Factors that contribute to patient length of stay in the emergency department: A time in motion observational study.
Increased Emergency Department length of stay impacts access to emergency care and is associated with increased patient morbidity, overcrowding, reduced patient and staff satisfaction. We sought to determine the contributing factors to increased length of stay in our mixed ED. A real-time observational study was conducted at Wollongong Hospital over a continuous 72-h period. Times of intervention, assessment and treatment were recorded by dedicated emergency medical or nurse observers. The time from triage to each event was calculated and descriptive analyses performed. Free text comments were analysed using inductive content analysis. Data were collected on 381 of 389 eligible patients. The largest time delays were experienced by patients who required a CT, specialist review and/or an inpatient bed. Registrars and nurse practitioners were the most efficient in reaching a decision to admit or discharge. The time from triage to specialist review increased with the number requested (148 min for one, 224 min for two and 285 min for three). The longest length of stay was experienced by mental health and paediatric patients. The main delays contributing to ED length of stay were CT imaging and specialist reviews. Overcrowding in ED need targeted, site-specific interventions.


Identification of novel bovine group A rotavirus G15P[14] strain from epizootic diarrhea of adult cows by de novo sequencing using a next-generation sequencer.
There are few reports describing diarrhea of adult cattle caused by group A rotaviruses. Here, we report the identification of a novel bovine group A rotavirus from diarrhea of adult cows. A group A rotavirus was detected from an epizootic outbreak of diarrhea in adult cows with a decrease in milk production in Japan in 2013. The comprehensive genomic analyses from fecal samples by viral metagenomics using a next-generation sequencer revealed that it had an unreported genotype combination G15P[14]. The genome constellation of this strain, namely, RVA/Cow-wt/JPN/Tottori-SG/2013/G15P[14] was G15-P[14]-I2-R2-C2-M2-A3-N2-T6-E2-H3 representing VP7-VP4-VP6-VP1-VP2-VP3-NSP1-NSP2-NSP3-NSP4-NSP5, respectively. Each gene segment of Tottori-SG was most closely related to Japanese bovine group A rotaviruses suggesting that Tottori-SG might have derived from multiple reassortment events from group A rotavirus strains circulating among Japanese cattle. No other diarrhea pathogen of adult cattle was detected by routine diagnosis and metagenomics. Viral metagenomics, using a next-generation sequencer, is useful to characterize group A rotaviruses from fecal samples and offers unbiased comprehensive investigations of pathogen.


Structural analysis of N-linked oligosaccharides by a combination of glycopeptidase, exoglycosidases, and high-performance liquid chromatography.
A simple, sensitive, and rapid method for the analysis of structures of N-linked carbohydrates is reported. The method involves four steps: preparation of carbohydrate chains from glycopeptides by N-oligosaccharide glycopeptidase digestion; derivatization of the reducing ends of carbohydrate chains with a fluorescent reagent, 2-aminopyridine, by using sodium cyanoborohydride; separation of oligosaccharide derivatives by reverse-phase high-performance liquid chromatography; and structural analysis of oligosaccharides by sequential exoglycosidase digestion. The elution positions of 50 standard oligosaccharide derivatives were determined by HPLC. The structure of an unknown oligosaccharide can be characterized by comparison of its elution position with those of the standard compounds. The method was applied to elucidate the structures of oligosaccharides in the myeloma IgG protein, Yot.


Effect of caffeine on urea biosynthesis and some related processes, ketone bodies, ATP and liver amino acids.
An increase in urea synthesis has been found in rats administered large doses of caffeine. A parallel increase in urea biosynthesis was also found in hepatocytes isolated from caffeine-treated rats, which confirms a greater capacity for urea synthesis induced by caffeine. This increase appeared only after some days of caffeine treatment; during the first days there was no increase in serum urea levels or in in vitro studies of urea synthesis in isolated hepatocytes. However, no appreciable changes were found in either cytosolic or mitochondrial redox states, or in ATP levels in in vivo and in vitro studies. A parallelism was observed between the decreased amino acid levels in caffeine-treated rats and in isolated hepatocytes incubated with different concentrations of caffeine. Several possible mechanisms to explain these findings are considered in the discussion.


Flexible multiplex PCR to detect SARS-CoV-2, coronavirus OC43 and influenza A virus in nasopharyngeal swab samples.
Quantitative reverse transcription PCR (RT-qPCR) is the leading tool to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Given that it will almost certainly continue to coexist with other respiratory viruses in the coming years, our study aimed to design a multiplex PCR system not affected by supplier outages and with reduced cost compared to the existing commercially available kits. In this study, combinations of four primers/probe sets were used to construct a flexible RT-qPCR assay which is capable of discriminating between SARS-CoV-2 and the seasonal human coronavirus HCoV-OC43, or even influenza A virus. Additionally, the human RPP30 gene was used as an internal control. To demonstrate the robustness of the assay, it was applied to a collection of 150 clinical samples. The results showed 100% sensitivity and specificity compared to the automatized system used at the hospital and were better when indeterminate samples were analysed. This study provides an efficient method for the simultaneous detection of SARS-CoV-2, HCoV-OC43 and influenza A virus, and its efficacy has been tested on clinical samples showing outstanding results. The multiplex RT-qPCR design offers an accessible and economical alternative to commercial detection kits for hospitals and laboratories with limited economic resources or facing situations of supply shortage.


Paul A. Castelfranco (1921-2021): a scientist par excellence, a man of lasting faith, and ever a humanist.
We present here the life and the work of Paul A. Castelfranco (1921-2021), a very special person who was not only a top chemist of chlorophyll biosynthesis, but also made major contributions on fatty acid oxidation, acetate metabolism and cellular organization. He led an extraordinary and exemplary life as a human being. We present here both his personal life as well as his scientific life, which is followed by reminiscences by William Breidenbach, Kevin Smith, Alan Stemler, Ann Castelfranco, and John Castelfranco. As the subtitle of this Tribute implies, till the end Paul was a scientist par excellence, an intellectual with unlimited curiosity, a humanist, and a man of enduring religious faith. We all miss him dearly.


Gene expression profiles of peripheral blood mononuclear cells in primary biliary cirrhosis.
Previous studies on gene expression profiles in primary biliary cirrhosis (PBC) have exclusively focused on liver tissue or intrahepatic cells. Since the pathological process is systemic, other complementary studies in blood cells seemed to be reasonable. In this research, we try to explore differentially expressed genes in peripheral blood mononuclear cells (PBMCs) of PBC patients. Nine PBC patients and 9 healthy controls were recruited as Cohort 1 for a microarray study of screening. Total RNA of PBMCs from each individual was isolated and screened by oligonucleotide microarray (22 K). Then, differentially expressed genes were categorized into signaling pathways. Expression levels of three important genes, tyrosine kinase binding protein (TYROBP), C–C motif chemokine 5 (CCL5) and cathepsin L (CTSL) were confirmed by quantitative real-time polymerase chain reaction (qRT-PCR) in a second Cohort 2 (30 PBC patients and 20 healthy controls). Results show that sixty-five genes differentially expressed in PBC were identified, 20 of which were up-regulated and 45 of which were down-regulated. Twenty-seven signaling pathways were identified. TYROBP and CCL5 were proved to be down-regulated in PBC, and CTSL was proved to be up-regulated (p < 0.05) in PBC, which were all consistent with the screening study. In conclusions, the analysis of gene expression in PBMCs of PBC and the comparison of gene profiles between PBMCs and the liver may provide new clues to the pathogenesis of the disease.


Trastuzumab uptake in HER2-positive breast cancer patients: a systematic review and meta-analysis of observational studies.
Overexpression of the HER2 gene is predictive of treatment benefit with trastuzumab therapy for breast cancer (BC) patients. The study objective was to investigate whether all eligible patients with HER2-positive BC initiated trastuzumab therapy. A systematic search was conducted through PubMed, Web of Science PsycINFO, Cumulative Index to Nursing and Allied Health Literature (CINAHL) and Cochrane Library. From 2651 studies identified, 107 observational studies were included for full text review, of which 26 met the inclusion criteria and an additional 7 studies were identified through citation searching. Two independent reviewers extracted data for accuracy and completeness. From 33 observational studies, 14,644 patients were exposed to trastuzumab therapy. Age range varied across studies; the youngest cohort had a median age of 50 and the oldest had a median age of 84. Sample sizes ranged from 11 to 1928 and included patients from 10 countries. Studies were heterogenous and few studies accounted for confounders. We identified large variability in uptake of trastuzumab in HER2-positive early BC patients (9.1-100%) and metastatic BC patients (50.8-84.0%). The pooled uptake was 71.3% (95% CI 64.6-77.9%), with high heterogeneity (I2 = 99.05%). The most conservative predictors of higher uptake included younger age (OR 2.09; 95% CI 1.36-3.20) and lower Charlson Comorbidity Index of patients (OR 1.62; 95% CI 1.32-1.99). In addition, tumour characteristics including higher tumour grade (OR 1.73; 95% CI 1.23-2.45), larger tumour size (OR 1.80; 95% CI 1.54-2.10), advanced tumour stage (OR 2.07; 95% CI 1.44-2.96) and hormone receptor negative tumor (OR 1.54; 95% CI 1.35-1.77) were associated with higher uptake. The uptake of trastuzumab therapy varied widely between studies and across subgroups suggesting that there may be some inequalities in the use of this agent. However, our findings should be interpreted with caution due to study heterogeneity and potential confounding, and thus additional studies of individual level data which control for confounders are needed to understand more about inequalities in uptake.


