COVID-19 susceptibility and clinical outcomes in inflammatory bowel disease: An updated systematic review and meta-analysis.

The susceptibility, risk factors, and prognosis of COVID-19 in patients with inflammatory bowel disease (IBD) remain unknown. Thus, our study aims to assess the prevalence and clinical outcomes of COVID-19 in IBD. We searched PubMed, EMBASE, and medRxiv from 2019 to 1 June 2022 for cohort and case-control studies comparing the prevalence and clinical outcomes of COVID-19 in patients with IBD and in the general population. We also compared the outcomes of patients receiving and not receiving 5-aminosalicylates (ASA), tumour necrosis factor antagonists, biologics, systemic corticosteroids, or immunomodulators for IBD. Thirty five studies were eligible for our analysis. Pooled odds ratio of COVID-19-related hospitalisation, intensive care unit (ICU) admission, or death in IBD compared to in non-IBD were 0.58 (95% confidence interval (CI) = 0.28-1.18), 1.09 (95% CI = 0.27-4.47), and 0.67 (95% CI = 0.32-1.42), respectively. Inflammatory bowel disease was not associated with increased hospitalisation, ICU admission, or death. Susceptibility to COVID-19 did not increase with any drugs for IBD. Hospitalisation, ICU admission, and death were more likely with 5-ASA and corticosteroid use. COVID-19-related hospitalisation (Odds Ratio (OR): 0.53; 95% CI = 0.38-0.74) and death (OR: 0.13; 95% CI = 0.13-0.70) were less likely with Crohn's disease than ulcerative colitis (UC). In conclusion, IBD does not increase the mortality and morbidity of COVID-19. However, physicians should be aware that additional monitoring is needed in UC patients or in patients taking 5-ASA or systemic corticosteroids.

An atlas of associations between 14 micronutrients and 22 cancer outcomes: Mendelian randomization analyses.

BACKGROUND: Micronutrients, namely vitamins and minerals, are associated with cancer outcomes; however, their reported effects have been inconsistent across studies. We aimed to identify the causally estimated effects of micronutrients on cancer by applying the Mendelian randomization (MR) method, using single-nucleotide polymorphisms associated with micronutrient levels as instrumental variables. METHODS: We obtained instrumental variables of 14 genetically predicted micronutrient levels and applied two-sample MR to estimate their causal effects on 22 cancer outcomes from a meta-analysis of the UK Biobank (UKB) and FinnGen cohorts (overall cancer and 21 site-specific cancers, including breast, colorectal, lung, and prostate cancer), in addition to six major cancer outcomes and 20 cancer subset outcomes from cancer consortia. We used sensitivity MR methods, including weighted median, MR-Egger, and MR-PRESSO, to assess potential horizontal pleiotropy or heterogeneity. Genome-wide association summary statistical data of European descent were used for both exposure and outcome data, including up to 940,633 participants of European descent with 133,384 cancer cases. RESULTS: In total, 672 MR tests (14 micronutrients × 48 cancer outcomes) were performed. The following two associations met Bonferroni significance by the number of associations (P < 0.00016) in the UKB plus FinnGen cohorts: increased risk of breast cancer with magnesium levels (odds ratio [OR] = 1.281 per 1 standard deviation [SD] higher magnesium level, 95% confidence interval [CI] = 1.151 to 1.426, P < 0.0001) and increased risk of colorectal cancer with vitamin B12 level (OR = 1.22 per 1 SD higher vitamin B12 level, 95% CI = 1.107 to 1.345, P < 0.0001). These two associations remained significant in the analysis of the cancer consortia. No significant heterogeneity or horizontal pleiotropy was observed. Micronutrient levels were not associated with overall cancer risk. CONCLUSIONS: Our results may aid clinicians in deciding whether to regulate the intake of certain micronutrients, particularly in high-risk groups without nutritional deficiencies, and may help in the design of future clinical trials.

Age at onset of mental disorders worldwide: large-scale meta-analysis of 192 epidemiological studies.

