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To provide an update on insights into the effectiveness of the green environment and forest on the mental health of city dwellers; and the role of mental health professionals in advocating green restorative therapies.The studies reviewed in this paper confirmed the mental health benefits on individuals who engaged in the green environment and forest. Results of studies showed that the participants reported significantly higher positive effects. However, it is difficult to compare studies because of marked differences in methodology and often lack of biological markers. With the recent global concern about climate warming, mental health professionals have a critical role to influence city planners on the importance of the green environment and the forest. In Singapore, the 'Therapeutic Garden' project and 'Therapeutic Rainforest' program are examples of mental health professionals working with government agencies for a 'city in nature'.The benefits of the green environment and forest are emphasized especially on the psychological well being. In the light of the danger of climate warming, this review highlights the need for city planners to collaborate with mental health professionals to incorporate high-quality green spaces when planning the city of the future. There is an urgent need for better consultation between health agencies and local city government to create an appealing and diverse green environment within the city.

Background Barrett's oesophagus (BO) is known precursor of oesophageal adenocarcinoma (EAC). Early EAC includes T1a (invasion into mucosa) and T1b (invasion into submucosa but not muscularis propria). Endoscopic mucosal resection (EMR) provides accurate histological staging and definitive treatment for early EAC. Post EMR, the remaining Barrett's is eradicated with radiofrequency ablation (RFA). However, there is a paucity of long-term Australian data. Aims To investigate the efficacy and long-term outcomes of EMR and RFA in management of early EAC. Methods Retrospective analysis of patients early EAC treated endoscopically at three Western Australian tertiary centres, with at least 12-months follow-up, over last 10-years. Results Sixty-seven patients with early EAC (61 T1a and 6 T1b) were treated with EMR. Complete Barrett's eradication was done by EMR in 31/67 patients whereas 36/67 patients underwent RFA for residual Barrett's. EMR changed pinch biopsy histology from HGD (n=33), HGD suspicious for IMC (n=5) and LGD (n=1) to early EAC in 58.2% (n=39) patients. During a mean follow-up of 37.2 months (IQR 20, 56), complete remission of dysplasia (CRD) and intestinal metaplasia (CRIM) was seen in 97% (n=65) and 89.5% (n=60) patients. One patient with T1b EAC underwent oesophagectomy. No cases developed metachronous EAC, progression to invasive adenocarcinoma or development of nodal/distant metastasis. Complications were endoscopically treated haematemesis (n=1) and strictures (n=16) requiring dilatations. 3 patients died due to causes unrelated to IMC. Conclusion EMR in conjunction with RFA is an effective and safe management for early EAC. EMR provides accurate staging and has low complication rates. This article is protected by copyright. All rights reserved.

The human PDZome represents one of the largest globular domain families in the human proteome, with 266 instances. These globular domains typically interact with C-terminal peptide motifs found in thousands of human proteins. Despite previous efforts, not all PDZ domains have experimentally solved structures and most of their complexes remain to be solved. Here, a simple and cost-effective strategy is proposed for the crystallization of PDZ domains and their complexes. A human annexin A2 fusion tag was used as a crystallization chaperone and the structures of nine PDZ domains were solved, including five domains that had not yet been solved. Finally, these novel experimental structures were compared with AlphaFold predictions and it is speculated how predictions and experimental methods could cooperate in order to investigate the structural landscapes of entire domain families and interactomes.

Objective For fenestrated endovascular aneurysm repair (FEVAR), the implementation of the VesselNavigator (Philips Healthcare, Best, The Netherlands) to provide a 3-dimensional vessel roadmap has been shown to reduce patient radiation exposure. Unfortunately, FEVAR radiation doses remain substantial despite utilization of this technology. Traditionally, registration of the live fluoroscopy with the pre-operative CTA is performed via the acquisition of a low-dose cone-beam CT scan. However, this registration can also be accomplished with the acquisition of 2D X-rays using the c-arm in 2 different projection angles. We hypothesized that the 2D image acquisition for vessel roadmap development would result in a significant reduction in patient radiation dose in comparison to the 3D CT registration without compromising image quality or increasing procedural length. Methods This single-center, retrospective study included FEVARs performed from January 2015 to May 2019. For patient data, the cumulative reference air kerma (RAK) was presented as geometric mean and standard deviation. A general linear model with log-normal distribution was used to test the difference in patient RAK between 2D X-ray and 3D CT VesselNavigator registration after adjusting for BMI and the number of vessel fenestrations (1 to 2 vs. 3 to 4). Fluoroscopy time was recorded and used as a surrogate for case complexity. All analyses were done in SAS 9.4 (SAS Institute, Inc., Cary, North Carolina). Results One hundred and sixty four FEVARs were performed on a Philips Allura Xper FD 20 fluoroscopy system equipped with clarity technology. The VesselNavigator registration was completed using 3D CT mapping in 99 cases and 2D X-rays in 65 procedures. On average, utilization of 2D mapping versus 3D mapping for the VesselNavigator resulted in a 20.4% reduction in patient RAK after controlling for BMI and number of vessel fenestrations, P = 0.0135. There was no significant difference in fluoroscopy time between the 2 study groups (P= 0.81) suggesting that image quality was not compromised by the use of 2D mapping leading to the need for additional fluoroscopy. Conclusion Acquisition of 2D films rather than a 3D CT scan for VesselNavigator registration allows for a significant reduction in patient radiation dose during FEVAR without increasing the case complexity or compromising image quality.

While primary lateral sclerosis (PLS) has traditionally been regarded as a pure upper motor neuron disorder, recent clinical, neuroimaging and postmortem studies have confirmed significant extra-motor involvement. Sporadic reports have indicated that in addition to the motor cortex and corticospinal tracts, the cerebellum may also be affected in PLS. Cerebellar manifestations are difficult to ascertain in PLS as the clinical picture is dominated by widespread upper motor neuron signs. The likely contribution of cerebellar dysfunction to gait disturbance, falls, pseudobulbar affect and dysarthria may be overlooked in the context of progressive spasticity. The objective of this study is the comprehensive characterization of cerebellar gray and white matter degeneration in PLS using multiparametric quantitative neuroimaging methods to systematically evaluate each cerebellar lobule and peduncle. Forty-two patients with PLS and 117 demographically-matched healthy controls were enrolled in a prospective MRI study. Complementary volumetric and voxelwise analyses revealed focal cerebellar alterations instead of global cerebellar atrophy. Bilateral gray matter volume reductions were observed in lobules III, IV and VIIb. Significant diffusivity alterations within the superior cerebellar peduncle indicate disruption of the main cerebellar outflow tracts. These findings suggest that the considerable intra-cerebellar disease-burden is coupled with concomitant cerebro-cerebellar connectivity disruptions. While cerebellar dysfunction is challenging to demonstrate clinically, cerebellar pathology is likely to be a significant contributor to disability in PLS.

AIMS: This study aimed to investigate the application of infrared thermal imaging and adopt deep learning to detect air leakage for determining the fitness of respirators during fit-checks. BACKGROUND: The outbreak of Covid-19 virus constitutes a public health crisis with substantial resultant morbidities and mortalities; has exerted profound impacts. METHODS: This was a prospective observational study, employing a non-probability sampling method on a convenience sample to recruit the participants and followed the Strengthening the Reporting of Observational Studies in Epidemiology statement guidelines. RESULTS: The use of infrared thermal imaging identified air leakage points as a disruption to the facial thermal pattern distribution at (a) front of face; (b) right lateral of the face; (c) left lateral of the face; (d) top of the facemask with the head facing down; and (e) bottom of the facemask with the head facing up. Results also indicated that artificial intelligence tools and the proliferation of deep learning have the potential to detect the location of air leakage locations. CONCLUSION: The use of infrared thermal imaging provides evidence of the feasibility and applicability of infrared thermal imaging techniques in detecting air leakage for individuals wearing respirators. CLINICAL RELEVANCE: The use of infrared thermal technology can serve a potential role in complement fit-checking of respiratory protective devices and offers promising practical utility in determining the fitness of respirators for nurses at the frontline to protect against the air-borne viruses.