Extracellular adenine nucleotides metabolism in astrocyte cultures from different brain regions.
Primary astrocyte cultures from hippocampus, cortex and cerebellum presented different extracellular pattern of adenine nucleotide hydrolysis. The ATP/ADP hydrolysis ratio was 8:1 for hippocampal and cortical astrocytes and 5:1 for cerebellar astrocytes. The AMP hydrolysis in cerebellar astrocytes was seven-fold higher than in cortical or hippocampal cells. No accumulation of extracellular adenosine in all structures studied was observed. Dipyridamol increased significantly inosine levels in the extracellular medium of hippocampal and cortical, but not in cerebellar astrocytes medium. A higher expression of ecto-5'-nucleotidase was identified by RT-PCR in cerebellum. The differences observed may indicate functional heterogeneity of nucleotides in the brain.


Ultrafast MRI of the fetus: an increasingly important tool in prenatal diagnosis of congenital anomalies.
To demonstrate the additional utility of ultrafast magnetic resonance imaging (MRI) of the fetus in the evaluation of sonographically detected or equivocal fetal congenital anomalies. Twenty five pregnant women with ultrasound detected fetal congenital anomalies underwent ultrafast fetal MRI. MRI findings altered the diagnosis of two cases of giant arachnoid cyst and sizable interhemispheric cyst associated with agenesis of the corpus callosum. MRI added additional findings of occult spinal diastematomyelia in two out of four cases of Chiari/meningocele malformation. MRI revealed impaired sulcation and unilateral cleft palate in suspected case of Walker-Warburg syndrome. In the remaining 18 cases MRI confirmed the diagnosis of Meckel-Gruber syndrome in three cases, hydronephrosis in six cases, cerebral ventriculomegaly in five cases, isolated omphalocele in three cases and findings suggestive of aneuploidy in the last case. Ultrasound is the screening method of choice for evaluation of the fetus. Ultrafast MRI is a complementary adjunctive modality with excellent tissue contrast that can image the fetus in multiple planes and add information in sonographically detected or equivocal congenital anomalies that may be significant to establish definitive accurate diagnosis and hence adequate management and counseling.


Incorporation of Cervista Human Papillomavirus 16/18 Assay Into Algorithms for Classifying Human Papillomavirus Status in Formalin-Fixed, Paraffin-Embedded Head and Neck Squamous Carcinoma Specimens.
Human papillomavirus (HPV) DNA in situ hybridization (ISH) assay and p16 immunohistochemistry (IHC) are used to determine high-risk HPV status in formalin-fixed, paraffin-embedded (FFPE) tissues in oropharyngeal squamous cell carcinoma (SCC). Although high sensitivity and specificity for HPV can be obtained by combined p16 IHC and HPV DNA ISH, the occasional discrepancy between these assays has prompted evaluation of Cervista HPV assays in FFPE tissue from patients with oropharyngeal SCC. To compare the efficacy of Cervista HPV 16/18 and Cervista HPV HR assay to that of HPV DNA ISH assay and p16 IHC in FFPE tissue in head and neck squamous cell carcinoma of oropharyngeal origin. Archived FFPE tissue from 84 patients with SCC of oropharyngeal origin and available HPV DNA ISH and p16 IHC test results were tested with the Cervista HPV 16/18 assay and further verified by polymerase chain reaction (PCR)-based HPV16/18 genotyping tests in cases with discrepancy. Of the 84 specimens, 75% (63 of 84) were positive and 16% (13 of 84) had discrepant or equivocal findings by p16 IHC and HPV DNA ISH testing. Use of Cervista HPV assays, either to clarify discrepant/equivocal findings or as confirmation after initial p16 IHC/HPV DNA ISH tests, identified 81% (68 of 84) of HPV-positive cases without equivocal HPV results. Five of 13 cases with discrepancy or equivocal HPV DNA ISH results tested positive for HPV16 or HPV18 by Cervista HPV 16/18 assay, which was further confirmed by PCR-based HPV 16/18 genotyping. The Cervista HPV assays are a reasonable alternative to HPV DNA ISH in determining HPV status in FFPE tissue specimens from patients with oropharyngeal SCC.


Transient Ingrowth of Lymphatic Vessels into the Physiologically Avascular Cornea Regulates Corneal Edema and Transparency.
Lymphangiogenesis is essential for fluid homeostasis in vascularized tissues. In the normally avascular cornea, however, pathological lymphangiogenesis mediates diseases like corneal transplant rejection, dry eye disease, and allergy. So far, a physiological role for lymphangiogenesis in a primarily avascular site such as the cornea has not been described. Using a mouse model of perforating corneal injury that causes acute and severe fluid accumulation in the cornea, we show that lymphatics transiently and selectively invade the cornea and regulate the resolution of corneal edema. Pharmacological blockade of lymphangiogenesis via VEGFR-3 inhibition results in increased corneal thickness due to delayed drainage of corneal edema and a trend towards prolonged corneal opacification. Notably, lymphatics are also detectable in the cornea of a patient with acute edema due to spontaneous Descemet´s (basement) membrane rupture in keratoconus, mimicking this animal model and highlighting the clinical relevance of lymphangiogenesis in corneal fluid homeostasis. Together, our findings provide evidence that lymphangiogenesis plays an unexpectedly beneficial role in the regulation of corneal edema and transparency. This might open new treatment options in blinding diseases associated with corneal edema and transparency loss. Furthermore, we demonstrate for the first time that physiological lymphangiogenesis also occurs in primarily avascular sites.


Endometrial expression of members of the IL-1 family: their involvement in delayed conception of dairy cows.
The cytokines of the interleukin-1 (IL-1) family are closely involved in the resolution of inflammation in cows with metritis and endometritis. However, little is known about the role of these cytokines beyond uterine regression in the absence of disease, especially around conception. Thus, the aim of this study was to examine the gene and protein expression of IL-1α, IL-1β, IL-1RI, IL-1RII and IL-1Ra in endometrial biopsies previous to conception, to evaluate the possible association of these cytokines with delayed conception in dairy cows. Gene and protein expression levels were evaluated by real-time PCR and immunohistochemistry, respectively. The gene expression levels of cytokines were not associated with the duration of the period to conception following parturition. However, high protein expression of IL-1β and low protein expression of IL-1Ra were significantly associated with early conception. These results suggest that an imbalanced protein expression of IL-1β and IL-1Ra in the endometrium of dairy cows could be part of the maternal immune response mechanism necessary to propitiate early conception and probably to maintain pregnancy.


Strongyloidiasis in northern Vietnam: epidemiology, clinical characteristics and molecular diagnosis of the causal agent.
Strongyloidiasis is a health problem in Vietnam, but appropriate information is still limited. The aim of this study was to determine the prevalence, geographical distribution, epidemiological aspects, symptoms and other health indicators of Strongyloides stercoralis infections in patients from 27 provinces of northern Vietnam attending the Hanoi Medical University Hospital during 2016 and 2017. Blood samples of 2000 patients were analyzed for S. stercoralis infection with an IgG ELISA test. Seroprevalence was analyzed by gender, age group, locality of origin (rural or urban areas) and symptoms. Stools from the seropositive patients were examined for the detection of worms which were subsequently used for species identification by morphology and rDNA ITS1 sequencing. A seroprevalence of 20% was detected, showing an increasing prevalence from young to older age groups but without significant gender difference. Seroprevalence was higher in rural areas than in urban areas, both in general and individually in all provinces without exception, and lower in the mountainous areas than in the large valley lowlands. The follow-up of the 400 patients showed eosinophilia in 100% of cases, diarrhoea in 64.5%, digestion difficulties in 58.0%, stomachache in 45.5%, stomach and duodenal ulcers in 44.5%, itching in 28.0% and fever in 9.5%. The prevalence of symptoms and signs were also higher in older age groups than in younger age groups. Worms were detected in stools of 10.5% of the patients. Sequencing of a 501-bp nuclear ribosomal DNA ITS1 fragment allowed for the verification of infection by Strongyloides stercoralis. To our knowledge, this study is the largest survey of human strongyloidiasis in Vietnam so far and the first molecular identification of this nematode species in this country. Long-term chronicity may probably be usual in infected subjects, mainly in the older age groups.


Comparison of high-dose Cisplatin-based chemoradiotherapy and Cetuximab-based bioradiotherapy for p16-positive oropharyngeal squamous cell carcinoma in the context of revised HPV-based staging.
To perform a comparison of Cisplatin vs. Cetuximab in p16-positive oropharyngeal squamous cell carcinoma (OPSCC) in the context of the revised HPV-based staging. Previous reports comparing these agents in head and neck cancer have included heterogenous disease and p16-status. A retrospective review was conducted from 2006 to 2016 of patients with p16-positive OPSCC who underwent definitive radiotherapy concurrent with either triweekly Cisplatin (n = 251) or Cetuximab (n = 40). AJCC 8th Edition staging was adapted. Median follow-up for surviving patients was 40 months. On multivariate analysis for all-comers, comparing Cisplatin and Cetuximab, 3-year locoregional recurrence (LRR): 6% vs. 16% (p = 0.07), 3-year distant metastasis (DM): 8% vs. 21% (p = 0.04), 3-year overall recurrence rate (ORR): 11% vs. 29% (p = 0.01), and 3-year cause-specific survival (CSS): 94% vs. 79% (p = 0.06), respectively. On stage-based subgroup analysis, for stage I-II disease, 3-year LRR: 5% vs. 10% (p = 0.51), 3-year DM: 7% vs. 16% (p = 0.32), 3-year ORR: 10% vs. 23% (p = 0.15), and 3-year CSS: 95% vs. 82% (p = 0.38). For stage III disease, 3-year LRR: 10% vs. 40% (p = 0.07), 3-year DM: 9% vs. 43% (p = 0.07), 3-year ORR: 15% vs. 55% (p = 0.04), and 3-year CSS: 94% vs. 57% (p = 0.048). When given concurrently with radiotherapy, Cetuximab and triweekly Cisplatin demonstrated comparable efficacy for AJCC 8th Edition stage I-II p16-positive OPSCC. However, Cetuximab appeared to be associated with higher rates of treatment failure and cancer-related deaths in stage III disease. Upon availability of the RTOG 1016 trial results, analysis based on the revised HPV-based staging should be performed to confirm these findings.


