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Objectives: Gastric involvement in patients with early systemic sclerosis (SSc) has not been previously investigated. We aim to evaluate the association of gastric dysrhythmias with gastrointestinal (GI) symptoms and nailfold video capillaroscopy (NVC)., Methods: Cross-sectional study. Patients with early SSc, completed the UCLA GIT 2.0 questionnaire, performed an NVC, and a surface Electrogastrography (EGG). Descriptive statistics was used for demographic and clinical characteristics and Fisher and Kendall Tau tests were used for association analysis., Results: 75 patients were screened, 30 patients were consecutively enrolled, 29 performed the EGG and 1 patient had a non-interpretable NVC. 29/30 were female with a mean age of 48.7 years (25-72). The mean disease duration from the first non-RP symptom was 22.6 +/-10.8 months and most of the patients had limited disease (76.6%). Total GIT 2.0 score symptoms were moderate-severe in 63% of the participants and 28/29 had an abnormal EGG. Bradygastria was the most common pattern present in 70% of the participants. NVC patterns: 17% early, 34% active, 28% scleroderma-like, 14% non-specific, and 2 patients had a normal NVC. There was no association between severe GI symptoms or NVC patterns and severely abnormal EGG, but the presence of bradygastria was associated with severe impairment in the social functioning area (p 0.018)., Conclusions: Gastric dysmotility is common in early SSc and there is a lack of correlation between GI symptoms and NVC scleroderma patterns. EGG is a sensitive, cheap, and non-invasive exam, that may be an alternative to early diagnosis of GI involvement., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Background: This research depicts the linkage of public leadership on public health delivery (PHD) and collaborative administration. The research is also focused to examine the effect of public leadership on public health delivery through the intervening variable of collaborative administration by using both social information processing theory and collaboration theory., Methods: This research is based on quantitative method. Data was collected from 464 public hospital administration in the context of Pakistan. This study evaluated data using SPSS, AMOS, and PROCESS Macro., Results: Public leadership has a positive profound effect on public health delivery and collaborative administration, and that collaborative administration significantly promotes public health delivery. The outcomes also exposed that public leadership has substantial influence on public health delivery through intervening collaborative administration., Conclusions: Whilst public leadership demonstrated positive outcomes on public health delivery and collaborative administration, there is a need for more rigor studies on collaborative governance leadership, collaborative ethics and collaborative norms in the public health service., (© 2024. The Author(s).)

Azathioprine (AZA) and 6-mercaptopurine (6-MP) are drugs widely used in the treatment of autoimmune diseases. Among the enzymes involved in the metabolism of AZA and 6-MP are thiopurine methyltransferase (TPMT) and nudix hydrolase 15 (NUDT15). The existence of single nucleotide polymorphisms in the genes that code for these enzymes could decreased enzymatic activity AND lead to severe myelosuppression. The most relevant polymorphism is NUDT15*3 (rs116855232), where the replacement of cytosine for thymine at position 415, which in turn leads to a loss of enzymatic activity. In a previous study, it was identified that together the polymorphisms in the TPMT gene reach an allelic frequency of 3.81%. There is no information regarding the rs116855232 polymorphism in the NUDT15 gene, so this corresponds to the objective of this report. Blood samples from Chilean adult patients with indications for the use of AZA or 6-MP for different pathologies and who had undergone a TPMT gene polymorphism study were retrospectively analyzed. A total of 253 blood samples were analyzed. Of the 253 patients, 47 presented the c.415C>T polymorphism in the NUDT15 gene, 3 being homozygous and 44 heterozygous. Four of the heterozygous patients for NUDT15 also had the *3A variant in the TPMT gene, also heterozygous. The allelic frequency of the minor T allele found (9.88%) was very similar to that found in patients of Asian origin, and much higher than that reported for the European Caucasian or Latin American population., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

