A systematic review of the association between environmental risk factors and the development of irritable bowel syndrome.

BACKGROUND AND AIM: Irritable bowel syndrome (IBS) is a common gastrointestinal disorder with roots in genetic, immune, psychological, and dietary factors. Recently, the potential correlation between environmental exposures, such as air pollution, and IBS has gained attention. This review aimed to systematically examine existing studies on environmental factors associated with IBS, elucidating this interplay and guiding future research. METHODS: A literature search was conducted in Medline, EMBASE, Scopus, and Cochrane databases from database inception to October 10, 2023, using the keywords "Irritable Bowel" or IBS or "Irritable Colon" or "Mucous Colitis" or "Spastic Colitis" or "Spastic Colon" AND "environment* exposure*". Studies were included if they were original, published in English, described defined environmental exposure(s), and had documented diagnosis of IBS. For the purposes of this review, articles reporting physical (e.g. radiation and climate change), biological (e.g. bacteria and viruses), and chemical (e.g. harmful gases) exposures were included while psychological and dietary factors, which have been reviewed in detail elsewhere, are outside of the scope. RESULTS: A total of seven studies focusing on air quality, microbial exposure, and other environmental factors were reviewed. Studies highlighted a potential association between air pollutants and increased IBS incidence. Microbial exposure, post-natural disaster or due to poor sanitation, was linked to IBS development and gut dysbiosis. Other exposures, such as early pet ownership, were also associated with IBS risk. CONCLUSION: Existing research demonstrates an epidemiologic relationship between environmental exposures and the development of IBS. Further research is needed to understand these associations.

Effectiveness of mindfulness-based interventions on the well-being of healthcare workers: a systematic review and meta-analysis.

Background: Growing evidence attests to the efficacy of mindfulness-based interventions (MBIs), but their effectiveness for healthcare workers remains uncertain. Aims: To evaluate the evidence for MBIs in improving healthcare workers' psychological well-being. Methods: A systematic literature search was conducted on Medline, Embase, Cumulative Index for Nursing and Allied Health Literature, PsycINFO and Cochrane Central Register of Controlled Trials up to 31 August 2022 using the keywords 'healthcare worker', 'doctor', 'nurse', 'allied health', 'mindfulness', 'wellness', 'workshop' and 'program'. Randomised controlled trials with a defined MBI focusing on healthcare workers and quantitative outcome measures related to subjective or psychological well-being were eligible for inclusion. R V.4.0.3 was used for data analysis, with the standardised mean difference as the primary outcome, employing DerSimonian and Laird's random effects model. Grading of Recommendations, Assessment, Development and Evaluation framework was used to evaluate the quality of evidence. Cochrane's Risk of Bias 2 tool was used to assess the risk of bias in the included studies. Results: A total of 27 studies with 2506 participants were included, mostly from the USA, involving various healthcare professions. MBIs such as stress reduction programmes, apps, meditation and training showed small to large effects on anxiety, burnout, stress, depression, psychological distress and job strain outcomes of the participants. Positive effects were also seen in self-compassion, empathy, mindfulness and well-being. However, long-term outcomes (1 month or longer postintervention) varied, and the effects were not consistently sustained. Conclusions: MBIs offer short-term benefits in reducing stress-related symptoms in healthcare workers. The review also highlights limitations such as intervention heterogeneity, reduced power in specific subgroup analyses and variable study quality. PROSPERO registration number: CRD42022353340.

Integrating UPLC-QTOF-MS/MS and UPLC-DAD to evaluate the influence of sulfur-fumigated Paeoniae Radix Alba on the overall quality of three Si-Wu-Tang formulations.