Spontaneous glycosylation of glycosaminoglycan substrates by adherent fibroblasts.
SV40-transformed mouse fibroblasts migrate upon, and spontaneously glycosylate, plastic substrates derivatized with chondroitin-6 sulfate and hyaluronic acid. Autoradiography of cultures prelabeled with 3H-glucose and 3H-galactose demonstrates the presence of silver grains near adherent cells. Silver grains are particularly dense near cells cultured on chondroitin sulfate. No significant grains are observed on control dishes or dishes derivatized with polygalacturonic acid. Radioactive material left by cells is not removed by boiling the dishes in 8 M urea and 10% sodium dodecylsulfate, suggesting that it is covalently linked to the derivatized plastic. Acid hydrolysis shows that the radioactive material consists of glucuronic acid and N-acetylglucosamine when the prelabeled cells are cultured on hyaluronic acid. When cells are cultured on chondroitin sulfate, the radioactive product consists only of glucuronic and and N-acetylgalactosamine sulfate. Sonicates of prelabeled cells or the supernatants from cultures of intact prelabeled cells add no SDS-urea-resistant radioactivity to dishes derivatized with these glycosaminoglycans.


An update on the assessment and management of the risk of transmission of variant Creutzfeldt-Jakob disease by blood and plasma products.
There have been four highly probable instances of variant Creutzfeldt-Jakob disease (vCJD) transmission by non-leucocyte depleted red cell concentrates and it is now clear that the infectious agent is transmissible by blood components. To date there in no reported evidence that the infectious agent has been transmitted by fractionated plasma products, e.g. factor VIII concentrate. This review outlines current and potential risk management strategies including donor deferral criteria, the potential for donor screening, blood component processing and prion reduction filters, plasma product manufacture and the difficulties in identification and notification of those considered 'at risk of vCJD for public health purposes'.


[The effect of actinomycin D on the survival and recoverability of irradiated human melanoma cells].
The presence of actinomycin D during gamma-irradiation of human melanoma cells leads to an increased radiosensitivity under aerobic and hypoxic conditions. This interaction of both treatment modalities depends upon the drug dose. Incubation of cells prior or after irradiation with essentially non-cytotoxic amounts of actinomycin D under normal conditions has only little effect on the shape of the radiation dose-response-curve, irrespectively of the time interval between drug treatment and irradiation. However, high doses of actinomycin D given immediately after irradiation increase the radiosensitivity of human cells. The drug does not effect recovery from sublethal or potentially lethal radiation damage.


Effect of temperature, salts, pH, and other factors on the development of peritrichous flagella in Vibrio alginolyticus.
The development of peritrichous flagella and, consequently, swarming of Vibrio alginolyticus depend on a complex relationship between temperature, salt concentrations and pH. At temperatures above 28 degrees C V. alginolyticus did not develop peritrichous flagella unless certain minimal concentrations of NaCl are present: the higher the temperature, the higher the NaCl concentrations required for peritrichous flagella synthesis. This requirement for NaCl at high temperatures is much more pronounced at pH 9 than at pH 6. High temperatures and low concentrations of NaCl also inhibited swarming of cells already armed with peritrichous flagella. Other cations, such as Li+, K+ and Mg2+. replaced NaCl only at temperatures below 28 degrees C.


Transformative adaptation through nature-based solutions: a comparative case study analysis in China, Italy, and Germany.
This paper explores how claims for transformative adaptation toward more equitable and sustainable societies can be assessed. We build on a theoretical framework describing transformative adaptation as it manifests across four core elements of the public-sector adaptation lifecycle: vision, planning, institutional frameworks, and interventions. For each element, we identify characteristics that can help track adaptation as transformative. Our purpose is to identify how governance systems can constrain or support transformative choices and thus enable targeted interventions. We demonstrate and test the usefulness of the framework with reference to three government-led adaptation projects of nature-based solutions (NBS): river restoration (Germany), forest conservation (China), and landslide risk reduction (Italy). Building on a desktop study and open-ended interviews, our analysis adds evidence to the view that transformation is not an abrupt system change, but a dynamic complex process that evolves over time. While each of the NBS cases fails to fulfill all the transformation characteristics, there are important transformative elements in their visions, planning, and interventions. There is a deficit, however, in the transformation of institutional frameworks. The cases show institutional commonalities in multi-scale and cross-sectoral (polycentric) collaboration as well as innovative processes for inclusive stakeholder engagement; yet, these arrangements are ad hoc, short-term, dependent on local champions, and lacking the permanency needed for upscaling. For the public sector, this result highlights the potential for establishing cross-competing priorities among agencies, cross-sectoral formal mechanisms, new dedicated institutions, and programmatic and regulatory mainstreaming. The online version contains supplementary material available at 10.1007/s10113-023-02066-7.


Effects of tension across the tendon repair site on tendon gap and ultimate strength.
Tendons repaired with varying amounts of tension result in different degrees of shortening of the tendon segment within core sutures, which may affect tensile strengths. We aimed to investigate the effects of tension across the repair site on gap formation forces and ultimate strength. Fifty-seven porcine flexor tendons were repaired with a 2-strand modified Kessler repair or a 4-strand cross-lock repair. For each type of repair, the tendons were divided into 3 groups: by 0%, 10%, or 20% shortening of tendon segment encompassed within core sutures. The repaired tendons had a single load-to-failure test in a materials testing machine. The forces required for initial and 2-mm gap formation and ultimate failure were recorded and statistically compared for each group. With either 2-strand or 4-strand repair, the tendons in the 10% tendon-segment shortening group withstood significantly higher initial and 2-mm gap formation forces than those in the group with no shortening, with average increases of 5 to 10 N after 10% shortening. Increasing the tendon-segment shortening to 20% produced a slight increase in the initial and 2-mm gap forces compared with those with 10% shortening, which was statistically significant only in the tendons with the 4-strand repair. The ultimate strengths were not significantly different among the tendons with either 2-strand or 4-strand repair of any degrees of shortening. Tensioning the core suture to shorten its encompassed tendon segment by 10% substantially increases resistance to postoperative gapping. Further tensioning to produce 20% shortening of the tendon segment increased the gapping forces by a much smaller amount. This study suggests that a slightly tensioned surgical repair, shortening the encompassed tendon segment by approximately 10%, is appropriate. Slightly tensioning core sutures across the tendon repair site, such as adding tension to cause 10% tendon-segment shortening, would greatly increase the gap resistance of the surgical repair.


Seasonal Variation of Atrial Fibrillation Admission and Quality of Care in the United States.
Background Currently, little is known regarding seasonal variation for atrial fibrillation (AF) in the United States and whether quality of care for AF varies between seasons. Methods and Results The GWTG-AFib (Get With The Guidelines-AFib) registry was initiated by the American Heart Association to enhance national guideline adherence for treatment and management of AF. Our analyses included 61 291 patients who were admitted at 141 participating hospitals from 2014 to 2018 across the United States. Outcomes included numbers of AF admissions and quality-of-care measures (defect-free care, defined as a patient's receiving all eligible measures). For quality-of-care measures, generalized estimating equations accounting for within-site correlations were used to estimate odds ratios (ORs) with 95% CIs, adjusting patient and hospital characteristics. The proportion of AF admissions for each season was similar, with the highest percentage of AF admissions being observed in the fall (spring 25%, summer 25%, fall 27%, and winter 24%). Overall, AF admissions across seasons were similar, with no seasonal variation observed. No seasonal variation was observed for incident AF. There were no seasonal differences in care quality (multivariable adjusted ORs and 95% CIs were 0.93 (0.87-1.00) for winter, 1.09 (1.01-1.18) for summer, and 1.08 (0.97-1.20) for fall, compared with spring). Conclusions In a nationwide quality improvement registry, no seasonal variation was observed in hospital admissions for AF or quality of care for AF.


The effect of cricoid pressure application on airway patency.
To assess the incidence of upper airway obstruction associated with the application of cricoid pressure (Sellick's maneuver) by experienced anesthetists. Randomized, blinded study. Anesthetic rooms at John Radcliffe Hospital, Oxford, United Kingdom. Fifty ASA I patients undergoing routine general anesthesia for elective surgery requiring tracheal intubation. Following induction of anesthesia and muscle relaxation, a senior anesthetist applied cricoia pressure in the manner described by Sellick. Patients were ventilated with or without cricoid pressure, with the order of intervention randomized, and the observer blinded to all maneuvers. Effect on airway patency was assessed by measuring expired tidal volume (VT) and peak inspiratory pressure (PIP) when ventilated using a face mask with and without cricoid pressure applied, and with and without an oropharyngeal airway in place. Application of cricoid pressure caused a significant reduction in mean expired VT (p < 0.001) and a significant increase in PIP (p < 0.001) compared with control values. Complete airway occlusion occurred in 11% of applications. The use of manual cricoid pressure, even by experienced anesthetists, causes a degree of airway obstruction and can cause complete airway occlusion.


