Sky1: at the intersection of prion-like proteins and stress granule regulation.
Serine-arginine (SR) protein kinases regulate diverse cellular activities, including various steps in RNA maturation and transport. The yeast Saccharomyces cerevisiae expresses a single SR kinase, Sky1. Sky1 has a bipartite kinase domain, separated by an aggregation-prone prion-like domain (PrLD). The assembly of PrLDs is involved in the formation of various membraneless organelles, including stress granules; stress granules are reversible ribonucleoprotein assemblies that form in response to a variety of stresses. Here, we review a recent study suggesting that Sky1's PrLD promotes Sky1 recruitment to stress granules, and that Sky1 regulates stress granule dissolution by phosphorylating the RNA-shuttling protein Npl3.


Insulin sensitivity modifies the relationship between thyroid function and lipid profile in euthyroid type 1 diabetic patients.
It has been suggested that association between hypothyroidism with dyslipidemia might be present already at the stage of normal thyroid function through altered insulin sensitivity. We analyzed the role of insulin sensitivity as a mediator of thyroid-induced lipid changes in euthyroid type 1 diabetic patients. Study included 304 patients with type 1 diabetes and normal thyroid function. Insulin sensitivity was measured with estimated glucose disposal rate calculated using the equation: eGDR = 24.31 - (12.22 × WHR) - (3.29 × HT) - (0.57 × HbA1c); WHR = waist-to-hip ratio, HT = hypertension. TSH, FT4, FT3, and serum lipids were measured. Correlations and multiple linear regressions analysis were performed to identify relationships between thyroid status and serum lipid parameters after stratifying patients in quartiles of eGDR. After adjustment for age, sex, BMI, duration of diabetes and insulin dose TSH, FT3, and FT4 was not significantly associated with serum lipids in all patients, independently of level of insulin sensitivity. However, after stratifying patients for the degree of insulin sensitivity in subjects in the lowest quartile of insulin sensitivity TSH was independently associated with LDL cholesterol (β = 0.210, p = 0.02). The independent relation of eGDR with TSH and LDL cholesterol suggests that the influence of thyroid function on lipid metabolism might extend into euthyroid range through altered insulin sensitivity.


Genetic characterisation of a complex class 1 integron in an NDM-1-producing Citrobacter freundii ST396 clinical strain isolated from a urine sample.
The aim of this study was to characterise a multidrug-resistant (MDR) Citrobacter freundii strain carrying a blaNDM-1-harbouring conjugative IncA/C2-type plasmid in China. The whole genome of C. freundii strain L75 was sequenced both on HiSeq® (Novogene Corp., China) and GridION X5 (GrandOmics Biosciences Co., Ltd.) platforms. De novo genome assembly, genome annotation, multilocus sequence typing (MLST) and plasmid replicon typing were performed. Citrobacter freundii L75 was assigned to ST396 and contains a 5.1-Mb chromosome and two plasmids (∼146 kb and ∼73 kb) designated pCf75 and pCf76, respectively. The antibiotic resistance determinants blaNDM-1, sul1, sul2, arr-3, mph(A), aadA16, aph(3")-Ib, aac(3)-IId, aph(6)-Id, aac(6')-Ib-cr and dfrA27 were located on plasmid pCf75, whilst blaCMY-78 was chromosomally encoded. A 22.1-kb MDR-encoding region (MDRR) in a complex class 1 integron contained all of the resistance genes of plasmid pCf75. We detected and characterised a plasmid carrying a novel MDRR in which a complex class 1 integron plays an essential role. In addition, this study provides fresh genomic insights into the diversity of C. freundii ST396 prevalent in Guangzhou Province, China, and underscores the increasing clinical relevance of the IncA/C2 plasmid family.


Identification of an unconventional nuclear localization signal in human ribosomal protein S2.
Ribosomal proteins must be imported into the nucleus after being synthesized in the cytoplasm. Since the rpS2 amino acid sequence does not contain a typical nuclear localization signal, we used deletion mutant analysis and rpS2-beta-galactosidase chimeric proteins to identify the nuclear targeting domains in rpS2. Nuclear rpS2 is strictly localized in the nucleoplasm and is not targeted to the nucleoli. Subcellular localization analysis of deletion mutants of rpS2-beta-galactosidase chimeras identified a central domain comprising 72 amino acids which is necessary and sufficient to target the chimeric beta-galactosidase to the nucleus. The nuclear targeting domain shares no significant similarity to already characterized nuclear localization signals in ribosomal proteins or other nuclear proteins. Although a Nup153 fragment containing the importinbeta binding site fused to VP22 blocks nuclear import of rpS2-beta-galactosidase fusion proteins, nuclear uptake of rpS2 could be mediated by several import receptors since it binds to importinalpha/beta and transportin.


Fracture resistance of soft tissue level implants after cyclic loading and external modification.
The exposure of the implant collar in the esthetic zone is a challenging complication of implant dentistry. The preparation of the exposed implant collar to create room for restorative material may decrease the strength of the abutment/implant assembly. The purpose of this in vitro study was to evaluate the effect on the failure load of preparing a 0.5-mm chamfer finish line on an implant collar at various apical depths. Thirty solid abutments and 30 implants were screwed into a customized metal mold at a 30-degree angle to the vertical axis. An intact group (IN) (control) (n=10) had no preparation, experimental group P1 had a 0.5-mm chamfer margin placed 1 mm apical to the implant/abutment interface, and experimental group P2 had the margin placed 2 mm apical. The specimens were subjected to a fatigue loading of 200 N for 1 000 000 cycles. Unfractured specimens were then loaded until failure. Mean fracture load (MFL) values were compared with 1-way ANOVA, and the Tukey test was used to identify differences among groups (α=.05). One specimen from both the IN and P1 groups and 2 specimens from the P2 group failed after fatigue loading. Significant differences in the MFL values were found between the IN group (3825) and P1 group (2944), P<.001 and between the IN group and the P2 group (2553), P<.001. The mean load required to fracture the abutment/implant assembly decreased significantly after various amounts of implant collar preparation.


Preparation and application of novel nanocomposites of magnetic-Au nanorod in SPR biosensor.
A novel nanocomposite Fe(3)O(4)-Au nanorod (AuNR) was prepared and used as the substrate in the surface plasmon resonance (SPR) biosensor to detect goat IgM. Fe(3)O(4)-AuNR nanocomposites were synthesized by a method of seed-mediated growth, and further characterized by molecular absorption spectroscopy, transmission electronic microscopy (TEM), energy-dispersive spectroscopy (EDS) and X-ray photoelectron spectroscopy (XPS). The nanocomposites exhibit both magnetic property and exceptional optical property, which are beneficial to the antibody immobilization and the sensitivity of detection. The sensing membrane can be regenerated easily and the experimental procedure is simplified. Moreover, the Au nanorods show two plasmon resonance wavelengths defined as transverse mode and longitudinal mode, and the longitudinal plasmon wavelengths are more sensitive to the changes in the dielectric properties of the surroundings. Fe(3)O(4)-AuNR nanocomposites got a high sensitivity in detection of antibody-antigen immunoassay. In the optimal conditions, the biosensor based on Fe(3)O(4)-AuNR nanocomposites exhibits a satisfactory response to goat IgM in the concentration range of 0.15-40.00 μg mL(-1). However, the biosensor without Fe(3)O(4)-AuNR nanocomposites shows a response to goat IgM in the concentration range of 1.25-40.00 μg mL(-1). As a result, the sensitivity of the biosensor based on Fe(3)O(4)-AuNR nanocomposites is enhanced significantly.


Single intra-articular injection of high molecular weight hyaluronic acid for hip osteoarthritis.
Intra-articular (IA) injection of hyaluronic acid (HA) into the hip joint appears to be safe and well tolerated but only a small number of randomized clinical trials in humans has been published. The objective of this prospective study was to evaluate the efficacy and safety of a single IA injection of high-molecular-weight (2800 kDa) HA (Coxarthrum) for hip osteoarthritis. All patients received a single IA administration of 2.5 % sodium hyaluronate (75 mg/3 mL) of high molecular weight. Fluoroscopy requires an iodized contrast medium (iopamidol, 1 ml) which highlights the capsule before administering HA. Patients were evaluated before IA injection (T0), after 3 months, after 6 months and after 1 year from injection. Results were evaluated by the Brief Pain Inventory (BPI II), Harris Hip Score and a visual analog scale of pain (pain VAS). All treated patients were considered for statistical analysis. Two hundred seven patients were included at T0. The mean age was 67 years (range 46-81). Regarding BPI severity score, changes in pain between T0 and the three following visits were statistically highly significant (p < 0.001). Changes in pain score compared to the previous visit were statistically significant for the worst pain in the second quarter post-intervention (p = 0.037) and for mean pain in the second semester post-intervention (p = 0.043) The evolution of the Harris Hip Score was statistically highly significant (p < 0.001) between T0 and the following visits (T0 + 3 months, T0 + 6 months and T0 + 12 months); after a significant change between T0 and T0 + 3 months, the score remained stable. The evolution of the pain VAS showed a statistically highly significant improvement (p < 0.001) between T0 and T0 + 3 months; thereafter it remained stable from the first quarter post-intervention. No serious adverse event was noted; 12 cases (0.5 %) of pain associated with transient synovitis are noteworthy. This study shows that a single IA injection of Coxarthrum is effective from the third month and that the results are stable or continue to improve up to 1 year. IV.


Predictive value of patency capsule and magnetic resonance enterography for capsule endoscopy retention in patients with established Crohn's disease.
retention is the most common adverse event of the small bowel capsule endoscopy procedure. Patency capsule (Medtronic, Dublin, Ireland) and magnetic resonance enterography are two diagnostic methods that can prevent small bowel capsule endoscopy retention. The aim of this study was to evaluate the predictive value of these two diagnostic methods. a prospective, comparative and observational study was performed in patients with established Crohn's disease. All patients had undergone magnetic resonance enterography and patency capsule procedures. If the patency capsule was not retained, the patient underwent a small bowel capsule endoscopy; otherwise, double balloon enteroscopy was performed to locate the stenosis. Magnetic resonance enterography predictive criteria for retention were analyzed in all cases. Sensitivity, specificity, positive predictive value and negative predictive value of the patency capsule and magnetic resonance enterography compared to small bowel capsule endoscopy or double balloon enteroscopy were calculated. forty patients were included (24 female, 55 ± 13 years old). Retention criteria with capsule endoscopy or double balloon enteroscopy were found in six patients, agreeing in five cases with patency capsule and in three cases with magnetic resonance enterography. Sensitivity, specificity, positive predictive value, negative predictive value and Kappa coefficient for predicting retention with the patency capsule were 83 %, 100 %, 100 % and 97 %, respectively, and 50 %, 91 %, 50 % and 91 %, respectively, with magnetic resonance enterography. patency capsule has a higher sensitivity and positive predictive value than magnetic resonance enterography for preventing small bowel capsule endoscopy retention in Crohn's disease patients.


