Association of weather variables with pathogens contributing to conjunctivitis worldwide.

PURPOSE: To identify weather variables associated with pathogens contributing to infectious conjunctivitis globally. METHODS: Sample collection and pathogen identification from patients with acute infectious conjunctivitis was performed from 2017 to 2023. We linked pathogens identified from 13 sites across 8 countries with publicly available weather data by geographic coordinates. Mixed effects logistic regression analysis was performed to estimate the associations between temperature, precipitation, and relative humidity exposures, and the prevalence of infection types (RNA virus, DNA virus, bacteria, and fungus). RESULTS: 498 cases from the United States, India, Nepal, Thailand, Burkina Faso, Niger, Vietnam, and Israel were included in the analysis. 8-day average precipitation (mm) was associated with increased odds of RNA virus infection (odds ratio (OR)=1.47, 95% confidence interval (CI): 1.12 to 1.93, P=0.01) and decreased odds of DNA infection (OR=0.62, 95% CI: 0.46 to 0.82, P<0.001). Relative humidity (%) was associated with increased odds of RNA virus infections (OR=2.64, 95% CI: 1.51 to 4.61, P<0.001), and fungal infections (OR=2.35, 95% CI: 1.19 to 4.66, P=0.01), but decreased odds of DNA virus (OR=0.58, 95%CI: 0.37 to 0.90, P=0.02) and bacterial infections (OR=0.42, 95% CI: 0.25 to 0.71, P<0.001). Temperature (°C) was not associated with ocular infections for any pathogen type. CONCLUSIONS: This study suggests that weather factors affect pathogens differently. Particularly, humidity and precipitation were predictors for pathogens contributing to conjunctivitis worldwide. Additional work is needed to clarify the effects of shifts in weather and environmental factors on ocular infectious diseases.

The Impact of Social Media Use on Sleep and Mental Health in Youth: a Scoping Review.

PURPOSE OF REVIEW: Social media use (SMU) and other internet-based technologies are ubiquitous in today's interconnected society, with young people being among the commonest users. Previous literature tends to support that SMU is associated with poor sleep and mental health issues in youth, despite some conflicting findings. In this scoping review, we summarized relevant studies published within the past 3 years, highlighted the impacts of SMU on sleep and mental health in youth, while also examined the possible underlying mechanisms involved. Future direction and intervention on rational use of SMU was discussed. RECENT FINDINGS: Both cross-sectional and longitudinal cohort studies demonstrated the negative impacts of SMU on sleep and mental health, with preliminary evidence indicating potential benefits especially during the COVID period at which social restriction was common. However, the limited longitudinal research has hindered the establishment of directionality and causality in the association among SMU, sleep, and mental health. Recent studies have made advances with a more comprehensive understanding of the impact of SMU on sleep and mental health in youth, which is of public health importance and will contribute to improving sleep and mental health outcomes while promoting rational and beneficial SMU. Future research should include the implementation of cohort studies with representative samples to investigate the directionality and causality of the complex relationships among SMU, sleep, and mental health; the use of validated questionnaires and objective measurements; and the design of randomized controlled interventional trials to reduce overall and problematic SMU that will ultimately enhance sleep and mental health outcomes in youth.

Dose-response effects of exercise and caloric restriction on visceral adiposity in overweight and obese adults: a systematic review and meta-analysis of randomised controlled trials.

OBJECTIVE: To determine and compare the dose-response effects of exercise and caloric restriction on visceral adipose tissue in overweight and obese adults, while controlling for the weekly energy deficit induced by the interventions. METHODS: PubMed, Embase, CINAHL and Web of Science were searched for randomised controlled trials comparing exercise or caloric restriction against eucaloric controls in overweight or obese adults. The primary outcome was the change in visceral fat measured by CT or MRI. Meta-analyses and meta-regressions were performed to determine the overall effect size (ES) and the dose-dependent relationship of exercise and caloric restriction on visceral fat. Heterogeneity, risk of bias and the certainty of evidence were also assessed. RESULTS: Forty randomised controlled trials involving 2190 participants were included. Overall, exercise (ES -0.28 (-0.37 to -0.19); p<0.001; I2=25%) and caloric restriction (ES -0.53 (-0.71 to -0.35); p<0.001; I2=33%) reduced visceral fat compared with the controls. Exercise demonstrated a dose-response effect of -0.15 ((-0.23 to -0.07); p<0.001) per 1000 calories deficit per week, whereas the effect of caloric restriction was not dose-dependent (ES 0.03 (-0.12 to 0.18); p=0.64). Most of the studies showed a moderate risk of bias. CONCLUSIONS: These findings support the dose-dependent effects of exercise to reduce visceral fat in overweight and obese adults. Caloric restriction did not demonstrate a dose-response relationship, although this may be attributed to the smaller number of studies available for analysis, compared with exercise studies. PROSPERO REGISTRATION NUMBER: CRD42020210096.