Human protein networks have been widely explored but most binding affinities remain unknown, hindering quantitative interactome-function studies. Yet interactomes rely on minimal interacting fragments displaying quantifiable affinities. Here we measured the affinities of 65,000 interactions involving PDZ domains and their target PDZ-binding motifs (PBM) within a human interactome region particularly relevant for viral infection and cancer. We calculate interactomic distances, identify hot spots for viral interference, generate binding profiles and specificity logos, and explain selected cases by crystallographic studies. Mass spectrometry experiments on cell extracts and literature surveys show that quantitative fragmentomics effectively complement protein interactomics by providing affinities and completeness of coverage, putting a full human interactome affinity survey within realistic reach. Finally, we show that interactome hijacking by the viral PBM of human papillomavirus (HPV) E6 oncoprotein deeply impacts the host cell proteome way beyond immediate E6 binders, illustrating the complex system-wide relationship between interactome and function.

People with diabetic foot frequently exhibit gait and balance dysfunction. Recent advances in wearable inertial measurement units (IMUs) enable to assess some of the gait and balance dysfunction associated with diabetic foot (i.e., digital biomarkers of gait and balance). However, there is no review to inform digital biomarkers of gait and balance dysfunction related to diabetic foot, measurable by wearable IMUs (e.g., what gait and balance parameters can wearable IMUs collect? Are the measurements repeatable?). Accordingly, we conducted a web-based, mini review using PubMed. Our search was limited to human subjects and English-written papers published in peer-reviewed journals. We identified 20 papers in this mini review. We found preliminary evidence of digital biomarkers of gait and balance dysfunction in people with diabetic foot, such as slow gait speed, large gait variability, unstable gait initiation, and large body sway. However, due to heterogeneities in included papers in terms of study design, movement tasks, and small sample size, more studies are recommended to confirm this preliminary evidence. Additionally, based on our mini review, we recommend establishing appropriate strategies to successfully incorporate wearable-based assessment into clinical practice for diabetic foot care.

Introduction: We aimed to provide a practical and evidence-based guide on the indications, performance and reporting of high-resolution oesophageal manometry (HRM) and ambulatory pH monitoring (PHM) in adult patients in Singapore. Methods: The guideline committee comprised local gastroenterologists from public and private sectors with particular expertise in aspects of HRM and PHM, and it was tasked to produce evidence-based statements on the indications, performance and reporting of these tests. Each committee member performed literature searches to retrieve relevant articles within the context of domains to which they were assigned. Results: Twelve recommendation statements were created and summarised. Conclusion: Standardising key aspects of HRM and PHM is imperative to ensure the delivery of high-quality care. We reported the development of recommendations for the performance and interpretation of HRM and ambulatory reflux monitoring in Singapore. Keywords: Gastro-oesophageal reflux disease, GERD, high-resolution oesophageal manometry, oesophagus, pH testing

Background Chronotype and chrononutrition, both are emerging research interests in nutritional epidemiology. However, its association with glycemic control in the Asia population is less clear. A better understanding of how activity/eating time can influence glucose levels in Asian prediabetic individuals may improve strategies for blood glucose control in Asian countries. The present paper describes the research protocol which aims to determine the associations of chronotype and chrononutrition with glucose tolerance among Malaysian prediabetic individuals. Methods This is a prospective longitudinal study named Chrono-DM™, that targets to recruit 166 newly diagnosed prediabetic individuals from the community clinics in Malacca, Malaysia. Respondents will be followed-up for 6 months: (1) baseline (1st oral glucose tolerance test (OGTT)); (2) second visit (at 3rd month); and (3) third visit (2nd OGTT at 6th month). Data collection includes sociodemographic and anthropometry measurements (weight, height, body fat, visceral fat, waist and hip circumference). Dietary intake and meal timing are collected using the 3-day dietary record while data on sleep pattern, light exposure, chronotype and chrononutrition will be collected using validated questionnaires. Physical activity will be recorded using a validated IPAQ questionnaire and pedometer during periods of using continuous glucose monitoring (CGM) sensor. CGM, fasting blood sugar (FBS), OGTT and HbA1c are performed to assess glycemic outcomes. Discussion The Chrono-DM™ study represents a novel approach to determining the association of chronotype and chrononutrition with glycemic control. We anticipate that this study will not only review the association of chronotype with glycemia measure but also provide greater insight into optimal meal time for glycemic control among prediabetic individuals in the Asian population. Trial registration NCT05163964 (Clinicaltrial.gov). Trial registration date: 20 December 2021.

Infant gastroesophageal reflux disease (GERD) is a significant cause of concern to parents. This study seeks to describe GERD prevalence in infants, evaluate possible risk factors and assess common beliefs influencing management of GERD among Asian parents.Mother-infant dyads in the Singapore PREconception Study of long-Term maternal and child Outcomes (S-PRESTO) cohort were prospectively followed from preconception to 12 months post-delivery. GERD diagnosis was ascertained through the revised Infant Gastroesophageal Reflux Questionnaire (I-GERQ-R) administered at 4 time points during infancy. Data on parental perceptions and lifestyle modifications were also collected.The prevalence of infant GERD peaked at 26.5% at age 6 weeks, decreasing to 1.1% by 12 months. Infants exclusively breastfed at 3 weeks of life had reduced odds of GERD by 1 year (adjusted odds ratio 0.43, 95% confidence interval 0.19-0.97,Prevalence of GERD in infants is highest in the first 3 months of life, and the majority outgrow it by 1 year of age. Infants exclusively breastfed at 3 weeks had reduced odds of GERD. Cultural-based changes such as elimination of "heaty or cold" food influence parental perceptions in GERD, which are unique to the Asian population. Understanding the cultural basis for parental perceptions and health-seeking behaviours is crucial in tailoring patient education appropriately for optimal management of infant GERD.

OBJECTIVES: To determine whether cataract surgery is associated with an increased risk of subsequent lower eyelid entropion and evaluate potential associated factors. METHODS: This retrospective cohort study included consecutive patients undergoing first eye cataract surgery over a 10-year period at a single institution (n = 14,574). The fellow phakic eye served as control. Patient records were evaluated up until either the time of second eye cataract surgery or any other intraocular or adnexal surgery. The primary outcome was the rate of entropion repair in both the pseudophakic (exposed) group and the phakic control group. Groups were compared using relative risk and Kaplan–Meier analysis. Multivariate logistic regression was used to compare pre-specified characteristics of those patients that underwent entropion repair in their pseudophakic eye with those that did not. RESULTS: A fourfold higher relative risk of undergoing entropion repair was observed in eyes that had undergone cataract surgery compared with the fellow unoperated eye (95% confidence interval 1.6–9.8; P

Background and aim Patients with functional dyspepsia (FD) often have concomitant anxiety and depression. Mindfulness-based cognitive therapy (MBCT) combines the principles of cognitive behavioral therapy and mindfulness. It is a group-based therapy and has been shown to be efficacious in functional gastrointestinal disorders. There are no randomized controlled trials (RCTs) evaluating MBCT in FD. We aimed to evaluate feasibility and efficacy of MBCT in FD management. Methods We performed a mixed-method single-center pilot randomized trial of 28 patients fulfilling ROME-III criteria for FD. Fifteen patients were randomized to an 8-week MBCT program while 13 underwent treatment-as-usual (TAU). Patients completed questionnaires at baseline and at week 8. Two focus-groups were conducted. Feasibility of recruitment, acceptability of randomization, procedures and intervention, handout compliance and feasibility of quantitative measures were assessed. The primary outcome was subjective-clinical-assessment of FD symptoms (SCA-FD). Secondary outcome measures included Short-form Nepean Dyspepsia Index (SF-NDI), subjective-clinical-assessment of general health (SCA-GH), EuroQoL-Visual Analog Scale (EuroQoL-VAS), and Depression, Anxiety and Stress Scale-21 Items (DASS-21). Results Twelve of 15 patients in the MBCT group completed the program. There was a trend towards symptom improvement, with 90% in the MBCT group reporting improvement in SCA-FD compared with 45% in TAU(P = 0.063). Patients who underwent MBCT reported greater improvement in SF-NDI (mean change: -8.8 (SD: 7.5) vs -0.7 (7.2), P = 0.018) and DASS-21 (-19.8 (29.5) vs -5.5 (6.6) P = 0.13) compared with TAU. There was no difference in SCA-GH and EuroQoL-VAS. Based on SCA-FD improvement, the eventual RCT will require 50 patients (25 in each group). Conclusions Mindfulness-based cognitive therapy is likely efficacious for FD, and it would be feasible to conduct a RCT.