Promotion of good mental health, prevention, and early intervention before/at the onset of mental disorders improve outcomes. However, the range and peak ages at onset for mental disorders are not fully established. To provide robust, global epidemiological estimates of age at onset for mental disorders, we conducted a PRISMA/MOOSE-compliant systematic review with meta-analysis of birth cohort/cross-sectional/cohort studies, representative of the general population, reporting age at onset for any ICD/DSM-mental disorders, identified in PubMed/Web of Science (up to 16/05/2020) (PROSPERO:CRD42019143015). Co-primary outcomes were the proportion of individuals with onset of mental disorders before age 14, 18, 25, and peak age at onset, for any mental disorder and across International Classification of Diseases 11 diagnostic blocks. Median age at onset of specific disorders was additionally investigated. Across 192 studies (n = 708,561) included, the proportion of individuals with onset of any mental disorders before the ages of 14, 18, 25 were 34.6%, 48.4%, 62.5%, and peak age was 14.5 years (k = 14, median = 18, interquartile range (IQR) = 11-34). For diagnostic blocks, the proportion of individuals with onset of disorder before the age of 14, 18, 25 and peak age were as follows: neurodevelopmental disorders: 61.5%, 83.2%, 95.8%, 5.5 years (k = 21, median=12, IQR = 7-16), anxiety/fear-related disorders: 38.1%, 51.8%, 73.3%, 5.5 years (k = 73, median = 17, IQR = 9-25), obsessive-compulsive/related disorders: 24.6%, 45.1%, 64.0%, 14.5 years (k = 20, median = 19, IQR = 14-29), feeding/eating disorders/problems: 15.8%, 48.1%, 82.4%, 15.5 years (k = 11, median = 18, IQR = 15-23), conditions specifically associated with stress disorders: 16.9%, 27.6%, 43.1%, 15.5 years (k = 16, median = 30, IQR = 17-48), substance use disorders/addictive behaviours: 2.9%, 15.2%, 48.8%, 19.5 years (k = 58, median = 25, IQR = 20-41), schizophrenia-spectrum disorders/primary psychotic states: 3%, 12.3%, 47.8%, 20.5 years (k = 36, median = 25, IQR = 20-34), personality disorders/related traits: 1.9%, 9.6%, 47.7%, 20.5 years (k = 6, median = 25, IQR = 20-33), and mood disorders: 2.5%, 11.5%, 34.5%, 20.5 years (k = 79, median = 31, IQR = 21-46). No significant difference emerged by sex, or definition of age of onset. Median age at onset for specific mental disorders mapped on a time continuum, from phobias/separation anxiety/autism spectrum disorder/attention deficit hyperactivity disorder/social anxiety (8-13 years) to anorexia nervosa/bulimia nervosa/obsessive-compulsive/binge eating/cannabis use disorders (17-22 years), followed by schizophrenia, personality, panic and alcohol use disorders (25-27 years), and finally post-traumatic/depressive/generalized anxiety/bipolar/acute and transient psychotic disorders (30-35 years), with overlap among groups and no significant clustering. These results inform the timing of good mental health promotion/preventive/early intervention, updating the current mental health system structured around a child/adult service schism at age 18.

The impact of urinary incontinence on multiple health outcomes: an umbrella review of meta-analysis of observational studies.

BACKGROUND AND AIM: We aimed to capture the breadth of health outcomes that have been associated with the presence of Urinary Incontinence (UI) and systematically assess the quality, strength, and credibility of these associations through an umbrella review and integrated meta-analyses. METHODS: We assessed meta-analyses of observational studies based on random-effect summary effect sizes and their p-values, 95% prediction intervals, heterogeneity, small-study effects, and excess significance. We graded the evidence from convincing (Class I) to weak (Class IV). RESULTS AND DISCUSSION: From 3172 articles returned in search of the literature, 9 systematic reviews were included with a total of 41 outcomes. Overall, 37 out of the 41 outcomes reported nominally significant summary results (p < 0.05), with 22 associations surviving the application of a more stringent p-value (p < 10-6). UI was associated with worse scores than controls in female sexual function (Class II), while it was also associated with a higher prevalence of depression (odds ratio [OR] = 1.815; 95% confidence interval [CI]: 1.551-2.124), and anxiety (OR = 1.498; 95% CI: 1.273-1.762) (Class IV). UI was associated with poorer quality of life (QoL), higher rate of mortality (hazard ratio = 2.392; 95% CI: 2.053-2.787) an increase in falls, frailty, pressure ulcers, diabetes, arthritis, and fecal incontinence (Class IV). CONCLUSIONS: UI is associated with female sexual dysfunction, with highly suggestive evidence. However, the evidence of other adverse outcomes including depression, anxiety, poorer QoL, higher mortality, falls, pressure ulcers, diabetes, arthritis, fecal incontinence, and frailty is only weak. A multidimensional approach should be taken in managing UI in the clinical setting.

Causes for Retraction in the Biomedical Literature: A Systematic Review of Studies of Retraction Notices.