Does failed natural opioid modulation in regional sympathetic ganglia cause reflex sympathetic dystrophy?
Early features of reflex sympathetic dystrophy in a limb resemble the general effects of autonomic arousal associated with opioid withdrawal. It is suggested that natural opioid peptide modulation in regional sympathetic ganglia normally rises to prevent excessive autonomic activity in an injured limb. After an injury (especially a trivial one) to a susceptible subject, this localised increase in opioid modulation may fail or may rapidly wane so that autonomic features of opioid withdrawal appear in the affected limb. Florid dystrophic changes may then occur because of passive complications of disuse associated with pain, or as a result of more active processes. Preservation of an appropriate opioid bias in the regional sympathetic ganglia might be an important factor in the successful management and prevention of reflex sympathetic dystrophy.


Etiology, Clinical Features, And Short-Term Outcome Of Seizures In Newborns Admitted To The University Of Gondar Hospital, Ethiopia.
Neonatal seizures are the most common neurological dysfunction in the neonatal period. Neonatal seizure patterns and short-term neurologic outcomes, particularly in the Ethiopian context, have not been adequately studied. The main aim of this study is to assess the pattern, probable etiology, short-term outcomes, and determinants of neonatal seizures in the neonatal intensive care unit of Gondar University Specialized Comprehensive Hospital. A hospital-based prospective observational cohort study was conducted from October 1, 2016, to September 30, 2018. Among the 117 neonates enrolled, the most common type of neonatal seizure was subtle (60.6%), followed by tonic (15.4%), and clonic (12.8%) seizures. The most common etiology for the seizure was perinatal asphyxia (PNA) with hypoxic-ischemic encephalopathy (HIE; 74.4%) followed by electrolyte disturbances (12.8%). In the follow-up, 23 (19.7%) died during the acute neonatal illness. The most common cause of death was PNA with HIE, accounting for 73.9% of the deaths. Among the surviving newborns, 10 (10.6%) had neurodevelopmental deficits at discharge. Being a multiparous mother (OR= 0.172; 95% CI: 0.033, 0.880), being female (OR= 0.171; 95% CI: 0.055, 0.538), and having tonic (OR= 0.164; 95% CI: 0.030, 0.885) and myoclonic seizures (OR= 0.040; 95% CI: 0.055, 0.538) were significantly associated with mortality poor short-term outcome. Subtle seizures were the most common seizure semiology. The most common etiology for seizure was PNA with HIE. Parity, gestational age, neonatal sex, and seizure type were determinants of short-term outcomes.


Can we trust cancer information on the Internet?--A comparison of interactive cancer risk sites.
To investigate the prevalence and quality of interactive cancer risk sites on the Internet. A cancer risk site was defined as a website that gave an estimate of the individual risk of developing cancer. Six search engines and one Meta crawler were used to search the Internet for cancer risk sites (including breast, prostate, colon, and lung cancer). A set of defined quality criteria for health related websites was used to evaluate the websites during 2001 and 2002. The number of cancer risk sites, as defined above, increased by 50% between 2001 and 2002. Only two out of 22 cancer risk sites fulfilled the quality criteria adequately. No signs of a change in trend (with regard to the quality criteria met) were noted in January 2005. The overall quality of the documentation on the cancer risk sites was poor and no improvement was seen during the study period. The majority of the cancer risk sites do not give reliable risk estimates.


The Vitamin D endocrine system of the gut--its possible role in colorectal cancer prevention.
While Vitamin D insufficiency in the US and European population is rising, epidemiological studies suggest an inverse correlation between low serum levels of 25-hydroxyvitamin D(3) (25-OH-D(3)) and colorectal cancer incidence. The antimitotic, prodifferentiating and proapoptotic active metabolite 1alpha,25-dihydroxyvitamin D(3) (1,25-(OH)(2)-D(3)) is synthesized also by colonocytes, since these possess Vitamin D synthesizing (CYP27B1) and catabolic (CYP24) hydroxylases similar to the kidney. Early during colon tumor progression, expression of CYP27B1 and of the Vitamin D receptor increases, suggesting an autocrine/paracrine growth control in colon tissue as a physiological restriction against tumor progression. However, in human adenocarcinomas expression of the catabolic CYP24 is also enhanced when compared with adjacent normal mucosa. Therefore, to maintain colonic accumulation of 1,25-(OH)(2)-D(3) its catabolism needs to be restricted. Our studies in mice show that low nutritional calcium causes hyperproliferation of colon crypts and significant elevation of CYP24 expression, which can be completely abrogated by soy feeding. We suggest that phytoestrogens in soy, known to be estrogen receptor modulators, are responsible for decreased CYP24 expression. These results and our observation that 17beta-estradiol can elevate CYP27B1 expression in rectal tissue of postmenopausal women, may underlie the observed protective effect of estrogens against colorectal cancer in females.


Staphylococcus aureus: determinants of human carriage.
Staphylococcus aureus is a common human commensal but carriage varies between e.g. geographic location, age, gender, ethnicity and body niche. The nares, throat and perineum are the most prevalent sites for carriage in the general adult population. Other sites of the skin and the intestine are also frequently colonised. Thus, a successful establishment is dependent on multiple factors. This review describes results from observational studies of S. aureus carriage and the influence bacterial, host and environmental/modifiable factors might have on the relationship.


Effects of fitspiration content on body image: a systematic review.
Fitspiration (also known as "fitspo") aims to inspire individuals to exercise and have healthy habits, but emerging research indicates that exposure to it can have a negative impact on body image. This study aims to analyze the relationship between individuals' exposure to fitspiration content and body image measures or associated variables (e.g., appearance comparison). A comprehensive search of peer-reviewed papers published in English between 2000 and August 2022 was conducted in PubMed, PsycINFO and Google Scholar, based on the PICOS model. To be included, studies had to analyze the relationship between exposure to fitspiration content (I) and body image or associated variables (O) in adolescents and adults (P). Study methodological quality was assessed using an adaptation of the EPHPP Quality Assessment Tool for Quantitative Studies. Outcome data were synthesized narratively and by vote counting. Twenty articles met the eligibility criteria and were included. Nineteen studies analyzed the relationship between fitspiration and body image, twelve analyzed the association between exposure to fitspiration and physical appearance comparison tendencies, and nine analyzed the association between fitspiration content and mood. One study analyzed the association between frequency of viewing fitspiration content and motives for exercise. Results showed that exposure to "fitspiration" increased individuals' body dissatisfaction, physical appearance comparisons, and negative mood, especially in younger populations. Fitspiration has been seen as a new and prolific digital trend, considered beneficial for health. However, our results showed that fitspo is associated with negative body image, especially in younger populations that are more exposed to this content. Most of the studies were conducted in females and young age participants, which limits the extrapolation of results by gender and age. Future studies are needed to confirm and extend these findings. Level 1, Systematic Review.


Effect of chemical sanitizer combined with modified atmosphere packaging on inhibiting Escherichia coli O157:H7 in commercial spinach.
Escherichia coli O157:H7 contaminated spinach has recently caused several outbreaks of human illness in the USA and Canada. However, to date, there has been no study demonstrating an effective way to eliminate E. coli O157:H7 in spinach. Therefore, this study was conducted to investigate the effect of chemical sanitizers alone or in combination with packaging methods such as vacuum and modified atmosphere packaging (MAP) on inactivating E. coli O157:H7 in spinach during storage time. Spinach inoculated with E. coli O157:H7 was packaged in four different methods (air, vacuum, N(2) gas, and CO(2) gas packaging) following treatment with water, 100 ppm chlorine dioxide, or 100 ppm sodium hypochlorite for 5 min at room temperature and stored at 7+/-2 degrees C. Treatment with water did not significantly reduce levels of E. coli O157:H7 in spinach. However, treatment with chlorine dioxide and sodium hypochlorite significantly decreased levels of E. coli O157:H7 by 2.6 and 1.1 log(10)CFU/g, respectively. Levels of E. coli O157:H7 in samples packaged in air following treatments grew during storage time, whereas levels were maintained in samples packaged in other packaging methods (vacuum, N(2) gas, and CO(2) gas packaging). Therefore there were significant differences (about 3-4 log) of E. coli O157:H7 populations between samples packed in air and other packaging methods following treatment with chemical sanitizers after 7 days storage. These results suggest that the combination of treatment with chlorine dioxide and packaging methods such as vacuum and MAP may be useful for improving the microbial safety of spinach against E. coli O157:H7 during storage.


Maternal imprinting of the neonatal microbiota colonization in intrauterine growth restricted piglets: a review.
Early colonization of intestinal microbiota during the neonatal stage plays an important role on the development of intestinal immune system and nutrients absorption of the host. Compared to the normal birth weight (NBW) piglets, intrauterine growth restricted (IUGR) piglets have a different intestinal microbiota during their early life, which is related to maternal imprinting on intestinal microbial succession during gestation, at birth and via suckling. Imbalanced allocation of limited nutrients among fetuses during gestation could be one of the main causes for impaired intestinal development and microbiota colonization in neonatal IUGR piglets. In this review, we summarized the potential impact of maternal imprinting on the colonization of the intestinal microbiota in IUGR piglets, including maternal undernutrition, imbalanced allocation of nutrients among fetuses, as well as vertical microbial transmission from mother to offspring during gestation and lactation. At the same time, we give information about the current maternal nutritional strategies (mainly breastfeeding, probiotics and prebiotics) to help colonization of the advantageous intestinal microbiota for IUGR piglets.


The functional and radiographic outcomes following distal radius fracture treatment in a cast for 4 and 6 weeks in the elderly: A randomized trial.
The optimal duration of cast immobilization following distal radius fractures (DRFs) in elderly patients has not been established. To assess the functional and radiological parameters following DRF treatment in elderly patients using 2 different periods of cast immobilization. We assessed 50 patients (33 women and 17 men). The mean age at the beginning of treatment was 71 years. The mean duration of follow-up was 1 year and 3 months. One subgroup (n = 26) included patients treated with a cast for 4 weeks, whereas the other subgroup (n = 24) included patients treated with a cast for 6 weeks. The following measures were assessed: union rate, radial inclination, volar tilt, radial height, Visual Analogue Scale (VAS) pain score, Mayo Wrist Score, and VAS activity score. The mean volar tilt was 9.13° in the group treated with a cast for 4 weeks and 3.29° in the group treated with a cast for 6 weeks (p = 0.043). There were no differences between the groups in terms of any other functional or radiological parameters. The VAS pain score, Mayo Wrist Score and VAS activity score were similar between the 2 study groups. The greatest volar tilt angle was observed after 6 weeks of cast immobilization. The study groups showed no significant differences in terms of radial inclination, union rate, radial height, or bone union. A period of 4 weeks of cast treatment was sufficient for elderly patients with DRFs.