The study intends to investigate the impact of servant leadership on pro-social rule-breaking directly and through the intervening mechanism of psychological safety. More, the study also plans to investigate whether compassion at work moderates the effect of servant leadership on psychological safety and pro-social rule-breaking and the indirect intervening effect of psychological safety between servant leadership and pro-social rule-breaking. Responses were collected from 273 frontline public servants in Pakistan. Using social information processing theory, the results revealed that servant leadership positively influences pro-social rule-breaking and psychological safety and that psychological safety influences pro-social rule-breaking. Results also revealed that psychological safety acts as an intervening mechanism in the relationship between servant leadership and pro-social rule-breaking. Moreover, compassion at work significantly moderates the relationships of servant leadership with psychological safety and pro-social rule-breaking, and that compassion at work ultimately alters the size of the intervening effect of psychological safety between the connection of servant leadership and pro-social rule-breaking., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Khan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Colorectal cancer (CRC) is the third most frequent malignant disease in the world. In some countries with established screening programs, its incidence and mortality have decreased, and survival has improved., Aims: To obtain reliable data about the epidemiology of CRC in Chile, we analyzed the trends in the last ten years and the influence of observable factors on survival, including a nationwide health program for CRC treatment access (GES program)., Methods: Publicly available data published by the Ministry of Health and National Institute of Statistics were used. Data were obtained from registries of mortality and hospital discharges, making follow-up of the individuals possible. Crude and age-standardized incidence and mortality rates were calculated, and individual survival was studied by constructing Kaplan-Meier curves. Finally, a Cox statistical model was established to estimate the impact of the observable factors., Results: We found 37,217 newly identified CRC patients between 2008 and 2019 in Chile, corresponding to 103,239 hospital discharges. In the same period, 24,217 people died of CRC. A nearly linear, steady increase in crude incidence, mortality and prevalence was observed. CRC incidence was the lowest in the North of the country, increasing toward the South and reaching a maximum value of 34.6/100,000 inhabitants/year in terms of crude incidence and 20.7/100,000 inhabitants/year in terms of crude mortality in the XII region in 2018. We found that older patients had lower survival rates, as well as men compared to women. Survival was significantly better for patients with private insurance than those under the public insurance system, and the treating hospital also played a significant role in the survival of patients. Patients in the capital region survived longer than those in almost every other part of the country. We found no significant effect on survival associated with the GES program., Conclusions: We found important inequalities in the survival probabilities for CRC patients in Chile. Survival depends mainly on the type of insurance, access to more complex hospitals, and geographical location; all three factors correlated with socioeconomic status of the population. Our work emphasized the need to create specific programs addressing primary causes to decrease the differences in CRC survival., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Mondschein et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Fused deposition modeling represents a flexible and relatively inexpensive alternative for the production of custom-made polymer lattices. However, its limited accuracy and resolution lead to geometric irregularities and poor mechanical properties when compared with the digital design. Although the link between geometric features and mechanical properties of lattices has been studied extensively, the role of manufacturing parameters has received little attention. Additionally, as the size of cells/struts nears the accuracy limit of the manufacturing process, the interaction between geometry and manufacturing parameters could be decisive. Hence, the influence of three geometric and two manufacturing parameters on the mechanical behavior was evaluated using a fractional factorial design of experiments. The compressive behavior of two miniature lattice structures, the truncated octahedron and cubic diamond, was evaluated, and multilinear regression models for the elastic modulus and plateau stress were developed. Cell size, unit cell type, and strut diameter had the largest impact on the mechanical properties, while the influence of feedstock material and layer thickness was very limited. Models based on factorial design, although limited in scope, could be an effective tool for the design of customized lattice structures.

How to regulate employee conduct and engage them in high performance works actively and continuously has always been the important topic for organizations. Based on affective events theory and social exchange theory, a moderated mediating model was constructed with the affective commitment as mediator and the supervisor-subordinate exchange guanxi as moderator. Regression analyses and conditional indirect effects were tested by SPSS and PROCESS with 374 matched supervisor-subordinate pairs. The paper explores the moderated mechanism of supervisor-subordinate guanxi to the chain of "ambidextrous leadership-employee's affective commitment-workplace deviance behavior." The results showed that the affective commitment mediated the effect between ambidextrous leadership and employees' workplace deviance behavior, and supervisor-subordinate exchange guanxi moderated the relationship between ambidextrous leadership and employees' workplace deviance behavior but also moderated the mediating effect of affective commitment. The results have significances to improve human resource management practices and reduce the workplace deviance behavior of employees.