BACKGROUND: Many studies have evaluated the prevalence of different reasons for retraction in samples of retraction notices. We aimed to perform a systematic review of such empirical studies of retraction causes. METHODS: The PubMed/MEDLINE database and the Embase database were searched in June 2023. Eligible studies were those containing sufficient data on the reasons for retraction across samples of examined retracted notices. RESULTS: A 11,181 potentially eligible items were identified, and 43 studies of retractions were included in this systematic review. Studies limited to retraction notices of a specific subspecialty or country, journal/publication type are emerging since 2015. We noticed that the reasons for retraction are becoming more specific and more diverse. In a meta-analysis of 17 studies focused on different subspecialties, misconduct was responsible for 60% (95% confidence interval [CI], 53-67%) of all retractions while error and publication issues contributed to 17% (95% CI, 12-22%) and 9% (95% CI, 6-13%), respectively. The end year of the retraction period in all included studies and the proportion of misconduct presented a weak positive association (coefficient = 1.3% per year, P = 0.002). CONCLUSION: Misconduct seems to be the most frequently recorded reason for retraction across empirical analyses of retraction notices, but other reasons are not negligible. Greater specificity of causes and standardization is needed in retraction notices.

Correlations between sleep problems, core symptoms, and behavioral problems in children and adolescents with autism spectrum disorder: a systematic review and meta-analysis.

Children and adolescents with autism spectrum disorder (ASD) experience various sleep problems. Sleep problems co-occur in a bidirectional relationship with ASD core symptoms and behavioral problems. However, studies on how these three factors are intricately linked to each other are limited. This meta-analysis examined the differential relationship between specific sleep problems, core symptoms, and behavioral problems in this population. This study was registered in PROSPERO (CRD42022339695). We systematically searched the PubMed/MEDLINE, Web of Science, and Scopus databases from inception to April 27, 2022. Observational studies that reported correlations between measures of sleep problems, ASD core symptoms, or ASD behavioral problems were included, and participants aged 18 years or below were enrolled. The correlation coefficient (r) was assessed as the primary effect metric. Total 22 cross-sectional studies were included, which comprised 2655 participants (mean age = 6.60 years old; mean percentage of boys = 80.64%). We found correlations between total sleep problems and total core symptoms (r 0.293 [95% confidence interval - 0.095 to 0.604]), total sleep problems and total behavioral problems (r 0.429 [0.299-0.544]), and total core symptoms and total behavioral problems (r - 0.050 [- 0.177 to 0.079]) and identified statistically significant correlations between specific components of sleep problems, ASD core symptoms, and ASD behavioral problems. Each specific sleep problem showed a unique association with core symptoms and behavioral problems. Sleep problems in ASD should be explored in detail, and the closely linked core symptoms and behavioral problems should be common therapeutic targets.

Lichen Sclerosus and Sexual Dysfunction: A Systematic Review and Meta-Analysis.

BACKGROUND: Lichen sclerosus (LS) is a common autoimmune dermatological condition that is often under-diagnosed in women and has been documented to affect quality of life and sexual function. AIM: To determine the prevalence of sexual dysfunction among women with vulvar lichen sclerosus. METHODS: The authors conducted a systematic review and meta-analysis of the existing research on LS and sexual function in database including PubMed using search terms: lichen sclerosus OR vulvar lichen sclerosus OR vulvar lichen sclerosus et atrophicus OR kraurosis vulvae) AND (sexual function OR sexual functions OR sexual disorder OR sexual disorders OR sexual activity OR sexual activities OR sexual dysfunction OR sexual dysfunctions OR dyspareunia OR vaginismus). OUTCOMES: Nearly 60% of women with lichen sclerosus suffer from sexual dysfunction. RESULTS: Two hundred and ten studies were initially identified. Twenty-six articles met inclusion criteria and 3 were excluded as they did not relate to sexual function, were regarding a surgical or medical intervention and sexual dysfunction and one was a review article. Therefore, 23 studies were included in the final analysis resulting in a cumulative 486 participants with LS with 208 patients experiencing any kind of sexual dysfunction. Meta-analysis presented prevalence of sexual dysfunction among LS patients as 59% (95% CI: 48 - 70%). Dyspareunia or generalized pain with intercourse was the most commonly reported type of dysfunction. CLINICAL IMPLICATIONS: Discussing sexual concerns with women with LS could empower them to seek treatment. STRENGTHS AND LIMITATIONS: Few articles met criteria for inclusion. CONCLUSION: A large proportion of women with LS experience sexual dysfunction. More research is needed, especially that which includes biopsy-proven LS and validated tools on sexual function. Pope R, Lee MH, Myers A, et al. Lichen Sclerosus and Sexual Dysfunction: A Systematic Review and Meta-Analysis. J Sex Med 2022;19:1616-1624.

Association between adiposity and cardiovascular outcomes: an umbrella review and meta-analysis of observational and Mendelian randomization studies.