Efficacy and safety of micro-needling combined with topical 5-fluorouracil and excimer light vs. excimer light alone in treatment of non-segmental vitiligo: A comparative study.
Vitiligo is one of the most challenging dermatological diseases with little improvement promises. Various modalities of treatment both medical and surgical have been used in the treatment of vitiligo. Some proved to be effective, others with controversial results and the rest were effective less. The aim of the present study was to evaluate the additional effect of topical 5-fluorouracil after micro-needling to excimer light (308 nm) in treatment of non-segmental vitiligo. Fifty patients were included in the present study, only 33 patients continued the treatment for 6 months. Two patches were selected in every patient to be treated, one patch with micro-needling then application of 5 FU and excimer (Group A), and the other with excimer only (Group B). The treatment with the combination of micro-needling then application of 5 FU and excimer showed significant earlier response versus excimer alone. Also, the percentage of re-pigmentation was higher in the patches treated with the combination especially in the face and trunk. The combination of 5 FU after micro-needling and Excimer is more suitable for localized and focal vitiligo. Topical 5 FU after micro-needling is a promising, rapid, and cost-effective therapeutic strategy for treatment of non-segmental vitiligo It had limited side effects, and the best response was reported for lesions affecting face and trunk.


Simple prognostic markers for optimal treatment of patients with unresectable pancreatic cancer.
Most patients with pancreatic cancer are ineligible for curative resection at diagnosis, resulting in poor prognosis. This study aimed to evaluate the prognostic factors in patients with unresectable pancreatic cancer.We retrospectively collected clinical data from 196 patients with unresectable pancreatic cancer who received palliative chemotherapy (N = 153) or palliative care alone (N = 43) from January 2011 to December 2013. Patients' background data and overall survival were analyzed using the Cox proportional hazard regression model.In patients receiving palliative chemotherapy (gemcitabine-based regimen, 88.2%) and palliative care alone, the median (range) ages were 68 (43-91) and 78 (53-90) years, and metastatic diseases were present in 80% (N = 123) and 86% (N = 37), respectively. Multivariate analysis in the palliative chemotherapy patients showed that liver metastasis (hazard ratio [HR] 2.25, 95% confidence interval [CI] 1.58-3.20, P < .001), neutrophil-to-lymphocyte ratio (>4.5 vs ≤4.5; HR 3.45, 95% CI 2.22-5.36, P < .001), and cancer antigen 19-9 (CA19-9) (≥900 vs <900 U/mL; HR 1.45, 95% CI 1.02-2.05, P = .036) were independent prognostic factors. In those receiving palliative care alone, lung (HR 3.27, 95% Cl 1.46-7.35, p = 0.004) and peritoneum (HR 2.50, 95% CI 1.20-5.18, P = .014) metastases and the C-reactive protein-to-albumin ratio (≥1.3 vs <1.3; HR 3.33, 95% Cl 1.51-7.35, P = .003) were independent prognostic factors. Furthermore, patients with multiple factors had worse prognosis in both groups. Median survival time of palliative chemotherapy patients with risk factors 0, 1, 2, and 3 were 13.1 (95% CI 8.0-16.9), 9.4 (95% CI 7.9-10.1), 6.6 (95% CI 4.9-7.8), and 2.5 (95% CI 1.7-4.0) months, respectively. Similarly, median survival time was 5.7 (95% CI 1.3 -8.0), 2.1 (95% CI 1.5-3.9), and 1.3 (95% CI 0.6-1.7) months, respectively, for palliative care alone patients with risk factor 0, 1, and 2 to 3.Prognostic markers for pancreatic cancer were neutrophil-to-lymphocyte ratio, liver metastasis, and CA19-9 in patients undergoing palliative chemotherapy and C-reactive protein-to-albumin ratio and lung/peritoneum metastases in patients undergoing palliative care alone. These simple markers should be considered when explaining the prognosis and therapeutic options to patients.


Kinematic versus mechanically aligned total knee arthroplasty: no difference in frequency of arthroscopic lysis of adhesions for arthrofibrosis.
Arthrofibrosis is a condition that can cause excessive scar tissue formation, leading to painful restriction of joint motion. Following total knee arthroplasty (TKA), significant arthrofibrosis can result in permanent deficits in range of motion (ROM) if not treated. Although arthroscopic lysis of adhesions (ALOA) reliably improves post-TKA ROM if performed in a timely fashion, it exposes patients to additional anesthesia, heightens the risk of infection, and increases overall medical expenses. Kinematically aligned TKA has emerged as an alternative method to mechanically aligned, basing bony cuts off of the patient's pre-arthritic anatomy while limiting need for soft tissue and ligamentous releases. This study aimed to determine whether there is a difference in the frequency of post-TKA arthrofibrosis requiring ALOA between kinematic and mechanically aligned TKA. Between 2012 and 2019, a retrospective analysis was conducted based on a single surgeon's experience. Two cohorts were made based on alignment technique. Postoperatively, patients were diagnosed with arthrofibrosis and indicated for ALOA if they had functional pain with < 90 degrees of terminal flexion at 6 weeks postoperatively despite aggressive physical therapy. Frequency of ALOA was recorded for each cohort and was regressed using independent samples t-test. The results showed no significant difference between the mechanical and kinematic cohorts for frequency of ALOA following TKA (13.2% vs. 7.3%; p = 0.2659). However, the kinematic cohort demonstrated significantly greater post-ALOA ROM compared to the mechanical group (129° vs. 113°; p = 0.0097). Future higher-powered, prospective studies are needed to clarify whether a significant difference in rates of MUA/ALOA exists between the two alignment techniques.


Fully automated cardiac MRI segmentation using dilated residual network.
Cardiac ventricle segmentation from cine magnetic resonance imaging (CMRI) is a recognized modality for the noninvasive assessment of cardiovascular pathologies. Deep learning based algorithms achieved state-of-the-art result performance from CMRI cardiac ventricle segmentation. However, most approaches received less attention at the bottom layer of UNet, where main features are lost due to pixel degradation. To increase performance, it is important to handle the bottleneck layer of UNet properly. Considering this problem, we enhanced the performance of main features at the bottom layer of network. We developed a fully automatic pipeline for segmenting the right ventricle (RV), myocardium (MYO), and left ventricle (LV) by incorporating short-axis CMRI sequence images. We propose a dilated residual network (DRN) to capture the features at full resolution in the bottleneck of UNet. Thus, it significantly increases spatial and temporal information and maintains the localization accuracy. A data-augmentation technique is employed to avoid overfitting and class imbalance problems. Finally, output from each expanding path is added pixel-wise to improve the training response. We used and evaluated our proposed method on automatic cardiac diagnosis challenge (ACDC). The test set consists of 50 patient records. The overall dice similarity coefficient (DSC) we achieved for our model is 0.924 ± 0.03, 0.907 ± 0.01, and 0.949 ± 0.05 for RV, MYO, and LV, respectively. Similarly, we obtained hausdorff distance (HD) scores of 10.09 ± 0.01, 7.25 ± 0.05, and 6.86 ± 0.02 mm for RV, MYO, and LV, respectively. The results show superior performance and outperformed state-of-the-art methods in terms of accuracy and reached expert-level segmentation. Consequently, the overall DSC and HD result improved by 1.0% and 1.5%, respectively. We designed a dilated residual UNet (DRN) for cardiac ventricle segmentation using short-axis CMRI. Our method has the advantage of restoring and capturing spatial and temporal information by expanding the receptive field without degrading the image main features in the bottleneck of UNet. Our method is highly accurate and quick, taking 0.28 s on average to process 2D MR images. Also, the network was designed to work on predictions of individual MR images to segment the ventricular region, for which our model outperforms many state-of-the-art methods.


Investigating microcrystalline cellulose crystallinity using Raman spectroscopy.
Microcrystalline cellulose (MCC) is a semi-crystalline material with inherent variable crystallinity due to raw material source and variable manufacturing conditions. MCC crystallinity variability can result in downstream process variability. The aim of this study was to develop models to determine MCC crystallinity index (%CI) from Raman spectra of 30 commercial batches using Raman probes with spot sizes of 100 µm (MR probe) and 6 mm (PhAT probe). A principal component analysis model separated Raman spectra of the same samples captured using the different probes. The %CI was determined using a previously reported univariate model based on the ratio of the peaks at 380 and 1096 cm-1. The univariate model was adjusted for each probe. The %CI was also predicted from spectral data from each probe using partial least squares regression models (where Raman spectra and univariate %CI were the dependent and independent variables, respectively). Both models showed adequate predictive power. For these models a general reference amorphous spectrum was proposed for each instrument. The development of the PLS model substantially reduced the analysis time as it eliminates the need for spectral deconvolution. A web application containing all the models was developed. The online version contains supplementary material available at 10.1007/s10570-021-04093-1.


N-acetylcysteine attenuates the decline in muscle Na+,K+-pump activity and delays fatigue during prolonged exercise in humans.
Reactive oxygen species (ROS) have been linked with both depressed Na(+),K(+)-pump activity and skeletal muscle fatigue. This study investigated N-acetylcysteine (NAC) effects on muscle Na(+),K(+)-pump activity and potassium (K(+)) regulation during prolonged, submaximal endurance exercise. Eight well-trained subjects participated in a double-blind, randomised, crossover design, receiving either NAC or saline (CON) intravenous infusion at 125 mg kg(-1) h(-1) for 15 min, then 25 mg kg(-1) h(-1) for 20 min prior to and throughout exercise. Subjects cycled for 45 min at 71% , then continued at 92% until fatigue. Vastus lateralis muscle biopsies were taken before exercise, at 45 min and fatigue and analysed for maximal in vitro Na(+),K(+)-pump activity (K(+)-stimulated 3-O-methyfluorescein phosphatase; 3-O-MFPase). Arterialized venous blood was sampled throughout exercise and analysed for plasma K(+) and other electrolytes. Time to fatigue at 92% was reproducible in preliminary trials (c.v. 5.6 +/- 0.6%) and was prolonged with NAC by 23.8 +/- 8.3% (NAC 6.3 +/- 0.5 versus CON 5.2 +/- 0.6 min, P < 0.05). Maximal 3-O-MFPase activity decreased from rest by 21.6 +/- 2.8% at 45 min and by 23.9 +/- 2.3% at fatigue (P < 0.05). NAC attenuated the percentage decline in maximal 3-O-MFPase activity (%Deltaactivity) at 45 min (P < 0.05) but not at fatigue. When expressed relative to work done, the %Deltaactivity-to-work ratio was attenuated by NAC at 45 min and fatigue (P < 0.005). The rise in plasma [K(+)] during exercise and the Delta[K(+)]-to-work ratio at fatigue were attenuated by NAC (P < 0.05). These results confirm that the antioxidant NAC attenuates muscle fatigue, in part via improved K(+) regulation, and point to a role for ROS in muscle fatigue.