Astaxanthin (ASX) is a carotenoid pigment with strong antioxidant properties. We have reported previously that ASX protects neurons from the noxious effects of amyloid-β peptide oligomers, which promote excessive mitochondrial reactive oxygen species (mROS) production and induce a sustained increase in cytoplasmic Ca 2+ concentration. These properties make ASX a promising therapeutic agent against pathological conditions that entail oxidative and Ca 2+ dysregulation. Here, we studied whether ASX protects neurons from N-methyl-D-aspartate (NMDA)-induced excitotoxicity, a noxious process which decreases cellular viability, alters gene expression and promotes excessive mROS production. Incubation of the neuronal cell line SH-SY5Y with NMDA decreased cellular viability and increased mitochondrial superoxide production; pre-incubation with ASX prevented these effects. Additionally, incubation of SH-SY5Y cells with ASX effectively reduced the basal mROS production and prevented hydrogen peroxide-induced cell death. In primary hippocampal neurons, transfected with a genetically encoded cytoplasmic Ca 2+ sensor, ASX also prevented the increase in intracellular Ca 2+ concentration induced by NMDA. We suggest that, by preventing the noxious mROS and Ca 2+ increases that occur under excitotoxic conditions, ASX could be useful as a therapeutic agent in neurodegenerative pathologies that involve alterations in Ca 2+ homeostasis and ROS generation.

Long-term potentiation (LTP) and long-term depression (LTD) are two forms of synaptic plasticity that have been considered as the cellular substrate of memory formation. Although LTP has received considerable more attention, recent evidences indicate that LTD plays also important roles in the acquisition and storage of novel information in the brain. Pannexin 1 (Panx1) is a membrane protein that forms non-selective channels which have been shown to modulate the induction of hippocampal synaptic plasticity. Animals lacking Panx1 or blockade of Pannexin 1 channels precludes the induction of LTD and facilitates LTP. To evaluate if the absence of Panx1 also affects the acquisition of rapidly changing information we trained Panx1 knockout (KO) mice and wild type (WT) littermates in a visual and hidden version of the Morris water maze (MWM). We found that KO mice find the hidden platform similarly although slightly quicker than WT animals, nonetheless, when the hidden platform was located in the opposite quadrant (OQ) to the previous learned location, KO mice spent significantly more time in the previous quadrant than in the new location indicating that the absence of Panx1 affects the reversion of a previously acquired spatial memory. Consistently, we observed changes in the content of synaptic proteins critical to LTD, such as GluN2 subunits of N-methyl-D-aspartate receptors (NMDARs), which changed their contribution to synaptic plasticity in conditions of Panx1 ablation. Our findings give further support to the role of Panx1 channels on the modulation of synaptic plasticity induction, learning and memory processes.

The relationship between Microscopic Colitis and Inflammatory Bowel Disease is unclear. However, when both are diagnosed they seem to be part of a broader spectrum of the same disease, more than just a coincidence. We report a 55 years old woman with Ulcerative Colitis limited to the rectum with complete clinical and endoscopic response to standard treatment and adequate surveillance for 13 years, who abandoned treatment and control. After eight years, she consulted for mild-to-moderate non-bloody diarrhea lasting several months. Colonoscopy and basic laboratory did not show any alterations. Nevertheless, random biopsies had a characteristically pattern compatible with Lymphocytic Colitis. After the first week of treatment with budesonide the patient was asymptomatic and still in clinical remission, with negative fecal calprotectin at 6 months’ follow-up.

