Aim
Recent studies have shown that sarcopenia is associated with negative postoperative outcomes. However, none of these studies analysed muscle strength or physical performance, which are also ...important components of sarcopenia. The present study aimed to investigate whether sarcopenia itself, as defined by low muscle mass, strength and physical performance, would predict complications after surgery for colorectal cancer.
Method
We conducted a prospective study of patients who underwent surgery for colorectal cancer at our department between August 2014 and February 2015. Sarcopenia was diagnosed by a combination of third lumbar vertebra muscle index (L3 MI), handgrip strength and 6‐m usual gait speed. Univariate and multivariate analyses evaluating the risk factors for postoperative complications were performed. Only complications classified as Grade II or above according to the Clavien–Dindo classification were analysed in this study.
Results
A total of 142 patients were included in the study, and 17 patients were diagnosed as having sarcopenia. Postoperative complications of Grade II or above occurred in 40 patients, including 10 with sarcopenia and 30 without sarcopenia. Multivariate analysis showed that sarcopenia and previous abdominal surgery were independent risk factors for postoperative complications. Patients with sarcopenia also had an obvious tendency to a higher incidence of infectious complications. By comparing two logistic regression models, sarcopenia showed a better predictive power for postoperative complications than did low muscle mass.
Conclusion
Sarcopenia and previous abdominal surgery are independent risk factors for complications after surgery for colorectal cancer. Including a functional aspect to the definition of sarcopenia may result in a better prediction of postoperative complications.
Upon binding to DNA breaks, poly(ADP-ribose) polymerase 1 (PARP1) ADP-ribosylates itself and other factors to initiate DNA repair. Serine is the major residue for ADP-ribosylation upon DNA damage, ...which strictly depends on HPF1. Here, we report the crystal structures of human HPF1/PARP1-CAT ΔHD complex at 1.98 Å resolution, and mouse and human HPF1 at 1.71 Å and 1.57 Å resolution, respectively. Our structures and mutagenesis data confirm that the structural insights obtained in a recent HPF1/PARP2 study by Suskiewicz et al. apply to PARP1. Moreover, we quantitatively characterize the key residues necessary for HPF1/PARP1 binding. Our data show that through salt-bridging to Glu284/Asp286, Arg239 positions Glu284 to catalyze serine ADP-ribosylation, maintains the local conformation of HPF1 to limit PARP1 automodification, and facilitates HPF1/PARP1 binding by neutralizing the negative charge of Glu284. These findings, along with the high-resolution structural data, may facilitate drug discovery targeting PARP1.
Summary Background Outbreaks of urinary tract infections (UTIs) due to contaminated ureteroscopes have been rarely reported. Aim To report such an outbreak at a regional teaching hospital in southern ...Taiwan. Methods From October to December 2010, ertapenem-resistant Enterobacter cloacae were identified from urine cultures of 15 patients who had undergone ureteroscopy prior to the infection. Three batches of surveillance cultures were obtained from the environmental objects and healthcare workers related to the procedures. Pulsed-field gel electrophoresis (PFGE) was used for bacterial typing. Antimicrobial susceptibility was assessed by disc diffusion and E-test methods. Polymerase chain reaction and sequencing were used to analyse β-lactamase genes. Findings A total of 70 specimens were obtained during the first surveillance operation. One ertapenem-resistant E. cloacae was isolated from a ureteroscope. Although the disinfection protocols for ureteroscopes were revised and implemented, seven additional UTI cases were identified thereafter. The pathogen was identified from two subsequent surveillance cultures and was not eliminated until ethylene oxide sterilization was added to the disinfection protocol. PFGE revealed that all 15 isolates from the patients and the three isolates from the ureteroscope shared a common pattern with minor variance. Most isolates were resistant to gentamicin, levofloxacin, ceftriaxone, ceftazidime, and ertapenem. All isolates were susceptible to amikacin, imipenem, and meropenem. SHV-12 and IMP-8 genes were simultaneously identified in 16 of the 18 isolates. Conclusion The outbreak of ertapenem-resistant E. cloacae was caused by a contaminated ureteroscope and was terminated by the implementation of a revised disinfection protocol for ureteroscopes.