AIMS: The aim of this study was to investigate the causal relationship and evidence of an association between increased adiposity and the risk of incident cardiovascular disease (CVD) events or mortality. METHODS AND RESULTS: Observational (informing association) and Mendelian randomization (MR) (informing causality) studies were assessed to gather mutually complementary insights and elucidate perplexing epidemiological relationships. Systematic reviews and meta-analyses of observational and MR studies that were published until January 2021 and evaluated the association between obesity-related indices and CVD risk were searched. Twelve systematic reviews with 53 meta-analyses results (including over 501 cohort studies) and 12 MR studies were included in the analysis. A body mass index (BMI) increase was associated with higher risks of coronary heart disease, heart failure, atrial fibrillation, all-cause stroke, haemorrhagic stroke, ischaemic stroke, hypertension, aortic valve stenosis, pulmonary embolism, and venous thrombo-embolism. The MR study results demonstrated a causal effect of obesity on all indices but stroke. The CVD risk increase for every 5 kg/m2 increase in BMI varied from 10% [relative risk (RR) 1.10; 95% confidence interval (CI) 1.01-1.21; certainty of evidence, low] for haemorrhagic stroke to 49% (RR 1.49; 95% CI 1.40-1.60; certainty of evidence, high) for hypertension. The all-cause and CVD-specific mortality risks increased with adiposity in cohorts, but the MR studies demonstrated no causal effect of adiposity on all-cause mortality. CONCLUSION: High adiposity is associated with increased CVD risk despite divergent evidence gradients. Adiposity was a causal risk factor for CVD except all-cause mortality and stroke. Half (49%; 26/53) of the associations were supported by high-level evidence. The associations were consistent between sexes and across global regions. This study provides guidance on how to integrate evidence from observational (association) and genetics-driven (causation) studies accumulated to date, to enable a more reliable interpretation of epidemiological relationships.

Predictors of mortality in thrombotic thrombocytopenia after adenoviral COVID-19 vaccination: the FAPIC score.

AIMS: The clinical manifestation and outcomes of thrombosis with thrombocytopenia syndrome (TTS) after adenoviral COVID-19 vaccine administration are largely unknown due to the rare nature of the disease. We aimed to analyse the clinical presentation, treatment modalities, outcomes, and prognostic factors of adenoviral TTS, as well as identify predictors for mortality. METHODS AND RESULTS: PubMed, Scopus, Embase, and Web of Science databases were searched and the resulting articles were reviewed. A total of 6 case series and 13 case reports (64 patients) of TTS after ChAdOx1 nCoV-19 vaccination were included. We performed a pooled analysis and developed a novel scoring system to predict mortality. The overall mortality of TTS after ChAdOx1 nCoV-19 vaccination was 35.9% (23/64). In our analysis, age ≤60 years, platelet count <25 × 103/µL, fibrinogen <150 mg/dL, the presence of intracerebral haemorrhage (ICH), and the presence of cerebral venous thrombosis (CVT) were significantly associated with death and were selected as predictors for mortality (1 point each). We named this novel scoring system FAPIC (fibrinogen, age, platelet count, ICH, and CVT), and the C-statistic for the FAPIC score was 0.837 (95% CI 0.732-0.942). Expected mortality increased with each point increase in the FAPIC score, at 2.08, 6.66, 19.31, 44.54, 72.94, and 90.05% with FAPIC scores 0, 1, 2, 3, 4, and 5, respectively. The FAPIC scoring model was internally validated through cross-validation and bootstrapping, then externally validated on a panel of TTS patients after Ad26.COV2.S administration. CONCLUSIONS: Fibrinogen levels, age, platelet count, and the presence of ICH and CVT were significantly associated with mortality in patients with TTS, and the FAPIC score comprising these risk factors could predict mortality. The FAPIC score could be used in the clinical setting to recognize TTS patients at high risk of adverse outcomes and provide early intensive interventions including intravenous immunoglobulins and non-heparin anticoagulants.

Is nutritional labeling associated with individual health? The effects of labeling-based awareness on dyslipidemia risk in a South Korean population.

BACKGROUND: In 1995, the South Korean government made nutrition labeling compulsory, which has positively impacted patients with certain chronic diseases, such as dyslipidemia. We investigated the association between nutrition labeling-based awareness and the risk of dyslipidemia among individuals not yet diagnosed. METHODS: Our study used data from the fifth Korea National Health and Nutrition Examination Surveys administered during 2010-2014 (n = 17,687). We performed multiple or logistic regression analysis to examine the association between nutritional analysis and various outcome variables. RESULTS: Approximately 70 % of the respondents (n = 11,513) were familiar with nutrition labeling, of which 20 % (n = 3172) decided what food to buy based on that information. This awareness yielded mostly positive results on outcome indicators, such as triglyceride and high-density lipoprotein cholesterol levels. In general, individuals who used nutritional labels to make decisions regarding food purchases had a lower risk of dyslipidemia than individuals who did not (OR: 0.806, 95 % CI: 0.709-0.917). CONCLUSION: Utilizing nutrition labels for making food choices correlated with a lower risk of dyslipidemia in certain subgroups. Based on our findings, we recommend that health policymakers and medical professionals consider promoting nutrition labeling as an alternative method for managing certain chronic diseases in South Korean patients.