The gap between ultrasonography and computed tomography in measuring the size of urinary calculi.
Due to a lack of studies regarding the need for computed tomography (CT) in measuring the size of each urinary calculus before surgery, this study was conducted to elucidate the difference between ultrasonography (US) and CT in measuring the size of urinary stones. A retrospective review of 100 stones from 83 patients. Each urinary stone was measured using both US and CT; both measurements were then compared. Of 83 patients, the mean age was 39.29 ± 23.76 years; 47 (56.62%) were male and 36 (43.37%) were female. Most of the urinary stones were <10 mm (50.0%) followed by 11-20 mm (42.0%), (P < 0.001). A cross-tabulation test revealed strong compatibility between US and CT in measuring the size of urinary stones (73.7% in stones <10 mm, 66.7% in stones 11-20 mm and 50% in stones >21 mm), (P < 0.001). Spearman's rho correlation test revealed strong compatibility between stone diameters measured by US and CT (r = 0.755), (P = 0 < 0.001). T-test for equality of means revealed no significant difference in the measured size using US and CT (mean = 11.80 ± 5.83 vs. 11.65 ± 6.59, respectively), mean difference = 0.15, and P = 0.865, 95% confidence interval: -1.584-1.884. No significant difference in measuring the size of urinary stones using US and CT. However, US may slightly overestimate small stones in some cases.


Detection of occult gallbladder disease by duodenal drainage.
Examination of gallbladder bile in the sediment of duodenal drainage obtained after magnesium sulfate stimulation was used to evaluate the presence or absence of gallbladder disease in thirty-four patients with symptoms suggestive of cholecystitis and normal or equivocal oral cholecystography. Ten patients had positive tests and nine of these had cholecystectomy. All nine had pathologically confirmed cholecystitis and seven of nine had cholelithiasis. Three patients with negative test results had laparotomy and normal gallbladders. The remaining twenty-one patients with negative tests have been followed up to three years, and none have returned with evidence of biliary tract disease. The results of this study suggest that duodenal drainage (Meltzer-Lyon test) is a valuable adjunctive diagnostic study in patients with gallbladder disease symptoms in whom normal or equivocal oral cholecystograms are obtained.


The impact of HBV-DNA fluctuations on virus-specific CD8+ T cells in HBeAg+ chronic hepatitis B patients treated with a steroid and lamivudine.
Restoration of anti-viral immune response may be a requisite for sustained virological response to treatment in chronic hepatitis B patients. Over a 13-month period, we examined the dynamics of hepatitis B virus (HBV)-specific CD8+ cells in six human leucocyte antigen (HLA)-A2+ hepatitis B e antigen (HBeAg)+ 'immunotolerant' chronic hepatitis B patients treated sequentially with corticosteroid and lamivudine. Our results show that the combination treatment did not result in a sustained restoration of anti-viral specific CD8+ cells in five of the six patients studied. However, HBV-specific CD8+ cells, despite being severely compromised, were not totally deleted. Paradoxically, steroid treatment was not associated with inhibition but with a minimal increase of the HBV-specific CD8 response, and we observed that nucleocapsid-specific CD8 responses were not rescued by stable and prolonged inhibition but became detectable after rapid rebounds of HBV replication. In most patients, the transient and minimal restoration of HBV-specific immunity was not associated with clinical benefits. Our results describe a dynamic relationship between HBV-specific CD8+ cells and HBV-DNA values, that could potentially be used for a better design of HBV treatment in HBeAg+ 'immunotolerant' chronic hepatitis B patients.


Shoulder pain prevalence and risk factors in middle-aged women: A cross-sectional study.
The aim of the current study was to investigate the prevalence of shoulder pain and to explore the possible associated risk factors in middle-aged women. A total of 500 middle-aged women, aged 45-65 years, participated in this cross-sectional study. The point and lifetime prevalence of shoulder pain were calculated. Linear and logistic regressions were used to determine the possible associations between the risk factors and present shoulder pain. The point and lifetime prevalence of shoulder pain were 18.6% and 27.6%, respectively. The logistic regression analysis demonstrated a significant association between present shoulder pain and history of shoulder pain and trauma, osteoporosis, trapezius muscle pain, and cervical radiculopathy (p < 0.05). However, there was no significant association between present shoulder pain and diabetes mellitus or postural deviation (p > 0.05). The results indicated that shoulder pain has considerable prevalence in middle-aged women. In addition, a history of shoulder pain and trauma, osteoporosis, trapezius muscle pain, and cervical radiculopathy were found to be associated with present shoulder pain. Future research should concentrate on longitudinal designs that explore preventive strategies and risk factors for shoulder pain.


Randomized phase II study of sunitinib versus standard of care for patients with previously treated advanced triple-negative breast cancer.
This randomized, open-label phase II study compared the efficacy of sunitinib monotherapy with that of single-agent standard-of-care (SOC) chemotherapy in patients with previously treated advanced triple-negative breast cancer (TNBC). Patients with advanced TNBC, relapsed after anthracycline- and taxane-based chemotherapy, were randomized to receive either sunitinib (37.5 mg/day) or the investigator's choice of SOC therapy. Progression-free survival was the primary endpoint. Median progression-free survival was 2.0 months with sunitinib and 2.7 months with SOC chemotherapy (one-sided P = 0.888). Median overall survival was not prolonged with sunitinib (9.4 months) compared with SOC chemotherapy (10.5 months; one-sided P = 0.839). The objective response rate was 3% with sunitinib and 7% with SOC chemotherapy (one-sided P = 0.962). Sunitinib monotherapy did not improve efficacy compared with SOC chemotherapy in patients with previously treated advanced TNBC, for which identification of effective treatments and therapeutic targets remains an urgent need. NCT00246571.


Genetic similarity and diversity among three camel populations reared in Egypt.
Molecular genetics has been extremely useful in determining the relation between animal populations and documenting the degrees of genetic variation found within them. The present study was undertaken to evaluate genetic diversity and the relationships between the three camel populations reared in Egypt: Maghrabi, Sudani, and Baladi using mitochondrial 16S sequences and other breeds of camels in the world. Blood samples were collected from camels belonging to these three populations. Genomic DNA was extracted from the collected blood samples and subjected to PCR using specific primers for mitochondrial 16S region. The amplified products were purified using DNA purification kit to remove residual primers and dNTPs. Sequencing was performed in the Macrogen Incorporation. The amplified products were submitted to GenBank/NCBI under accession numbers OM 278349 and OM 278350 RESULTS: Sequencing was done on the partial mitochondrial 16S amplified fragments at 530 bp. This amplified area had two haplotypes. There was one substitution (G/A) at nucleotide 309 of the amplified segment. The nucleotide (π) and Hd stand for haplotype diversity, respectively, at 0.00008 and 0.042, and the average number of pairwise nucleotide differences, k, is 0.042, according to Fu's Fs statistic and Tajima's D, which is -1.10686. Genetic distance percentages between the three populations under study range from 0.000 to 0.0312. A phylogenetic analysis of Egyptian camel populations and other Camelus dromedarius populations revealed a strong relationship between them. This study suggests that the 16S rRNA sequencing in mitochondria plays a critical role in genetic variation studies and analysis of phylogeny between camel populations and breeds.


Multiple imputation as one tool to provide longitudinal databases for modelling human height and weight development.
Besides large efforts regarding field work, provision of valid databases requires statistical and informational infrastructure to enable long-term access to longitudinal data sets on height, weight and related issues. To foster use of longitudinal data sets within the scientific community, provision of valid databases has to address data-protection regulations. It is, therefore, of major importance to hinder identifiability of individuals from publicly available databases. To reach this goal, one possible strategy is to provide a synthetic database to the public allowing for pretesting strategies for data analysis. The synthetic databases can be established using multiple imputation tools. Given the approval of the strategy, verification is based on the original data. Multiple imputation by chained equations is illustrated to facilitate provision of synthetic databases as it allows for capturing a wide range of statistical interdependencies. Also missing values, typically occurring within longitudinal databases for reasons of item non-response, can be addressed via multiple imputation when providing databases. The provision of synthetic databases using multiple imputation techniques is one possible strategy to ensure data protection, increase visibility of longitudinal databases and enhance the analytical potential.


Impact of age on the diagnostic performance of unstimulated salivary flow rates and salivary gland ultrasound for primary Sjögren's syndrome.
Age-related changes and different patterns of salivary gland abnormalities according to age may affect the diagnostic performance of unstimulated salivary flow rate (USFR) and salivary gland ultrasound (SGUS) for primary Sjögren's syndrome (pSS). We aimed to evaluate the threshold and diagnostic performance of USFR and whether incorporating SGUS or replacing USFR with SGUS affects the performance of the ACR/EULAR criteria for pSS according to age. This medical chart review study included patients with suspected pSS who completed evaluations for pSS. Patients were classified based on age at pSS evaluation: elderly (≥65 years), middle-aged (40-64), and young (< 40). The USFR's optimal thresholds were evaluated using the ROC curve. The diagnostic performances of the USFR and modified ACR/EULAR criteria were compared. In total, 239 pSS patients and 92 patients with idiopathic sicca syndrome were included. The cut-off of USFR ≤ 0.1 mL/min was irrelevant to age, demonstrating the best sensitivity (44.3-53.0%) and specificity (74.1-90.9%). SGUS had a significantly better AUC than USFR in the young (p < 0.01) and middle-aged groups (p < 0.01). The middle-aged group demonstrated better diagnostic performance of the ACR/EULAR criteria incorporating SGUS (AUC 0.957) (p < 0.01) and criteria replacing USFR with SGUS (AUC 0.957) (p < 0.001) compared to the original criteria (AUC 0.916). In the young and elderly groups, adding SGUS to the ACR/EULAR criteria or replacing USFR with SGUS did not significantly increase the AUC. The thresholds of USFR ≤ 0.1 mL/min was optimal, irrespective of age. Using SGUS can improve diagnostic accuracy of ACR/EULAR criteria by supplementing the USFR, especially in middle-aged patients.