To evaluate the effectiveness of online memory training interventions in improving memory of patients diagnosed with early-stage dementia. The secondary outcomes comprised cognitive and psychological outcomes.This review was conducted for accordance to the Cochrane Handbook for Systematic Reviews of Interventions.A comprehensive search from six electronic databases: PubMed, Embassy, The Cochrane Library, The Cumulative Index to Nursing and Allied Health Literature, Scopus and Web of Science was conducted (2000-2020).The populations included in this review comprised adults who had been clinically diagnosed with early-stage dementia and involved in online memory training interventions. Two reviewers appraised the risks of bias through the Cochrane Collaboration's tool and performed the meta-analysis, including the assessment of heterogeneity.Eleven randomized controlled trials retrieved from six databases demonstrated low to moderate levels of quality of evidence according to the GRADE approach. The meta-analysis revealed that online memory training interventions have demonstrated a moderate effect size in improving memory outcomes (d = 0.57; 95% confidence interval 0.28-0.85; p = 0.0001). Additionally, such interventions have shown improvements in secondary outcomes of cognition and psychological with small to medium effects. Duration of each online memory training session and its frequencies did not affect the memory outcome. As opposed to the conventional face-to-face interventions conducted for a group, it is more effective to be conducted for an individual setting.Online memory training intervention was effective in improving the memory for adults with dementia.Memory interventions have the prospect of reducing everyday problems caused by lapses in memory and improving well-being. With factors such as limited resources and restriction of social gathering due to pandemic, this review could offer relevant information for clinical decision-makers when planning online memory training interventions for adults with dementia.目的: 评价在线记忆训练干预对改善被诊断为早期痴呆症患者记忆力的有效性。次要结果包括认知和心理结果。 设计: 根据《Cochrane干预系统性评估手册》进行本次评估。 数据来源: 对PubMed、Embassy、The Cochrane Library、护理学及医疗相关文献累计索引、Scopus和Web of Science这6个电子数据库进行全面检索(2000年-2020年) 。 评估方法: 本评估中纳入的人群包括临床上被诊断为患有早期痴呆症并参与在线记忆训练干预的成年人。两名评估员通过Cochrane Collaboration工具评估了偏倚风险, 并进行了荟萃分析, 包括异质性评估。 结果: 从6个数据库中检索的11项随机对照试验显示,根据GRADE方法,证据质量为低至中等水平。荟萃分析显示, 在线记忆训练干预在改善记忆结果方面表现出中等效果 (d=0.57;95%置信区间: 0.28-0.85;p=0.0001) 。此外, 此类干预亦改善了认知和心理的次要结果, 具有小到中等的效果。每次在线记忆训练课程的持续时间及其频率并不影响记忆结果。相对于传统的针对群体进行的面对面干预, 针对个体环境进行的干预更为有效。 结论: 在线记忆训练干预能有效改善成人痴呆症患者的记忆力。 影响: 记忆干预有可能减少因记忆丧失而引起的日常问题, 并改善健康状况。由于资源有限、流行病导致社交聚会受限等因素, 本评估为临床决策者在规划成人痴呆症患者在线记忆训练干预时提供了相关信息。.

Ceramides plays a crucial role in maintaining skin barrier function. Although foregoing evidence supported beneficial effects of topical ceramides for restoration of the skin barrier, studies on oral ceramides are extremely scarce, with most published data collected from in vivo and in vitro models. Thus, this study aimed to evaluate the efficacy of rice ceramides (RC) supplementation to improve skin barrier function and as a depigmenting agent through comprehensive clinical assessments. This study investigated the beneficial effects of orally administered RC supplementation in 50 voluntary participants. Skin hydration, firmness and elasticity, transepidermal water loss (TEWL), melanin index (MI), erythema index (EI), sebum production, pH, and wrinkle severity were assessed at baseline and during monthly follow-up visits. RC supplementation was found to significantly (

International audience; Persistent infection with some mucosal a-genus human papillomaviruses (HPVs; the most prevalent one being HPV16) can induce cervical carcinoma, anogenital cancers, and a subset of head and neck squamous cell carcinoma (HNSCC). Cutaneous b-genus HPVs (such as HPV5 and HPV8) associate with skin lesions that can progress into squamous cell carcinoma with sun exposure in Epidermodysplasia verruciformis patients and immunosuppressed patients. Here, we analyzed mechanisms used by E6 proteins from the aand b-genus to inhibit the interferon-b (IFNB1) response. HPV16 E6 mediates this effect by a strong direct interaction with interferon regulatory factor 3 (IRF3). The binding site of E6 was localized within a flexible linker between the DNAbinding domain and the IRF-activation domain of IRF3 containing an LxxLL motif. The crystallographic structure of the complex between HPV16 E6 and the LxxLL motif of IRF3 was solved and compared with the structure of HPV16 E6 interacting with the LxxLL motif of the ubiquitin ligase E6AP. In contrast, cutaneous HPV5 and HPV8 E6 proteins bind to the IRF3-binding domain (IBiD) of the CREB-binding protein (CBP), a key transcriptional coactivator in IRF3-mediated IFN-b expression. IMPORTANCE Persistent HPV infections can be associated with the development of several cancers. The ability to persist depends on the ability of the virus to escape the host immune system. The type I interferon (IFN) system is the first-line antiviral defense strategy. HPVs carry early proteins that can block the activation of IFN-I. Among mucosal a-genus HPV types, the HPV16 E6 protein has a remarkable property to strongly interact with the transcription factor IRF3. Instead, cutaneous HPV5 and HPV8 E6 proteins bind to the IRF3 cofactor CBP. These results highlight the versatility of E6 proteins to interact with different cellular targets. The interaction between the HPV16 E6 protein and IRF3 might contribute to the higher prevalence of HPV16 than that of other high-risk mucosal HPV types in HPV-associated cancers.

Background The authors estimate the probability of successful development and duration of clinical trials for medications to treat neuropathic and nociceptive pain. The authors also consider the effect of the perceived abuse potential of the medication on these variables. Methods This study uses the Citeline database to compute the probabilities of success, duration, and survivorship of pain medication development programs between January 1, 2000, and June 30, 2020, conditioned on the phase, type of pain (nociceptive vs. neuropathic), and the abuse potential of the medication. Results The overall probability of successful development of all pain medications from phase 1 to approval is 10.4% (standard error, 1.5%). Medications to treat nociceptive and neuropathic pain have a probability of successful development of 13.3% (standard error, 2.3%) and 7.1% (standard error, 1.9%), respectively. The probability of successful development of medications with high abuse potential and low abuse potential are 27.8% (standard error, 4.6%) and 4.7% (standard error, 1.2%), respectively. The most common period for attrition is between phase 3 and approval. Conclusions The authors’ data suggest that the unique attributes of pain medications, such as their abuse potential and intended pathology, can influence the probability of successful development and duration of development. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

To evaluate the effectiveness of psychological interventions in reducing fear of cancer recurrence in breast cancer survivors.A systematic review and meta-analysis.PubMed, Embase, Cochrane Central Register of Controlled Trials, CINAHL, Scopus, PsycINFO, Web of Science and ClinicalTrials.gov were searched for relevant studies published from 1 January 1976 to 28 November 2020.Eligible randomized controlled trials on psychological interventions for reducing fear of cancer recurrence in breast cancer survivors were included in meta-analysis. Review Manager 5.4 was used to conduct the meta-analysis, and the fear of cancer recurrence score was calculated by using standardized mean differences and 95% confidence intervals. Risk of bias was assessed with the Cochrane risk-of-bias tool. Quality of evidence, sensitivity analyses, and subgroup analyses were also conducted.This systematic review included 16 randomized controlled trials. We found psychological interventions significantly reduced fear of cancer recurrence. Subgroup analyses indicated that mindfulness and acceptance therapy-based interventions reduced fear of cancer recurrence, whereas cognitive-behavioural therapy combined with psychoeducation did not. Interventions with three to eight sessions were effective, while interventions with nine or more sessions were not. Face-to-face interventions were effective, whereas online interventions were not. The quality of evidence for fear of cancer recurrence was evaluated as moderate due to moderate heterogeneity in the included studies.Psychological interventions were effective in reducing fear of cancer recurrence in breast cancer survivors. Mindfulness and acceptance therapy-based interventions and short-term interventions are recommended. Future well-designed randomized controlled trials aiming to examine the effectiveness of psychological interventions in reducing fear of cancer recurrence are needed.The findings of this systematic review may guide the development of psychological interventions and encourage the use of psychological interventions for reducing fear of cancer recurrence in breast cancer survivors.