Although the importance of DNA methylation-dependent gene expression to neuronal plasticity is well established, the dynamics of methylation and demethylation during the induction and expression of synaptic plasticity have not been explored. Here, we combined electrophysiological, pharmacological, molecular, and immunohistochemical approaches to examine the contribution of DNA methylation and the phosphorylation of Methyl-CpG-binding protein 2 (MeCP2) to synaptic plasticity. We found that, at twenty minutes after theta burst stimulation (TBS), the DNA methylation inhibitor 5-aza-2-deoxycytidine (5AZA) impaired hippocampal long-term potentiation (LTP). Surprisingly, after two hours of TBS, when LTP had become a transcription-dependent process, 5AZA treatment had no effect. By comparing these results to those in naive slices, we found that, at two hours after TBS, an intergenic region of the RLN gene was hypomethylated and that the phosphorylation of residue S80 of MeCP2 was decreased, while the phosphorylation of residue S421 was increased. As expected, 5AZA affected only the methylation of the RLN gene and exerted no effect on MeCP2 phosphorylation patterns. In summary, our data suggest that tetanic stimulation induces critical changes in synaptic plasticity that affects both DNA methylation and the phosphorylation of MeCP2. These data also suggest that early alterations in DNA methylation are sufficient to impair the full expression of LTP.

Background: The chronic inflammation of the intestinal mucosa, the extra-intestinal manifestations of the disease and the immunosuppressive treatment of inflammatory bowel disease may increase cancer risk., Aim: To report the demographic and clinical features of patients with IBD who developed a malignant tumor., Material and Methods: Retrospective analysis of an IBD patient registry of a private clinic, diagnosed between 1976 and 2014., Results: 437 subjects were included, aged 15-88 years (58% women). Seventy two percent of patients had ulcerative colitis. The median time of follow up was 6 years. Ten patients (2.3%) developed a malignant tumor. In four, the tumor could be related to IBD (two colorectal cancers, one cholangiocarcinoma and one chronic myeloid leukemia (CML)). Two of 45 patients treated with biological therapy developed a tumor (CML and hypernephroma). Three of 170 patients on immunosuppressive treatment developed tumors. Only one had a tumor possibly related with the use of azathioprine (non-melanoma skin cancer). In only two patients, the treatment was changed at the time of their cancer diagnosis, from immunosuppressive medications to mesalamine., Conclusions: Only a small proportion of these patients with IBD developed a malignant tumor. The treatment of IBD has to be determined by the severity of the disease and not by the fear of developing a neoplasia. Following recommendations is fundamental to decrease the possibility of developing this complication.

Background: Approximately, 15% of patients with Inflammatory Bowel Disease (IBD) are diagnosed at 60 years of age or more., Aim: To characterize and compare clinical variables between patients with IBD aged 60 years or more and their younger counterparts., Material and Methods: Retrospective study based on a registry of IBD patients diagnosed between the years 1976 and 2014., Results: Four hundred and nine IBD patients were included. Among them, 294 had Ulcerative Colitis (UC), 104 had Crohn's Disease (CD) and eleven had an indeterminate IBD. Forty-six patients (11.2%) were older than 60 years and 16 (3.9%) had been diagnosed after this age. When comparing patients by age, those aged 60 years or more had a higher frequency of CD and indeterminate IBD (p < 0.01) and a lower ileocolic location in CD (p = 0.02). Both groups were similar in terms of hospitalization due to IBD flare, surgery, use of steroids, immunosuppressive or biological therapies and drug-related adverse events. When analyzing age at diagnosis of IBD, patients diagnosed at ages of 60 years or more had a lower frequency of UC (p < 0.01), a higher frequency of exclusive colonic involvement (p = 0.01), and lower use of mesalamine (p < 0.01). There were no differences in drug-related adverse events, hospitalizations due to IBD flares and surgery according to age at diagnosis., Conclusions: In this population, clinical features of IBD in older patients were similar to those in younger patients.

