = 1.88; 95% confidence interval [CI] = 1.08-3.26), especially those aged >40 years (aHR = 2.14; 95% CI = 1.16-3.94). The number of computed tomography examinations was positively correlated, but not statistically significant, with an increased risk of cataract occurrence. CONCLUSIONS: Neuro-interventional procedures might be significantly associated with an increased risk of cataract occurrence.

A prospective randomized controlled trial evaluating the short-term outcomes of transanal hemorrhoidal dearterialization versus tissue-selecting technique.

BACKGROUND: Tissue-selecting technique (TST) is a novel stapled hemorrhoidectomy technique which targets the hemorrhoids, leaving uninvolved mucosal bridges intact and avoiding circumferential circular stapling. The aim of this study was to compare the short-term outcomes of TST and transanal hemorrhoidal dearterialization (THD). METHODS: Patients presenting with symptomatic hemorrhoids were recruited. Patients were randomized into two groups: (1) TST and (2) THD. Patient demographics, perioperative data, postoperative pain scores, recurrence and patient satisfaction scores were evaluated. Patients with acute thrombosed hemorrhoids, external hemorrhoids only, or other concomitant anal diseases were excluded. RESULTS: From January 2013 to December 2015, 80 patients were included in the study, 40 in each group. There were no significant differences between groups as regards demographic data, perioperative data and postoperative pain scores. The median symptom scores for bleeding and prolapse were significantly lower in the TST group at 1 year (bleeding 1 vs. 2, p = 0.001; prolapse 1 vs. 2, p = 0.025). There was significantly less recurrence requiring reintervention in the TST group (4/40 vs. 17/40, p = 0.001). Satisfaction was significantly greater after TST. The median satisfaction scores after TST and THD were 4 and 3 (on a scale of 1-4; 4 = excellent satisfaction) (p < 0.00001), respectively. CONCLUSIONS: Both THD and TST are safe, and they appear to have similar short-term outcomes; however, TST is associated with better improvement in symptoms, lower recurrence rates and greater patient satisfaction.

Effects of Gender Difference and Caffeine Supplementation on Anaerobic Muscle Performance.

The primary purpose of this study was to investigate the effects of gender difference and caffeine supplementation to maximal voluntary isometric contractions (MVIC) and submaximal voluntary isometric contractions (T(lim)). 10 male (age: 20.10 ± 2.18 years, BMI: 22.23±1.96 kg/m(2)) and 10 female (age: 19.90±0.99 years, BMI: 21.76±2.65 kg/m(2)) elite collegiate athletes were recruited. Subjects ingested caffeine (6 mg/kg) or a placebo in a randomized, double-blind, placebo-control, and counter-balanced fashion. MVIC and T(lim) were measured after supplementations. T(lim) result was calculated based on the time to exhaustion of isometric contraction with 50% MVIC. Fatigue index (FI%) referred to the MVIC tested 20 s after the cessation of T(lim) test, and was indexed by the percentage of MVIC decline. No significant interaction effect was found between the gender factor and the supplementation factor for all dependent variables. Compared to the placebo, caffeine supplementation significantly increased MVIC (5.9%) and T(lim) (15.5%) (p<0.05) whereas it had no significant effect on FI%. This study demonstrates that caffeine supplementation at a 6 mg/kg dosage facilitates performances in MVIC and T(lim). The ergogenic effect of caffeine on muscle power and muscle endurance does not show a gender bias.

A new groin hernia classification with clinical relevance.