Plasma exchange for anti GAD associated non paraneoplastic limbic encephalitis.
Limbic encephalitis (LE) is a neurological syndrome usually presenting in a paraneoplastic form. Recently many cases were reported with no concurring neoplasia, presenting with specific antibodies for voltage-gated potassium channel or for neuronal membrane antigens. Anti-glutamic acid decarboxylase (GAD) antibodies act against GABAergic receptors of the central nervous system. These antibodies were found in coeliac disease serum and in neurologic patients. We are reporting a case of a 21-year-old coeliac woman manifesting complex multiple-daily partial drug-resistant seizures for 7 years. The diagnosis was of a non paraneoplastic limbic encephalitis, unresponsive to high dose cortisone and IGIV infusion. The use of therapeutic plasma exchange (TPE) has resulted in an improvement in symptoms with quite a long disease-free period of time. When the frequency of the procedures was decreased, seizures appeared again and, after suspension of TPE, the clinical status worsened. The role of TPE in the treatment of LE still has to be defined.


Effect of insulin on oxidation of intracellularly and extracellularly derived glucose in patients with NIDDM. Evidence for primary defect in glucose transport and/or phosphorylation but not oxidation.
Insulin-stimulated glucose oxidation is decreased in patients with non-insulin-dependent diabetes mellitus (NIDDM). It is not known whether this decrease is due to a primary defect in the oxidative pathway or is secondary to impaired glucose transport and/or phosphorylation. To address this issue, glucose oxidation was measured under steady-state conditions at low (approximately 270 pmol) and high (approximately 17 mumol) insulin concentrations in seven patients with NIDDM and seven healthy nondiabetic subjects matched for sex, age, and obesity. Glucose oxidation was measured simultaneously by indirect calorimetry and the isotopedilution technique. Although glucose oxidation and nonoxidative storage were lower (P less than 0.05) in diabetic than nondiabetic subjects during the low- and high-dose insulin infusions, oxidation of intracellularly derived glucose, estimated by subtracting the rate of oxidation measured isotopically (i.e., glucose oxidation derived from the extracellular space) from that measured by indirect calorimetry (i.e., total glucose oxidation), did not differ in diabetic and nondiabetic subjects during the low-dose insulin infusion (3.3 +/- 0.1 vs. 3.0 +/- 0.1 mumol.kg-1.min-1). Both techniques provided identical estimates of glucose oxidation during the high-dose insulin infusion. Impaired oxidation of extracellularly but not intracellularly derived glucose strongly suggests that the cause of decreased glucose oxidation in patients with NIDDM is secondary to impaired glucose transport and/or phosphorylation rather than a primary abnormality in the oxidative pathway.


Self-care and quality of life among patients with heart failure.
The purpose of this cross-sectional, descriptive study was to determine if there were specific self-care deficits among patients with heart failure at the time of discharge in an acute care setting, which may be related to a decreased quality of life. Patients admitted with acute, chronic congestive heart failure were recruited to complete both the Self-care of Heart Failure Index and the Minnesota Living with Heart Failure questionnaires. Data analyses were conducted to determine if there were any significant relationships between self-care abilities and quality of life. Results from this study were promising as "self-care confidence" and perceived better health were found to be significantly related to improved quality of life. Heart failure is a chronic disease that requires patients to develop confidence in their self-care abilities to maintain and improve quality of life. Findings from this research study suggest that nurse practitioners need to first identify patients with heart failure who lack the self-care confidence required to manage their condition at home, and then focus on specific educational interventions to build confidence in self-care prior to discharge.


Effects of low water supplementation and nutrient addition on the aboveground biomass production of annual plants in a Chilean coastal desert site.
The effects of low water supplementation and nutrients on the aboveground biomass production of annual plants was tested in the field by mimicking small rainfall events of 5mm per month and by adding fertilizers to experimental quadrats. Field measurements were made during an extremely dry year, so the potential additional effects of rainfall probably had no important effect on plant responses. Biomass of non-native species was higher in irrigated than in non-irrigated quadrats. No significant responses to irrigation treatments were detected in native species. This lack of response may be due to higher thresholds of watering being required for either germination and/or growth. Because of the low water inputs, fertilizer additions did not promote any biomass response in either native or non-native species. Responses of non-native species to low and frequent pulses of water, which is characteristic of this arid system, may be important for the persistence of these species in this environment.


Premaxillary hyperdontia in medieval Norwegians: a radiographic study.
An excavation of a part of the graveyard of St Olav's church, Trondheim, Norway, uncovered 389 tombs from the medieval period (1100-1600). Radiographic examination of 140 skulls with an intact premaxilla revealed hyperdontia in the form of a mesiodens in two (1.4%) cases. This is within the same range as similar medieval and present Nordic populations. Change in functional pattern does not seem to influence the prevalence.


Associations of deformation-based brain morphometry with cognitive level and decline within older Blacks without dementia.
Blacks are at higher risk of developing cognitive impairment with age than non-Hispanic Whites, yet most brain morphometry and cognition research is performed with White samples or with mixed samples that control for race or compare across racial groups. A deeper understanding of the within-group variability in associations between brain structure and cognitive decline in Blacks is critically important for designing appropriate outcomes for clinical trials, predicting adverse outcomes, and developing interventions to preserve cognitive function, but no studies have examined these associations longitudinally within Blacks. We performed deformation-based morphometry in 376 older Black participants without dementia and examined associations of deformation-based morphometry with cognitive level and decline for global cognition and five cognitive domains. After correcting for widespread age-associated effects, there remained regions with less tissue and more cerebrospinal fluid associated with level and rate of decline in global cognition, memory, and perceptual speed. Further study is needed to examine the moderators of these associations, identify adverse outcomes predicted by brain morphometry, and deepen knowledge of underlying biological mechanisms.


The Brain-Derived Neurotrophic Factor (BDNF) gene Val66Met (rs6265) polymorphism and stress among preclinical medical students in Malaysia.
This study aimed to determine the allelic and genotypic association of the Val66Met (rs6265) polymorphism in the BDNF gene with stress levels in preclinical medical students of Universiti Sultan Zainal Abidin (UniSZA), Terengganu, Malaysia. In this cross-sectional study, we recruited all 122 preclinical medical students. The validated depression anxiety stress scales-21 (DASS-21) questionnaire was distributed and blood samples were collected from each subject for DNA extraction. Genotyping analysis of the BDNF gene (Val66Met) polymorphism was performed via an optimised polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. A total of 105 subjects agreed to participate in this study. Indian students were found to more likely have the Val/Val genotype, whereas Malay students were more likely to have the Met/Met genotype (p = 0.027). Individuals carrying any one of the three BDNF genotypes (Val/Val, Val/Met and Met/Met) differed significantly from each other in terms of their perception of stress (p = 0.010); students carrying the Val/Val genotype (M = 10.6) perceived significantly lower stress than students carrying the Val/Met (M = 14) and Met/Met (M = 15.1) genotypes. In our study, the Met-allele was associated with higher stress levels. To the best of our knowledge, this is the first study investigating this stress-related gene in medical students. The findings from this study should trigger more investigators to focus on the impact of stress on genetically predisposed medical students.


Arbuscular mycorrhizal fungi, Collembola and plant growth.
Arbuscular mycorrhizal fungi are ubiquitous in field soils, as are mycophagous animals such as Collembola. It has been suggested that these animals reduce the functioning of the mycorrhiza and are thus detrimental to plant growth. However, recent choice experiments suggest that Collembola preferentially feed on nonmycorrhizal fungi in the rhizosphere. If these preferences also occur in field soils, then Collembola might indirectly benefit plants through an enhancement of mycorrhizal functioning and indirect multitrophic links to foliar-feeding insect herbivores.


Impaired allocentric spatial memory in patients with affective disorders.
Memory disturbances are frequent in unipolar depression (UD) and bipolar disorder (BD) and may comprise important predisposing and maintaining factors. Previous studies have demonstrated hippocampal abnormalities in UD and BD but there is a lack of studies specifically assessing hippocampus-dependent memory. We used a virtual task to assess hippocampus-dependent (allocentric) vs non-hipppocampal (egocentric) spatial memory in remitted and partially remitted patients with UD or BD (N = 22) and a healthy control group (N = 32). Participants also completed a range of standard neuropsychological and functional assessments. Participants in the UD/BD group showed selective impairments on high-load hippocampal (allocentric) memory compared to egocentric memory and this effect was independent of residual mood symptoms. Across both samples, both allocentric and egocentric spatial memory correlated with more general measures of memory and other aspects of cognition measured on standard neuropsychological tests but only high-load allocentric memory showed a significant relationship with functional capacity. Results show a selective impairment in high-load allocentric spatial memory compared to egocentric memory in the patient group, suggesting impaired hippocampal functioning in patients with remitted UD/BD.