Elevated lipoprotein (a) blood levels as the single treatable atherosclerotic risk factor in patients with coronary artery disease.
An elevated blood level of lipoprotein (a) [Lp(a)] has been studied as an independent risk factor for coronary artery disease. We report a series of nine consecutive patients with clinical onset or recurrence of coronary artery disease who presented without treatable atherosclerosis risk factors, five of whom had elevated Lp (a) blood levels. Indications for measuring Lp (a) levels and usefulness of niacin therapy are reviewed.


Pancreatic pseudocyst involving the spleen.
Pancreatic pseudocyst involving the spleen in a 52-year-old man is reported, with review of the literature. Physical examination and laboratory data revealed no specific abnormalities. A CT scan demonstrated multiple calcifications throughout the pancreas, with a cystic mass in the tail of the pancreas involving the spleen. Endoscopic retrograde cholangiopancreatography (ERCP) revealed a dilated main pancreatic duct with a direct communication to the cyst. Distal pancreatectomy with splenectomy was performed on a diagnosis of pancreatic pseudocyst. The 10 x 9.5 x 7 cm in size cyst had no epithelial lining on its wall. The amylase level in the cystic fluid was 23424 IU/l. The literature reveals that hemorrhagic complications are common and often serious. Timely surgical intervention is advocated to reduce mortality and morbidity from complications.


Alpha interferon dose-dependent suppression of secondary clones in a patient with Philadelphia-positive chronic myelogenous leukemia.
A patient whose chronic myelogenous leukemia (CML) was treated with interferon alpha (IFN-alpha) is described. The disease showed karyotypic evolution during the chronic phase and the later myeloid acceleration. Both of these secondary clonal phenomena responded to IFN-alpha dose escalation. The case illustrates the dose dependence of CML responses to IFN-alpha. The phenomenon of clonal evolution is discussed in the context of this patient's disease.


Medical service quality, psychological contract, and patient loyalty: An empirical study among patients in China.
The purpose of this study is to examine the mediating effect of psychological contracts (including relational and transactional psychological contracts) on the relationship between medical service quality and patient loyalty.A cross-sectional survey was conducted between September and December 2017. Questionnaires assessing medical service quality, the psychological contract, and patient loyalty were distributed to a random sample of 600 patients across 6 hospitals. The final sample consisted of 469 participants. Hierarchical regression analyses were conducted to examine the mediating effect of psychological contracts on the relationship between medical service quality and patient loyalty.The mean scores of medical service quality, psychological contracts, and patient loyalty were 3.497 ± 0.571, 3.699 ± 0.503, and 3.342 ± 0.724, respectively. Medical service quality is positively related to psychological contract (β = 0.612, 95% confidence interval [CI] = 0.476-0.603) and patient loyalty (β = 0.676, 95% CI = 0.773-0.944). Further, psychological contract is positively related to patient loyalty (β = 0.599, 95% CI = 0.757-0.968). Both relational psychological contract and transactional psychological contract mediate the relationship between medical service quality and patient loyalty.Our findings reveal that medical service quality is associated with patient loyalty and that this association is mediated by relational and transactional psychological contracts. Therefore, in order to improve patient loyalty, psychological contracts should be reinforced, and medical service quality should be improved.


SNARE regulators: matchmakers and matchbreakers.
SNAREs (soluble N-ethylmaleimide-sensitive fusion protein attachment protein receptors) are membrane-associated proteins that participate in the fusion of internal membranes in eukaryotic cells. SNAREs comprise three distinct and well-conserved families of molecules that act directly as membrane fusogens or, at the least, as elements that bring membranes into close apposition and allow for subsequent fusion events to occur. While the molecular events leading to fusion are still under debate, it is clear that a number of additional factors are required to bring about SNARE-mediated membrane fusion in vivo. Many of these factors, which collectively can be called SNARE regulators (e.g. Sec1/Munc18, synaptotagmin, GATE-16, LMA1, Munc13/UNC-13, synaptophysin, tomosyn, Vsm1, etc.), bind directly to SNAREs and are involved in the regulation of SNARE assembly as well as the ability of SNAREs to participate in trafficking events. In addition, recent studies have suggested a role for posttranslational modification (e.g., phosphorylation) in the regulation of SNARE functions. In this review the possible role of SNARE regulators in SNARE assembly and the involvement of SNARE phosphorylation in the regulation of intracellular membrane trafficking will be discussed.


Vaccines Through Centuries: Major Cornerstones of Global Health.
Multiple cornerstones have shaped the history of vaccines, which may contain live-attenuated viruses, inactivated organisms/viruses, inactivated toxins, or merely segments of the pathogen that could elicit an immune response. The story began with Hippocrates 400 B.C. with his description of mumps and diphtheria. No further discoveries were recorded until 1100 A.D. when the smallpox vaccine was described. During the eighteenth century, vaccines for cholera and yellow fever were reported and Edward Jenner, the father of vaccination and immunology, published his work on smallpox. The nineteenth century was a major landmark, with the "Germ Theory of disease" of Louis Pasteur, the discovery of the germ tubercle bacillus for tuberculosis by Robert Koch, and the isolation of pneumococcus organism by George Miller Sternberg. Another landmark was the discovery of diphtheria toxin by Emile Roux and its serological treatment by Emil Von Behring and Paul Ehrlih. In addition, Pasteur was able to generate the first live-attenuated viral vaccine against rabies. Typhoid vaccines were then developed, followed by the plague vaccine of Yersin. At the beginning of World War I, the tetanus toxoid was introduced, followed in 1915 by the pertussis vaccine. In 1974, The Expanded Program of Immunization was established within the WHO for bacille Calmette-Guerin, Polio, DTP, measles, yellow fever, and hepatitis B. The year 1996 witnessed the launching of the International AIDS Vaccine Initiative. In 1988, the WHO passed a resolution to eradicate polio by the year 2000 and in 2006; the first vaccine to prevent cervical cancer was developed. In 2010, "The Decade of vaccines" was launched, and on April 1st 2012, the United Nations launched the "shot@Life" campaign. In brief, the armamentarium of vaccines continues to grow with more emphasis on safety, availability, and accessibility. This mini review highlights the major historical events and pioneers in the course of development of vaccines, which have eradicated so many life-threatening diseases, despite the vaccination attitudes and waves appearing through history.


[Quantitative thin-layer chromatography and its use in clinical pharmacology (author's transl)].
Different methods of in situ determination of drugs on TLC-plates are described and discussed. Suitable examples are given demonstrating the value for pharmacokinetics.


Gender differences in factors related to eating competence in college students: Weight-and-body shame and guilt, weight satisfaction, weight loss effort, and eating disorder risk.
This study aimed to determine which weight-and-body-related attitudes and behaviors were most predictive of Eating Competence (EC) in college students amidst COVID-19, according to gender. This cross-sectional study was part of a larger study in which an online survey was administered during autumn quarter 2020 to undergraduate students at a northwestern U.S. public university. Measures included EC (ecSI 2.0™), weight-and-body shame and/or guilt (WEBSG), weight satisfaction, current weight loss effort, and eating disorder risk. Of the 1996 respondents included in the final analyses, 40.2 % were eating competent (ecSI 2.0™ ≥32). Gender distribution was 71.6 % women, 23.1 % men, and 4.6 % trans-and-gender non-conforming (TGNC). WEBSG and WEB-S were higher in women and TGNC than in men. Weight satisfaction was lower in women and TGNC students than men, and 47.3 % of the sample was trying to lose weight at the time of the study. Eating disorder (ED) risk was prevalent with nearly 34 % scoring ≥2 on SCOFF and 33 % reporting they saw themselves as having an ED now or in the past. Significant factors of EC varied for each gender, although WEB-S was a shared model factor for all genders. EC may be protective, as this was related to less WEB-S in all genders; less WEB-G and greater weight satisfaction in men and women; and lower likelihood of ED risk and trying to lose weight among women. Further research is needed to elucidate whether these maladaptive weight-and-body attitudes and behaviors in college students can be improved to increase EC. Level V, descriptive cross-sectional study.


Torso trauma.
This monograph represents an overview of torso trauma. The torso should be viewed as a single unit and injuries may affect the thoracic and abdominal viscera. My approach to the various injuries is pragmatic and usually fairly aggressive. The purpose is to reduce complications and missed injuries and it applies equally well to the surgeon whose practice is extensive or to the surgeon who treats only occasional injuries.


[The history and the present conditions of the occupational bladder cancer in our country].
We examined the history and the present conditions of the occupational bladder cancer of our country and a chemical carcinogenesis study career of the bladder cancer. We performed consideration from literatures mainly on document and Ministry of Health, Labor and Welfare, Labor Standards Bureau, Accident compensation element document and documents of Association of Formation Product Industry. Production of aromatic amine was started in about 1920 in our country, and the first occupational bladder cancer case was reported in 1940. It arrived at the greatest amount of production time of aromatic amine caused by Communist China Trade in 1955. The production, the import of benzidine and 2-naphthylamine were prohibited in 1972 by Safe Hygiene Method Official Announcement. During this time, 3,310 people were exposed by these materials, and the occupational bladder cancer of 357 people was registered by 1985. A number authorized from 1976 through 2006 that Workmen's comp was started is 341 cases of urinary tract system tumors by duties exposed to benzidine, 150 cases of urinary tract system tumors by duties exposed to 2-naphthylamine and one case of urinary tract tumors by o-dianisidine in total 492 cases. The occupational urinary tract cancer patient almost reaches a retirement age, and it is thought that they reach the end in about 2025. We reported the history and the present conditions of the occupational bladder cancer which occurred from 3,310 people of aromatic amine revelation in our country and we commented on a trend of the recent occupational bladder cancer for consideration from literatures.