Irritable bowel syndrome (IBS) is a highly prevalent disorder of gut brain interaction with a multifactorial etiology. Food trigger avoidance is common among individuals with IBS and exclusion diets are gaining popularity. However, recent guidelines on IBS management cautioned regarding the use of unsupervised dietary therapy with concerns of development of poor eating habits and even nutritional deficiencies. We aimed to review the available literature on the effect of habitual and exclusion diets on micronutrient status as well as the role of micronutrient supplementation in alleviating IBS symptoms.Four electronic databases (PubMed, Embase, Cochrane, Web of Science) were searched for articles that reported micronutrient data in patients with IBS. Serum micronutrient levels and dietary intake of micronutrients in patients with IBS were collected. The extracted data were tabulated and organized by micronutrient type to observe for trends.Twenty-six articles were included in this systematic review (12 interventional and 14 observational studies). Studies showed that generally IBS subjects had lower levels of vitamin B2, vitamin D, calcium, and iron at baseline compared with non-IBS subjects. Studies also found that exclusion diets were associated with lower intake of micronutrients especially vitamin B1, B2, calcium, iron, and zinc. There was a lack of interventional studies on micronutrients.Irritable bowel syndrome patients are at risk of developing multiple micronutrient deficiencies that may have both localized gastrointestinal as well as systemic effects. Dietary management of IBS patients should include a proper dietitian review to ensure nutritional adequacy where possible.

DiGeorge syndrome is a genetic disorder that is related to a wide range of defects affecting various parts of the body. The clinical expression shows marked variability making the diagnosis often missed or underdiagnosed. Here, we describe a neonate who presented with loud inspiratory stridor secondary to hypocalcaemia at birth. Physical examination revealed no abnormality other than evidence of congenital cardiac defect. Laboratory evaluations confirmed the diagnosis of maternal vitamin D deficiency that led to symptomatic hypocalcaemia in the newborn infant. The presence of hypocalcaemia coupled with episodes of recurrent infections led to the clinical suspicion of DiGeorge, which was later confirmed by fluorescence in situ hybridisation test.

Presymptomatic studies in ALS have consistently captured considerable disease burden long before symptom manifestation and contributed important academic insights. With the emergence of genotype-specific therapies, however, there is a pressing need to address practical objectives such as the estimation of age of symptom onset, phenotypic prediction, informing the optimal timing of pharmacological intervention, and identifying a core panel of biomarkers which may detect response to therapy. Existing presymptomatic studies in ALS have adopted striking different study designs, relied on a variety of control groups, used divergent imaging and electrophysiology methods, and focused on different genotypes and demographic groups. We have performed a systematic review of existing presymptomatic studies in ALS to identify common themes, stereotyped shortcomings, and key learning points for future studies. Existing presymptomatic studies in ALS often suffer from sample size limitations, lack of disease controls and rarely follow their cohort until symptom manifestation. As the characterisation of presymptomatic processes in ALS serves a multitude of academic and clinical purposes, the careful review of existing studies offers important lessons for future initiatives.

BACKGROUND AND AIM Singapore is a multi-ethnic country that has undergone rapid development over the last few decades, with increasing influence of western culture, and faces an aging population. Previously, a varying prevalence of colonic diverticulosis (CD) was reported by a few small studies. This study aims to evaluate the prevalence of CD in Singapore and identify associations with common gastrointestinal symptoms and risk factors. METHODS We reviewed retrospective data of 20 395 consecutive colonoscopies performed from 2006 to 2016 for presence of CD and indications of screening, diarrhea, constipation, and abdominal pain. RESULTS The prevalence of CD progressively increased from 2006 to 2016 (14.9% vs 23.9%, adjusted trend

Background Accidental awareness during general anaesthesia (AAGA) is a complex and rare outcome to investigate in surgical patient populations, particularly obstetric patients. We report the protocol of the Direct Reporting of Awareness in Maternity patients (DREAMY) study, illustrating how the research was designed to address practical and methodological challenges for investigating AAGA in an obstetric cohort. Methods This is the trial protocol of a prospective, multicentre cohort study of patients undergoing obstetric surgery under general anaesthesia. Accidental awareness during general anaesthesia will be detected using three repetitions of standardised direct questioning over 30 days, with responses indicating memories during general anaesthesia verified using structured interviews. Reports will be adjudicated, then classified, in accordance with pre-defined and pre-validated structures, including the Michigan Awareness Classification tool. Quantitative data will be collected on general anaesthesia conduct for all participants. This descriptive study is being conducted in England and aims to recruit a minimum of 2015 patients. Results The DREAMY study was prospectively registered (ClinicalTrials.gov Identifier: NCT03100396) and ethical approval granted. Participant recruitment began in May 2017 and one year follow up concluded in August 2019. Publication of the results is anticipated in 2020. Conclusions The DREAMY study will provide data on incidence, experience and implications of AAGA for obstetric patients, using a robust methodology that will reliably detect and translate subjective AAGA reports into objective outcomes. In addition, the study is expected to improve vigilance for AAGA in participating hospitals and encourage adoption of recommendations for support of patients experiencing AAGA.

Aim This review aimed to elucidate the effectiveness of structured handovers in improving patient outcomes in the wards. Background Studies have reported that the lack of quality handovers is one of the main causes of adverse effects. Evaluation A search over six electronic databases: MEDLINE; CINAHL; Web of Science; EMBASE; Scopus; and CENTRAL via Ovid concluded nine studies and synthesized by two independent reviewers based on the Cochrane Handbook for Systematic Reviews of Interventions. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement was used to guide the undertaking of this review and meta-analysis. All studies published up to February 2019 were considered in this review. Key issues This review has demonstrated that structured handovers reduced the incidences of patient complications, medication errors and general adverse events. However, the results were not statistically significant. Conclusion Current structured handover formats were effective in reducing problematic handovers such as omission of information, inaccurate information and documentation errors. Implications for nursing management Although there is limited high-quality and rigorous research conducted to gain a clearer understanding of the impacts on patient-related outcomes in nursing care, structured handovers remained effective in reducing the number of mistakes in information transfer.

Background Platelet-rich plasma (PRP), processed from autologous peripheral blood, is used to treat androgenetic alopecia (AGA). Objective To determine the efficacy of PRP for hair growth promotion in AGA patients in a randomized, blinded, placebo-controlled, pilot clinical trial (NCT02074943). Methods The efficacy of an 8 week, five session, PRP treatment course was determined by measuring hair density and hair caliber changes in 10 AGA affected patients. For each PRP sample, the concentrations of selected growth factors were determined using a multiplex assay system. The clinical results were then correlated with the growth factor concentrations in PRP. Results At 16 weeks, 8 weeks after the last PRP injection, treated areas exhibited increased mean hair density (+12.76%) over baseline compared to placebo (+0.99%). Mean hair caliber decreased in both treated and placebo regions (-16.22% and -19.46%, respectively). Serial analysis of PRP significant variability in concentrations between patients. Overall, there was a positive correlation between GDNF concentration and hair density (P = .004). Trends, though not statistically significant, were also observed for FGF2 and VEGF. Limitations Small sample size and lack of comparative cohorts receiving protocol variations limit confidence in the study data. Conclusions This small pilot clinical trial suggests PRP treatment may be beneficial for AGA. However, the variable hair growth responses between patients indicate there is a significant opportunity to improve PRP therapy protocols for hair growth promotion. The variability in growth factor concentration in PRP suggests standardization of growth factors postprocessing might improve hair growth responses.