Estrogens encompass steroid hormones which display physiological roles not only in the female reproductive system but also in other organ systems of non‐reproductive controls, including the ...peripheral and central nervous systems. Traditionally, estrogen signals in neurons through a “genomic pathway”: binding to estrogen receptors (ERs) which then interact with nuclear estrogen response elements to initiate transcription. This effect is usually delayed at onset (within several hours to days) and prolonged in duration. In addition to these classical ERs, recent data suggest that other ERs function through pregenomic signaling pathways. Estrogen's pregenomic pathways cause intracellular changes within seconds to minutes and go through a novel, 7‐transmembrane spanning G protein‐coupled receptor (GPER, formerly known as GPR30). In this review, we will briefly cover the cellular and molecular mechanisms of GPER and then discuss newly discovered roles of GPER in cognition, depression, homeostasis, pain processing, and other associated neuronal functions.
Estrogens exert physiological effects via genomic pathways by way of estrogen receptors ERα and β as well as the pregenomic pathways by way of the G protein‐coupled estrogen receptor (GPER)—the receptor recognized as responsible for rapid responses to estrogen. The pregenomic effects of GPER on neuronal function include cognition, depression, homeostasis, pain processing, neuroprotection, and intestinal motility. Though preclinical data demonstrate important roles of GPER on neurological functions, GPER's therapeutic potential and its interaction with classical ERs remains to be investigated.
Summary
Psoriasis is an immune‐mediated inflammatory skin disease that mainly affects the skin barrier. Treatment for psoriasis mainly includes conventional immunosuppressive drugs. However, ...long‐term treatment with global immunosuppressive agents may cause a variety of side effects, including nephrotoxicity and infections. Kaempferol, a natural flavonol present in various plants, is known to possess potent anti‐inflammatory, anti‐oxidant and anti‐cancerous properties. However, it is unknown whether kaempferol is also anti‐psoriatic. Here we established an imiquimod (IMQ)‐induced psoriatic mouse model to explore the potential therapeutic effects of kaempferol on psoriatic skin lesions and inflammation. In this study, we demonstrated that treatment with kaempferol protected mice from developing psoriasis‐like skin lesions induced by topical administration of IMQ. Kaempferol reduced CD3+ T cell infiltration and gene expression of major proinflammatory cytokines, including interleukin (IL)‐6, IL‐17A and tumor necrosis factor (TNF)‐α, in the psoriatic skin lesion. It also down‐regulated proinflammatory nuclear factor kappa B (NF‐κB) signaling in the skin. The therapeutic effects were associated with a significant increase in CD4+forkhead box protein 3 (FoxP3)+ regulatory T cell (Treg) frequency in the spleen and lymph nodes as well as FoxP3‐positive staining in the skin lesion. Conversely, depletion of CD4+CD25+ Tregs reversed the therapeutic effects of kaempferol on the skin lesion. Kaempferol also lowered the percentage of IL‐17A+CD4+ T cells in the spleen and lymph nodes of IMQ‐induced psoriatic mice. Finally, kaempferol suppressed the proliferation of T cells in vitro and their mTOR signaling. Thus, our findings suggest that kaempferol may be a therapeutic drug for treating human psoriasis in the near future.
Kaempferol, a natural flavonol, is known to possess potent anti‐inflammatory and anti‐oxidant properties. Here, we found that kaempferol protected mice from developing psoriasis‐like skin inflammation and lesion induced by imiquimod. It also induced CD4+FoxP3+ regulatory T cells while inhibiting Th17 cell development in the psoriatic mice.