Effects of Tai Chi and cognitive behavioral therapy for insomnia on improving sleep in older adults: Study protocol for a non-inferiority trial.

Background: Insomnia is a prevailing health problem among older adults. Tai Chi, a popular mind-body exercise practiced by older people in various oriental communities, has been shown to improve sleep. However, Tai Chi has not been directly compared to cognitive behavioral therapy for insomnia (CBT-I), which is the first-line non-pharmacological treatment for insomnia in older adults. This study aims to examine whether Tai Chi is non-inferior to CBT-I as a treatment for insomnia in older adults. Methods: This is a single-center, assessor-blinded, non-inferiority randomized controlled trial comparing Tai Chi and CBT-I in 180 older adults aged ≥50 years with chronic insomnia according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Participants will be randomly assigned to either the Tai Chi or CBT-I group. Interventions will last for 3 months with a 12-month follow-up. The primary outcome is self-perceived insomnia severity measured by Insomnia Severity Index (ISI) at 3 months and at 15 months. The secondary outcomes include the remission rate of chronic insomnia, insomnia treatment response, subjective sleep quantity and quality, 7-day actigraphy, 7-day sleep diary, sleep medication, health-related quality of life, mental health, body balance and lower extremity function, adverse events, habitual physical activity, and dietary intake. Measurements will be conducted at baseline, 3 months, and 15 months by outcome assessors who are blinded to the group allocation. Discussion: This will be the first non-inferiority randomized controlled trial to compare the efficacy and long-term outcomes of Tai Chi versus CBT-I for treating insomnia in older adults. This study will be of clinical importance as it supports the use of Tai Chi as an alternative non-pharmacological approach for insomnia treatment and sustainable management.

Effects of one-year once-weekly high-intensity interval training on body adiposity and liver fat in adults with central obesity: Study protocol for a randomized controlled trial.

Objective: This study aims to examine the effects of one-year, once-weekly high-intensity interval training (HIIT) on body adiposity and liver fat in adults with central obesity. Methods: One-hundred and twenty adults aged 18-60 years with central obesity (body mass index ≥25, waist circumference ≥90 cm for men and ≥80 cm for women). This is an assessor-blinded randomized controlled trial. Participants will be randomly assigned to the HIIT group or the usual care control group. Each HIIT session will consist of 4 × 4-min bouts at 85%-95% maximal heart rate, interspersed with 3-min bouts at 50%-70% maximal heart rate. The HIIT group will complete one session per week for 12 months, whereas the usual care control group will receive health education. The primary outcomes of this study are total body adiposity and intrahepatic triglyceride content. The secondary outcomes include abdominal visceral adipose tissue, subcutaneous adipose tissue, body mass index, waist circumference, hip circumference, cardiorespiratory fitness, lean body mass, bone mineral density, blood pressure, fasting blood glucose, insulin, triglycerides, glycated hemoglobin, cholesterol profile, liver function enzymes, medications, adherence to exercise, adverse events, quality of life, and mental health. Outcome measure will be conducted at baseline, 12 months (post-intervention), and 24 months (one-year follow-up). Impact of the project: This study will explore the benefits of long-term once-weekly HIIT with a follow-up period to assess its effectiveness, adherence, and sustainability. We expect this intervention will enhance the practical suitability of HIIT in inactive adults with central obesity, and provide insights on low-frequency HIIT as a novel exercise option for the management of patients with central obesity and liver fat. Trial registration: ClinicalTrials.gov (NCT03912272) registered on 11 April 2019.