INTRODUCTION: Sulfur-fumigation of Paeoniae Radix Alba (PRA) could induce the chemical transformation of its bioactive component paeoniflorin into a sulfur-containing derivative paeoniflorin sulfite, and thus alter the quality, bioactivities, pharmacokinetics, and toxicities of PRA. However, how sulfur-fumigated PRA (S-PRA) affects the quality of PRA-containing complex preparations has not been intensively evaluated. OBJECTIVES: We intend to evaluate the influence of S-PRA on the overall quality of three kinds of Si-Wu-Tang (SWT) formulations, i.e., decoction (SWT-D), granule (SWT-G), and mixture (SWT-M). MATERIAL AND METHODS: An UPLC-DAD multi-components quantification method was used to compare the transfer rates of paeoniflorin sulfite and other 10 bioactive components between S-PRA-containing and NS-PRA-containing SWT formulations. An UPLC-QTOF-MS/MS-based target metabolomics approach was applied to explore the differential sulfur-containing derivatives in S-PRA-containing SWT formulations. RESULTS: The transfer rates of paeoniflorin sulfite in three S-PRA-containing SWT formulations were all higher than 100%. Moreover, S-PRA also increased the transfer rate of 5-hydroxymethylfurfural, 1,2,3,4,6-O-pentagalloylglucose, whereas decreased that of paeoniflorin, albiflorin, and ferulic acid in three SWT formulations. Six pinane monoterpene glucoside sulfites originally identified in S-PRA, were also detectable in three S-PRA-containing SWT formulations. In addition, seven phenolic acid sulfites including (3Z)-6-sulfite-ligustilide, (3E)-6-sulfite-ligustilide, 6,8-disulfite-ligustilide, ferulic acid sulfite, neochlorogenic acid sulfite, chlorogenic acid sulfite, and angelicide sulfite (or isomer) were newly identified in these three S-PRA-containing formulations. CONCLUSION: S-PRA could differentially affect the transfer rate of paeoniflorin sulfite and other bioactive components during the preparation of three SWT formulations and subsequently the overall quality thereof.

Metals/bisulfite system involved generation of 24-sulfonic-25-ene ginsenoside Rg1, a potential quality control marker for sulfur-fumigated ginseng.

Ginseng is a most popular health-promoting food with ginsenosides as its main bioactive ingredients. Illegal sulfur-fumigation causes ginsenosides convert to toxic sulfur-containing derivatives, and reduced the efficacy/safety of ginseng. 24-sulfo-25-ene ginsenoside Rg1 (25-ene SRg1), one of the sulfur-containing derivatives, is a potential quality control marker of fumigated ginseng, but with low accessibility owing to its unknown generation mechanism. In this study, metals/bisulfite system involved generation mechanism was investigated and verified. The generation of 25-ene SRg1 in sulfur-fumigated ginseng is that SO2, formed during sulfur-fumigation, reacted with water and ionized into HSO3-. On the one hand, under the metals/bisulfite system, HSO3- generates HSO5- and free radicals which converted ginsenoside Rg1 to 24,25-epoxide Rg1; on the other hand, as a nucleophilic group, HSO3- reacted with 24,25-epoxide Rg1 and further dehydrated to 25-ene SRg1. This study provided a technical support for the promotion of 25-ene SRg1 as the characteristic quality control marker of sulfur-fumigated ginseng.

The effects of anti-TNF-α biologics on insulin resistance and insulin sensitivity in patients with rheumatoid arthritis: An update systematic review and meta-analysis.

BACKGROUND AND AIM: Increasing evidence demonstrates a link between the chronic inflammatory state in patients with rheumatoid arthritis (RA) and the development of insulin resistance. It is thought that anti-TNF-α biologic therapy may improve insulin sensitivity and ameliorate insulin resistance by the downregulation of inflammatory cytokines, however, pre-clinical and clinical studies have yielded conflicting results. A meta-analysis on this topic is necessary to summarize current evidence and generate hypotheses for future research. METHODS: Literature search was performed in four databases, namely PubMed, EMBASE, Scopus, and The Cochrane Library, from inception till April 9, 2023, querying studies reporting peripheral insulin resistance with and without anti-TNF-α use in patients with RA. Peripheral insulin resistance or sensitivity was quantified by the Homeostasis Model Assessment of Insulin Resistance (HOMA) index or the Quantitative Insulin Sensitivity Check Index (QUICKI) respectively. The difference in insulin resistance or sensitivity between the treatment and control group was calculated using standardized mean difference (SMD) for the purposes of the meta-analysis. RESULTS: Twelve articles were reviewed, with 10 longitudinal studies with a total of 297 patients included in the meta-analysis. The pooled standardized mean difference (SMD) from baseline HOMA was -0.82 (95% CI: -1.38 to -0.25) suggesting significant beneficial effects of anti-TNF-α therapy on insulin resistance. CONCLUSION: Current evidence supports the significant clinical efficacy of anti-TNF-α biologics in alleviating insulin resistance and improving insulin sensitivity in patients with active RA.