3D reconstruction of skin pathological tissue: the understanding of microrelief pattern and dermal ridge.

AIM: Most studies about the structures of the human skin have been on the general histologic features of the skin. The purpose of this study was to understand the relationship between the microrelief (MR) pattern and histologic structure of the human skin, and to find the usefulness of the three-dimensional reconstruction (3DR) technique of pathological skin tissue. MATERIALS, SUBJECTS, AND METHODS: Human skin specimens were obtained from the medial forearm, abdomen, and volar aspects of the finger tips of cadavers. Two-dimensional surface-viewed images of the skin showing MR patterns were obtained using dry dermoscopy. Histologic structures of the skin were evaluated by 3D images obtained using the 3DR technique. RESULTS: MR was deeper and wider in the abdomen than in the medial side of the forearm. In the medial side of the forearm, 10.27 rete ridges were distributed in a plateau, on average. In the abdomen, about 14.37 rete ridges were distributed in a plateau. From 3DR technique, MR pattern thought to be a superordinate concept to rete ridges. CONCLUSION: The 3DR technique was useful and may allow a better understanding of the pathogenetic changes in the skin surface in aging skin.

Association of bariatric surgery with indicated and unintended outcomes: An umbrella review and meta-analysis for risk-benefit assessment.

Bariatric surgery can cause numerous functional changes to recipients, some of which are unintended. However, a systematic evaluation of wide-angled health benefits and risks following bariatric surgery has not been conducted. We systematically evaluated published systematic reviews of randomized controlled trials and observational studies reporting the association between bariatric surgery and health outcomes. We performed subgroup analyses by surgery type and sensitivity analysis, excluding gastric band. Thirty systematic reviews and 82 meta-analyzed health outcomes were included in this review. A total of 66 (80%) health outcomes were significantly associated with bariatric surgery, of which 10 were adverse outcomes, including suicide, fracture, gastroesophageal reflux after sleeve gastrectomy, and neonatal morbidities. The other 56 outcomes were health benefits including new-onset diabetes mellitus (DM) (odds ratio [OR] = 0.39; 95% confidence interval [CI] = 0.19-0.79), hypertension (OR = 0.36; 95% CI = 0.33-0.40), dyslipidemia (OR = 0.33; 95% CI = 0.14-0.81), cancers (OR = 0.65; 95% CI = 0.53-0.80), cardiovascular diseases (CVDs), and women's health. Surgery is associated with reductions in all-cause mortality and death due to cancer, DM, and CVD. Bariatric surgery has both beneficial and harmful effects on a broader than expected array of patients' health outcomes. An expansion of the indication for bariatric surgery could be discussed to include a broader population with metabolic vulnerabilities.

Pharmacological and non-pharmacological interventions for irritability in autism spectrum disorder: a systematic review and meta-analysis with the GRADE assessment.

BACKGROUND: Numerous interventions for irritability in autism spectrum disorder (ASD) have been investigated. We aimed to appraise the magnitude of pharmacological and non-pharmacological interventions for irritability in ASD without any restrictions in terms of eligible interventions. METHODS: We systematically searched PubMed/MEDLINE, Scopus, and Web of Science until April 15, 2023. We included randomized controlled trials (RCTs) with a parallel design that examined the efficacy of interventions for the treatment of irritability in patients of any age with ASD without any restrictions in terms of eligible interventions. We performed a random-effects meta-analysis by pooling effect sizes as Hedges' g. We classified assessed interventions as follows: pharmacological monotherapy, risperidone plus adjuvant therapy versus risperidone monotherapy, non-pharmacological intervention, and dietary intervention. We utilized the Cochrane tool to evaluate the risk of bias in each study and the GRADE approach to assess the certainty of evidence for each meta-analyzed intervention. RESULTS: Out of 5640 references, we identified 60 eligible articles with 45 different kinds of interventions, including 3531 participants, of which 80.9% were males (mean age [SD] = 8.79 [3.85]). For pharmacological monotherapy, risperidone (Hedges' g - 0.857, 95% CI - 1.263 to - 0.451, certainty of evidence: high) and aripiprazole (Hedges' g - 0.559, 95% CI - 0.767 to - 0.351, certainty of evidence: high) outperformed placebo. Among the non-pharmacological interventions, parent training (Hedges' g - 0.893, 95% CI - 1.184 to - 0.602, certainty of evidence: moderate) showed a significant result. None of the meta-analyzed interventions yielded significant effects among risperidone + adjuvant therapy and dietary supplementation. However, several novel molecules in augmentation to risperidone outperformed risperidone monotherapy, yet from one RCT each. LIMITATIONS: First, various tools have been utilized to measure the irritability in ASD, which may contribute to the heterogeneity of the outcomes. Second, meta-analyses for each intervention included only a small number of studies and participants. CONCLUSIONS: Only risperidone, aripiprazole among pharmacological interventions, and parent training among non-pharmacological interventions can be recommended for irritability in ASD. As an augmentation to risperidone, several novel treatments show promising effects, but further RCTs are needed to replicate findings. Trial registration PROSPERO, CRD42021243965.