Purpose To describe 10 patients with Morbihan syndrome, a rare condition characterized by the slow appearance of erythema and solid edema on the upper portion of the face, and review the literature. Methods Retrospective case series and review. Results The majority of patients were male (80%), and the mean age at presentation was 67 years (range, 48-88 years); 60% had asymmetrical disease (affecting mainly the right side). All subjects underwent a lid biopsy to support the diagnosis of Morbihan syndrome, which showed features of inflammation and vascular dysfunction, highly suggestive of a rosacea histological picture complicated by chronic lymphoedema. A range of medical and surgical treatment were used with variable success. The most effective ones included oral isotretinoin, intralesional triamcinolone injections, and debulking surgery. Conclusions Morbihan syndrome is a rare and chronic condition. It can be difficult to treat and may require a range of interventions.

To clarify whether there were any significant differences in clinical symptoms and eating patterns between functional dyspepsia (FD) patients and FD with pancreatic enzyme abnormalities (FD-P) patients as refractory FD, we compared these factors in multicenter studies in Singapore and Japan.One hundred ninety-eight consecutive patients presenting with FD (n = 88), FD-P patients (n = 81) based on Rome III classification and controlled group (n = 39) recruited from six institutions in Singapore and Japan. Clinical characteristics, clinical symptoms for dietary fat intake, and eating behaviors were estimated using questionnaires. Anxiety and health-related quality of life were determined by STAI-state/-trait and SF-8, respectively.There were no significant differences in age, sex, BMI, smoking, alcohol intake, past medical history, and history of allergy in FD and FD-P patients between Singapore and Japan. There were no significant differences in FD subtypes, gastrointestinal symptom rating scale score, severity of FD symptoms, and eating pattern in Singapore and Japan. Moreover, there were significant differences in certain eating behaviors between FD and FD-P patients in Singapore and Japan. Interestingly, epigastric pain and early satiety following fat meals in FD-P patients were significantly (P = 0.003 and P = 0.008, respectively) higher compared with those in FD patients in Japan. Physical component score in FD-P patients was significantly (P = 0.019) disturbed compared with those in FD patients in Japan.Epigastric pain and early satiety following fat meals in FD-P patients may be useful tools to differentiate FD-P patients from FD patients in Japan.

To assess the improvements during patient follow-up after implementing a proactive plan for retrieval of inferior vena cava (IVC) filters.A retrospective study was undertaken including all patients who had a temporary IVC filter inserted over a 10-year period. Patient demographics, insertion dates, retrieval dates, retrieval rates, and complications were recorded. Patients were categorised into three groups as follows: group A, no intervention where retrieval was not suggested; group B, passive intervention where retrieval was suggested but no appointment made; and group C, proactive intervention where a retrieval date was booked by the radiologist.Five hundred and nine patients had a temporary IVC filter inserted at Royal Liverpool University Hospital over the study period. One per cent of patients in group C were lost to follow-up compared to 41% and 29% in groups A and B respectively (p0.001). The number of patients who had an IVC retrieval attempt also increased to 80% in group C compared to 53% and 64% in groups A and B (p0.001).Incorporation of a proactive retrieval booking system has significantly reduced the number of patients lost to follow-up to 1%, leading to an increased number of IVC filter retrieval attempts.

Background Few data exist on the cognitive and academic functioning of children with chronic kidney disease (CKD) over the trajectory of their illness. We aimed to determine the association between CKD stages and cognitive and academic performance in children over time. Methods We included 53 participants (aged 6–18 years) with CKD stages 1–5 (n = 37), on dialysis (n = 3), or with functioning kidney transplant (n = 22) from three units in Australia from 2015 to 2019. Participants undertook a series of psychometric tests and were invited for repeated assessments annually. We used linear regression and linear mixed models to investigate the effect of CKD stage, adjusted for socioeconomic status. Results At baseline, full-scale intelligence quotient (FSIQ) (95%CI) of children on kidney replacement therapy (KRT) was in the low average range (87: 78, 96) and average (101: 95, 108) for children with CKD 1–5. Mean (95%CI) FSIQ, word reading, numerical operations, and spelling scores for children on KRT were 14.3 (− 25.3, − 3.3), 11 (− 18.5, − 3.6), 8.5 (− 17.6, 0.76), and 10 (− 18.6, − 1.3) points lower than children with CKD Stages 1–5. Spelling and numerical operations scores declined by 0.7 (− 1.4, − 0.1) and 1.0 (− 2.0, 0.2) units per year increase in age, regardless of CKD stage. Conclusions Children treated with KRT have low average cognitive abilities and lower academic performance for numeracy and literacy compared to both children with CKD 1–5 and to the general population. However, the rate of decline in academic performance over time is similar for children across the full spectrum of CKD. Graphical abstract A higher resolution version of the Graphical abstract is available as Supplementary information.

Long-term radiation exposure from fluoroscopically guided interventions (FGIs) can cause cataracts and brain tumors in the operator. We have previously demonstrated that leaded eyewear does not decrease the operator eye radiation dose unless lead shielding has been added to the lateral and inferior portions. Therefore, we have developed a disposable, lightweight, lead-equivalent shield that can be attached to the operator's eyewear that conforms to the face and adheres to the surgical mask. In the present study, we evaluated the efficacy of our new prototype in lowering the operator brain and eye radiation dose when added to both leaded and nonleaded eyewear.The attenuating efficacy of leaded eyewear alone, leaded eyewear plus the prototype, and nonleaded eyewear plus the prototype were compared with no eyewear protection in both a simulated setting and clinical practice. In the simulation, optically stimulated, luminescent nanoDot detectors (Landauer, Inc, Glenwood, Ill) were placed inside the ocular, temporal lobe, and midbrain spaces of a head phantom (ATOM model-701; CIRS, Norfolk, Va). The phantom was positioned to represent a primary operator performing right femoral access. Fluorography was performed on a plastic scatter phantom at 80 kVp for an exposure of 3 Gy reference air kerma. In the clinical setting, nanoDots were placed below the operator's eye both inside and outside the prototype during the FGIs. The median and interquartile ranges were calculated for the dose at each nanoDot location for the phantom and clinical studies. The average dose reduction was also recorded.Wearing standard leaded eyewear alone did not decrease the operator ocular or brain radiation dose. In the phantom experiment, the leaded glasses plus the prototype reduced the radiation dose to the lens, temporal lobe, and midbrain by 83% (P .001), 78% (P .001), and 75% (P .001), respectively. The nonleaded glasses plus the prototype also reduced the dose to the lens, temporal lobe, and midbrain by 85% (P .001), 81% (P .001), and 71% (P .001), respectively. A total of 15 FGIs were included in the clinical setting, with a median reference air kerma of 98.4 mGy. The use of our prototype led to an average operator eye dose reduction of 89% (P .001).Attaching our prototype to both leaded and nonleaded glasses significantly decreased the eye and brain radiation dose to the operator. This face shield attachment provided meaningful radiation protection and should be considered as either a replacement or an adjunct to routine eyewear.

AIM Examined the evidence of low-to-moderate-intensity physical activities to assess the effect in managing hypertension, diabetes mellitus and hyperlipidaemia conditions among community-dwelling older adult. BACKGROUND Physical activity is recommended for the maintenance and improvement of health. However, high-intensity physical activity may adversely impact exercise adherence by older adults. DESIGN This review was conducted with reference to methods set out in the Cochrane Handbook for Systematic Reviews of Interventions. The PRISMA statement was employed to guide the reporting of the systematic review and meta-analyses. DATA SOURCES Seven electronic databases were searched to identify relevant articles that were published in English from 1 January 2000 to 31 December 2020. REVIEW METHOD This review included randomised controlled trials and cluster-randomised controlled trials on interventions of physical activities with low-to-moderate intensities compared against usual care without physical activities. Two reviewers independently extracted data and assessed the risk of bias using the Cochrane Risk of Bias Tool. Meta-analysis was performed using RevMan, with Cochran Q and I2 used for determining heterogeneity. The overall effect was reviewed with z scores. RESULTS Fifteen randomised controlled trials with 940 total participants were evaluated. Low-to-moderate-intensity physical activity significantly improved systolic blood pressure [Z = 3.59, p = .0003], HbA1C [Z = 2.10, p = .04] and high-density lipoprotein (HDL) levels [Z = 3.83, p = .0001], compared to usual care. A further subgroup analysis found no significant difference in systolic blood pressure level after three sessions a week as well as after three months. There were insufficient papers to evaluate for both HbA1C and HDL levels. CONCLUSION Regular physical activity ranging from low-to-moderate intensity should be encouraged among older adults with chronic diseases. RELEVANCE FOR CLINICAL PRACTICE This review suggested that low-to-moderate levels of physical activity could be encouraged among community-dwelling older adults to improve their physical health.