More potential uses of specific perforator flaps in the calf - A cadaveric study on the subdermal vascular structure of the lower leg.

BACKGROUND: The perforator flap has garnered significant interest since its inception due to its advantage of not needing a vascular network at the deep fascial level. Perforator flaps are commonly utilized in different flap transplant surgeries, and the thigh flap is presently the most widely used perforator flap. Is it possible for the calf to replace the thigh as a more suitable site for harvesting materials? Currently, there is a lack of relevant anatomical research. This study aims to address this question from an anatomical and imaging perspective. METHODS: This study used cadavers to observe the branches and courses of perforators on the calf and the distribution of skin branches using microdissection techniques, digital X-ray photography, and micro-computed tomography techniques. RESULTS: The perforators had three main branches: the vertical cutaneous branch, the oblique cutaneous branch, and the superficial fascial branch. The superficial fascial branch traveled in the superficial fascia and connected with the nearby perforators. The vertical and oblique cutaneous branches entered the subdermal layer and connected with each other to create the subdermal vascular network. CONCLUSIONS: We observed an intact calf cutaneous branch chain between the cutaneous nerve and the perforator of the infrapopliteal main artery at the superficial vein site. Utilizing this anatomical structure, the calfskin branch has the potential to serve as a substitute for thigh skin flap transplantation and may be applied to perforator flap transplantation in more locations.

Intraoperative adverse events among surgeons in Singapore: a multicentre cross-sectional study on impact and support.

BACKGROUND: It is known that many surgeons encounter intraoperative adverse events which can result in Second Victim Syndrome (SVS), with significant detriment to their emotional and physical health. There is, however, a paucity of Asian studies in this space. The present study thus aimed to explore the degree to which the experience of an adverse event is common among surgeons in Singapore, as well as its impact, and factors affecting their responses and perceived support systems. METHODS: A self-administered survey was sent to surgeons at four large tertiary hospitals. The 42-item questionnaire used a systematic closed and open approach, to assess: Personal experience with intraoperative adverse events, emotional, psychological and physical impact of these events and perceived support systems. RESULTS: The response rate was 57.5% (n = 196). Most respondents were male (54.8%), between 35 and 44 years old, and holding the senior consultant position. In the past 12 months alone, 68.9% recalled an adverse event. The emotional impact was significant, including sadness (63.1%), guilt (53.1%) and anxiety (45.4%). Speaking to colleagues was the most helpful support source (66.7%) and almost all surgeons did not receive counselling (93.3%), with the majority deeming it unnecessary (72.2%). Notably, 68.1% of the surgeons had positive takeaways, gaining new insight and improving vigilance towards errors. Both gender and surgeon experience did not affect the likelihood of errors and emotional impact, but more experienced surgeons were less likely to have positive takeaways (p = 0.035). Individuals may become advocates for patient safety, while simultaneously championing the cause of psychological support for others. CONCLUSIONS: Intraoperative adverse events are prevalent and its emotional impact is significant, regardless of the surgeon's experience or gender. While colleagues and peer discussions are a pillar of support, healthcare institutions should do more to address the impact and ensuing consequences.

Dehydrozaluzanin C- derivative protects septic mice by alleviating over-activated inflammatory response and promoting the phagocytosis of macrophages.