Neuropilin-1 is upregulated in Sjögren's syndrome and contributes to pathological neovascularization.
Neuropilin-1 (NRP1) is a transmembrane co-receptor for members of the vascular endothelial growth factor family. Recent studies revealed an important role of NRP1 in angiogenesis and progression of many diseases. The role of NRP1 in the development of Sjögren's syndrome (SS), one of the most common rheumatic diseases, has not yet been investigated. Molecular studies and protein expression techniques were performed to elucidate the gene and protein expression profile of NRP1 in human salivary gland epithelial cells (SGEC) from primary SS. We used human microarrays and transient transfection with a mutant form of the negative inhibitory κBα proteins (IκBαDN) to investigate whether selective inhibition of nuclear Factor-κB (NF-κB) improves NRP1-mediated pro-angiogenic factors release from SS SGEC. The selective NRP1 function inhibition with an antibody to human NRP1, was employed to evaluate the therapeutic potential of targeting NRP1. We demonstrate that NRP1 is expressed in SGEC of both human healthy biopsies and in SS samples, and increased NRP1 expression in SS SGEC is significantly associated with pro-angiogenic factors release. Neutralizing anti-NRP1 antibody decreased pro-angiogenic factor production from SS SGEC and blocking NF-κB activation could be a way to inhibit NRP1-mediated angiogenesis in Sjögren's syndrome.


Combination chemotherapy and radiotherapy for Hodgkin's disease in children.
31 children with Hodgkin's disease were treated at the Children's Hospital, University of Munich, between 1963-1976. Before 1971 the diagnosis of abdominal involvement was based solely on physical findings and radiological studies. Treatment consisted of involved-field radiation; chemotherapy was added in selected cases. Of 15 children treated between 1963-1971, 5 are still in their first remission and 2 in their second remission. Since 1971 exploratory laparotomy and splenectomy have been performed. Radiation therapy was changed from involved- to extended-field therapy and combination chemotherapy was added in all the children. No patient from this group of 16 children relapsed during a median observation time of 24 months (range 12-55 months). The toxicity of the combined treatment does not seem to be prohibitive.


Can dexamethasone improve postoperative sleep and postoperative delirium in elderly patients undergoing robot-assisted laparoscopic radical prostatectomy? Protocol for a prospective, randomized, double-blind, controlled study.
Perioperative sleep disorders (PSD) are an independent risk factor for postoperative delirium (POD), which is a common complication after surgery. Elderly patients who undergo robot-assisted radical prostatectomy (RARP) often experience perioperative sleep disorders (PSD). Dexamethasone, a medication that works by inhibiting the hypothalamic-pituitary-suprarenal cortical axis, can reduce the negative effects of surgical stress. The objective of this study was to determine whether intravenous administration of dexamethasone at the time of anesthesia induction could improve postoperative sleep quality in elderly patients, thereby indirectly reducing the risk of postoperative cognitive impairment and accelerating postoperative rehabilitation. This study is a randomized, double-blind, placebo-controlled trial that was conducted at a single center. A sample size of 116 patients was determined through calculation, and these patients were randomly assigned to either the dexamethasone group (group D, n = 58) or the blank control group (group C, n = 58). On the day of surgery, the anesthesia nurse prepared either diluted dexamethasone or saline in advance, according to the patient's assigned group. The blinded anesthesiologist administered the medication during induction, and a dedicated person followed up with the patient for three consecutive postoperative days. All other aspects of care were managed equally between the two groups. The primary outcome measure was sleep quality, while secondary outcome measures included postoperative sleep time, postoperative delirium (POD), pain scores, and other complications. Relevant test measures were recorded for analysis. This study aims to investigate the impact of intravenous dexamethasone on sleep quality and duration of patients undergoing robot-assisted radical prostatectomy (RARP). If the findings of this study protocol are affirmative, it could enhance the sleep quality of elderly patients after surgery, thereby minimizing the risk of postoperative delirium (POD), and providing substantial evidence for the perioperative enhanced recovery management of elderly patients. Chinese clinical trial registry: ChiCTR2200063488, Registered on 5 October 2022.


Zinc alpha-2 glycoprotein is implicated in dyslipidaemia in HIV-1-infected patients treated with antiretroviral drugs.
Treated HIV-1-infected patients with lipodystrophy often develop insulin resistance and proatherogenic dyslipidaemia. Zinc alpha-2 glycoprotein (ZAG) is a recently characterized adipokine which has been shown to be involved in the development of obesity and metabolic syndrome in uninfected subjects. We assessed the relationship between circulating ZAG levels and metabolic derangements in HIV-1-infected patients receiving antiretroviral drugs. Plasma ZAG levels were assessed in 222 individuals: 166 HIV-1-infected patients treated with antiretroviral drugs (77 with lipodystrophy and 89 without lipodystrophy) and 56 uninfected controls. Plasma ZAG levels were assessed by enzyme-linked immunosorbent assay (ELISA) and were correlated with fat distribution abnormalities and metabolic parameters. HIV-1-infected patients had lower plasma ZAG levels compared with uninfected controls (P < 0.001). No differences were found in ZAG plasma levels according to the presence of lipodystrophy, components of the metabolic syndrome or type of antiretroviral treatment regimen. Circulating ZAG levels were strongly determined by high-density lipoprotein cholesterol (HDLc) in men (B = 0.644; P < 0.001) and showed a positive correlation with total cholesterol (r = 0.312; P < 0.001) and HDLc (r = 0.216; P = 0.005). HIV-1-infected patients have lower plasma ZAG levels than uninfected controls. In infected patients, plasma ZAG levels are in close relationship with total cholesterol and HDLc.


Sigmoidoduodenal fistula as a rare complication of colonic carcinoma: report of a case.
We report a very unusual case of malignant sigmoidoduodenal communication. To the best of our knowledge, this is the first documentation of this entity in the English language literature. A 76-year-old man presented with weakness, severe weight loss, foul-smelling eructations, anemia, constipation, and episodes of diarrhea. A sigmoidoduodenal fistula was found by barium enema, and a diagnosis of ulcerative colonic adenocarcinoma was made from the colonoscopy findings. Thus, we performed sigmoid colectomy with resection of the fistula and the involved anterior wall of the third duodenal part, followed by primary closure of the duodenal defect. Histological examination confirmed a Dukes' B (Stage II - T(4)N(0)M(0)) colonic adenocarcinoma, and the excision margins of the resected duodenal specimen were clear. We gave adjuvant chemotherapy with 5-fluorouracil and leucovorin. The patient is still alive and disease-free, 2 years postoperatively.


DeepFake knee osteoarthritis X-rays from generative adversarial neural networks deceive medical experts and offer augmentation potential to automatic classification.
Recent developments in deep learning have impacted medical science. However, new privacy issues and regulatory frameworks have hindered medical data sharing and collection. Deep learning is a very data-intensive process for which such regulatory limitations limit the potential for new breakthroughs and collaborations. However, generating medically accurate synthetic data can alleviate privacy issues and potentially augment deep learning pipelines. This study presents generative adversarial neural networks capable of generating realistic images of knee joint X-rays with varying osteoarthritis severity. We offer 320,000 synthetic (DeepFake) X-ray images from training with 5,556 real images. We validated our models regarding medical accuracy with 15 medical experts and for augmentation effects with an osteoarthritis severity classification task. We devised a survey of 30 real and 30 DeepFake images for medical experts. The result showed that on average, more DeepFakes were mistaken for real than the reverse. The result signified sufficient DeepFake realism for deceiving the medical experts. Finally, our DeepFakes improved classification accuracy in an osteoarthritis severity classification task with scarce real data and transfer learning. In addition, in the same classification task, we replaced all real training data with DeepFakes and suffered only a [Formula: see text] loss from baseline accuracy in classifying real osteoarthritis X-rays.


Novel compound heterozygous variant of TOE1 results in a mild type of pontocerebellar hypoplasia type 7: an expansion of the clinical phenotype.
The target of EGR1 protein 1 (TOE1) is a 3-exonuclease belonging to the Asp-Glu-Asp-Asp deadenylase family that plays a vital role in the maturation of a variety of small nuclear RNAs (snRNAs). Bi-allelic variants in TOE1 have been reported to cause a rare and severe neurodegenerative syndrome, pontocerebellar hypoplasia type 7 (PCH7) (OMIM # 614,969), which is characterized by progressive neurodegeneration, developmental delay, and ambiguous genitalia. Here, we describe the case of a 5-year-6-month-old female Chinese patient who presented with cerebral dysplasia, moderate intellectual disability, developmental delay, and dystonia. Trio whole-exome sequencing revealed two previously unreported heterozygous variants of TOE1 in the patient, including a maternal inherited splicing variant c.237-2A > G and a de novo missense variant c.551G > T, p.Arg184Leu. TA clone sequencing showed trans status of the two variants, indicating the missense variant occurred on the paternal strand in the patient. Clinical features of the patient were mostly concordant with previous reports but brain deformities (enlarged lateral ventricle and deepened cerebellum sulcus without microcephaly and reduced cerebellar volume) were less severe than in typical PCH7 patients. Moreover, the patient had no gonadal malformation, which is common and variable in patients with PCH7. In summary, we report the case of a Chinese patient with atypical PCH7 caused by a novel TOE1 compound variant. Our work suggests that variations in the TOE1 gene can lead to highly variable clinical phenotypes.


Synthesis and Characterization of Ferric Vanadate Nanorods for Efficient Electrochemical Detection of Ascorbic Acid.
This study reports the synthesis of ferric vanadate (FeVO4) via a facile hydrothermal method, focusing on demonstrating its exceptional electrochemical (EC) properties on detecting low-density ascorbic acid (AA). The phase purity, crystallinity, structure, morphology, and chemical compositional properties were characterized by employing X-ray diffraction, energy-dispersive X-ray spectroscopy, scanning electron microscopy, Raman spectroscopy, and X-ray photoelectron spectroscopy techniques. EC impedance spectroscopy and cyclic voltammetry techniques were also adopted in order to assess the EC response of a FeVO4-modified glassy carbon electrode for sensing AA at room temperature. The AA concentration range adopted in this experiment is 0.1-0.3 mM at a working electric potential of -0.13 V. The result showed functional excellence of this material for the EC determination of AA with good stability and reproducibility, promising its potentiality in connection with relevant sensing applications.