INTRODUCTION: Groin hernia is one of the most commonly managed surgical diseases around the world. The typical question asked by patients is "Does my hernia require urgent surgery?". The currently available classifications are insufficient to stratify patients into different groups. We propose a new classification that incorporates diverse clinical elements together with anatomical and other vital information, which allows us to stratify patients into different groups. METHOD: A task force was formed by the Hong Kong Hernia Society, working with international expert hernia surgeons. The framework of the classification system was formulated. Clinical elements that are important in groin disease stratification were identified. A comprehensive literature review was conducted using PubMed. Those which dictate the severity of the disease were selected and compiled to form the new proposed classification. Application of this classification model to a single hernia surgeon's registry in The Hong Kong Adventist Hospital Hernia Centre was done for initial evaluation. RESULT: This new classification incorporates important clinical characteristics forming a total of nine grades of differentiation, together with the anatomical details and special information. This comprehensive system allows the stratification of patients into different groups based on disease severity. It also enables more accurate data collection for future audits, comparisons of disease progression over time, and the effect of different management strategies for different-stage patients. CONCLUSION: This is the first classification system which incorporates essential clinical parameters, which allows the stratification of groin hernia into different stages. Further studies and validation should be performed to evaluate the usefulness and value of this classification in groin hernia management.

GSTP1 is a hub gene for gene-air pollution interactions on childhood asthma.

There is growing evidence that multiple genes and air pollutants are associated with asthma. By identifying the effect of air pollution on the general population, the effects of air pollution on childhood asthma can be better understood. We conducted the Taiwan Children Health Study (TCHS) to investigate the influence of gene-air pollution interactions on childhood asthma. Complete monitoring data for the ambient air pollutants were collected from Taiwan Environmental Protection Agency air monitoring stations. Our results show a significant two-way gene-air pollution interaction between glutathione S-transferase P (GSTP1) and PM10 on the risk of childhood asthma. Interactions between GSTP1 and different types of air pollutants have a higher information gain than other gene-air pollutant combinations. Our study suggests that interaction between GSTP1 and PM10 is the most influential gene-air pollution interaction model on childhood asthma. The different types of air pollution combined with the GSTP1 gene may alter the susceptibility to childhood asthma. It implies that GSTP1 is an important hub gene in the anti-oxidative pathway that buffers the harmful effects of air pollution.

Spontaneous autoimmune gastritis and hypochlorhydria are manifest in the ileitis-prone SAMP1/YitFcs mice.

SAMP1/YitFcs mice serve as a model of Crohn's disease, and we have used them to assess gastritis. Gastritis was compared in SAMP1/YitFcs, AKR, and C57BL/6 mice by histology, immunohistochemistry, and flow cytometry. Gastric acid secretion was measured in ligated stomachs, while anti-parietal cell antibodies were assayed by immunofluorescence and enzyme-linked immunosorbent spot assay. SAMP1/YitFcs mice display a corpus-dominant, chronic gastritis with multifocal aggregates of mononuclear cells consisting of T and B lymphocytes. Relatively few aggregates were observed elsewhere in the stomach. The infiltrates in the oxyntic mucosa were associated with the loss of parietal cell mass. AKR mice, the founder strain of the SAMP1/YitFcs, also have gastritis, although they do not develop ileitis. Genetic studies using SAMP1/YitFcs-C57BL/6 congenic mice showed that the genetic regions regulating ileitis had comparable effects on gastritis. The majority of the cells in the aggregates expressed the T cell marker CD3 or the B cell marker B220. Adoptive transfer of SAMP1/YitFcs CD4(+) T helper cells, with or without B cells, into immunodeficient recipients induced a pangastritis and duodenitis. SAMP1/YitFcs and AKR mice manifest hypochlorhydria and anti-parietal cell antibodies. These data suggest that common genetic factors controlling gastroenteric disease in SAMP1/YitFcs mice regulate distinct pathogenic mechanisms causing inflammation in separate sites within the digestive tract.

Glutathione S-transferase, incense burning and asthma in children.