REIN: a tool at the service of vigilance and pharmaco-epidemiology
On the occasion of the 20th anniversary of the REIN (French Renal Epidemiology and Information Network), a summary work on the contributions of the national French ESKD register was carried out. On the issue of its role in vigilance, the following key messages were retained. The vigilance system consists, among other things, of collecting information that is useful for the surveillance of health products that are drugs for pharmacovigilance, and medical devices for materiovigilance. This includes the reporting of adverse events by health professionals and manufacturers as well as the use of any information concerning the risk of adverse events. Vigilance enables improving and optimising product and patient safety by reducing the risks of adverse events and better understanding the risks and benefits. Using data from the REIN registry, cross-referenced with other external sources, it is possible to conduct post-marketing studies of these products. These studies generate hypotheses, are low-cost and are yet to be confirmed by randomised studies. Following the presentation of a study suggesting an unfavourable role of citrate dialysates on mortality, and thanks to the mobilisation of all the operators of the network, the REIN registry was able to conduct a study in a few months that made it possible to conclude that the use of citric acid in dialysates does not present a risk of excess mortality for the patients. With this example, the REIN registry has shown its adaptability and utility as a vigilance tool.


Variability of Pinus halepensis Mill. Essential Oils and Their Antioxidant Activities Depending on the Stage of Growth During Vegetative Cycle.
The impact of growth stages during vegetative cycle (B0 - B5 ) on chemical composition and antioxidant activities of Pinus halepensis Mill. needles essential oils was investigated for the first time. GC and GC/MS analyses pointed to a quantitative variability of components; terpene hydrocarbons derivatives, represented by α-pinene (8.5 - 12.9%), myrcene (17.5 - 21.6%), p-cymene (7.9 - 11.9%) and (Z)-β-caryophyllene (17.3 - 21.2%) as major components, decreased from 88.9% at B0 growth stage to 66.9% at B5 growth stage, whereas oxygenated derivatives, represented by caryophyllene oxide (5.4 - 12.6%) and terpinen-4-ol (0.4 - 3.3%) as major components, increased from 7% at B0 growth stage to 28.4% at B5 growth stage. Furthermore, our findings showed that essential oil of P. halepensis needles collected at B5 growth stage possess higher antioxidant activities by four different testing systems than those collected at B0 - B4 growth stages. This highlighted variability led to conclude that we should select essential oils to be investigated carefully depending on growth stage, in order to have the highest effectiveness of essential oil in terms of biological activities for human health purposes.


FDG-PET/CT and FLT-PET/CT for differentiating between lipid-poor benign and malignant adrenal tumours.
To compare F-18-fluorodeoxyglucose (FDG) and F-18-fluorothymidine (FLT) PET/CT examinations for differentiating between benign and malignant adrenal tumours. Thirty lipid-poor benign and 11 malignant tumours of 40 patients were included. FDG- and FLT-based indices including visual score, maximum standardized uptake value (SUVmax) and FDG adrenal lesion/liver SUVmax (A/L SUVmax) or FLT adrenal lesion/back muscle SUVmax (A/B SUVmax) ratio were compared between benign and malignant tumours using the Mann-Whitney's U or Wilcoxon signed-rank test, and their diagnostic performances were evaluated by means of the area under the curve (AUC) values derived from the receiver operating characteristic analysis. All indices were significantly higher in malignant than benign tumours on both images (p < 0.05 each). On FDG-PET/CT, the sensitivity, specificity, and accuracy were 91 %, 63 % and 71 % for visual score, 91 %, 67 % and 73 % for SUVmax, and 100 %, 70 % and 78 % for A/L SUVmax ratio, respectively. On FLT-PET/CT, they were 100 %, 97 % and 98 % for visual score, SUVmax and A/B SUVmax ratio, respectively. All FLT indices were significantly higher than those of FDG in AUC (p < 0.05 each). FLT-PET/CT may be superior to FDG-PET/CT in differentiating lipid-poor benign from malignant adrenal tumours because of higher specificity and accuracy. • All FDG indices were significantly higher in malignant than in benign tumours. • All FLT indices were significantly higher in malignant than in benign tumours. • All FLT indices were significantly higher than those of FDG in AUC.


Participatory mapping of sex trade and enumeration of sex workers using capture-recapture methodology in Diego-Suarez, Madagascar.
Capture-recapture methodology has been employed to estimate the size of hidden or difficult-to-reach human populations such as sex workers, homeless persons, and intravenous drug users. This study took place in the context of efforts to improve the quality of curative and preventive services for sexually transmitted infections offered to sex workers in Diego-Suarez, Madagascar in partnership with sex workers. The goal of this study was to better understand sex-trading practices, map out sex work sites, and estimate the size of a mobile sex-worker population in Diego-Suarez, Madagascar using methods that can be reproduced in other resource-poor settings. Forty sex workers were trained to function as field researchers. Key informants in designated neighborhoods were identified and interviewed. Basic maps of sex-trade sites were designed by hand. The number of sex workers in Diego-Suarez was estimated using capture-recapture methodology. An educational brochure was used to "capture" sex workers during a first phase, and "recapture" 2 weeks later. Most sex trade was street based and mobile. Capture-recapture methods estimated a total of 2684 sex workers (95% CI: 2588-2780) in Diego-Suarez, or approximately 12% of the 15- to 49-year-old female population in the city. Geographic mapping and capture-recapture proved to be low-cost and relatively easy to use techniques for counting a hard-to-reach population, such as female street-based sex workers. Sex workers can be capable fieldworkers, and their active participation in research concerning sex work should be considered whenever possible. A high proportion of women of reproductive age were found to engage in sex work, indicating that there is an urgent need to scale up sexually transmitted infection and HIV prevention activities targeting sex workers, their sexual partners, and the general population.


Myelodysplastic Syndrome related alterations of MAPK signaling in the bone marrow of experimental mice including stem/progenitor compartment.
Myelodysplastic syndrome is considered globally as heterogenous group of neoplasm which often proclaims leukemic progression. The heterogeneity is reflected not only in clinical manifestations of the disease but also in salient causes of disease development. In spite of multiple therapeutic modalities, shortfall towards treatment of this disorder still persists. The focal point of tussle suggested toward defects, which are not confined to any unifying cellular signalling. The pathobiology of the disease often experiences an intriguing paradox involving 'hyperproliferative bone marrow with pancytopenic peripheral blood'. In our present study we have reported about MAPK signaling in the hematopoietic stem progenitor compartmental (HSPC) dysregulation during the course of alkylator(ENU) induced myelodysplasia. The phospho-protein status of RTK's(FLT3, PDGFR, EGFR) were markedly increased that activated MAPK signaling proteins which finally executed their tasks by transcription of c-Myc and Rb leading to uncontrolled cellular proliferation, simultaneously the activated c-Jun revealed stress related apoptosis. Altogether, the role of activated MAPK signaling in the HSPC's may have led to hyperproliferation and concurrent enhanced apoptosis of abnormal cells which gradually headed towards premalignant transformations during the course of disease. The phenotypic expression of the HSPC markers CD 150 and CD 90 also established a mechanistic correlation with MAPK signalling alterations and overall scenario.


Draft Genome Sequence of Lactobacillus casei DPC6800, an Isolate with the Potential to Diversify Flavor in Cheese.
Lactobacillus casei is a nonstarter lactic acid bacterium commonly present in various types of cheeses. It is believed that strains of this species have a significant impact on the development of cheese flavor. The draft genome sequence of L. casei DPC6800, isolated from a semi-hard Dutch cheese, is reported.


Correlation of the Iranian Voice Quality of Life Profile (IVQLP) with Acoustic Measurements across Three Common Voice Disorders.
The Iranian Voice Quality of Life Profile (IVQLP) is a recent culture-based developed tool for assessing the quality of life of dysphonic patients. The research questions addressed here are as follows: (1) Are the correlations between IVQLP scores and values of objective voice measures? (2) Do the correlations differ across the three different voice disorders? The subjects were divided into three groups: muscle tension dysphonia (MTD) (n = 62), benign midmembranous vocal fold lesions (n = 56), and unilateral vocal fold paralysis (UVFP) (n = 32). The study sample consisted of 91 males and 59 females. The individuals had a mean age of 46.53 ± 13.84 years. All of the participants completed the IVQLP questionnaire. The PRAAT software was used to provide acoustic analyses. The correlations between fundamental frequency (F0), perturbation analyses, harmonics-to-noise ratio, and IVQLP data of the three groups of patients were measured using Pearson's correlation. There was a significant correlation between the total score and jitter in the MTD group. For the benign vocal fold lesion group, correlations were significant and relatively strong for numerous analyses. Again, there were numerous significant and strong correlations for the UVFP group. Results may indicate two interpretations. One interpretation of the results is that patients with morphological tissue changes (lesions, paralysis) appear to associate their sense of how their voice problem negatively affects their lives. A second interpretation is that there is perhaps a threshold of vocal perturbation or instability that lends itself to a patient's connection to his or her sense of how the voice affects his or her quality of life.


Penetrating keratoplasty combined with flexible anterior chamber lens implantation.
We present an initial report on flexible anterior chamber lens implantation in 14 aphakic or pseudophakic bullous keratopathy patients undergoing penetrating keratoplasty. With a minimum follow-up of 12 months, the improvement in visual acuity and graft clarity is encouraging.


Preparation and characterization of chitosan/pullulan film loading carvacrol for targeted antibacterial packaging of chilled meat.
In this research, the common microorganisms in chilled meat were used as the targeted antibacterial objects. Chitosan, pullulan, and carvacrol were chosen to prepare the edible antibacterial film. The effects of different concentrations of carvacrol on the microstructure, physical properties and antibacterial properties of the films were investigated. The results showed that the antibacterial activity of chitosan/pullulan film (CS/PU) was unsatisfactory, when carvacrol was added, the antibacterial activity of the chitosan/pullulan/carvacrol film (CS/PU/CAR) improved significantly (p < 0.05), and the water vapor permeability (WVP) of the CS/PU/CAR decreased significantly (p < 0.05). When the carvacrol concentration was higher than 1.25% (w/v), the tensile strength and percentage elongation at break of the CS/PU/CAR increased significantly (p < 0.05), and the CS/PU/CAR exhibited satisfying antibacterial activity against the common bacteria in chilled meat such as Pseudomonas fluorescens, Listeria monocytogenes, Escherichia coli, Pseudomonas putida, Enterobacter cloacae, and Staphylococcus aureus. Finally, the CS/PU/CAR film was applied to the preservation of chilled goat meat and extended the shelf life of goat meat to more than 15 days. These results suggested that the targeted CS/PU/CAR film can be used as biodegradable films for the active packaging of chilled meat.