GLUT4 trafficking in a test tube.
Insulin regulates glucose transport in muscle and fat cells by stimulating the translocation of GLUT4 from intracellular vesicles to the plasma membrane. In this issue of Cell Metabolism, Holman and colleagues reconstitute this process in vitro, providing a system that promises new breakthroughs in our understanding of this important metabolic process.


Reduction of glycerol production to improve ethanol yield in an engineered Saccharomyces cerevisiae using glycerol as a substrate.
Ethanol plays an important role in substituting the increasingly limited oil as the high-value, renewable fuel. In our previous studies, we successfully established the conversion of glycerol to ethanol by overexpression of pGcyaDak with pGup1Cas in Saccharomyces cerevisiae. In addition to increasing ethanol production using glycerol as substrate, we minimized the synthesis of glycerol, which is the main by-product in ethanol fermentation processing. The glycerol production pathway was impaired by deletion of the genes FPS1 and GPD2. Strains deleted for both FPS1 and GPD2 reduce glycerol production and become highly sensitive to osmotic stress. We provide osmotic protection in YPH499fps1Δgpd2Δ by overexpression of Gup1. In this study, S. cerevisiae using glycerol as substrate was modified through one-step gene disruption for redirection of glycerol carbon flux into ethanol by the deletion of two glycerol production genes, FPS1 and GPD2. The overall ethanol production in the modified strain YPH499fps1Δgpd2Δ (pGcyaDak, pGupCas) was about 4.4 gl⁻¹. These results demonstrate the possibility of providing protection against osmotic stress while simultaneously increasing ethanol and reducing glycerol production in S. cerevisiae strains using glycerol as a carbon source.


Building bridges of understanding through continuing education and professional development of Arabs and Israelis.
In this article, we present an educational approach uniquely linked to humanitarian and peace-building goals in conflicted regions of the world. We examine the Canada International Scientific Exchange Program and its lead program, the Middle East Association for Managing Hearing Loss, as a case study. Under a Canadian umbrella, continuing medical education and continuous professional development are used to gather academics from regions in conflict for mutually beneficial professional activities. Larger scale international prospects for educational programming, extending beyond the health sector, are ways of addressing the primary determinants of health and creating social capital.


Isolation and identification of stem cells from adult cashmere goat skin.
Continuously renewing epithelia are maintained by stem cells that slowly proliferate and remain in the tissues for life. It has been known for decades that mouse epithelial stem cells can be selected by adherence to specific integrins. The adherence of cashmere goat epidermal cells to collagen type IV for 10 min was used to obtain enriched epidermal stem cells. The characteristics of the rapidly adherent epidermal cells were determined. The rapidly adherent epidermal cells exhibited the stem cell characteristics of immaturity, were quiescent, showed a high colony formation efficiency, and expressed candidate surface markers for epidermal stem cells (keratin 15, keratin 19, p63, CD34, and beta1-integrin). The rapidly adherent epidermal cells represented the epidermal stem cell population.


Glycine potentiates N-methyl-D-aspartate-induced [3H]TCP binding to rat cortical membranes.
In extensively washed preparations of rat cortical membranes, N-methyl-D-aspartate (NMDA) increases the specific binding of [3H]TCP by over 4-fold in a concentration dependent manner (EC50 = 3.1 microM). Glycine (1 microM) potentiates the maximal effect of NMDA by a factor of 1.7. The effect of glycine is concentration dependent (EC50 = 380 nM) and strychnine insensitive. These data are discussed with reference to the recently reported effects of glycine on the NMDA operated cation channel and the relationship between the PCP and NMDA receptors.


Ferumoxtran-10, a superparamagnetic iron oxide as a magnetic resonance enhancement agent for imaging lymph nodes: a phase 2 dose study.
Dextran-coated ultrasmall superparamagnetic iron oxide ferumoxtran-10 (Combidex) is used in reticuloendothelial MR imaging. Our purpose was to determine the optimal dose and imaging time for lymph node evaluation. Twenty-four healthy volunteers underwent neck MR imaging before and 6, 12, 24, and 36 hours after receiving 1.1, 1.7, 2.6, or 3.4 mg Fe/kg ferumoxtran-10. Vital signs, serum and urine levels, and adverse events were monitored. Qualitative nodal architecture, size, and signal-intensity changes were assessed on T1-, T2-, and T2*-weighted (fast field-echo 25 degrees or 80 degrees flip angle [FFE-25 or FFE-80]) images. Region-of-interest intensities were measured quantitatively. Consistently strong enhancement in normal nodes was found with 24- and 36-hour T2- and T2*-weighted imaging after 2.6 and 3.4 mg Fe/kg doses. No serious adverse events occurred. With 2.6 mg Fe/kg, unblinded (vs blinded) specificities at 24 and 36 hours, respectively, were 100% and 100% (vs 88% and 88%) with T2-weighted, 96% and 96% (vs 73% and 85%) with FFE-25, and 100% and 92% (vs 85% and 88%) with FFE-80 sequences. With 3.4 mg Fe/kg, unblinded (vs blinded) specificities at 24 and 36 hours, respectively, were 89% and 79% (vs 75% and 75%) with T2-weighted, 84% and 79% (vs 95% and 100%) with FFE-25, and 95% and 79% (vs 95% and 80%) with FFE-80 sequences. Ferumoxtran-10 nodal imaging appears to be effective and safe. Signal intensity and specificity for normal nodes were best 24 or 36 hours after 2.6 and 3.4 mg Fe/kg doses. Nodal conspicuity was best with T2- and T2*-weighted sequences.


Investigating the role of the foveal cortex in peripheral object discrimination.
Peripheral object discrimination is hindered by a central dynamic mask presented between 150 and 300 ms after stimulus onset. The mask is thought to interfere with task-relevant feedback coming from higher visual areas to the foveal cortex in V1. Fan et al. (2016) supported this hypothesis by showing that the effect of mask can be further delayed if the task requires mental manipulation of the peripheral target. The main purpose of this study was to better characterize the temporal dynamics of foveal feedback. Specifically, in two experiments we have shown that (1) the effect of foveal noise mask is sufficiently robust to be replicated in an online data collection (2) in addition to a change in sensitivity the mask affects also the criterion, which becomes more conservative; (3) the expected dipper function for sensitivity approximates a quartic with a global minimum at 94 ms, while the best fit for criterion is a quintic with a global maximum at 174 ms; (4) the power spectrum analysis of perceptual oscillations in sensitivity data shows a cyclic effect of mask at 3 and 12 Hz. Overall, our results show that foveal noise affects sensitivity in a cyclic manner, with a global dip emerging earlier than previously found. The noise also affects the response bias, even though with a different temporal profile. We, therefore, suggest that foveal noise acts on two distinct feedback mechanisms, a faster perceptual feedback followed by a slower cognitive feedback.


Infections as risk factor for autoimmune diseases - A nationwide study.
Viruses, bacteria and other infectious pathogens are the major postulated environmental triggers of autoimmunity. In the present nation-wide study we describe the association between infections and 29 autoimmune diseases. We used the Danish Civil Registration System to identify 4.5 million persons born between 1945 and 2000. Information on infections and autoimmune diseases was obtained from the Danish Hospital Register. The cohort was followed from 1977 to 2012. Incidence rate ratios for developing an autoimmune disease were estimated using poisson regression. We found an association between hospital admission for an infection and 29 autoimmune diseases. This study shows that infections are risk factors for a broad spectrum of autoimmune diseases in a dose-response and temporal manner, in agreement with the hypothesis that infections are an environmental risk factor contributing to the etiology of autoimmune diseases together with genetic factors.


Reversed-phase high-performance liquid chromatography method with coulometric electrochemical and ultraviolet detection for the quantification of vitamins B(1) (thiamine), B(6) (pyridoxamine, pyridoxal and pyridoxine) and B(12) in animal and plant foods.
A rapid and sensitive high-performance liquid chromatography (HPLC) method with coulometric electrochemical and ultraviolet detections for analysis of vitamin B (B(1), B(6) and B(12)) in animal and plant foods has been developed. A combination of acid digestion and enzymatic extraction to release protein bound and phosphorylated vitamins followed by HPLC analysis was applied. The analyses were carried out on a LC18 column 5 microm (25 cm x 4.6 mm), using the mobile phase consisting of methanol-phosphate buffer (10:90) and 0.018 M trimethylamine, pH 3.55, following at 1.0 ml min(-1). The method offers excellent linearity with regression coefficient r>0.998, good repeatability and reproducibility and relatively short analysis time (17 min). The relative standard deviation (RSD) of the intermediate precision was satisfactory for all the vitamins studied and amounted to <7.3%. The repeatability of the method was <4.7%. The limits of quantification (LOQ) for pyridoxamine, pyridoxal, pyridoxine, vitamins B(1) and B(12) in seafood products were as follows: 2.1, 2.01, 0.99, 62.0 and 0.11 ng ml(-1), respectively. The mean recovery values from a food products spiked with all five vitamins ranged from 92.3 to 101.3%, with a relative standard deviation less than 3.4%. The proposed separation and detection procedures were successfully applied for the simultaneous determination of vitamins B(1), B(6) and B(12) in fruit juices and vitamins B(6) and B(12) in seafood.