Incense burning is a popular practice in many family homes and temples. However, little is known about the effects of indoor incense burning and genetic polymorphisms on asthma. This study evaluated the effects of indoor incense burning and glutathione S-transferase (GST) genetic polymorphisms on asthma and wheeze. In 2007, 3,764 seventh-grade schoolchildren (mean±sd age 12.42±0.65 yrs) were evaluated using a standard questionnaire for information about respiratory symptoms and environmental exposures. Multiple logistic regressions were performed to assess the association between GST polymorphisms and incense burning frequency on asthma and wheeze, after adjusting for potential confounders. The frequency of incense burning at home was associated with increased risk of current asthma (p=0.05), medication use (p=0.03) and exercise wheeze (p=0.001). GST1 (GSTT1) null genotypes were associated with current asthma (OR 1.43, 95% CI 1.00-2.04) and medication use (OR 1.46, 95% CI 1.01-2.22). GSTT1 showed a significant interactive effect with incense burning on current asthma, current wheeze and nocturnal wheeze. The frequency of incense burning was associated with increased risk of current asthma, medication use, lifetime wheeze, nocturnal wheeze and exercise wheeze in an exposure-response manner among children with GSTT1 null genotype (p<0.05). Incense burning is a risk factor for asthma and wheezing, especially in GSTT1 genetically susceptible children.

Aod2, the locus controlling development of atrophy in neonatal thymectomy-induced autoimmune ovarian dysgenesis, co-localizes with Il2, Fgfb, and Idd3.

In genetically susceptible strains of mice, such as A/J and (C57BL/6J x A/J)F1 hybrids, neonatal thymectomy-induced autoimmune ovarian dysgenesis (AOD) is characterized by the development of antiovarian autoantibodies, oophoritis, and atrophy. Temporally, atrophy may be observed during and after the regression of inflammatory infiltrates from the ovary. Histologically, lesions appear as areas devoid of ovarian follicles in all stages of development that have been replaced by luteinized interstitial cells. We report here the mapping of Aod2, the locus that controls this phenotype, to mouse chromosomes 3 within a region encoding Il2 and Fgfb. Most significant, however, is the co-localization of Aod2 to Idd3, a susceptibility gene that plays a role in autoimmune insulin-dependent type 1 diabetes mellitus in the nonobese diabetic mouse.

The relative contribution of the CD28 and gp39 costimulatory pathways in the clonal expansion and pathogenic acquisition of self-reactive T cells.

The zona pellucida (ZP), an ovarian extracellular structure, contains three major glycoproteins: ZP1, ZP2, and ZP3. A ZP3 peptide contains both an autoimmune oophoritis-inducing T cell epitope and a B cell epitope that induces autoantibody to ZP. This study investigates two major T cell costimulation pathways in this disease model. Herein we show that blockage of glycoprotein (gp)39 and CD40 interaction with gp39 monoclonal antibody (mAb) results in the failure to induce both autoimmune oophoritis and autoantibody production. Inhibition of ligand binding to the CD28 receptor with the fusion protein, murine CTLA4-immunoglobulin (Ig), also results in failure to generate antibody to ZP and significantly reduces disease severity and prevalence. Surprisingly, the frequencies of antigen-specific T cells in anti-gp39 mAb-treated mice, CTLA4-Ig treated mice, and in mice given control hamster IgG or control fusion protein L6, were equivalent as determined by limiting dilution analysis (approximately equals 1:5,000). These T cells, which produced comparable amounts of interleukin 4 and interferon gamma in vitro, were able to transfer oophoritis to normal recipients. When anti-gp39 mAb and CTLA4-Ig were given together, the effect was additive, leading to inhibition of T cell activation as determined by in vitro proliferation and limiting dilution analysis (approximately equals 1:190,000); disease and antibody responses were absent in these mice. By studying these two costimulatory pathways in parallel, we have shown that autoimmune disease and autoantibody production are inhibitable by blocking either the gp39 or the CD28 pathway, whereas inhibition of clonal expansion of the effector T cell population occurs only when both pathways are blocked.

The black mink (Mustela vison). A natural model of immunologic male infertility.