Seventeen-year study shows rise in parapneumonic effusion and empyema with higher treatment failure after chest tube drainage.

AIM: To evaluate epidemiology, pre-admission characteristics and management of paediatric parapneumonic effusions (PPEs) and empyema in a tertiary paediatric pulmonary centre between 1993 and 2010. METHODS: Retrospective chart review study using paediatric and thoracic database searches, with particular emphasis on pre-admission characteristics, disease stage (simple or complex effusion or empyema), general management and surgical procedures. RESULTS: One hundred children were eligible, exhibiting a significant increase in incidence from 0.5 to 2.6 per 100 000 across the study period. Baseline characteristics were similar across disease stages. Streptococcus pneumoniae was the most common pathogen. Surgical intervention beyond chest tube drainage (CTD) was required in 50%; this rate showed a particular increase in children aged 0-5 years (OR, 3.1), but was otherwise not influenced by baseline characteristics, disease stage or use of intrapleural fibrinolytics. Length of hospitalisation did not differ across disease stages or primary interventional procedures. CONCLUSION: This study confirmed an increasing incidence of PPEs and empyema in a Scandinavian tertiary paediatric pulmonary centre. Young children exhibited higher treatment failure after CTD. Length of hospitalisation was similar across disease stages and was comparable to previous reports according to primary interventional procedure.

Human Conjunctival Transcriptome in Acanthamoeba Keratitis: An Exploratory Study.

PURPOSE: The purpose of this study was to identify conjunctival transcriptome differences in patients with Acanthamoeba keratitis compared with keratitis with no known associated pathogen. METHODS: The host conjunctival transcriptome of 9 patients with Acanthamoeba keratitis (AK) is compared with the host conjunctival transcriptome of 13 patients with pathogen-free keratitis. Culture and/or confocal confirmed Acanthamoeba in 8 of 9 participants with AK who underwent metagenomic RNA sequencing as the likely pathogen. Cultures were negative in all 13 cases where metagenomic RNA sequencing did not identify a pathogen. RESULTS: Transcriptome analysis identified 36 genes differently expressed between patients with AK and patients with presumed sterile, or pathogen-free, keratitis. Gene enrichment analysis revealed that some of these genes participate in several biologic pathways important for cellular signaling, ion transport and homeostasis, glucose transport, and mitochondrial metabolism. Notable relatively differentially expressed genes with potential relevance to Acanthamoeba infection included CPS1 , SLC35B4 , STEAP2 , ATP2B2 , NMNAT3 , and AKAP12 . CONCLUSIONS: This research suggests that the local transcriptome in Acanthamoeba keratitis may be sufficiently robust to be detected in the conjunctiva and that corneas infected with Acanthamoeba may be distinguished from the inflamed cornea where no pathogen was identified. Given the low sensitivity for corneal cultures, identification of differentially expressed genes may serve as a suggestive transcriptional signature allowing for a complementary diagnostic technique to identify this blinding parasite. Knowledge of differentially expressed genes may also direct investigation of disease pathophysiology and suggest novel pathways for therapeutic targets.

Etiologies of Infectious Keratitis in Malawi.

Infectious keratitis is a leading cause of corneal blindness worldwide with little information known about causative etiologies in Malawi, Africa. This area is resource-limited with ophthalmologist and microbiology services. The Department of Ophthalmology at the Kamuzu College of Health Sciences in Blantyre, Malawi, is a participating site of an international corneal ulcer consortium, capriCORN (Comprehensive Analysis of Pathogens, Resistomes, and Inflammatory-markers in the CORNea). In this study, 50 patients with corneal ulcers were swabbed for pathogen identification using RNA-sequencing. Corneal trauma was reported in 41% and 19% of the patients worked in agriculture. A pathogen was identified in 58% of the cases. Fungal pathogens predominated, followed by viruses and bacteria. Aspergillus, Fusarium, HSV-1, and Gardnerella were the most common pathogens detected. 50% of patients reported treatment with an antibiotic before presentation. Pathogens unusual for infectious keratitis, such as Subramaniula asteroids, Aureobasidium pullulans, and Gardnerella vaginalis, were also detected.