Host-directed therapy (HDT) is a new adjuvant strategy that interfere with host cell factors that are required by a pathogen for replication or persistence. In this study, we assessed the effect of dehydrozaluzanin C-derivative (DHZD), a modified compound from dehydrozaluzanin C (DHZC), as a potential HDT agent for severe infection. LPS-induced septic mouse model and Carbapenem resistant Klebsiella pneumoniae (CRKP) infection mouse model was used for testing in vivo. RAW264.7 cells, mouse primary macrophages, and DCs were used for in vitro experiments. Dexamethasone (DXM) was used as a positive control agent. DHZD ameliorated tissue damage (lung, kidney, and liver) and excessive inflammatory response induced by LPS or CRKP infection in mice. Also, DHZD improved the hypothermic symptoms of acute peritonitis induced by CRKP, inhibited heat-killed CRKP (HK-CRKP)-induced inflammatory response in macrophages, and upregulated the proportions of phagocytic cell types in lungs. In vitro data suggested that DHZD decreases LPS-stimulated expression of IL-6, TNF-α and MCP-1 via PI3K/Akt/p70S6K signaling pathway in macrophages. Interestingly, the combined treatment group of DXM and DHZD had a higher survival rate and lower level of IL-6 than those of the DXM-treated group; the combination of DHZD and DXM played a synergistic role in decreasing IL-6 secretion in sera. Moreover, the phagocytic receptor CD36 was increased by DHZD in macrophages, which was accompanied by increased bacterial phagocytosis in a clathrin- and actin-dependent manner. This data suggests that DHZD may be a potential drug candidate for treating bacterial infections.

Comparison of the Efficacy of Different Radiofrequency Techniques for the Treatment of Lumbar Facet Joint Pain: Combined with Anatomy.

PURPOSE OF REVIEW: Lumbar facet pain is generally considered to be one of the major causes of chronic low back pain. Each lumbar facet joint is innervated by the medial branch of the posterior spinal nerve from its own level and above. Radiofrequency (RF) of the medial branch of the posterior branch of the spinal nerve is an effective method for the treatment of lumbar facet pain. RF technology is diverse, including traditional radiofrequency (TRF), pulsed radiofrequency (PRF), cooled radiofrequency (CRF), low-temperature plasma radiofrequency ablation (CA), and other treatment methods. The purpose of this paper is to compare the efficacy of different radiofrequency techniques and to analyze the reasons for this in the context of anatomy. RECENT FINDINGS: There have been studies confirming the differences in efficacy of different RF techniques. However, most of the studies only compared two RF techniques, not four techniques, TRF, CRF, PRF, and CA, and did not analyze the reasons for the differences in efficacy. This article reviews the differences in the efficacy of the above four RF techniques, clarifies that the differences are mainly due to the inability to precisely localize the medial branch of the posterior branch of the spinal nerve, analyzes the reasons for the inability to precisely localize the posterior branch of the spinal nerve in conjunction with anatomy, and proposes that the development of RF technology for lumbar facet pain requires more in-depth anatomical, imaging, and clinical studies.

Biological activities, Molecular mechanisms, and Clinical application of Naringin in Metabolic syndrome.

Metabolic syndrome has become major health problems in recent decades, and natural compounds receive considerable attention in the management of metabolic syndrome. Among them, naringin is abundant in citrus fruits and tomatoes. Many studies have investigated the therapeutic effects of naringin in metabolic syndrome. This review discusses in vitro and in vivo studies on naringin and implications for clinical trials on metabolic syndrome such as diabetes mellitus, obesity, nonalcoholic fatty liver disease, dyslipidemia, and hypertension over the past decades, overviews the molecular mechanisms by which naringin targets metabolic syndrome, and analyzes possible correlations between the different mechanisms. This review provides a theoretical basis for the further application of naringin in the treatment of metabolic syndrome.

Exploring the interactions between metabolic dysfunction-associated fatty liver disease and micronutrients: from molecular mechanisms to clinical applications.