Electrophoretic separation of gold nanoparticles according to bifunctional molecules-induced charge and size.

Gold nanospheres modified with bifunctional molecules have been separated and characterized by using agarose gel electrophoresis as well as optical spectroscopy and electron microscopy. The electrophoretic mobility of a gold nanosphere capped with 11-mercaptoundecanoic acid (MUA) has been found to depend on the number of MUA molecules per gold nanosphere, indicating that it increases with the surface charge of the nanoparticle. The extinction spectrum of gold nanospheres capped with MUA at an MUA molecules per gold nanosphere value of 1000 and connected via 1,6-hexanedithiol (HDT) decreases by 33% in magnitude and shifts to the red as largely as 22 nm with the increase of the molar ratio of HDT to MUA (R(HM)). Gold nanospheres capped with MUA and connected via HDT have been separated successfully using gel electrophoresis and characterized by measuring reflectance spectra of discrete electrophoretic bands directly in the gel and by monitoring transmission electron microscope images of gold nanoparticles collected from the discrete bands. Electrophoretic mobility has been found to decrease substantially with the increment of HDT to MUA, indicating that the size of aggregated gold nanoparticles increases with the concentration of HDT.

Laser-induced silver nanojoining of gold nanoparticles.

Gold nanoparticles have been silver-joined to fabricate nanowires by irradiating gold nanospheres of 25 nm in diameter and silver nanospheres of 8 nm in diameter held together on a carbon-coated copper grid with a 30 ps laser pulse of 532 nm for 20 min at a fluence of 3.0 mJ/cm2. Laser-induced nanojoining of silver nanoparticles as well as that of gold nanoparticles has also been carried out by varying the wavelength and fluence of irradiation laser pulses. Irradiation at an optimum condition of laser fluence is essential for the proper silver nanojoining of gold nanospheres to produce gold@silver core-shell composite nanowires. The excitation of the surface plasmon resonances of the base-metallic gold nanospheres rather than the filler-metallic silver nanospheres paves the way for the silver nanojoining of gold nanoparticles.

The basic chromospheres of skin that might not be differentiated visually: observations on aneurysmal fibrous histiocytomas and malignant melanomas.

AIM: Aneurysmal fibrous histiocytoma (AFH) is a variant of fibrous histiocytoma, which has a cleft-like cavernous blood-filled space in the tumor. It appears as a single reddish black tumor with variable levels of pain and size from its bleeding. And, it must be differentiated from other similar looking malignant conditions such as malignant melanoma. The visual mimicry of AFH to melanoma was raised by some careful dermatologists, but never be confirmed objectively by colorimetric analysis. MATERIALS, SUBJECTS, AND METHODS: In this study, we simply analyzed conventionally photographed digital images of thirty-seven cases of fibrous histiocytomas, including three AFH cases into colorimetrically useful color space, CIELAB, of which coordinates are L*, a*, and b* representing lightness, red to green, and yellow to blue axis, respectively. In addition, we also analyzed the clinical digital images of seven cases of malignant melanomas. Using statistical package, each coordinates of CIELAB were compared using Wilcoxon rank sum test between AFH and melanomas. The CIELAB coordinates of AFH and non-aneurysmal fibrous histiocytomas were compared statistically as well. RESULTS: Comparing with banal fibrous histiocytomas, the colors of AFH showed significantly smaller a* and b* coordinates (P = 0.008, 0.008, respectively), which implies more green and blue hue of AFH lesion. Rather, they were more like melanomas (P = 0.2839, 0.2040, respectively). As for L*, there were no significant differences for all comparisons. CONCLUSIONS: As a result, more objective analysis of the digital images using colorimetric color space confirmed the visual mimicry of AFH to melanoma.

Subjective and objective sleep alterations in medication-naïve children and adolescents with autism spectrum disorder: a systematic review and meta-analysis.