Coxsackievirus A24 causing acute conjunctivitis in a 2023 outbreak in Vietnam.

OBJECTIVES: To determine the associated pathogen during the 2023 conjunctivitis outbreak in Vietnam METHODS: RNA-sequencing was used to identify pathogens before and during the outbreak. RESULTS: 24 patients with infectious conjunctivitis between March and October 2023 from Hai Yen Vision Institute in Vietnam were swabbed. Coxsackievirus A24v was the most common pathogen identified. Phylogenetic analysis of these strains demonstrates similarities to the Coxsackievirus identified in the 2022 India outbreak. Human adenovirus D was also circulating. Ocular findings of tearing, purulence, and itching were common in this outbreak. CONCLUSIONS: Multiple viruses can co-circulate during conjunctivitis outbreaks. Hemorrhagic conjunctivitis, commonly associated with coxsackievirus conjunctivitis, was not a common clinical sign in this outbreak. Repeat genetic surveillance, with the notable inclusion of RNA virus detection strategies, is important for outbreak detection.

Comparison of moderate and vigorous walking exercise on reducing depression in middle-aged and older adults: A pilot randomized controlled trial.

The optimal intensity of physical activity for alleviating depression in middle-aged and older adults remains unclear. The World Health Organization (WHO) physical activity guidelines recommend adults and older adults to accumulate at least 150-300 minutes of moderate or 75-150 minutes of vigorous aerobic-type physical activity weekly or an equivalent combination of both for health benefits including reduced risk of depression. This parallel, assessor-blinded, pilot randomized controlled trial preliminarily compared the effectiveness of the minimal volume of aerobic-type physical activity at different intensities as recommended by WHO (150 minutes of moderate walking exercise and 75 minutes of vigorous walking exercise weekly) on alleviating depression in middle-aged and older adults. Thirty-five participants were randomized to the control group (CON), moderate walking exercise group (MOD), or vigorous walking exercise group (VIG). The exercise frequency was three times a week and the intervention duration was 12 weeks. The primary outcome was the severity of depression assessed by Beck Depression Inventory. Secondary outcomes included severity of anxiety, sleep quality, quality of life, and cardiorespiratory fitness. Thirty participants completed the study (CON: n = 10, MOD: n = 10, VIG: n = 10). Participants in both MOD and VIG had significantly decreased depression severity after the intervention compared to CON (both p < 0.001). There was no significant difference between MOD and VIG (p = 0.92). Both MOD and VIG interventions also mitigated anxiety severity, improved quality of life and cardiorespiratory fitness. The minimum volume of walking exercise at either moderate or vigorous intensity was found to alleviate depression in middle-aged and older adults.Trial registration: ClinicalTrials.gov identifier: NCT04403373.HighlightsThe 12-week 150-minute moderate walking exercise and 75-minute vigorous walking exercise (the minimal weekly volumes of aerobic-type physical activity recommended by WHO guidelines) similarly reduced the severity of depression in middle-aged and older adults.The 12-week walking exercise interventions significantly reduced anxiety severity concomitant with improved quality of life and cardiorespiratory fitness in middle-aged and older adults with depression.

Effectiveness of Exercise, Cognitive Behavioral Therapy, and Pharmacotherapy on Improving Sleep in Adults with Chronic Insomnia: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials.

Despite the well-established treatment effectiveness of exercise, cognitive behavioral therapy for insomnia (CBT-I), and pharmacotherapy on improving sleep, there have been no studies to compare their long-term effectiveness, which is of clinical importance for sustainable management of chronic insomnia. This study compared the long-term effectiveness of these three interventions on improving sleep in adults with chronic insomnia. MEDLINE, PsycINFO, Embase, and SPORTDiscus were searched for eligible reports. Trials that investigated the long-term effectiveness of these three interventions on improving sleep were included. The post-intervention follow-up of the trial had to be ≥6 months to be eligible. The primary outcome was the long-term effectiveness of the three interventions on improving sleep. Treatment effectiveness was the secondary outcome. A random-effects network meta-analysis was carried out using a frequentist approach. Thirteen trials were included in the study. After an average post-intervention follow-up period of 10.3 months, both exercise (SMD, -0.29; 95% CI, -0.57 to -0.01) and CBT-I (-0.48; -0.68 to -0.28) showed superior long-term effectiveness on improving sleep compared with control. Temazepam was the only included pharmacotherapy, which demonstrated superior treatment effectiveness (-0.80; -1.25 to -0.36) but not long-term effectiveness (0.19; -0.32 to 0.69) compared with control. The findings support the use of both exercise and CBT-I for long-term management of chronic insomnia, while temazepam may be used for short-term treatment.