Incarcerated fracture fragments of Longevity polyethylene liners after total hip arthroplasty.
Highly cross-linked polyethylene liners are widely used in total hip arthroplasty because they experience lower wear rates than conventional polyethylene liners. However, the cross-linking process does decrease the resistance of polyethylene to fatigue failure and fracture. This report describes 2 cases of highly cross-linked polyethylene liner fracture occurring in association with hip dislocation and unsuccessful closed reduction consequent to blockage by an incarcerated liner fragment. These cases highlight the known polyethylene fracture risk factors of thin and unsupported polyethylene and large bearing sizes. They also reinforce the importance of a careful evaluation of postreduction radiographs for the presence of a concentric reduction and provide a possible explanation for postoperative hip instability, multiple dislocations, and incomplete seating of the femoral head on attempts at closed reduction.


Ultra Fast Imaging NMR method for measuring fast transport processes in thin porous media.
Measuring moisture distributions during fast transport processes in thin porous media is a challenging task. In this paper, Ultra Fast Imaging (UFI) NMR is proposed as a valuable measurement technique for investigating moisture uptake in porous media by achieving a temporal resolution of 10 ms and spatial resolution between 14.5 and 18 μm. This paper gives a detailed explanation about the methodology and the interpretation of the signal intensity. It is shown that there exist specific T1- and T2- relaxation time conditions for performing UFI experiments with signal-to-noise ratios that are sufficiently high. In most cases, a contrast agent is required to optimize these relaxation times and achieve the optimal measurement conditions. In the first part of this paper, both CuSO4 and Clariscan are discussed as possible contrast agents. Furthermore, it is shown that the signal intensity can be linked to the moisture content for water based liquids. The second part of this paper covers penetration experiments on porous PVDF membranes. These measurements show that the technique is able to measure moisture profiles during fast capillary penetration and allows to extract moisture front positions. Those front positions follow a linear time behavior in PVDF membranes. Lastly the NMR-measurements showed similar results when compared to scanning absorptometry (ASA).


Engineering soil organic matter quality: Biodiesel Co-Product (BCP) stimulates exudation of nitrogenous microbial biopolymers.
Biodiesel Co-Product (BCP) is a complex organic material formed during the transesterification of lipids. We investigated the effect of BCP on the extracellular microbial matrix or 'extracellular polymeric substance' (EPS) in soil which is suspected to be a highly influential fraction of soil organic matter (SOM). It was hypothesised that more N would be transferred to EPS in soil given BCP compared to soil given glycerol. An arable soil was amended with BCP produced from either 1) waste vegetable oils or 2) pure oilseed rape oil, and compared with soil amended with 99% pure glycerol; all were provided with 15N labelled KNO3. We compared transfer of microbially assimilated 15N into the extracellular amino acid pool, and measured concomitant production of exopolysaccharide. Following incubation, the 15N enrichment of total hydrolysable amino acids (THAAs) indicated that intracellular anabolic products had incorporated the labelled N primarily as glutamine and glutamate. A greater proportion of the amino acids in EPS were found to contain 15N than those in the THAA pool, indicating that the increase in EPS was comprised of bioproducts synthesised de novo. Moreover, BCP had increased the EPS production efficiency of the soil microbial community (μg EPS per unit ATP) up to approximately double that of glycerol, and caused transfer of 21% more 15N from soil solution into EPS-amino acids. Given the suspected value of EPS in agricultural soils, the use of BCP to stimulate exudation is an interesting tool to consider in the theme of delivering sustainable intensification.


Formation of secondary allo-bile acids by novel enzymes from gut Firmicutes.
The gut microbiome of vertebrates is capable of numerous biotransformations of bile acids, which are responsible for intestinal lipid digestion and function as key nutrient-signaling molecules. The human liver produces bile acids from cholesterol predominantly in the A/B-cis orientation in which the sterol rings are "kinked", as well as small quantities of A/B-trans oriented "flat" stereoisomers known as "primary allo-bile acids". While the complex multi-step bile acid 7α-dehydroxylation pathway has been well-studied for conversion of "kinked" primary bile acids such as cholic acid (CA) and chenodeoxycholic acid (CDCA) to deoxycholic acid (DCA) and lithocholic acid (LCA), respectively, the enzymatic basis for the formation of "flat" stereoisomers allo-deoxycholic acid (allo-DCA) and allo-lithocholic acid (allo-LCA) by Firmicutes has remained unsolved for three decades. Here, we present a novel mechanism by which Firmicutes generate the "flat" bile acids allo-DCA and allo-LCA. The BaiA1 was shown to catalyze the final reduction from 3-oxo-allo-DCA to allo-DCA and 3-oxo-allo-LCA to allo-LCA. Phylogenetic and metagenomic analyses of human stool samples indicate that BaiP and BaiJ are encoded only in Firmicutes and differ from membrane-associated bile acid 5α-reductases recently reported in Bacteroidetes that indirectly generate allo-LCA from 3-oxo-Δ4-LCA. We further map the distribution of baiP and baiJ among Firmicutes in human metagenomes, demonstrating an increased abundance of the two genes in colorectal cancer (CRC) patients relative to healthy individuals.


Theoretical distinction between functional states in working memory and their corresponding neural states.
Working memory (WM) is important for guiding behaviour, but not always for the next possible action. Here we define a WM item that is currently relevant for guiding behaviour as the functionally "active" item; whereas items maintained in WM, but not immediately relevant to behaviour, are defined as functionally "latent". Traditional neurophysiological theories of WM proposed that content is maintained via persistent neural activity (e.g., stable attractors); however, more recent theories have highlighted the potential role for "activity-silent" mechanisms (e.g., short-term synaptic plasticity). Given these somewhat parallel dichotomies, functionally active and latent cognitive states of WM have been associated with storage based on persistent-activity and activity-silent neural mechanisms, respectively. However, in this article we caution against a one-to-one correspondence between functional and activity states. We argue that the principal theoretical requirement for active and latent WM is that the corresponding neural states play qualitatively different functional roles. We consider a number of candidate solutions, and conclude that the neurophysiological mechanisms for functionally active and latent WM items are theoretically independent of the distinction between persistent activity-based and activity-silent forms of WM storage.


Specific loss of connexin 26 expression in ductal sweat gland epithelium associated with the deletion mutation del(GJB6-D13S1830).
A whole array of cutaneous syndromes is associated with distinct dominant mutations in GJB2 encoding the gap junction protein connexin 26 (C x 26), including Vohwinkel's syndrome and keratitis-ichthyosis-deafness syndrome. In contrast, recessive GJB2 mutations occur in a large proportion of individuals with hearing loss but no obvious dermatological phenotype. Recently, a large deletion of approximately 342 kb, encompassing the coding region of GJB6 encoding C x 30, but not affecting GJB2, was shown to be associated with hearing loss. From analysis of patient skin, we provide immunohistochemical and bioinformatic data to show that the expression of C x 26 is affected by del(GJB6-D13S1830) in a cell-type-specific manner within the sweat gland. This putative regulatory element of C x 26 expression may be a key factor related to the severe or profound deafness associated with del(GJB6-D13S1830).


Case report: malignant peritoneal mesothelioma in two siblings.
Mesothelioma is a rare tumor, linked with occupational asbestos exposure. This association has been used to explain clustering of cases within families. Newer evidence, however, supports a possible genetic predisposition for this tumor. Our patient's brother was diagnosed with advanced stage malignant peritoneal mesothelioma in August 1995 at age of 42, he underwent tumor-reductive surgery followed by chemotherapy. He underwent a repeat cytoreductive surgery in September 1996 and further chemotherapy. He died of disease in December 1996. Our patient underwent cytoreductive surgery in May 1999 at age of 49 for advanced stage malignant peritoneal mesothelioma with suboptimal debulking. She received multiple chemotherapy regimens, including most recently experimental targeted agents, for slow progressing disease. She is presently alive with clinical disease 6 years from diagnosis. This is the first report of two siblings of different gender with malignant peritoneal mesothelioma and only average environmental asbestos exposure. It is highly likely that the family described in this case report has some form of inherited susceptibility to malignancy cancer gene, HLA type, or tumor suppressor gene mutation.


Long-term follow-up and recurrence rate after mesorectum-sparing bowel resection among women with rectovaginal endometriosis.
To demonstrate the quality of a combined vaginal-abdominal surgical approach to rectovaginal endometriosis by analyzing long-term outcome and recurrence rates. In a prospective cohort study in Berlin, Germany, women with endometriosis of the rectovaginal septum were enrolled between September 2004 and December 2012. Bowel infiltration was verified intraoperatively and treated by a nerve-sparing, mesentery-preserving vaginal-abdominal operative approach. Operative results were evaluated by assessing short- and long-term complications and recurrence rates. During the study period, 110 women underwent surgery. For 71 (64.5%) patients, bowel infiltration was confirmed intraoperatively. Overall, 15% of the patients had peri- or postoperative complications. No long-term complications occurred. After a median follow-up of 64 months, no recurrence in the rectovaginal septum was observed among the study patients. The recurrence of pelvic endometriosis was 15%. The surgical nerve-sparing approach to rectovaginal endometriosis was confirmed to facilitate precise diagnosis and treatment with minimal morbidity and a long-term complication rate of 0%.


The rational administration of colloids.
The safe administration of i.v. fluids is one of the most significant advances in the care of critically ill patients this century. However, despite advances in the monitoring of cardiovascular variables, the questions of what? when? and how much? remain areas of enormous controversy. Ironically as the choice of i.v. fluids becomes greater and the monitoring more sophisticated the controversy grows. This article will concentrate on the diagnosis of hypovolaemia, the consequences of hypovolaemia and the rational use of i.v. fluids, particularly colloids, to treat it.


Singlet oxygen induced DNA damage and mutagenicity in a single-stranded SV40-based shuttle vector.
The effects of singlet oxygen (1O2), generated by the thermal decomposition of water soluble NDPO2 (endoperoxide of the disodium 3,3'-(1,4-naphthylidene) dipropionate), on a single-stranded shuttle vector were analysed. 1O2 induces a much higher level of breaks in the phosphodiester backbone of single-stranded than double-stranded DNA. This may be due to a higher accessibility of guanine residue, primarily damaged by 1O2. The damaged vector was transfected into monkey COS7 cells where single-stranded DNA was converted to the double-stranded replicative form DNA. After 3 days, extrachromosomal DNA was extracted and the plasmids rescued in E. coli to study mutagenesis. There is a significant increase in mutation frequency of damaged single-stranded DNA in comparison to untreated DNA. It is concluded that 1O2 induces breaks in the backbone of single-stranded DNA and that the 1O2-damaged molecules are mutated after passage through mammalian cells.