Summary
Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with abnormal T cell immune responses. We hypothesized that aberrant expression of microRNAs (miRNAs) in T cells may ...contribute to the pathogenesis of SLE. First, we analysed the expression profiles of 270 human miRNAs in T cells from five SLE patients and five healthy controls and then validated those potentially aberrant‐expressed miRNAs using real‐time polymerase chain reaction (PCR). Then, the expression of mRNAs regulated by these aberrant‐expressed miRNAs was detected using real‐time PCR. Finally, miRNA transfection into Jurkat T cells was conducted for confirming further the biological functions of these miRNAs. The initial analysis indicated that seven miRNAs, including miR‐145, miR‐224, miR‐513‐5p, miR‐150, miR‐516a‐5p, miR‐483‐5p and miR‐629, were found to be potentially abnormally expressed in SLE T cells. After validation, under‐expressed miR‐145 and over‐expressed miR‐224 were noted. We further found that STAT1 mRNA targeted by miR‐145 was over‐expressed and apoptosis inhibitory protein 5 (API5) mRNA targeted by miR‐224 was under‐expressed in SLE T cells. Transfection of Jurkat cells with miR‐145 suppressed STAT1 and miR‐224 transfection suppressed API5 protein expression. Over‐expression of miR‐224 facilitates activation‐induced cell death in Jurkat cells. In the clinical setting, the increased transcript levels of STAT1 were associated significantly with lupus nephritis. In conclusion, we first demonstrated that miR‐145 and miR‐224 were expressed aberrantly in SLE T cells that modulated the protein expression of their target genes, STAT1 and API5, respectively. These miRNA aberrations accelerated T cell activation‐induced cell death by suppressing API5 expression and associated with lupus nephritis by enhancing signal transducer and activator of transcription‐1 (STAT)‐1 expression in patients with SLE.
We present X-ray timing results of the new black hole candidate MAXI J1535−571 during its 2017 outburst from Hard X-ray Modulation Telescope (Insight-HXMT) observations taken from 2017 September 6 to ...23. Following the definitions given by Belloni, we find that the source exhibits transitions from the low/hard state to the hard intermediate state, and eventually to the soft intermediate state. Quasi-periodic oscillations (QPOs) are found in the intermediate states, which suggest different types of QPOs. With the large effective area of Insight-HXMT at high energies, we are able to present the energy dependence of the QPO amplitude and centroid frequency up to 100 keV, which has rarely been explored by previous satellites. We also find that the phase lag at the type-C QPOs centroid frequency is negative (soft lag) and strongly correlated with the centroid frequency. Assuming a geometrical origin of type-C QPOs, the source is consistent with being a high-inclination system.
The epidemiology of candidaemia varies between hospitals and geographic regions. Although there are many studies from Asia, a large-scale cross-sectional study across Asia has not been performed. We ...conducted a 12-month, laboratory-based surveillance of candidaemia at 25 hospitals from China, Hong Kong, India, Singapore, Taiwan and Thailand. The incidence and species distribution of candidaemia were determined. There were 1601 episodes of candidaemia among 1.2 million discharges. The overall incidence was 1.22 episodes per 1000 discharges and varied among the hospitals (range 0.16–4.53 per 1000 discharges) and countries (range 0.25–2.93 per 1000 discharges). The number of Candida blood isolates and the total number of fungal isolates were highly correlated among the six countries (R² = 0.87) and 25 hospitals (R² = 0.77). There was a moderate correlation between incidence of candidaemia and the intensive care unit (ICU)/total bed ratio (R² = 0.47), although ICUs contributed to only 23% of candidaemia cases. Of 1910 blood isolates evaluated, Candida albicans was most frequently isolated (41.3%), followed by Candida tropicalis (25.4%), Candida glabrata (13.9%) and Candida parapsilosis (12.1%). The proportion of C. tropicalis among blood isolates was higher in haemato-oncology wards than others wards (33.7% versus 24.5%, p 0.0058) and was more likely to be isolated from tropical countries than other Asian countries (46.2% versus 18.9%, p 0.04). In conclusion, the ICU settings contribute, at least in part, to the incidence variation among hospitals. The species distribution is different from Western countries. Both geographic and healthcare factors contribute to the variation of species distribution.