Heterogenous pathogen profile associated with acute conjunctivitis in Nepal.

BACKGROUND: Infectious conjunctivitis is common in Nepal. MATERIALS AND METHODS: This prospective study recruited 60 patients with presumed acute infectious conjunctivitis from the B.P. Koirala Lions Center for Ophthalmic Studies in Kathmandu, Nepal. Swabs from the conjunctiva and anterior nares were processed for metagenomic RNA deep sequencing (RNA-seq). RESULTS: Pathogens were identified in 55% of cases. RNA viruses were the most common pathogen class identified. Severe acute respiratory syndrome coronavirus 2 was the most common RNA virus identified. CONCLUSIONS: Acute infectious conjunctivitis varies by location. Contrary to expectations, RNA viruses predominated. Repeat surveillance may be useful and RNA-seq allows for detection of the unexpected pathogen including RNA viruses.

Apollo Rising: Acute Conjunctivitis Outbreak in India, 2022.

Purpose: To identify pathogens associated with the 2022 conjunctivitis outbreak in Tamil Nadu, India. Methods: This prospective study was conducted in November of 2022. Patients with presumed acute infectious conjunctivitis presenting to the Aravind Eye Clinic in Madurai, India were eligible. Anterior nares and conjunctival samples from participants were obtained and processed for metagenomic RNA deep sequencing (RNA-seq). Results: Samples from 29 patients were sequenced. A pathogen was identified in 28/29 (97%) patients. Coxsackievirus A24v, a highly infectious RNA virus, was the predominant pathogen and detected in 23/29 patients. Human adenovirus D (HAdV-D), a DNA virus commonly associated with conjunctivitis outbreaks, was detected in the remaining patients (5/29). Hemorrhagic conjunctiva was documented in both HAdV-D and coxsackievirus A24v affected patients but was not the predominant clinical presentation. Phylogenetic analysis of coxsackievirus A24v revealed a recent divergence from the 2015 outbreak. Conclusions: Coxsackievirus A24v and HAdV-D were co-circulating during the 2022 conjunctivitis outbreak in Tamil Nadu, India. Clinical findings were similar between patients with HAD-V and coxsackievirus A24v associated conjunctivitis. As high-throughput technologies become more readily accessible and cost-effective, unbiased pathogen surveillance may prove useful for outbreak surveillance and control.

Pathogen Profiles of Infectious Conjunctivitis in Ho Chi Minh City, Vietnam.

Purpose: Conjunctivitis epidemics and pandemics remain a global burden. This study aims to comprehensively identify pathogens associated with conjunctivitis in Vietnam. Methods: Patients with acute conjunctivitis presented to an outpatient clinic in Ho Chi Minh City, Vietnam, were enrolled from September 2022 to March 2023. Swabs were obtained from conjunctiva and anterior nares of all patients. Unbiased RNA deep sequencing (RNA-seq) was used to identify any replicating pathogens in the samples. Results: Samples from 35 patients were analyzed. A pathogen was identified in 80% of the patients. 72% (95% confidence interval: 54% to 85%) were infected with either HAdV-D or HAdV-B. RNA viruses detected were rhinoviruses and human coronavirus 229E. Bacteria etiologies included Streptococcus pneumoniae, Hemophilus influenza, and Pseudomonas spp. One patient had co-infection of rhinovirus A and HAdV-B. Vittaforma corneae, a fungus, was identified in one patient. Corneal sub-epithelial infiltrates, pseudomembranes, or pre-auricular lymphadenopathy were not reported in any patient. Conclusions: Human adenoviruses are the common circulating pathogens associated with infectious conjunctivitis in Vietnam. HAdV species, however, appear to vary between geographic locations within Vietnam. Other under-recognized pathogens identified in this study, such as RNA viruses, suggest broader pathogen surveillance may be beneficial.