Simultaneous resection of synchronous bilateral bronchogenic carcinoma using median sternotomy.
Despite the increasing use of median sternotomy for pulmonary resection, only two successful cases of simultaneous resection of bilateral primary bronchogenic carcinoma by this approach have been reported. We report the third case of successful resection of synchronous primary bronchogenic carcinoma by median sternotomy, and the fourth successful case of simultaneous resection, as the first reported case of simultaneous resection was accomplished via bilateral anterolateral thoracotomy incisions. We believe at present that the ideal surgical approach for patients with bilateral primary bronchogenic carcinoma is simultaneous resection by median sternotomy.


Interaction of indomethacin and ciprofloxacin in the cornea following phototherapeutic keratectomy.
We report a case in which stromal deposits were produced due to drug interaction in a 61-year-old patient following phototherapeutic keratectomy (PTK). In our case, the patient herself added the use of indomethacin eye drops to the prescribed topical antibiotic treatment and eye gel (5x ciprofloxacin plus 3x indomethacin, eye gel overnight) following PTK. At 5 days the central stroma was not reepithelialised; instead, whitish, round deposits were found in the stroma. Mixing indomethacin and ciprofloxacin eye drops 1:1, the pH of the mixture changed to 5.6, and a yellow precipitate was formed; this was analysed by (1)H-NMR spectroscopy. To investigate the solubility of the two drugs at the pH of the mixture, the pH of each solution was independently set to 5.6 by addition of hydrochloric acid or sodium hydroxide. In the precipitate both indomethacin and ciprofloxacin were detected. After setting the pH to 5.6, a yellow precipitate was observed in the indomethacin solution; however, the ciprofloxacin solution remained clear. Interaction may occur if ciprofloxacin and indomethacin are used together. It is better to avoid the use of the two drugs at the same time, particularly in the case of a large epithelial defect when stromal deposition of the drugs may be produced.


Congener-specific characterization and sources of polychlorinated dibenzo-p-dioxins, dibenzofurans and dioxin-like polychlorinated biphenyls in marine sediments from industrialized bays of Korea.
Polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and dioxin-like polychlorinated biphenyls (DLPCBs) were determined in 122 coastal sediments from heavily industrialized areas in Korea. Toxic equivalent (TEQ) concentrations of PCDD and PCDF (PCDD/F) and DLPCB ranged from 0.44 to 38.5 pg/g dry weight and from 0.01 to 38.4 pg/ g dry weight, respectively. Overall PCDD/F and DLPCB concentrations were elevated in estuarine and inner bay locations close to industrial complexes, indicating that these contaminants derived from local discharges. Concentrations of PCDD/F measured in the present study were comparable to those in industrialized areas of other countries. Nonparametric multidimensional scaling ordination and congener-specific characterization showed that combustion processes occurring in industrial complexes, including the steel industry, are the major source of PCDD/Fs in Korean coastal waters. There were no significant correlations among PCDD/ Fs, DLPCBs, and total organic carbon; however, there was moderate correlation between PCDD/Fs and DLPCBs in some coastal bays, suggesting that these chemicals have similar sources and movements in these locations.


Percutaneous fixation of displaced proximal humeral fractures: indications based on the correlation between clinical and radiographic results.
We evaluated 74 patients with displaced proximal humeral fractures (mean age, 70.9 years) treated with closed reduction and percutaneous pinning. Fractures were classified radiographically following Neer's system, and the quality of reduction was assessed according to Kristiansen and Kofoed. Patients were also evaluated clinically with the Constant scale. Overall, the reduction was good in 72% of fractures, but the probability of obtaining a satisfactory reduction of displaced tuberosities was significantly lower in comparison to the humeral head. Four-part fractures obtained the worst radiographic results. The mean Constant scores were 65.8 +/- 18 points for the injured shoulder and 79.5 +/- 9.1 points for the opposite shoulder. Clinical results correlated with the quality of reduction. Closed reduction and percutaneous pinning should be reserved for 2-part fractures, but the technique can also be used in 3-part fractures in elderly patients, in whom an incomplete reduction can yield satisfactory clinical results.


Prediabetes and incident heart failure in hypertensive patients: Results from the Swedish Primary Care Cardiovascular Database.
The cardiovascular risk conferred by concomitant prediabetes in hypertension is unclear. We aimed to examine the impact of prediabetes on incident heart failure (HF) and all-cause mortality, and to describe time in therapeutic blood pressure range (TTR) in a hypertensive real-world primary care population. In this retrospective cohort study, 9628 hypertensive individuals with a fasting plasma glucose (FPG) in 2006-2010 but no diabetes, cardiovascular or renal disease were followed to 2016; median follow-up was 9 years. Prediabetes was defined as FPG 5.6-6.9 mmol/L, and in a secondary analysis as 6.1-6.9 mmol/L. Study outcomes were HF and all-cause mortality. Hazard ratios (HR) were compared for prediabetes with normoglycemia using Cox regression. All blood pressure values from 2001 to the index date (first FPG in 2006-2010) were used to calculate TTR. At baseline, 51.4% had prediabetes. The multivariable-adjusted HR (95% confidence intervals) was 0.86 (0.67-1.09) for HF and 1.06 (0.90-1.26) for all-cause mortality. For FPG defined as 6.1-6.9 mmol/L, the multivariable-adjusted HR were 1.05 (0.80-1.39) and 1.42 (1.19-1.70), respectively. The prediabetic group had a lower TTR (p < 0.05). Prediabetes was not independently associated with incident HF in hypertensive patients without diabetes, cardiovascular or renal disease. However, prediabetes was associated with all-cause mortality when defined as FPG 6.1-6.9 mmol/L (but not as 5.6-6.9 mmol/L). TTR was lower in the prediabetic group, suggesting room for improved blood pressure to reduce incident heart failure in prediabetes.


DDT residue contamination in sediments from Lake Sibaya in northern KwaZulu-Natal, South Africa: implications for conservation in a World Heritage Site.
Maputaland in northern KwaZulu-Natal is a biodiversity hotspot and host to a number of ecologically important systems, including Lake Sibaya, southern Africa's largest natural freshwater lake. The region is malaria endemic and this study reports the presence of DDT and its metabolites in the sediments of Lake Sibaya that have resulted from the widespread and continued use of DDT in the region. DDT residues (p,p'-DDT, p,p'-DDD, and p,p'-DDE) were detected at all 11 sites sampled, with total concentrations ranging from 0.8 to 123 ng g(-1). Total DDT concentrations at Lake Sibaya represent some of the highest levels reported in South Africa, with most samples exceeding sediment quality guideline values. The findings from this study raise concerns and indicate that urgent further work is needed to investigate the potential for bioaccumulation, which could adversely affect breeding fish, bird, and crocodile populations in the region. While this study represents the first report on DDT contamination in Lake Sibaya, results have important implications for a number of other aquatic ecosystems within the Maputaland ecoregion, as well as the many local people who depend on them.


Glycosylation of lactase-phlorizin hydrolase in rat small intestine during development.
Age-specific changes in glycosylation of rat intestinal lactase-phlorizin hydrolase were analyzed using enzyme immunoprecipitated from microvillus membranes of suckling, weaning, and adult rats, and carbohydrate moieties were examined by lectin affinity binding, metabolic labeling, and neuraminidase treatment. Lectin binding indicated the presence of N-linked and O-linked oligosaccharide chains containing mannose and galactose throughout development. An age-dependent shift in sialic acid and fucose was seen during the period of weaning; no fucose was detectable in lactase-phlorizin hydrolase until after the rats were 20 days of age, whereas sialic acid was reduced in adult lactase-phlorizin hydrolase. The presence of sialic acid in suckling intestines and fucose in adult was confirmed by metabolic labeling with appropriate radioactive precursors. Sodium dodecyl phosphate-polyacrylamide gel electrophoresis analysis of immunoprecipitated lactase-phlorizin hydrolase from the proximal and mid small intestine showed two bands of approximately 220 and 130 kilodaltons in all age groups. In the distal part of the adult small intestine, lactase-phlorizin hydrolase appeared as two bands of similar size to those found in the proximal and mid portions. In contrast, during the suckling and weaning periods, these distal bands were approximately 225 and 135 kilodaltons. [35S]-methionine labeling and fluorography of neonatal intestines confirmed these observations. The size difference between proximal and distal small intestines was virtually eliminated by neuraminidase treatment. These data indicate that the core structure of microvillus membrane lactase-phlorizin hydrolase, consisting of both N-linked and O-linked oligosaccharides, remains constant during development, although terminal sugars shift from predominantly sialic acid during the suckling period to fucose in adulthood. This alteration in glycosylation of the protein occurs in a different pattern from the postweaning decline in lactase specific activity. Consequently, age-dependent changes in glycosylation cannot account for the decrease in lactase-phlorizin hydrolase-specific activity observed during development.


Linking molecular and cellular events in T-cell activation and synapse formation.
The complex sequence of events in which T cells recognize foreign entities on other cells is not well understood. However, the development of new techniques and approaches in both the molecular and cellular aspects of this problem have provided significant insights into the mechanisms of T-cell recognition and synapse formation. In particular, we have a clearer picture of T-cell sensitivity, the role of co-stimulation in formation of the immunological synapse, and how TCR signaling acts to maintain synapse structure and potentiate the T cells over many hours of engagement. We also are aware of new complexities in the way T-cell receptor molecules bind peptide-MHC (pMHC) ligands and what that may mean for TCR scanning, cross-reactivity, and activation. Ultimately, we want to integrate these cellular aspects of T-cell recognition with key features of the molecular interactions that drive specific events.


LH (Trp8Arg/Ile15Thr), LHR (insLQ) and FSHR (Asn680Ser) polymorphisms genotypic prevalence in women with endometriosis and infertility.
To verify if polymorphisms of LH (Trp8Arg/Ile15Thr), LH receptor (insLQ), and FSH receptor (Asn680Ser) are associated with endometriosis and infertility. This is a prospective case-control study. Sixty-seven patients with endometriosis and infertility (study group) and 65 healthy fertile patients (control group) were enrolled in the study between July 2010 and July 2013. All patients had their endometriosis diagnosis made or excluded by laparoscopic surgery; study group was submitted to the surgery for infertility investigation and control group for tubal ligation. Day-3 serum hormones were collected from all patients. Analysis of nucleotide mutations for LH polymorphisms (Trp8Arg and Ile15Thr), LHR polymorphism (insLQ), and FSHR polymorphism (Asn680Ser) were performed by PCR. Day-3 FSH, estradiol and LH serum levels were not different between the groups, while CA-125 was higher in patients with endometriosis and infertility. All polymorphisms studied were in Hardy-Weinberg equilibrium. The prevalence of insLQ was significantly higher in patients with endometriosis and infertility (P = 0.005). Allele occurrence in control group was 0.10 versus 0.25 in infertile endometriosis group (P = 0.001). There was no difference regarding Trp8Arg/Ile15Thr (P > 0.05) and Asn680Ser (P > 0.05) prevalence between groups. This is the first time that prevalence of insLQ was shown to be higher in patients with endometriosis and infertility than in healthy fertile patients. There was no difference in LH and FSHR polymorphisms' prevalence between groups.