Breeding for fine black fur has generated a colony of mink wherein 20-30% of the males are infertile. Two clinical groups are distinguishable: one being infertile from the start (primary infertility), and the other infertile after one or more years of fertility (secondary fertility). Although the etiology of primary infertility is unknown, the available data indicate that secondary infertility is associated with an autoimmune disease of the testis. Thus, male mink with secondary infertility have (a) higher prevalence and levels of anti-sperm antibody when compared with animals with primary infertility, and the antibody prevalence varies with fur color; (b) severe monocytic orchitis (47%) and/or aspermatogenesis (75%) with negative cultures for bacterial, fungal, mumps, or Coxsackie B viral organisms; (c) massive and extensive granular deposits of mink IgG and/or C3 (71%), typical of immune complexes, along the basal lamina of seminiferous tubules; (d) testes that when eluted with buffer or low pH yielded IgG that was 10-fold enriched in anti-sperm antibody activity as compared with serum IgG; and (e) no immunopathologic evidence of Aleutian mink disease. Although the sperm antigen-antibody complexes in the testis may be important as a pathogenetic mechanism of the testicular disease, there is no correlation between fluorescent anti-sperm antibody detection in the serum and the infertile state. The infertile black mink is a new model of infertility associated with naturally occurring autoimmune disease of the testis.

Increased turnover of T lymphocytes in HIV-1 infection and its reduction by antiretroviral therapy.

The mechanism of CD4(+) T cell depletion in human immunodeficiency virus (HIV)-1 infection remains controversial. Using deuterated glucose to label the DNA of proliferating cells in vivo, we studied T cell dynamics in four normal subjects and seven HIV-1-infected patients naive to antiretroviral drugs. The results were analyzed using a newly developed mathematical model to determine fractional rates of lymphocyte proliferation and death. In CD4(+) T cells, mean proliferation and death rates were elevated by 6.3- and 2.9-fold, respectively, in infected patients compared with normal controls. In CD8(+) T cells, the mean proliferation rate was 7.7-fold higher in HIV-1 infection, but the mean death rate was not significantly increased. Five of the infected patients underwent subsequent deuterated glucose labeling studies after initiating antiretroviral therapy. The lymphocyte proliferation and death rates in both CD4(+) and CD8(+) cell populations were substantially reduced by 5-11 weeks and nearly normal by one year. Taken together, these new findings strongly indicate that CD4(+) lymphocyte depletion seen in AIDS is primarily a consequence of increased cellular destruction, not decreased cellular production.

Immune responses to Ro60 and its peptides in mice. I. The nature of the immunogen and endogenous autoantigen determine the specificities of the induced autoantibodies.

Anti-Ro60 autoantibodies are found in a variety of autoimmune disorders including systemic lupus erythematosus (SLE), Sjögren's syndrome, primary biliary cirrhosis, and active hepatitis. They are the most prevalent autoantibodies in normal individuals and in asymptomatic mothers of infants afflicted with neonatal lupus. In the present study, immune responses to recombinant human Ro60 (rhRo60) and recombinant mouse Ro60 (rmRo60) and selected Ro60 peptides in non-SLE-prone mice were investigated. Multiple T and B cell epitopes were identified in Ro60. Immunizations with either xenogeneic or autologous Ro60 induced autoantibodies to a diverse group of autoantigens. In addition to La and Ro52, proteins in the small nuclear ribonucleoprotein (snRNP) particles such as SmA, SmB, SmD, and 70-kD U1-RNP were unexpectedly identified as targeted antigens. In the studies involving synthetic Ro60 peptides, both human and mouse Ro60316-335 peptides, which differ in three amino acids, were found to contain dominant cross-reactive T cell determinants. Immunizations with these peptides induced autoantibodies to Ro60, La, SmD, and 70-kD U1-RNP without autoantibodies to Ro52, SmA, or SmB. With human Ro60316-335 as the immunogen, additional autoantibodies reactive with the Golgi complex were found. In contrast to the immunodominance of both human and mouse Ro60316-335 peptides, the T cell determinant in human Ro60441-465 was dominant, whereas that in the mouse peptide was cryptic. Immunization with human Ro60441-465 induced primarily anti-peptide Abs. Mouse Ro60441-465 failed to induce an antibody response. These results show that both the nature of the immunogen and the immunogenicity of the related endogenous antigen are important in determining the specificities of the autoantibodies generated. They have significant implications for proposed mechanisms on the generation of complex patterns of autoantibodies to a diverse group of autoantigens in SLE patients.