Research objectives Clostriodiodes difficile infection (CDI) is a major cause of healthcare-associated diarrhoea with high mortality. There is a lack of validated predictors for severe outcomes in CDI. The aim of this study is to derive and validate a clinical prediction tool for CDI in-hospital mortality using a large critical care database. Methodology The demographics, clinical parameters, laboratory results and mortality of CDI were extracted from the Medical Information Mart for Intensive Care-III (MIMIC-III) database. We subsequently trained three machine learning models: logistic regression (LR), random forest (RF) and gradient boosting machine (GBM) to predict in-hospital mortality. The individual performances of the models were compared against current severity scores (Clostridiodes difficile Associated Risk of Death Score (CARDS) and ATLAS (Age, Treatment with systemic antibiotics, leukocyte count, Albumin and Serum creatinine as a measure of renal function) by calculating area under receiver operating curve (AUROC). We identified factors associated with higher mortality risk in each model. Summary of results From 61 532 intensive care unit stays in the MIMIC-III database, there were 1315 CDI cases. The mortality rate for CDI in the study cohort was 18.33%. AUROC was 0.69 (95% CI, 0.60 to 0.76) for LR, 0.71 (95% CI, 0.62 to 0.77) for RF and 0.72 (95% CI, 0.64 to 0.78) for GBM, while previously AUROC was 0.57 (95% CI, 0.51 to 0.65) for CARDS and 0.63 (95% CI, 0.54 to 0.70) for ATLAS. Albumin, lactate and bicarbonate were significant mortality factors for all the models. Free calcium, potassium, white blood cell, urea, platelet and mean blood pressure were present in at least two of the three models. Conclusion Our machine learning derived CDI in-hospital mortality prediction model identified pertinent factors that can assist critical care clinicians in identifying patients at high risk of dying from CDI.

Aim To compare the associated discomfort and safety between transcutaneous (Tskin) and transconjunctival (Tconj) approaches of local anaesthetic (LA) administration in lower eyelid surgery. Methods A prospective randomised controlled trial comparing Tskin and Tconj LA in patients undergoing bilateral lower eyelid surgeries for horizontal laxity. Patients were randomised to receive LA via Tskin to one side and Tconj to the fellow side. LA injection was administered in a slow fashion accompanied by distraction (tapping of patient's forehead). Self-reported discomfort from the injections was rated using a 0-10 numerical rating scale. A single blinded assessor graded photographs for eyelid bruising (0 = absent, 1 = mild, 2 = moderate, 3 = severe). Results A total of 30 patients (mean age ± SD, 75.9 ± 6.7 years) were enrolled. The overall pain score (mean ± SD) was statistically lower for the Tconj than the Tskin group (3.90 ± 2.28 versus 5.33 ± 2.23, p = 0.017). More patients in the Tconj group reported substantially less pain (score of ≤3) in comparison to the Tskin group (56.7% versus 23.3%, p = 0.017). In individual patients, the Tconj pain score was found to be significantly lower than the Tskin side (p = 0.008). Bruising scores were higher in the Tskin group, but this was not statistically significant (p = 0.13). No other adverse effects were found. Conclusion Tconj delivery of LA in lower eyelids with horizontal laxity is safe and associated with less discomfort and bruising than the conventional Tskin route. Trial registration number NCT04102878.

To determine the factors affecting the referral rates of patients with diabetes from primary care to secondary care.\ud Methods\ud A study based on 66 GP surgeries in the Cardiff and Vale University Health Board (population: 515,581) was conducted. We included patients who had an established clinical diagnosis of diabetes (type 1 and type 2) from September 2017 to September 2018.\ud HbA1c outcome data of GP surgeries were obtained from the Quality and Outcomes Framework (QOF) database published for 2018. Referral rates were obtained from the electronic referral database of Cardiff and Vale University Health Board over the same period, and this was adjusted according to the number of patients with diabetes in each GP surgery. Confidence level on the treatment of diabetes among GPs was assessed as a sub-study conducted in nine GP surgeries in the same area, using a self-administered questionnaire. Linear regression was undertaken to assess the relationship between adjusted referral rate and key factors which might influence prescribing rate.\ud Results\ud The average adjusted referral rate to secondary care in one year was 4.23% of patients with diabetes in each GP surgery, with a wide variation of 1.24% to 16.28%. The average percentage of patients with diabetes with HbA1c

Irritable bowel syndrome (IBS) is a functional gastrointestinal disease and the most common cause of prolonged abdominal pain and bowel disturbances in the developed world. While initially thought to be functional or psychosomatic in nature, IBS is now recognized as a heterogeneous group of conditions. A subset of IBS patients and patients with allergic diseases share some characteristic inflammatory features. In fact, atopic children show an increased likelihood of developing IBS as adults. Given these findings, a subset of IBS may be suffering from allergy-related gut diseases. In this review, we present the allergy-related comorbidities of IBS, including genetic, environmental, and immunologic factors. We discuss studies demonstrating an increased sensitization of IBS patients to aeroallergens compared to food allergens. We then postulate potential pathophysiological mechanisms underlying both IBS and aeroallergens in the gut, followed by potential implications in the screening and treatment of allergies in IBS patients.

Congenital anomalies of the kidney and urinary tract (CAKUT) are a leading cause of end-stage kidney failure in the young. However, there is limited information on long-term outcomes after kidney transplantation in this group. We explored the outcomes of kidney transplant in patients with the 3 most common severe forms of CAKUT: posterior urethral valves (PUV), reflux nephropathy and renal hypoplasia/dysplasia. Data were extracted from the Australian & New Zealand Dialysis & Transplant Registry on first kidney transplants performed between 1985 and 2015 in recipients with a primary diagnosis of PUV, renal hypoplasia/dysplasia or reflux nephropathy (under the age of 30 years). Using multivariate Cox regression, we compared death-censored graft survival between the three groups. One hundred twenty-seven patients with PUV, 245 with hypoplasia/dysplasia and 727 with reflux nephropathy were included. A 10-year graft survival in PUV, hypoplasia/dysplasia and reflux nephropathy was 70%, 76% and 70%, respectively and a 20-year graft survival was 30%, 53% and 49%. After adjusting for age at transplant, graft source and HLA matching, there was evidence for poorer graft survival in PUV (HR, 1.65; 95% CI, 1.15 to 2.38). Graft survival of the first transplant in CAKUT is favourable at 10 years; however, recipients with PUV have increased risk of graft loss beyond a 10-year post-transplant, which may be related to bladder dysfunction.

The accurate assessment of peripheral perfusion is a critical step in caring for a diabetic patient with active ulceration. This article guides the provider through diagnostic and therapeutic options. The perfusion assessment begins with a physical examination and augmented using noninvasive tests. Although some of these tests can be performed at the bedside, often a dedicated vascular laboratory is required. Additional cross-sectional imaging studies or formal angiography should be performed as well. These tools aid in the creation of the best therapeutic plan, which aims to restore perfusion and allow for rapid wound healing via open or endovascular means.

ObjectivesTo describe the distribution of albuminuria among Australian children aged 11–12 years and their parents, and assess its intergenerational concordance within parent–child dyads.DesignPopulation-based cross-sectional study (the Child Health CheckPoint), nested within the Longitudinal Study of Australian Children.SettingAssessment centres (seven Australian cities and eight regional towns) and home visits across Australia, February 2015 to March 2016.ParticipantsOf all participating CheckPoint families (n=1874), 1557 children (46.2% girls) and 1454 parents (85.5% mothers) provided random urine samples at the visit; samples from menstruating females were excluded.Outcome measuresUrine albumin-to-creatinine ratio (ACR) and its components (urine albumin and creatinine concentration); albuminuria was defined as an ACR ≥3.4 mg/mmol. Pearson’s correlation coefficients and multivariable linear regression models assessed parent–child concordance, using log-transformed data due to skewing. Survey weights and methods were applied to account for the complex sample design.ResultsThe median ACR for children was 1.03 mg/mmol (IQR 0.65–1.97) and 1.01 mg/mmol (IQR 0.60–2.09) for adults. The median ACR was higher in girls (1.20, IQR 0.71–2.65) than boys (0.90, IQR 0.61–1.65) and in mothers (1.13, IQR 0.63–2.33) than fathers (0.66, IQR 0.41–1.05). Albuminuria was detected in 15.1% of children (girls 20.8%, boys 10.1%) and 13.5% of adults (15.1% mothers, 4.0% fathers) had albuminuria. There was a small correlation between parent and child ACR (Pearson correlation coefficient 0.06, 95% CI 0.01 to 0.12).ConclusionsAlbuminuria is common among Australian children and adults, which is of concern because it predicts risk for kidney and cardiovascular disease, and mortality. The weak concordance among intergenerational pairs for urine ACR suggests either that genetic heritability is low or that it becomes evident only at later offspring life stages.