AIMS: This study aimed to summarize the evidence on sleep alterations in medication-naïve children and adolescents with autism spectrum disorder (ASD). METHODS: We systematically searched PubMed/Medline, Embase and Web of Science databases from inception through March 22, 2021. This study was registered with PROSPERO (CRD42021243881). Any observational study was included that enrolled medication-naïve children and adolescents with ASD and compared objective (actigraphy and polysomnography) or subjective sleep parameters with typically developing (TD) counterparts. We extracted relevant data such as the study design and outcome measures. The methodological quality was assessed through the Newcastle-Ottawa Scale (NOS). A meta-analysis was carried out using the random-effects model by pooling effect sizes as Hedges' g. To assess publication bias, Egger's test and p-curve analysis were done. A priori planned meta-regression and subgroup analysis were also performed to identify potential moderators. RESULTS: Out of 4277 retrieved references, 16 studies were eligible with 981 ASD patients and 1220 TD individuals. The analysis of objective measures showed that medication-naïve ASD patients had significantly longer sleep latency (Hedges' g 0.59; 95% confidence interval [95% CI] 0.26 to 0.92), reduced sleep efficiency (Hedges' g -0.58; 95% CI -0.87 to -0.28), time in bed (Hedges' g -0.64; 95% CI -1.02 to -0.26) and total sleep time (Hedges' g -0.64; 95% CI -1.01 to -0.27). The analysis of subjective measures showed that they had more problems in daytime sleepiness (Hedges' g 0.48; 95% CI 0.26 to 0.71), sleep latency (Hedges' g 1.15; 95% CI 0.72 to 1.58), initiating and maintaining sleep (Hedges' g 0.86; 95% CI 0.39 to 1.33) and sleep hyperhidrosis (Hedges' g 0.48; 95% CI 0.29 to 0.66). Potential publication bias was detected for sleep latency, sleep period time and total sleep time measured by polysomnography. Some sleep alterations were moderated by age, sex and concurrent intellectual disability. The median NOS score was 8 (interquartile range 7.25-8.75). CONCLUSION: We found that medication-naïve children and adolescents with ASD presented significantly more subjective and objective sleep alterations compared to TD and identified possible moderators of these differences. Future research requires an analysis of how these sleep alterations are linked to core symptom severity and comorbid behavioural problems, which would provide an integrated therapeutic intervention for ASD. However, our results should be interpreted in light of the potential publication bias.

Causal effect of adiposity on the risk of 19 gastrointestinal diseases: a Mendelian randomization study.

OBJECTIVE: Although the association between adiposity and gastrointestinal (GI) diseases has been explored, the causal effects of adiposity on GI diseases are largely unknown. METHODS: Mendelian randomization was conducted using single-nucleotide polymorphisms associated with BMI and waist circumference (WC) as instrumental variables, and the causal associations of BMI or WC with GI conditions were estimated among >400,000 UK Biobank participants, >170,000 Finnish-descent participants, and numerous consortia participants of predominantly European ancestry. RESULTS: Genetically predicted BMI was robustly associated with increased risk of nonalcoholic fatty liver disease (NAFLD), cholecystitis, cholelithiasis, and primary biliary cholangitis. For the diseases, the odds ratio per 1-SD increase in genetically predicted BMI (4.77 kg/m2 ) ranged from 1.22 (95% CI: 1.12-1.34; p < 0.0001) for NAFLD to 1.65 (95% CI: 1.31-2.06; p < 0.0001) for cholecystitis. Genetically predicted WC was robustly associated with increased risk of NAFLD, alcoholic liver disease, cholecystitis, cholelithiasis, colon cancer, and gastric cancer. Alcoholic liver disease was consistently associated with WC even after adjusting for alcohol consumption in a multivariable Mendelian randomization analysis. The odds ratio per 1-SD increase in genetically predicted WC (12.52 cm) for such associations ranged from 1.41 (95% CI: 1.17-1.70; p = 0.0015) for gastric cancer to 1.74 (95% CI: 1.21-1.78; p < 0.0001) for cholelithiasis. CONCLUSIONS: High genetically predicted adiposity was causally associated with an increased risk of GI abnormalities, particularly of hepatobiliary organs (liver, biliary tract, and gallbladder) that are functionally related to fat metabolism.

Balancing risks and benefits of cannabis use: umbrella review of meta-analyses of randomised controlled trials and observational studies.