Correlation between Klebsiella pneumoniae carrying pLVPK-derived loci and abscess formation.

Klebsiella pneumoniae-caused liver abscess (KLA) is an emerging infectious disease. However, factors other than K1-specific loci that contribute to the pathogenesis of this disease have not been identified. pLVPK is a 219,385-bp plasmid of K. pneumoniae CG43, an invasive K2 strain associated with KLA. We aimed in this study to evaluate the involvement of pLVPK in K. pneumoniae virulence and its clinical significance in abscess formation. A pLVPK-cured CG43 was isolated and its virulence was examined in a mouse model. The prevalence of pLVPK-derived loci terW, iutA, rmpA, silS, and repA was investigated in 207 clinical isolates by screening with specific primers. Loss of pLVPK abolished the ability of K. pneumoniae to disseminate into extraintestinal sites and, consequently, attenuated abscess formation in mice. Primary K. pneumoniae abscess isolates (n = 94) were more likely to be terW (+)-iutA (+)-rmpA (+)-silS (+) than those related to non-abscess infections (n = 113) (62% vs. 27%; p < 0.0001). Logistic regression analysis indicated that the presence of the terW-rmpA-iutA-silS loci was a significant risk factor (odds ratio, 4.12; 95% confidence interval, 2.02-8.4; p < 0.0001) for abscess formation. pLVPK is a determinant for K. pneumoniae virulence and infection with strains carrying the pLVPK-derived terW-rmpA-iutA-silS loci may predispose patients to abscess formation.

Allergic orchitis lesions are adoptively transferred from vasoligated guinea pigs to syngeneic recipients.

Histopathology typical of allergic orchitis developed in testes of inbred guinea pigs 16 months after vasoligation. A similar histopathology was found in unoperated testes after unilateral vasoligation. Peritoneal exudate cells from vasoligated guinea pigs transferred identical lesions to syngeneic recipients. The testicular lesions in long-term vasoligated guinea pigs have an immunological basis.

Autoantibodies from vasectomized guinea pigs inhibit fertilization in vitro.

Immunoglobulin G and Fab antibodies were isolated from the serum of vasectomized guinea pigs, and the effects of the antibodies on fertilization in vitro were investigated. These antibodies had profound inhibitory effects on (i) sperm-to-sperm adhesion, (ii) the acrosome reaction, (iii) sperm-zona binding, and (iv) sperm-ovum fusion. This finding may explain certain cases of infertility after vasovasostomy in men.

Neonatal thymectomy results in a repertoire enriched in T cells deleted in adult thymus.

In B6AF1 mice, T lymphocytes that use the V beta 11-positive (and not V beta 6-positive or V beta 8-positive) segment in their receptor for antigen are greatly reduced in the thymus and peripheral lymphoid tissues, most likely as a result of clonal deletion. The relative number of V beta 11-positive cells in adult lymph nodes was ten times as high in B6AF1 mice thymectomized 1 to 4 days after birth as in normal mice. Moreover, for the first 10 days of life of B6AF1 mice, mature V beta 11-positive T cells were readily detected in the thymus and spleen. Thus neonatal thymectomy results in the maintenance of the receptor repertoire of early postnatal life, and this correlates with the subsequent development of organ-specific autoimmune diseases.

Bax-deficient mice with lymphoid hyperplasia and male germ cell death.