Role of post-operative serum C-reactive protein levels as a predictor of complications in upper gastrointestinal surgery.
This study was undertaken to assess the value of C-reactive protein (CRP) in predicting infective complications after elective upper gastrointestinal surgery. Demographic data, clinical outcomes and serial CRPs preoperatively to post-operative day (POD) 7 were collected for patients undergoing pancreatectomy, hepatectomy and oesophago-gastrectomy between 2005 and 2016. Areas under the curve (AUC) were used to evaluate diagnostic accuracy per day of measurement. Of the 249 patients, 63 (25.3%) developed infective complications and 25 (10%) developed severe infective complications (≥Clavien-Dindo Grade III). Patients with infective complications trended towards higher CRP levels on POD1-POD4 and had significantly higher CRP levels on POD5 (156 versus 114 mg/dL; P = 0.03), POD6 (146 versus 93 mg/dL; P < 0.01) and POD7 (135 versus 84.6 mg/dL; P < 0.01). CRP had the best diagnostic accuracy for severe infective complications on POD6 (AUC: 0.73) and POD7 (AUC: 0.63). A CRP cut-off of 120 mg/dL on POD6 had a negative predictive value of 96.1% and a CRP cut-off of 80 mg/dL on POD7 had a negative predictive value of 94.9%. CRP measurements can be used as a negative predictive marker of infective complications in the first post-operative week after major elective upper gastrointestinal surgery.


Dynamic Restructuring of Coordinatively Unsaturated Copper Paddle Wheel Clusters to Boost Electrochemical CO2 Reduction to Hydrocarbons.
The electrochemical reduction of CO2 to hydrocarbons involves a multistep proton-coupled electron transfer (PCET) reaction. Second coordination sphere engineering is reported to be effective in the PCET process; however, little is known about the actual catalytic active sites under realistic operating conditions. We have designed a defect-containing metal-organic framework, HKUST-1, through a facile "atomized trimesic acid" strategy, in which Cu atoms are modified by unsaturated carboxylate ligands, producing coordinatively unsaturated Cu paddle wheel (CU-CPW) clusters. We investigate the dynamic behavior of the CU-CPW during electrochemical reconstruction through the comprehensive analysis of in situ characterization results. It is demonstrated that Cu2 (HCOO)3 is maintained after electrochemical reconstruction and that is behaves as an active site. Mechanistic studies reveal that CU-CPW accelerates the proton-coupled multi-electron transfer (PCMET) reaction, resulting in a deep CO2 reduction reaction.


Detectability of Medication Errors With a STOPP/START-Based Medication Review in Older People Prior to a Potentially Preventable Drug-Related Hospital Admission.
Multimorbidity and polypharmacy are risk factors for drug-related hospital admissions (DRAs) in the ageing population. DRAs caused by medication errors (MEs) are considered potentially preventable. The STOPP/START criteria were developed to detect potential MEs in older people. The aim of this study was to assess the detectability of MEs with a STOPP/START-based in-hospital medication review in older people with polypharmacy and multimorbidity prior to a potentially preventable DRA. Hospitalised older patients (n = 963) with polypharmacy and multimorbidity from the intervention arm of the OPERAM trial received a STOPP/START-based in-hospital medication review by a pharmacotherapy team. Readmissions within 1 year after the in-hospital medication review were adjudicated for drug-relatedness. A retrospective assessment was performed to determine whether MEs identified at the first DRA were detectable during the in-hospital medication review. In total, 84 of 963 OPERAM intervention patients (8.7%) were readmitted with a potentially preventable DRA, of which 72 patients (n = 77 MEs) were eligible for analysis. About half (48%, n = 37/77) of the MEs were not present during the in-hospital medication review and therefore were not detectable at that time. The pharmacotherapy team recommended a change in medication regimen in 50% (n = 20/40) of present MEs, which corresponds to 26% (n = 20/77) of the total identified MEs at readmission. However, these recommendations were not implemented. MEs identified at readmission were not addressed by a prior single in-hospital medication review because either these MEs occurred after the medication review (~50%), or no recommendation was given during the medication review (~25%), or the recommendation was not implemented (~25%). Future research should focus on optimisation of the timing and frequency of medication review and the implementation of proposed medication recommendations. ClinicalTrials.gov identifier: NCT02986425. December 8, 2016. European Union HORIZON 2020, Swiss State Secretariat for Education, Research and Innovation (SERI), Swiss National Science Foundation (SNSF).


The development of adrenergic innervation in some human foetal blood vessels.
The development of adrenergic innervation was examined in saphenous and brachial veins, femoral, brachial and superficial temporal arteries from human foetuses of 7-19 weeks gestation. Fluorescence histochemical and electron microscopic techniques were used on transverse sections of the vessels. No specific adrenergic fluorescence was detected within any of the vessels before 11 weeks gestation, by which time the arteries showed specific adrenergic fluorescence. However, there was no evidence of adrenergic innervation of veins even at 19 weeks gestation. Incubation of the vessels with alpha-methylnoradrenaline did not lead to earlier detection of fluorescence. Electron microscopy showed that the adrenergic nerves found in the arteries were arranged as bundles of axons partially enclosed within Schwann cell processes, often lying close to capillaries in the outer regions of the tunica adventitia.


Structural Biology: Parkin's Serpentine Shape Revealed in the Year of the Snake.
Parkin is an E3 ubiquitin ligase, mutations in which are responsible for autosomal recessive juvenile parkinsonism. Recently, several structures of Parkin have been solved, revealing its serpentine shape and modes of auto-inhibition.


ITMIG consensus statement on the use of the WHO histological classification of thymoma and thymic carcinoma: refined definitions, histological criteria, and reporting.
The 2004 version of the World Health Organization classification subdivides thymic epithelial tumors into A, AB, B1, B2, and B3 (and rare other) thymomas and thymic carcinomas (TC). Due to a morphological continuum between some thymoma subtypes and some morphological overlap between thymomas and TC, a variable proportion of cases may pose problems in classification, contributing to the poor interobserver reproducibility in some studies. To overcome this problem, hematoxylin-eosin-stained and immunohistochemically processed sections of prototypic, "borderland," and "combined" thymomas and TC (n = 72) were studied by 18 pathologists at an international consensus slide workshop supported by the International Thymic Malignancy Interest Group. Consensus was achieved on refined criteria for decision making at the A/AB borderland, the distinction between B1, B2, and B3 thymomas and the separation of B3 thymomas from TCs. "Atypical type A thymoma" is tentatively proposed as a new type A thymoma variant. New reporting strategies for tumors with more than one histological pattern are proposed. These guidelines can set the stage for reproducibility studies and the design of a clinically meaningful grading system for thymic epithelial tumors.


Analysis of free chlorine in aqueous solution at very low concentration with lateral flow tests.
Test strips are convenient tools for rapid, semi-quantitative analysis of a variety of parameters by dipping them for a few seconds in a sample solution followed by a simple colorimetric read-out. Their sensitivity is mainly determined by the reactivity of the test dyes on the reaction zone and is not sufficient for some applications. The detection limit of commercially available free chlorine test strips, for example, is at present not low enough to confirm the absence of this analyte as disinfectant in rinsing solutions after disinfection or to control required residual amounts of chlorine in drinking water. Therefore, we developed a user-friendly lateral flow test which is capable to detect very low amounts of free chlorine. The latter relies on a larger sample volume passing the reaction zone as compared to simple dip test strips. An amount of as low as 0.05 ppm chlorine can, however, only be detected if oxidation stable flow test substrates are used. The eventually developed flow test reaches a 10x higher sensitivity than a commercial dip test. The result is obtained within 4-5 min flow time, whereby no action is required by the user during this analysis time.


A cost-effective colorimetric assay for phenolic O-methyltransferases and characterization of caffeate 3-O-methyltransferases from Populus trichocarpa.
S-adenosyl-L-methionine (AdoMet)-dependent O-methyltransferases (OMTs) catalyze the transmethylation of a variety of phenolics in bacteria, plants, and humans. To rapidly characterize phenolic OMT activities, we adapted Gibbs' reagent, the dye originally used for detecting phenols, to develop a convenient assay method for measuring the catalytic properties of enzymatic transmethylation of phenolics. We demonstrated that Gibbs' reagent reacted with phenolics yielding distinct absorptive characters that we used to further develop the assay to monitor the reactivities of phenolic OMTs. To validate the method, we identified two caffeate/5-hydroxyferulate 3/5-O-methyltransferases (COMTs) from the black cottonwood, Populus trichocarpa. Together with a few other plant type I OMTs, we demonstrated that our Gibbs' reagent-mediated colorimetric assay could reliably determine the functions and kinetic parameters of phenolic OMTs. Because Gibbs' reagent reacting with different regioselectively modified phenolics displays different colorimetric properties, the assay method can be used to monitor both substrate specificity and the regioselectivity of phenolic OMTs.


Biodegradability of polyethylene by efficient bacteria from the guts of plastic-eating waxworms and investigation of its degradation mechanism.
Polyethylene (PE) has been regarded as non-biodegradable for decades, and the evidence for its degradation by bacteria remains unclear in the literature. Waxworms have recently gained attention for their ability to degrade natural long-chain polymers and synthetic plastic. This study aims to explore the potential of low-density polyethylene (LDPE)-degrading bacteria from the gut symbionts of lesser waxworm (Achroia grisella) larvae for the effective biodegradation of LEDP. Two bacterial isolates (LDPE-DB1 and LDPE-DB2) exhibited the greatest reduction in tensile strength among all isolates (P < 0.0001), reaching 51.3% and 58.3%, respectively. The bacterial strains LDPE-DB1 and LDPE-DB2 stand for molecularly identified species, Citrobacter freundii and Bacillus sp., respectively. After 5 days of incubation, the cell density of LDPE-DB1 and LDPE-DB2 reached 2.20 × 108 and 1.8 × 108 CFU/mL, respectively. However, after 30 days of incubation, the cell density reached 7.3 × 108 and 5.9 × 108, respectively. The formed cavities indicate the high activity of the isolated bacteria from Achroia grisella larvae where the cavities reach a depth of up to 1.2 µm. The findings of this study demonstrated the presence of LDPE-degrading bacteria in Achroia grisella and provide promising evidence for the biodegradation of plastic waste management in the environment.