Objective: Imaging techniques are accurate and reliable in diagnosing inflammatory bowel disease (IBD). However, the main disadvantage of computed tomography (CT) compared with magnetic resonance imaging (MRI) is radiation exposure and the potential risk of cancer, especially since IBD patients are at increased risk of malignancies. This study aims to quantify and characterize effective radiation exposure of IBD patients., Methods: A cohort of IBD patients were retrospectively enrolled in the Clínica las Condes IBD registry between 2011 and 2013. High cumulative radiation exposure (CED) was defined as ≥-50 mSv., Results: A total of 325 IBD patients were enrolled in our registry, including 243 (74.8%) with UC and 82 (25.2%) with CD. The patients with CD were more commonly to reach a high CED seen compared with those with UC (19.5% vs 2.5%). Higher exposure to radiation was associated with longer duration of disease, ileal involvement, stricturing behavior, treatments with steroids and biological agents and CD-related hospitalization or surgery. Abdominopelvic CT and enteroclysis CT accounted for 93.6% of total CED., Conclusions: A high percentage of IBD patients are exposed to high CED. Radiation-free cross-sectional examinations, such as MRI, should be used, especially in young patients, those who have undergone prior surgery and those with severe IBD., (© 2014 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.)

Background: The incidence and prevalence of Inflammatory Bowel Disease (IBD) has increased., Aim: To determine demographic and clinical characteristics of patients with IBD in a Chilean private hospital., Patients and Methods: Review of a prospective registry of patients with IBD, started on 2012. It includes clinical, imaging, endoscopical and pathological information of patients., Results: Data of 316 patients with IBD, aged 16 to 86 years (56% females), were analyzed. Ulcerative Colitis (UC), Crohn´s and non-classifiable IBD were diagnosed in 230, 77 and 9 patients, respectively. The disease was diagnosed in 82% of patients in the period between 2002 and 2012. There was a peak in the diagnosis of both UC and CD between 20 and 39 years of age, without gender differences. The disease switched from UC to CD in six patients. In four, there was a change in disease behavior. Thirty eight patients were treated with biological therapy. The median lapse between the diagnosis and the use of biological therapy was 1 year in patients diagnosed after 2007, compared with 5.5 years among those patients diagnosed before 2007 (p = 0.001). There was a trend towards a higher requirement of surgery until 2006. Subsequently there was a stabilization of the requirement, concomitant with the incorporation of biological therapy., Conclusions: An adequate registry of IBD patients is necessary to improve demographic and clinical characteristics. A national registry is needed to assess the epidemiological changes of IBD in Chile.

Background: Laparoscopic colorectal surgery (LCRS) has several advantages over open surgery, but LCRS has been associated with a higher rate of postoperative complications (POCs) among obese patients [body mass index (BMI), ≥30 kg/m(2)]. The prevalence of obesity in Chile is increasing, up to 25.1% in 2010, suggesting that a higher percentage of patients undergoing LCRS will be obese. This study compared POC rates between obese and nonobese patients undergoing LCRS., Methods: This study included case and control patients in a prospectively maintained LCRS database who underwent LCRS between July 2007 and June 2012 at Clinica Las Condes, Santiago, Chile. Obese and nonobese (BMI <30 kg/m(2)) patients were paired by gender, age, American Society of Anesthesiologists class, preoperative diagnosis, and type of surgery. Intraoperative complications and POCs were documented up to 30 days. The severity of each POC was classified by Clavien-Dindo score., Results: In this study, 449 patients who underwent LCRS during the study period were identified. The study paired 53 obese patients (mean BMI 33.1 kg/m(2)) with 53 nonobese patients (mean BMI 25.9 kg/m(2)). The median age was 55 years in the obese group and 57 years in the nonobese group, and 60% of the patients in both groups were men. The findings showed POCs in 13 obese (24.5%) and 15 nonobese (28.3%) patients (p = 0.66). Stratified by severity of POCs, the two groups were similar (p = 0.62). The two groups did not differ in terms of the median time to the first feeding (1 day each) or the hospital length of stay (4 days each). Similar percentages of patients in the two groups required reoperation (p = 0.4), intensive care unit (ICU) admission (p = 0.77), and readmission to the hospital (p = 0.65) because of POCs., Conclusion: The frequency of POCs after LCRS was no higher among the obese patients than among the nonobese patients.