BAX, a heterodimeric partner of BCL2, counters BCL2 and promotes apoptosis in gain-of-function experiments. A Bax knockout mouse was generated that proved viable but displayed lineage-specific aberrations in cell death. Thymocytes and B cells in this mouse displayed hyperplasia, and Bax-deficient ovaries contained unusual atretic follicles with excess granulosa cells. In contrast, Bax-deficient males were infertile as a result of disordered seminiferous tubules with an accumulation of atypical premeiotic germ cells, but no mature haploid sperm. Multinucleated giant cells and dysplastic cells accompanied massive cell death. Thus, the loss of Bax results in hyperplasia or hypoplasia, depending on the cellular context.

Impact of integrated PET/CT in the staging of oesophageal cancer: a UK population-based cohort study.

AIM: To document the impact of integrated positron-emission tomography and computed tomography (PET/CT) on the management of a cohort of UK patients undergoing PET/CT as part of their staging investigations for potentially curable oesophageal cancer. MATERIALS AND METHODS: A multicentre, prospective study of newly diagnosed patients with oesophageal cancer undergoing PET/CT was set up across five cancer networks covering a total population of 6.6 million. Data were prospectively collected for cases diagnosed between 1 November 2006 and 31 October 2007. RESULTS: One hundred and ninety-one patients underwent PET/CT, with 31 (16%) positive for possible metastatic disease. Amongst the 31 positive examinations, 18 (9.4%) were confirmed to have metastatic disease, and 13 (6.5%) patients had no subsequent evidence of metastatic disease, although in three (1.6%) of these a second previously unsuspected pathology was diagnosed. Two patients had false-negative PET/CT and were found to have metastatic disease. The results of the PET/CT examination down-staged 10 (5%) patients thought to have coeliac/M1a node involvement on CT. Fifteen of 110 (13%) patients with stage 3 or 4 disease at CT and endoscopic ultrasound (EUS) had confirmed metastatic disease at PET/CT, compared with none of 18 with stage 2b, three of 52 (6%) with stage 2a, and none of 10 with stage 1 disease. CONCLUSION: This study confirms the role of PET/CT in a multicentre UK setting in the management of patients with potentially curable carcinoma of the oesophagus, improving the accuracy of pre-treatment staging compared with CT and EUS alone. Early tumours infrequently show evidence of metastasis on PET/CT, although further data are required to confidently determine the stage of tumours where PET/CT has no additional value.

Construction and analysis of a modular model of caspase activation in apoptosis.

BACKGROUND: A key physiological mechanism employed by multicellular organisms is apoptosis, or programmed cell death. Apoptosis is triggered by the activation of caspases in response to both extracellular (extrinsic) and intracellular (intrinsic) signals. The extrinsic and intrinsic pathways are characterized by the formation of the death-inducing signaling complex (DISC) and the apoptosome, respectively; both the DISC and the apoptosome are oligomers with complex formation dynamics. Additionally, the extrinsic and intrinsic pathways are coupled through the mitochondrial apoptosis-induced channel via the Bcl-2 family of proteins. RESULTS: A model of caspase activation is constructed and analyzed. The apoptosis signaling network is simplified through modularization methodologies and equilibrium abstractions for three functional modules. The mathematical model is composed of a system of ordinary differential equations which is numerically solved. Multiple linear regression analysis investigates the role of each module and reduced models are constructed to identify key contributions of the extrinsic and intrinsic pathways in triggering apoptosis for different cell lines. CONCLUSION: Through linear regression techniques, we identified the feedbacks, dissociation of complexes, and negative regulators as the key components in apoptosis. The analysis and reduced models for our model formulation reveal that the chosen cell lines predominately exhibit strong extrinsic caspase, typical of type I cell, behavior. Furthermore, under the simplified model framework, the selected cells lines exhibit different modes by which caspase activation may occur. Finally the proposed modularized model of apoptosis may generalize behavior for additional cells and tissues, specifically identifying and predicting components responsible for the transition from type I to type II cell behavior.