Metabolic (dysfunction)-associated fatty liver disease (MAFLD) has emerged as a significant global health concern, representing a major cause of liver disease worldwide. This condition spans a spectrum of histopathologic stages, beginning with simple fatty liver (MAFL), characterized by over 5% fat accumulation, and advancing to metabolic (dysfunction)-associated steatohepatitis, potentially leading to hepatocellular carcinoma. Despite extensive research, there remains a substantial gap in effective therapeutic interventions. This condition's progression is closely tied to micronutrient levels, crucial for biological functions like antioxidant activities and immune efficiency. The levels of these micronutrients exhibit considerable variability among individuals with MAFLD. Moreover, the extent of deficiency in these nutrients can vary significantly throughout the different stages of MAFLD, with disease progression potentially exacerbating these deficiencies. This review focuses on the role of micronutrients, particularly vitamins A, D, E, and minerals like iron, copper, selenium, and zinc, in MAFLD's pathophysiology. It highlights how alterations in the homeostasis of these micronutrients are intricately linked to the pathophysiological processes of MAFLD. Concurrently, this review endeavors to harness the existing evidence to propose novel therapeutic strategies targeting these vitamins and minerals in MAFLD management and offers new insights into disease mechanisms and treatment opportunities in MAFLD.

On Orthorexia Nervosa: A Systematic Review of Reviews.

INTRODUCTION: Orthorexia nervosa (ON), characterized by a pathological preoccupation with "extreme dietary purity," is increasingly observed as a mental health condition among young adults and the general population. However, its diagnosis is not formally recognized and has remained contentious. OBJECTIVE: In this systematic review, we attempt to overview previous reviews on ON, focusing on the methodological and conceptual issues with ON. This would serve both as a summary and a way to highlight gaps in earlier research. METHODS: This systematic review took reference from the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines, and using combinations of the search terms ("orthorexia" OR "orthorexia nervosa" OR "ON") AND ("review" OR "systematic review" OR "meta-analysis"), a literature search was performed on EMBASE, Medline and PsycINFO databases from inception up to October 31, 2023. Articles were included if (1) they were written or translated into English and (2) contained information pertaining to the diagnostic stability or validity of ON, or instruments used to measure ON symptoms and behaviors. Only review articles with a systematic literature search approach were included. RESULTS: A total of 22 reviews were qualitatively reviewed. Several studies have reported variable prevalence of ON and highlighted the lack of thoroughly evaluated measures of ON with clear psychometric properties, with no reliable estimates. ORTO-15 and its variations such as ORTO-11, ORTO-12 are popularly used, although their use is discouraged. Existing instruments lack specificity for pathology and several disagreements on the conceptualization and hence diagnostic criteria of ON exist. DISCUSSION: Previous reviews have consistently highlighted the highly variable (and contradictory) prevalence rates with different instruments to measure ON, lack of stable factor structure and psychometrics across ON measures, paucity of data on ON in clinical samples, and a need for a modern re-conceptualization of ON. The diagnosis of ON is challenging as it likely spans a spectrum from "normal" to "abnormal," and "functional" to "dysfunctional." "Non-pathological" orthorexia is not related to psychopathological constructs in the same way that ON is.

Molecular and cellular pruritus mechanisms in the host skin.

Pruritus, also known as itching, is a complex sensation that involves the activation of specific physiological and cellular receptors. The skin is innervated with sensory nerves as well as some receptors for various sensations, and its immune system has prominent neurological connections. Sensory neurons have a considerable impact on the sensation of itching. However, immune cells also play a role in this process, as they release pruritogens. Disruption of the dermal barrier activates an immune response, initiating a series of chemical, physical, and cellular reactions. These reactions involve various cell types, including keratinocytes, as well as immune cells involved in innate and adaptive immunity. Collective activation of these immune responses confers protection against potential pathogens. Thus, understanding the molecular and cellular mechanisms that contribute to pruritus in host skin is crucial for the advancement of effective treatment approaches. This review provides a comprehensive analysis of the present knowledge concerning the molecular and cellular mechanisms underlying itching signaling in the skin. Additionally, this review explored the integration of these mechanisms with the broader context of itch mediators and the expression of their receptors in the skin.

Going beyond compliance: A qualitative study of the practice of surgical safety checklist.