OBJECTIVE: To systematically assess credibility and certainty of associations between cannabis, cannabinoids, and cannabis based medicines and human health, from observational studies and randomised controlled trials (RCTs). DESIGN: Umbrella review. DATA SOURCES: PubMed, PsychInfo, Embase, up to 9 February 2022. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Systematic reviews with meta-analyses of observational studies and RCTs that have reported on the efficacy and safety of cannabis, cannabinoids, or cannabis based medicines were included. Credibility was graded according to convincing, highly suggestive, suggestive, weak, or not significant (observational evidence), and by GRADE (Grading of Recommendations, Assessment, Development and Evaluations) (RCTs). Quality was assessed with AMSTAR 2 (A Measurement Tool to Assess Systematic Reviews 2). Sensitivity analyses were conducted. RESULTS: 101 meta-analyses were included (observational=50, RCTs=51) (AMSTAR 2 high 33, moderate 31, low 32, or critically low 5). From RCTs supported by high to moderate certainty, cannabis based medicines increased adverse events related to the central nervous system (equivalent odds ratio 2.84 (95% confidence interval 2.16 to 3.73)), psychological effects (3.07 (1.79 to 5.26)), and vision (3.00 (1.79 to 5.03)) in people with mixed conditions (GRADE=high), improved nausea/vomit, pain, spasticity, but increased psychiatric, gastrointestinal adverse events, and somnolence among others (GRADE=moderate). Cannabidiol improved 50% reduction of seizures (0.59 (0.38 to 0.92)) and seizure events (0.59 (0.36 to 0.96)) (GRADE=high), but increased pneumonia, gastrointestinal adverse events, and somnolence (GRADE=moderate). For chronic pain, cannabis based medicines or cannabinoids reduced pain by 30% (0.59 (0.37 to 0.93), GRADE=high), across different conditions (n=7), but increased psychological distress. For epilepsy, cannabidiol increased risk of diarrhoea (2.25 (1.33 to 3.81)), had no effect on sleep disruption (GRADE=high), reduced seizures across different populations and measures (n=7), improved global impression (n=2), quality of life, and increased risk of somnolence (GRADE=moderate). In the general population, cannabis worsened positive psychotic symptoms (5.21 (3.36 to 8.01)) and total psychiatric symptoms (7.49 (5.31 to 10.42)) (GRADE=high), negative psychotic symptoms, and cognition (n=11) (GRADE=moderate). In healthy people, cannabinoids improved pain threshold (0.74 (0.59 to 0.91)), unpleasantness (0.60 (0.41 to 0.88)) (GRADE=high). For inflammatory bowel disease, cannabinoids improved quality of life (0.34 (0.22 to 0.53) (GRADE=high). For multiple sclerosis, cannabinoids improved spasticity, pain, but increased risk of dizziness, dry mouth, nausea, somnolence (GRADE=moderate). For cancer, cannabinoids improved sleep disruption, but had gastrointestinal adverse events (n=2) (GRADE=moderate). Cannabis based medicines, cannabis, and cannabinoids resulted in poor tolerability across various conditions (GRADE=moderate). Evidence was convincing from observational studies (main and sensitivity analyses) in pregnant women, small for gestational age (1.61 (1.41 to 1.83)), low birth weight (1.43 (1.27 to 1.62)); in drivers, car crash (1.27 (1.21 to 1.34)); and in the general population, psychosis (1.71 (1.47 to 2.00)). Harmful effects were noted for additional neonatal outcomes, outcomes related to car crash, outcomes in the general population including psychotic symptoms, suicide attempt, depression, and mania, and impaired cognition in healthy cannabis users (all suggestive to highly suggestive). CONCLUSIONS: Convincing or converging evidence supports avoidance of cannabis during adolescence and early adulthood, in people prone to or with mental health disorders, in pregnancy and before and while driving. Cannabidiol is effective in people with epilepsy. Cannabis based medicines are effective in people with multiple sclerosis, chronic pain, inflammatory bowel disease, and in palliative medicine but not without adverse events. STUDY REGISTRATION: PROSPERO CRD42018093045. FUNDING: None.

A case of spitzoid melanoma with lymph node metastasis in a child.

The distinction of a spitz nevus from a melanoma can be difficult and in some cases, impossible. A misdiagnosed spitz nevus can metastasize and lead to fatal outcomes, especially in children. A 5-yr-old girl presented with a 1-yr history of a solitary pinkish nodule on her left hand. On physical examination, she had a palpable left axillary lymph node. We performed biopsy and checked 3 sentinel lymph nodes (SLN) on her axillary area. The biopsy specimen showed multiple variably sized and shaped nests with large spindle or polygonal cells and SLN biopsy showed 3 of 3 lymph nodes that were metastasized. Under the diagnosis of spitzoid melanoma, she was treated with excision biopsy and complete left axillary lymph nodes were dissected. She received interferon-α2b subcutaneously at a dose of 8 MIU per day, 3 times weekly for 12 months, and shows no recurrence.