Comprehensive Profile of Pathogens and Antimicrobial Resistance in Conjunctivitis Cases from Niger.

Infectious conjunctivitis outbreaks remain a public health burden. This study focuses on the pathogen and antimicrobial resistance (AMR) profiles identified in Niger. Sixty-two patients with acute infectious conjunctivitis who presented to health posts were enrolled from December 2021 to May 2022. Nasal and conjunctival swabs were obtained from each patient. Unbiased RNA deep sequencing (RNA-seq) was used to identify associated pathogens. A pathogen was identified in 39 patients (63%; 95% CI, 50-74). Of those, an RNA virus was detected in 23 patients (59%; 95% CI, 43-73). RNA viruses were diverse and included human coronaviruses (HCoVs): SARS-CoV-2, HCoV-229E, HCoV-HKU1, and HCoV-OC43. A DNA virus was identified in 11 patients (28%; 95% CI, 17-44). Of those, four patients had a coinfection with an RNA virus and two patients had a coinfection with both an RNA virus and a bacterium. DNA viruses were predominantly human herpesvirus (cytomegalovirus, Epstein-Barr virus, human herpesvirus 8) and human adenovirus species B, C, and F. Eighteen patients (46%; 95% CI, 32-61) had a bacteria-associated infection that included Haemophilus influenza, Haemophilus aegyptius, Staphylococcus aureus, Streptococcus pneumoniae, and Moraxella spp. Antimicrobial resistance determinants were detected in either the conjunctiva or nasal samples of 20 patients (32%; 95% CI, 22-45) and were found to be more diverse in the nose (Shannon alpha diversity, 1.12 [95% CI, 1.05-1.26] versus 1.02 [95% CI, 1.00-1.05], P = 0.01). These results suggest the potential utility of leveraging RNA-seq to surveil pathogens and AMR for ocular infections.

Physical activity and exercise for cancer-related cognitive impairment among individuals affected by childhood cancer: a systematic review and meta-analysis.

BACKGROUND: Individuals affected by childhood cancer can have cognitive dysfunction that persists into adulthood and negatively affects quality of life. In this study, we aimed to evaluate the effects of physical activity and exercise on cognitive function among individuals affected by childhood cancer. METHODS: In this systematic review and meta-analysis, we searched seven databases (CINAHL Plus, Cochrane Library, Embase, MEDLINE, PsycINFO, SPORTDiscus, and Web of Science) and two clinical trial registries (ClinicalTrials.gov and the International Clinical Trials Registry Platform) for randomised controlled trials (RCTs) and non-randomised studies of interventions (NRSIs) published (or registered) from database inception to Jan 30, 2022, with no language restrictions. We included studies that compared the effects of physical activity or exercise interventions with controls (no intervention or usual care) on cognitive function among individuals diagnosed with any type of cancer at age 0-19 years. Two reviewers (JDKB and FR) independently screened records for eligibility and searched references of the selected studies; extracted study-level data from published reports; and assessed study risk of bias of RCTs and NRSIs using the Cochrane risk of bias tool for randomised trials (RoB 2) and Risk Of Bias In Non-randomised Studies-of Interventions (ROBINS-I) tools, certainty of the evidence using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach, and any adverse events. We used intention-to-treat data and unpublished data if available. Cognitive function was assessed by standardised cognitive performance measures (primary outcome) and by validated patient-reported measures (secondary outcome). A random-effects meta-analysis model using the inverse-variance and Hartung-Knapp methods was used to calculate pooled estimates (Hedges' g) and 95% CI values. We estimated the heterogeneity variance by the restricted maximum likelihood method and calculated I2 values to measure heterogeneity. We examined funnel plots and used Egger's regression test to assess for publication bias. This study is registered with PROSPERO, CRD42021261061. FINDINGS: We screened 12 425 titles and abstracts, which resulted in full-text assessment of 131 potentially relevant reports. We evaluated 22 unique studies (16 RCTs and six NRSIs) with data on 1277 individuals affected by childhood cancer and low-to-moderate risk of bias. Of the 1277 individuals, 674 [52·8%] were male and 603 [47·2%] were female; median age at study start was 12 (IQR 11-14) years, median time since the end of cancer treatment was 2·5 (IQR -1·1 to 3·0) years, and median intervention period was 12 [IQR 10-24] weeks. There was moderate-quality evidence that, compared with control, physical activity and exercise improved cognitive performance measures (five RCTs; Hedges' g 0·40 [95% CI 0·07-0·73], p=0·027; I2=18%) and patient-reported measures of cognitive function (13 RCTs; Hedges' g 0·26 [0·09-0·43], p=0·0070; I2=40%). No evidence of publication bias was found. Nine mild adverse events were reported. INTERPRETATION: There is moderate-certainty evidence that physical activity and exercise improves cognitive function among individuals affected by childhood cancer, which supports the use of physical activity for managing cancer-related cognitive impairment. FUNDING: Research Impact Fund of Research Grants Council of the Hong Kong University Grants Committee (R7024-20) and Seed Fund for Basic Research of the University of Hong Kong. COPYRIGHT: © 2022 Published by Elsevier Ltd. All rights reserved.