BACKGROUND: The World Health Organization Surgical Safety Checklist (SSC) is a tool designed to enhance team communication and patient safety. When used properly, the SSC acts as a layer of defence against never events. In this study, we performed secondary qualitative analysis of operating theatres (OT) SSC observational notes to examine how the SSC was used after an intensive SSC re-implementation effort and drew on relevant theories to shed light on the observed patterns of behaviours. We aimed to go beyond assessing checklist compliance and to understand potential sociopsychological mechanisms of the variations in SSC practices. METHODS: Direct observation notes of 109 surgical procedures across 13 surgical disciplines were made by two trained nurses in the OT of a large tertiary hospital in Singapore from February to April 2022, three months after SSC re-implementation. Only notes relevant to the use of SSC were extracted and analyzed using reflexive thematic analysis. Data were coded following an inductive process to identify themes or patterns of SSC practices. These patterns were subsequently interpreted against a relevant theory to appreciate the potential sociopsychological forces behind them. RESULTS: Two broad types of SSC practices and their respective sub-themes were identified. Type 1 (vs. Type 2) SSC practices are characterized by patience and thoroughness (vs. hurriedness and omission) in carrying out the SSC process, dedication and attention (vs. delegation and distraction) to the SSC safety checks, and frequent (vs. absence of) safety voices during the conduct of SSC. These patterns were conceptualized as safety-seeking action vs. ritualistic action using Merton's social deviance theory. CONCLUSION: Ritualistic practice of the SSC can undermine surgical safety by creating conditions conducive to never events. To fully realize the SSC's potential as an essential tool for communication and safety, a concerted effort is needed to balance thoroughness with efficiency. Additionally, fostering a culture of collaboration and collegiality is crucial to reinforce and enhance the culture of surgical safety.

Cost-of-illness studies of inherited retinal diseases: a systematic review.

BACKGROUND: While health care and societal costs are routinely modelled for most diseases, there is a paucity of comprehensive data and cost-of-illness (COI) studies for inherited retinal diseases (IRDs). This lack of data can lead to underfunding or misallocation of resources. A comprehensive understanding of the COI of IRDs would assist governmental and healthcare leaders in determining optimal resource allocation, prioritizing funding for research, treatment, and support services for these patients. METHODS: Following PRISMA guidelines, a literature search was conducted using Medline, EMBASE and Cochrane databases, from database inception up to 30 Jun 2023, to identify COI studies related to IRD. Original studies in English, primarily including patients with IRDs, and whose main study objective was the estimation of the costs of IRDs and had sufficiently detailed methodology to assess study quality were eligible for inclusion. To enable comparison across countries and studies, all annual costs were standardized to US dollars, adjusted for inflation to reflect their current value and recalculated on a "per patient" basis wherever possible. The review protocol was registered in PROSPERO (registration number CRD42023452986). RESULTS: A total of nine studies were included in the final stage of systematic review and they consistently demonstrated a significant disease burden associated with IRDs. In Singapore, the mean total cost per patient was roughly US$6926/year. In Japan, the mean total cost per patient was US$20,833/year. In the UK, the mean total cost per patient with IRD ranged from US$21,658 to US$36,549/year. In contrast, in the US, the mean total per-patient costs for IRDs ranged from about US$33,017 to US$186,051 per year. In Canada, these mean total per-patient costs varied between US$16,470 and US$275,045/year. Non-health costs constituted the overwhelming majority of costs as compared to healthcare costs; 87-98% of the total costs were due to non-health costs, which could be attributed to diminished quality of life, poverty, and increased informal caregiving needs for affected individuals. CONCLUSION: IRDs impose a disproportionate societal burden outside health systems. It is vital for continued funding into IRD research, and governments should incorporate societal costs in the evaluation of cost-effectiveness for forthcoming IRD interventions, including genomic testing and targeted therapies.

The Diagnostic Value of Carnett's Test with Chronic Abdominal Pain: A Narrative Review.

PURPOSE OF REVIEW: Chronic abdominal wall pain is a poorly recognized cause of chronic abdominal pain, and patients frequently go misdiagnosed despite a battery of medical tests. The Carnett's test is a diagnostic tool used to distinguish between abdominal wall pain and visceral pain. This review synthesizes the current literature on the Carnett's test, merges the viewpoints of diverse writers, and evaluates and reports on the Carnett's test's applicability. RECENT FINDINGS: Several clinical investigations have established the usefulness of the Carnett's test in the diagnosis of chronic abdominal wall pain. Furthermore, the Carnett's test is quite useful in determining the depth of the mass and detecting psychogenic abdominal pain. However, its diagnostic use for acute abdominal pain is limited. The Carnett's test is a simple and safe point-of-care diagnostic technique, with several studies supporting its usefulness. Early detection of abdominal wall pain is critical for chronic abdominal wall pain therapy. Carnett's test is very useful in patients with chronic, unexplained local abdominal discomfort who are compliant and do not have a clear rationale for surgery.