To evaluate the effectiveness of educational interventions in improving medication adherence among adult patients diagnosed with hypertension, hyperlipidaemia and/or diabetes.This review was conducted with reference to methods set out in the Cochrane Handbook for Systematic Reviews of Interventions (PROSPERO registration number: CRD42016053402).A search from seven electronic databases (2003-2016).The quality of evidence and strength of the studies was evaluated systematically, followed by an assessment of risks of bias by two reviewers with the Cochrane Collaboration's tool.Eighteen randomized controlled trials demonstrated a low to moderate quality evidence on the improvements of medication adherence with educational interventions. Participants with type 2 diabetes benefited from education interventions but not those with hypertension. No randomized controlled trials (RCT) was found for participants with hyperlipidaemia. Education that was conducted at home showed better medication adherence than education conducted in clinics. Medication adherence was improved after two to three sessions but no significant differences found after three sessions.Through education, health literacy is improved, thus improving medication adherence.A plethora of educational interventions have been implemented in the clinical settings, but no reviews have hitherto been conducted on their effectiveness. This review suggested that education improves health literacy which is directly proportionate to optimal disease management including medication adherence. The suggestions proposed in this review may impact the individual in terms of their adherence to medication to tackle exacerbation and relapse of chronic diseases and also proposed suggestions for future implementation of an education intervention.目的: 在于评价,教育干预措施能有效提高高血压、高脂血症和/或糖尿病成年患者的服药依从性。 设计: 通过参考《Cochrane 干预措施系统评价手册》(PROSPERO 登记号:CRD42016053402)中规定的方法进行审查。 资料来源: 搜索了七个电子数据库(从2003年至2016年)。 综述方法: 系统性地评估了证据质量和研究强度,然后由两位审查者使用Cochrane 协作组织的工具评估了偏倚风险。 结果: 十八项随机对照试验展现了教育干预措施改善服药依从性的低至中等质量证据。2型糖尿病患者受益于教育干预措施,但高血压患者则没有。没有发现针对高脂血症参与者进行的随机对照试验(RCT)。在家进行的教育比在诊所进行的教育显示出更好的服药依从性。虽然两到三次疗程后的服药依从性有所改善,但三次疗程后却没有发现显著性差异。 结论: 通过教育,提高了健康素养,从而改改善了服药依从性。 影响: 在临床环境中采取了大量的教育干预措施,但迄今为止尚未对其有效性进行审查。这篇综述表明,教育可以提高健康素养,而健康素养与最佳疾病管理(包括服药依从性)成正比。本综述中提出的建议可能会对个体在坚持治疗慢性疾病恶化和复发方面产生影响,并对未来实施教育干预提供了建议。.

Cancer chemotherapy possesses high toxicity, particularly when a higher concentration of drugs is administered to patients. Therefore, searching for more effective compounds to reduce the toxicity of treatments, while still producing similar effects as current chemotherapy regimens, is required. Currently, the search for potential anticancer agents involves a random, inaccurate process with strategic deficits and a lack of specific targets. For this reason, the initial in vitro high‑throughput steps in the screening process should be reviewed for rapid identification of the compounds that may serve as anticancer agents. The present study aimed to investigate the potential use of the Pichia pastoris strain SMD1168H expressing DNA topoisomerase I (SMD1168H‑TOPOI) in a yeast‑based assay for screening potential anticancer agents. The cell density that indicated the growth of the recombinant yeast without treatment was first measured by spectrophotometry. Subsequently, the effects of glutamate (agonist) and camptothecin (antagonist) on the recombinant yeast cell density were investigated using the same approach, and finally, the effect of camptothecin on various cell lines was determined and compared with its effect on recombinant yeast. The current study demonstrated that growth was enhanced in SMD1168H‑TOPOI as compared with that in SMD1168H. Glutamate also enhanced the growth of the SMD1168H; however, the growth effect was not enhanced in SMD1168H‑TOPOI treated with glutamate. By contrast, camptothecin caused only lower cell density and growth throughout the treatment of SMD1168H‑TOPOI. The findings of the current study indicated that SMD1168H‑TOPOI has similar characteristics to MDA‑MB‑231 cells; therefore, it can be used in a yeast‑based assay to screen for more effective compounds that may inhibit the growth of highly metastatic breast cancer cells.

Frontal fibrosing alopecia (FFA) is a recently described inflammatory and scarring type of hair loss affecting almost exclusively women. Despite a dramatic recent increase in incidence the aetiopathogenesis of FFA remains unknown. We undertake genome-wide association studies in females from a UK cohort, comprising 844 cases and 3,760 controls, a Spanish cohort of 172 cases and 385 controls, and perform statistical meta-analysis. We observe genome-wide significant association with FFA at four genomic loci: 2p22.2, 6p21.1, 8q24.22 and 15q2.1. Within the 6p21.1 locus, fine-mapping indicates that the association is driven by the HLA-B*07:02 allele. At 2p22.1, we implicate a putative causal missense variant in CYP1B1, encoding the homonymous xenobiotic- and hormone-processing enzyme. Transcriptomic analysis of affected scalp tissue highlights overrepresentation of transcripts encoding components of innate and adaptive immune response pathways. These findings provide insight into disease pathogenesis and characterise FFA as a genetically predisposed immuno-inflammatory disorder driven by HLA-B*07:02., Frontal fibrosing alopecia (FFA) features lichenoid cutaneous inflammation and scarring hair loss. Here, Tziotzios et al. identify four genetic loci associated with FFA by GWAS followed by Bayesian fine-mapping, co-localisation and HLA imputation which highlights HLA-B*07:02 as a risk factor.

Hypertension is increasingly recognized as a disease spanning the entire life course. Continued efforts to refine the diagnosis and management of hypertension in children are highlighted by the recent American Academy of Pediatrics (AAP) guidelines, which include lower threshold values than the previous reference standard (Fourth Report). We aimed to determine the population-based prevalence of children exceeding thresholds for hypertension using these two guidelines. We also sought to identify the correlates of blood pressure (BP) among Australian children. Cross-sectional data from the Growing Up in Australia: Longitudinal Survey of Australian Children were analyzed. Blood pressure was measured in 7139 Australian children aged 10–12 years and sampled using population-based methodology. The association between BP and explanatory variables linked to BP in other populations was examined using multiple linear regression with fractional polynomial terms for continuous, non-linear relationships. The threshold for hypertension was exceeded in 3.1% and 5.4%, and prehypertension in 3.0% and 3.7% of children, using the Fourth Report and AAP guidelines respectively. Children at the threshold for obesity had a 9.1 mmHg higher adjusted BP than those on the 50th centile for body mass index (BMI) (95% CI 8.4 to 9.9). BMI had a non-linear relationship with BP, and the magnitude of association between BMI and BP increased with BMI. Socioeconomic status, hypertension during pregnancy, birth weight, and sports participation were also independently associated with BP. Using the AAP guidelines is likely to substantially increase the population prevalence of hypertension. The association between BMI and BP was strongest and non-linear for obese children, who should be the focus of interventional trials.