Effects of exercise intensity and frequency on improving cognitive performance in middle-aged and older adults with mild cognitive impairment: A pilot randomized controlled trial on the minimum physical activity recommendation from WHO.

Background: The World Health Organization physical activity guidelines recommend adults and older adults to accumulate at least 150-300 min of moderate or 75-150 min of vigorous aerobic-type physical activity weekly for health benefits including improvements of cognitive performance. However, the optimal exercise intensity and frequency for maximizing the cognitive benefits remain unclear. Purpose: We conducted a parallel, assessor-blinded, pilot randomized controlled trial to evaluate the effectiveness of different intensities and frequencies of the WHO-recommended minimal volume of aerobic-type physical activity on improving cognitive performance in middle-aged and older adults with mild cognitive impairment (MCI). Methods: Participants were randomly allocated to the stretching exercise control group (CON), once-a-week and thrice-a-week moderate-intensity walking groups (M1 and M3), and once-a-week and thrice-a-week vigorous-intensity walking groups (V1 and V3). Intervention duration was 12 weeks. The primary outcome was global cognitive performance assessed by the Hong Kong version of Montreal Cognitive Assessment. Secondary outcomes were self-report and objective cognitive performances, mental health, sleep quality, and cardiorespiratory fitness. Results: Thirty-seven participants completed the study (CON: n = 7, M1: n = 7, M3: n = 7, V1: n = 8, V3: n = 8). Participants in all four walking exercise groups demonstrated significant improvements in global cognitive performance assessed by the Hong Kong version of the Montreal Cognitive Assessment after the intervention when compared to CON (p < 0.001). The walking exercise interventions also significantly mitigated the anxiety severity (p < 0.005) and improved the cardiorespiratory fitness (p < 0.05) of the participants in the walking exercise groups. Conclusion: 150-min moderate- or 75-min vigorous-intensity walking exercise performed once- or thrice-weekly showed similar effects on improving cognitive performance in middle-aged and older adults with MCI. The 12-week walking exercise interventions also reduced anxiety severity and improved cardiorespiratory fitness of the participants. Clinical Trial Registration: clinicaltrials.gov, identifier NCT04515563.

Tai Chi versus conventional exercise for improving cognitive function in older adults: a pilot randomized controlled trial.