Inter and intra-host diversity of RSV in hematopoietic stem cell transplant adults with normal and delayed viral clearance.

Respiratory syncytial virus (RSV) infection in immunocompromised individuals often leads to prolonged illness, progression to severe lower respiratory tract infection, and even death. How the host immune environment of the hematopoietic stem cell transplant (HCT) adults can affect viral genetic variation during an acute infection is not understood well. In the present study, we performed whole genome sequencing of RSV/A or RSV/B from samples collected longitudinally from HCT adults with normal (<14 days) and delayed (≥14 days) RSV clearance who were enrolled in a ribavirin trial. We determined the inter-host and intra-host genetic variation of RSV and the effect of mutations on putative glycosylation sites. The inter-host variation of RSV is centered in the attachment (G) and fusion (F) glycoprotein genes followed by polymerase (L) and matrix (M) genes. Interestingly, the overall genetic variation was constant between normal and delayed clearance groups for both RSV/A and RSV/B. Intra-host variation primarily occurred in the G gene followed by non-structural protein (NS1) and L genes; however, gain or loss of stop codons and frameshift mutations appeared only in the G gene and only in the delayed viral clearance group. Potential gain or loss of O-linked glycosylation sites in the G gene occurred both in RSV/A and RSV/B isolates. For RSV F gene, loss of N-linked glycosylation site occurred in three RSV/B isolates within an antigenic epitope. Both oral and aerosolized ribavirin did not cause any mutations in the L gene. In summary, prolonged viral shedding and immune deficiency resulted in RSV variation, especially in structural mutations in the G gene, possibly associated with immune evasion. Therefore, sequencing and monitoring of RSV isolates from immunocompromised patients are crucial as they can create escape mutants that can impact the effectiveness of upcoming vaccines and treatments.

Road dust exposure and human corneal damage in a plateau high geological background provincial capital city: Spatial distribution, sources, bioaccessibility, and cytotoxicity of dust heavy metals.

Ocular surface diseases are common in the plateau city, Kunming China, the continued daily exposure to heavy metals in dust may be an important inducement. In this study, the 150 road dust samples from five functional areas in Kunming were collected. The concentrations, distribution, possible sources, and bioaccessibility of heavy metals were analyzed. The adverse effects of dust extracts on human corneal epithelial cells and the underlying mechanisms were also assessed. The concentrations (mg·kg-1) of As (19.1), Cd (2.67), Cr (90.5), Cu (123), Pb (78.4), and Zn (389) in road dust were higher than the soil background, with commercial and residential areas showing the highest pollution. Their bioaccessibility in artificial tears was As (6.59 %) > Cu (5.11 %) > Ni (1.47 %) > Cr (1.17 %) > Mn (0.84 %) > Cd (0.76 %) > Zn (0.50 %) > Pb (0.31 %). The two main sources of heavy metals included tire and mechanical abrasion (24.5 %) and traffic exhaust (21.6 %). All dust extracts induced cytotoxicity, evidenced by stronger inhibition of cell viability, higher production of ROS, and altered mRNA expression of antioxidant enzymes and cell cycle-related genes, with commercial- areas-2 (CA2)-dust extract showing the greatest oxidative damage and cell cycle arrest. Our data may provide new evidence that dust exposure in high geological background cities could trigger human cornea damage.

Scoping review of the second victim syndrome among surgeons: Understanding the impact, responses, and support systems.