Objectives Stenotrophomonas maltophilia is an opportunistic pathogen known to form biofilms on contact lens and case surfaces that may result in permanent visual loss in cases of microbial keratitis. Because of its multiple drug resistance and extremely low incidence, there is little consensus on treatment. We investigated the predisposing factors, management, and visual outcomes in a small case series of patients to better inform the management of this rarely reported keratitis. Methods Retrospective analysis of medical records was performed at a single tertiary referral center between 2011 and 2017. The case notes of each microbiology confirmed S. maltophilia keratitis were examined. Results Six cases were identified (four men) with a median age of 62 years (range 1 month-90 years) and pre-existing ocular surface disease in all cases. At presentation, four patients were using bandage contact lenses and three were on topical antibiotic and steroid medications. Initial antibiotic treatment was intensive topical 0.3% ofloxacin and 5% cefuroxime, which was modified based on corneal scrape culture and sensitivity and clinical findings. One patient chose not to complete the treatment course. The 5 remaining patients had complete resolution of ulceration over a mean of 2.9 months (SD 0.8 months). Conclusions Contact lens in the context of ocular surface problems, prolonged topical antibiotic and steroid treatments may predispose to S. maltophilia, a rare cause of keratitis. We report successful treatment with case-specific combinations of topical antibiotics such as fluoroquinolone, cotrimoxazole, and/or cephalosporin agents, although visual outcomes remain poor due to corneal scar.

Blunt abdominal aortic injury in children is a rare clinical entity with which most vascular surgeons have minimal experience. The evidence for management recommendations is limited. We have reported a single institution's experience in the care of pediatric abdominal aortic injuries.We performed a retrospective review of consecutive pediatric patients who had been diagnosed with blunt traumatic abdominal aortic injury at our institution from 2008 to 2019.A total of 16 pediatric patients (50% male) were identified. They ranged in age from 4 to 17 years. All had been involved in motor vehicle collisions and had been restrained passengers with a seatbelt in use. Five patients (31%) were hypotensive en route or on arrival. Seven patients (44%) had been transferred from another hospital. The median injury severity score was 34 (interquartile range, 19-35). The infrarenal aortic injuries were stratified using the aortic injury grading classification (five, two, seven, and two with grade 1, 2, 3, and 4, respectively). Concurrent nonaortic injuries included solid organ (63%; n = 10), hollow viscus (88%; n = 14), brain (25%; n = 4), hemothorax or pneumothorax (25%; n = 4), spine fractures (81%; n = 13), and nonspine fractures (75%; n = 12). Of the 16 patients, 9 (56%) had required aortic repair. Three had required immediate revascularization for distal ischemia. The remaining six patients (38%) had undergone delayed repair, with a median interval to repair of 52 days (range, 2-916 days). One half of the delayed repairs were performed during the index hospitalization. On repeat axial imaging, the three patients who had undergone delayed repair were found to have enlarging pseudoaneurysms or flow-limiting dissections and had subsequently undergone repair during the index hospitalization. Only one patient had undergone endovascular repair. No deaths occurred, and the median follow-up was 7 months (interquartile range, 3-28 months) for our study population. All postoperative patients demonstrated stable imaging findings without requiring further intervention. Seven patients, whose injury grades had ranged from 1 to 3, were observed. Their repeat imaging studies demonstrated either stability or resolution of their aortic injury. However, one half of the patients had been lost to follow-up after discharge or after their first postoperative clinic visit.Delayed aortic intervention can be safely performed for most pediatric patients with blunt abdominal aortic injuries with preserved distal perfusion to the lower extremities. This finding suggests that transfer to a tertiary center with vascular expertise is a safe and feasible management strategy. However, the progression of aortic injuries was seen as early as within 48 hours and as late as 30 months after injury, underscoring the importance of long-term surveillance. However, in our cohort, 50% of the children were lost to follow-up, highlighting the need for a more structured surveillance strategy.

In this day and age, the expectation of cosmetic products to effectively slow down skin photoaging is constantly increasing. However, the detrimental effects of UVB on the skin are not easy to tackle as UVB dysregulates a wide range of molecular changes on the cellular level. In our research, irradiated keratinocyte cells not only experienced a compromise in their redox system, but processes from RNA translation to protein synthesis and folding were also affected. Aside from this, proteins involved in various other processes like DNA repair and maintenance, glycolysis, cell growth, proliferation, and migration were affected while the cells approached imminent cell death. Additionally, the collagen degradation pathway was also activated by UVB irradiation through the upregulation of inflammatory and collagen degrading markers. Nevertheless, with the treatment of Swietenia macrophylla (S. macrophylla) seed extract and fractions, the dysregulation of many genes and proteins by UVB was reversed. The reversal effects were particularly promising with the S. macrophylla hexane fraction (SMHF) and S. macrophylla ethyl acetate fraction (SMEAF). SMHF was able to oppose the detrimental effects of UVB in several different processes such as the redox system, DNA repair and maintenance, RNA transcription to translation, protein maintenance and synthesis, cell growth, migration and proliferation, and cell glycolysis, while SMEAF successfully suppressed markers related to skin inflammation, collagen degradation, and cell apoptosis. Thus, in summary, our research not only provided a deeper insight into the molecular changes within irradiated keratinocytes, but also serves as a model platform for future cosmetic research to build upon. Subsequently, both SMHF and SMEAF also displayed potential photoprotective properties that warrant further fractionation and in vivo clinical trials to investigate and obtain potential novel bioactive compounds against photoaging.

The COVID‐19 pandemic is a unique challenge that has disrupted endoscopy training. Initial infection control measures aimed at protecting patients and staff meant nonessential endoscopic activity was suspended in many countries. The decrease in elective caseload from the pandemic also reduced training numbers during this period. While hands‐on training took a backseat, more efforts were directed to didactic training of cognitive competencies. We review the literature describing the impact of COVID‐19 on endoscopy training and summarize key measures aimed at mitigating this effect. These include leveraging on web‐based didactic material and video‐conferences, increased use of simulation and models to hone technical competencies, and a shift in focus from numbers‐based accreditation to competency‐based accreditation. While COVID‐19 was hoped to be short‐lived, it is clear the impact is long‐lasting. Hence, it is crucial for training programs to take stock of how endoscopy training is evolving and use this opportunity to implement new paradigms into their endoscopic training curricula. COVID‐19 might just be the catalyst that transforms endoscopy training into a new digital era.

Background and aim: Gastrointestinal manifestations of the coronavirus disease 2019 (COVID-19) pandemic may mimic irritable bowel syndrome (IBS), and social distancing measures may affect IBS patients negatively. We aimed to study the impact of COVID-19 on respondents with self-reported IBS. Methods: We conducted an anonymized survey from May to June 2020 in 33 countries. Knowledge, attitudes, and practices on personal hygiene and social distancing as well as psychological impact of COVID-19 were assessed. Statistical analysis was performed to determine differences in well-being and compliance to social distancing measures between respondents with and without self-reported IBS. Factors associated with improvement or worsening of IBS symptoms were evaluated. Results: Out of 2704 respondents, 2024 (74.9%) did not have IBS, 305 (11.3%) had self-reported IBS, and 374 (13.8%) did not know what IBS was. Self-reported IBS respondents reported significantly worse emotional, social, and psychological well-being compared with non-IBS respondents and were less compliant to social distancing measures (28.2% vs 35.3%, P = 0.029); 61.6% reported no change, 26.6% reported improvement, and 11.8% reported worsening IBS symptoms. Higher proportion of respondents with no change in IBS symptoms were willing to practice social distancing indefinitely versus those who deteriorated (74.9% vs 51.4%, P = 0.016). In multivariate analysis, willingness to continue social distancing for another 2-3 weeks (vs longer period) was significantly associated with higher odds of worsening IBS. Conclusion: Our study showed that self-reported IBS respondents had worse well-being and compliance to social distancing measures than non-IBS respondents. Future research will focus on occupational stress and dietary changes during COVID-19 that may influence IBS.

BACKGROUND Research into environmentally friendly alternatives to conventional plant protection products, to promote sustainable agriculture and healthy food, is strongly encouraged. RESULTS In this context, 20 naturally occurring terpenoids and phenolic compounds were selected and evaluated in vitro as crop protection compounds against Zymoseptoria tritici, the causal agent of Septoria tritici blotch of wheat. After selection of the most active compounds, some hemisynthetic modifications were conducted to modify their lipophilicity. These modifications led to the discovery of sesamol esters as promising antifungal agents, with IC50 around 10 μg/mL and a total absence of cytotoxicity against human cells. CONCLUSION These sesamol-based derivatives should be selected for further evaluations in planta to validate their use as wheat crop protection agents. Moreover, the importance of a balanced hydrophily/lipophilicity ratio should be further studied. © 2021 Society of Chemical Industry.