Studies have shown that Tai Chi and conventional exercise can modify the brain through distinct mechanisms, resulting in different brain adaptations. Therefore, it is conceivable to speculate that these two exercise modalities may have different effects on improving cognitive function. This study was a parallel group, assessor-blinded, pilot randomized controlled trial comparing the effects of Tai Chi and conventional exercise on improving cognitive function in older persons with mild cognitive impairment (MCI). A total of 34 adults aged ≥ 50 years with MCI were randomized (1:1:1) to the Tai Chi group (TC, n = 10, 3 sessions of 60-min Yang-style Tai Chi training per week for 24 weeks), conventional exercise group (EX: n = 12, 3 sessions of 60-min fitness training per week for 24 weeks), or control group (CON: n = 12, no intervention). Global cognitive function assessed by the Hong Kong version of the Montreal Cognitive Assessment (MoCA-HK) and performance in various cognitive domains were examined at baseline, and 12 and 24 weeks of the intervention. Both exercise groups showed improved global cognitive function as measured by MoCA-HK compared with the control group after 12 and 24 weeks of the intervention, (all P < 0.001). Only TC achieved clinically relevant improvement on global cognitive function at week 12. Both exercise groups achieved clinically relevant improvements at the end of the interventions at week 24. Compared with EX, TC exhibited greater improvements on global cognitive function indicated by MoCA-HK after 12 weeks of the intervention (P < 0.001) and cognitive flexibility indicated by part B/A ratio score of the Trail Making Test throughout the study (all P < 0.05). Both interventions were equally effective in improving the other examined cognitive domains. Further studies are needed to substantiate the superior long-term benefits of Tai Chi on global cognitive function compared with conventional exercise, and dissect the underlying mechanisms of the two exercises on improving cognitive domains and the corresponding brain adaptations. Trial registration: This study was registered at clinicaltrials.gov (Trial registration number: NCT04248400; first registration date: 30/01/2020).

Short-chain fatty acid level and field cancerization show opposing associations with enteroendocrine cell number and neuropilin expression in patients with colorectal adenoma.

BACKGROUND: Previous reports have suggested that the VEGF receptor neuropilin-1 (NRP-1) is expressed in a singly dispersed subpopulation of cells in the normal colonic epithelium, but that expression becomes dysregulated during colorectal carcinogenesis, with higher levels in tumour suggestive of a poor prognosis. We noted that the spatial distribution and morphology if NRP-1 expressing cells resembles that of enteroendocrine cells (EEC) which are altered in response to disease state including cancer and irritable bowel syndrome (IBS). We have shown that NRP-1 is down-regulated by butyrate in colon cancer cell lines in vitro and we hypothesized that butyrate produced in the lumen would have an analogous effect on the colon mucosa in vivo. Therefore we sought to investigate whether NRP-1 is expressed in EEC and how NRP-1 and EEC respond to butyrate and other short-chain fatty acids (SCFA - principally acetate and propionate). Additionally we sought to assess whether there is a field effect around adenomas. METHODOLOGY: Biopsies were collected at the mid-sigmoid, at the adenoma and at the contralateral wall (field) of 28 subjects during endoscopy. Samples were fixed for IHC and stained for either NRP-1 or for chromogranin A (CgA), a marker of EEC. Stool sampling was undertaken to assess individuals' butyrate, acetate and propionate levels. RESULT: NRP-1 expression was inversely related to SCFA concentration at the colon landmark (mid-sigmoid), but expression was lower and not related to SCFA concentration at the field. Likewise CgA+ cell number was also inversely related to SCFA at the landmark, but was lower and unresponsive at the field. Crypt cellularity was unaltered by field effect. A colocalisation analysis showed only a small subset of NRP-1 localised with CgA. Adenomas showed extensive, weaker staining for NRP-1 which contrastingly correlated positively with butyrate level. Field effects cause this relationship to be lost. Adenoma tissue shows dissociation of the co-regulation of NRP-1 and EEC. CONCLUSION: NRP-1 is inversely associated with levels of butyrate and other SCFA in vivo and is expressed in a subset of CgA expressing cells. EEC number is related to butyrate level in the same way.

Human pluripotent stem cell-derived DDX4 and KRT-8 positive cells participate in ovarian follicle-like structure formation.

Understanding the mechanisms of human pluripotent stem cells (hPSCs) specification, development and differentiation to gametes are useful for elucidating the causes of infertility and potential treatment. This study aims to examine whether hPSCs can be induced to DDX4 extracellularly expressing primordial germ cell-like cells (DDX4ec PGCLCs) and further into ovarian follicle stage in a combined in vitro and in vivo model. The transcriptional signatures show that these DDX4ec PGCLCs are characteristic of PGCs and express ovarian folliculogenesis markers. We also verify that keratin (KRT)-8 is highly expressed in the DDX4ec PGCLCs and plays a crucial role in germ cell migration. By co-culturing DDX4ec PGCLCs with human granulosa cells (GCs), these cells are further induced into ovarian follicle-like structures in a xenograft mice model. This approach can in the future design practical strategies for treating germ cell-associated issues of infertility.