BACKGROUND: It is thought that 50% of healthcare providers experience Second Victim Syndrome (SVS) in the course of their practice. The manifestations of SVS varies between individuals, with potential long-lasting emotional effects that impact both the personal lives and professional clinical practice of affected persons. Although surgeons are known to face challenging and high-stress situations in their profession, which can increase their vulnerability to SVS, majority of studies and reviews have focused squarely on nonsurgical physicians. METHODS: This scoping review aimed to consolidate existing studies pertaining to a surgeon's experience with SVS, by broadly examining the prevalence and impact, identifying the types of responses, and evaluating factors that could influence these responses. The scoping review protocol was guided by the framework outlined by Arksey and O'Malley and ensuing recommendations made by Levac and colleagues. Three databases (MEDLINE, EMBASE and Cochrane Library) were searched from inception till March 19, 2023. RESULTS: A total of 13 articles were eligible for thematic analysis based on pre-defined inclusion criteria. Effects of SVS were categorized into Psychological, Physical and Professional impacts, of which Psychological and Professional impacts were particularly significant. Factors affecting the response were categorized into complication type, surgeon factors and support systems. CONCLUSION: SVS adds immense psychological, emotional and physical burden to the individual surgeon. There are key personal, interpersonal and environmental factors that can mitigate or exacerbate the effects of SVS, and greater emphasis needs to be placed on improving availability and access to services to help surgeons at risk of SVS.

Mechanism of Astragaloside Ⅳ on db/db Mice with Type 2 Diabetes Mellitus and Non-alcoholic Fatty Liver Disease Based on AMPK Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo study the mechanism of astragaloside Ⅳ （AS Ⅳ） on db/db mice with type 2 diabetes mellitus （T2DM） and non-alcoholic fatty liver disease （NAFLD） based on network pharmacology and experimental validation. MethodA total of 24 db/db mice were randomly divided into four groups： model group， metformin group， and low-dose and high-dose AS Ⅳ groups. Six C57 mice were used as the blank group. The low-dose and high-dose AS Ⅳ groups were given AS Ⅳ of 0.015 and 0.030 g·kg-1 by gavage， and the metformin group was given 0.067 g·kg-1 by gavage. The blank and model groups were given equal volumes of distilled water by gavage. After intragastric administration， fasting blood glucose （FBG） was detected， and an oral glucose tolerance test was performed. Serum lipid level and liver histopathology were detected. The target and enrichment pathway of AS Ⅳ for treating T2DM and NAFLD were predicted by network pharmacology， and the main enrichment pathway was verified by molecular biology techniques. The protein expressions of AMPK， p-AMPK， sterol regulatory element-binding protein-1 （SREBP-1）， and fatty acid synthetase （FAS） in liver tissue were detected by Western blot. ResultCompared with the blank group， the levels of body mass， liver weight coefficient， fasting blood glucose， serum total cholesterol， triglyceride， and low-density lipoprotein cholesterol in mice treated with AS Ⅳ were decreased （P<0.05， P<0.01）. The pathology of liver tissue showed significant improvement in lipid accumulation， and imaging results showed that the degree of fatty liver was reduced after AS Ⅳ therapy. Network pharmacological prediction results showed that vascular endothelial growth factor α （VEGFA）， galactoagglutinin 3 （LGALS3）， serine/threonine kinase B2 （Akt2）， RHO-associated coiled-coil protein kinase 1 （ROCK1）， serine/threonine kinase B1 （Akt1）， signaling and transcriptional activator protein （STAT3）， and messtimal epidermal transformation factor （MET） were key targets in "drug-disease" network. The results from the Kyoto encyclopedia of genes and genomes （KEGG） enrichment showed that the AMP-dependent protein kinase （AMPK） signaling pathway was strongly associated with T2DM and NAFLD. Western blot results showed that compared with the blank group， the expression levels of p-AMPK/AMPK in the model group were significantly down-regulated， while those of SREBP-1 and FAS proteins were significantly up-regulated （P<0.01）. Compared with the model group， the expression levels of p-AMPK/AMPK in the metformin group and high-dose AS Ⅳ group were significantly up-regulated， while those of SREBP-1 and FAS proteins were significantly down-regulated （P<0.05， P<0.01）. ConclusionAS Ⅳ regulates the expression of lipid proteins by activating the AMPK signaling pathway， thereby improving lipid metabolism.