Background. The study aimed to evaluate the risk of hepatitis C virus (HCV) infection on hepatic and extrahepatic deaths. Methods. A cohort of 23 820 adults aged 30—65 years old were enrolled during ...1991—1992. The seromarkers hepatitis B surface antigen (HBsAg), anti-HCV, and serum HCV RNA levels at study entry were tested. The vital status was ascertained through computerized linkage with national death certification profiles from 1991 to 2008. Results. There were 19 636 HBsAg-seronegatives, including 18 541 anti-HCV seronegatives and 1095 anti-HCV seropositives. Among anti-HCV seropositives, 69.4% had detectable serum HCV RNA levels. There were 2394 deaths that occurred during an average follow-up period of 16.2 years. Compared with anti-HCV seronegatives, anti-HCV seropositives had higher mortality from both hepatic and extrahepatic diseases, showing multivariate-adjusted hazard ratio (95% confidence interval) of 1.89 (1.66—2.15) for all causes of death; 12.48 (9.34—16.66) for hepatic diseases; 1.35 (1.15—1.57) for extrahepatic diseases; 1.50 (1.10—2.03) for circulatory diseases; 2.77 (1.49—5.15) for nephritis, nephrotic syndrome, and nephrosis; 4.08 (1.38—12.08) for esophageal cancer; 4.19 (1.18—14.94) for prostate cancer; and 8.22 (1.36—49.66) for thyroid cancer. Anti-HCV seropositives with detectable HCV RNA levels had significantly higher mortality from hepatic and extrahepatic diseases than anti-HCV seropositives with undetectable HCV RNA. Conclusions. Monitoring HCV RNA in anti-HCV seropositives is essential for the prediction of mortality associated with hepatitis C.
Aims
To report the annual incidence rate and the socio‐demographic and clinical characteristics of childhood Type 1 diabetes in Taiwan in the period 2003–2008.
Methods
A total of 1306 incident cases ...of childhood (0–14 years) Type 1 diabetes were identified from Taiwan's National Health Insurance claim datasets from the period 2003–2008. The temporal trend of the incidence rate of Type 1 diabetes and the features of hospitalizations in the first year after diagnosis were investigated. The associations of patient characteristics, child population density and the urbanization level of the residential areas with the risk of Type 1 diabetes were assessed using Poisson regression analysis.
Results
The annual incidence rate was stable, irrespective of age and gender, with a mean annual incidence rate of 5.3 per 100 000 children. Girls were more likely than boys to develop Type 1 diabetes (6.0 vs 4.7 per 100 000 children) and the incidence rate increased with age. There was no apparent geographic variation in the incidence rates. Despite the 60% decrease in the rate of admission (from 11.0 to 5.8%) over the study period, ketoacidosis remained the major diabetes complication leading to admission for childhood Type 1 diabetes. The multivariate analysis suggested that female gender and older age were significant predictors of the incidence of Type 1 diabetes, whereas the population density of children and the urbanization levels of the residential areas were not.
Conclusions
Girls and older children should receive particular attention when formulating preventive strategies targeting Type 1 diabetes. Additionally, clinicians should still carefully optimize the management of children with Type 1 diabetes to further reduce the occurrence of ketoacidosis.
What's new?
The incidence of childhood (<15 years) Type 1 diabetes was stable between 2003 and 2008 in Taiwan, with a mean annual incidence rate of 5.3 per 100 000 children.
Female gender and older age were significant predictors for the incidence of Type 1 diabetes.
Although the rate of admission for Type 1 diabetes decreased by 60% over the study period, ketoacidosis still accounted for 24.6% of all admissions of Type 1 diabetes in 2007–2008 and remained the major complication of diabetes leading to admission in the first year after the onset of Type 1 diabetes.
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