Malignant Phyllodes Tumor in a Pubertal Girl: A Report of a Case.
Malignant phyllodes tumor (MPT) is a rare breast disease that is extremely rare in children. A few cases of pediatric malignant phyllodes tumors have been reported, including some with a poor prognosis. A 14-year-old girl presented with a growing lump on her right breast. On the basis of imaging tests and a core needle biopsy, MPT was diagnosed, and right mastectomy was performed. The postoperative course was uneventful. MPT is an infrequent disease in adult females and is extremely rare in pubertal females. It occasionally shows rapid growth, metastasis, and recurrence with a poor prognosis. Early surgical resection is necessary to obtain a cure. When a rapidly growing breast tumor is observed in pubertal females, MPT should be considered.


MR findings of hypoxic damage of the bilateral striate cortices: a case report.
MR imaging of a patient with cortical blindness revealed areas of abnormal signal bilaterally in the lateral putamen and the striate cortices. The coronal T2-weighted image clearly demonstrated the selective involvement of the bilateral striate cortices. The differential diagnosis and the vulnerability of the striate cortex are discussed.


Investigating energy literacy and its structural model for citizens of Mashhad.
Today, one of the most crucial environmental problems is energy consumption. Excessive energy consumption has led to environmental damage such as climate change. Energy and climate change are interrelated. Energy literacy is one of the tools to achieve energy sustainability. Energy literacy can reduce energy consumption by citizens. This research aimed to a sociological analysis of energy literacy among the citizens of Mashhad. The research method is a survey in which 384 citizens of Mashhad were selected based on a multi-stage cluster sampling method and data gathered by a questionnaire. The results showed that knowledge of energy consumption and attitude and effectiveness towards energy have a significant and direct relationship with energy consumption behavior. The attitude and effectiveness towards energy have a significant and direct relationship with the knowledge of energy consumption. Estimating the goodness of fit indices and the structural and measurement coefficients confirmed the model. Teaching proper behavioral patterns in energy consumption at the family and school can effectively improve citizens' energy literacy.


Spatial methods to analyze the relationship between Spanish soil properties and cadmium content.
In this study, concentrations of cadmium using 3778 samples encompassing the total size of Spain (about 505 km2) were investgated. Two novel spatial methods namely Moran eigenvector spatially varying coefficient (MESVC) and spatially filtered unconditional quantile regression (SF-UQR) were employed with the aim of avoiding the problem of local collinearity which is prevalent in regression models. Additionally, the spatially varying coefficients methods were applied to assess the influence of soil properties together with soil texture on the spatial variations of cadmium. It was indicated that the overall level of cadmium is low compared to the concentrations found around the world. In particular, the values of Cd varied between 0.01 and 2.00 mgkg-1, with the median of 0.23 mgkg-1. The residual standard error and adjusted R2 produced by MESVC were 0.16 and 0.69, respectively which are better than 0.21 and 0.39 yielded by the SF-UQR model. Both of these models outperformed compared to the geographically weighted regression (GWR) and the performance of MESVC was also better than the traditional method of kriging. For instance, in terms of willmott index (d) and root mean squared relative error (RMSRE), the MESVC had superior performance with values equal to 0.612 and 0.275 compared to 0.399 and 0.379 obtained for the ordinary kriging. The MESVC and GWR demonstrated that CaCO3, sand, silt and clay had a negligible influence on spatial variations of cadmium whereas, EC had the largest contribution followed by SOM and pH.


Circulating stromal cell derived factor-1alpha (SDF-1alpha) is predictive of distant metastasis in gastric carcinoma.
This study was conducted to investigate the value of the pretreatment circulating stromal cell derived factor-1alpha(SDF-1alpha) in patients with gastric carcinoma. We measured SDF-1alpha serum concentrations and evaluated the relationship between serum SDF-1alpha and serum vascular endothelial growth factor (VEGF) levels and clinical factors in 107 gastric cancer patients. Serum levels of SDF-1alpha and VEGF levels were higher in gastric cancer patients than in controls (p < 0.001). Serum SDF-1alpha levels were higher in metastatic patients than non-metastatic patients (p < 0.001). SDF-1alpha levels were correlated with the presence of distant metastases (r = 0.528; p < 0.001) and correlated with VEGF levels (r = 0.789; p < 0.001). SDF-1alpha might serve as a possible marker for predicting or monitoring distant metastasis in gastric carcinoma.


A universal method for generating knockout mice in multiple genetic backgrounds using zygote electroporation.
Genetically engineered mouse models are essential tools for understanding mammalian gene functions and disease pathogenesis. Genome editing allows the generation of these models in multiple inbred strains of mice without backcrossing. Zygote electroporation dramatically removed the barrier for introducing the CRISPR-Cas9 complex in terms of cost and labour. Here, we demonstrate that the generalised zygote electroporation method is also effective for generating knockout mice in multiple inbred strains. By combining in vitro fertilisation and electroporation, we obtained founders for knockout alleles in eight common inbred strains. Long-read sequencing analysis detected not only intended mutant alleles but also differences in read frequency of intended and unintended alleles among strains. Successful germline transmission of knockout alleles demonstrated that our approach can establish mutant mice targeting the same locus in multiple inbred strains for phenotyping analysis, contributing to reverse genetics and human disease research.


Multilayer microfluidic poly(ethylene glycol) diacrylate hydrogels.
Development of robust, in vivo like tissues in vitro holds the potential to create regenerative medicine-based therapeutics, provide more physiologically significant preclinical models and supply a pharmacological and toxicological screening platform that reflects in vivo systems in both complexity and function. This protocol describes a simple, robust, multilayer replica molding technique in which poly(dimethylsiloxane) (PDMS) and poly(ethylene glycol) diacrylate (PEGDA) are serially replica molded to develop microfluidic PEGDA hydrogel networks embedded within independently fabricated PDMS housings, using a combination of soft and photo-lithography. This work has direct applications toward the development of robust, complex, cell-laden hydrogels for in vitro diagnostics and regenerative medicine applications.


The Role of Nrf2 signaling in cancer stem cells: From stemness and self-renewal to tumorigenesis and chemoresistance.
Cancer stem cells (CSCs) are subpopulation of tumor mass with exclusive abilities in self-renewing, stemness maintaining, and differentiation into the various non-stem cancer cells to provoke tumorigenesis, metastasis dissemination, drug-resistant, and cancer recurrence. Reactive oxygen species (ROS) impair cellular function by oxidizing cell components containing proteins, lipids, and DNA. Tumor oxidant status is elevated due to high metabolic activity under influence of abnormal growth factors, cytokines and function ROS-producing enzymes, including nitric oxide synthases, cyclooxygenases, and lipoxygenases. Nuclear factor-erythroid 2-related factor 2 (NRF2) is a transcriptional master regulator element which is believed to recognize cellular oxidative stress followed by binding to promoter of cyto-protective and anti-oxidative genes to maintain cellular redox status through promoting antioxidant response participants (glutathione peroxidase, glutathione reductase, thioredoxin reductase, ferritin, NADPH: quinone oxidoreductase 1). However, Nrf2 signaling protects malignant cells from ROS damage against tumor growth and chemoresistance. In addition, Nrf2 is able to participate in differentiation of certain stem cells by modulating autophagy procedure, also NRF2 provokes DNA damage response and facilitates drug metabolism and drug resistance by controlling of downstream enzyme and transporter members. In this review, we discuss the role of NRF2 in stemness, self-renewal ability, tumorigenesis and chemoresistance of CSCs.


In vitro induction of secondary xylem-like tracheary elements in calli of hybrid poplar (Populus sieboldii × P. grandidentata).
The formation of tracheary elements was induced in calli derived from petioles of hybrid poplar (Populus sieboldii × P. grandidentata) after 10 days of culture on medium that lacked auxin but contained 1 μM brassinolide. Some differentiated cells formed broad regions of cell walls and bordered pits, which are typical features of tracheary elements of secondary xylem. Other differentiated cells resembled tracheary elements of primary xylem, with spiral or reticulate thickening of cell walls. The tracheary elements that developed in calli were formed within cell clusters. This induction system provides a new model for studies of the mechanism of differentiation of secondary xylem cells in vitro.


Simultaneous double contrast cystography and modified polycystography in the evaluation of bladder carcinoma.
Accurate knowledge about the morphology and degree of infiltration of a bladder tumor is an essential prerequisite to correctly plan, and forecast the results of, the treatment of these tumors. Among the radiological investigations double contrast cystography is superior to excretory cystogram or conventional cystogram in delineating the morphology of bladder tumors. Polycystography demonstrates, radiologically, the degree of infiltration of a bladder tumor. By simultaneously performing these procedures, the information necessary for planning the treatment is obtained in a single sitting, with one catheterization. This procedure was performed in 15 patients, in good correlation with other parameters such as cystoscopy, bimanual examination under general anesthesia and biopsy.


Nitric oxide transfer from the NO-donor S-nitroso-N-acetylpenicillamine to monomers and dimers of water-soluble iron-porphyrins.
The nitrosylation of two water-soluble iron-porphyrins, the anionic Fe(III)-meso-tetrakis(p-sulfonatophenyl)porphyrin (FeTPPS(4)) and the cationic Fe(III)-meso-tetrakis(4-N-methylpyridiniumyl)porphyrin (FeTMPyP), by the nitric oxide donor S-nitroso-N-acetylpenicillamine (SNAP) was studied using optical absorption spectroscopy. The influence of ionic and non-ionic micelles on rates of nitric oxide transfer was investigated. Initially, the effect of the micelles on the pH-dependent equilibrium between monomeric and micro-oxo-dimeric species of the iron-porphyrins was examined. It is not affected in micelle-porphyrin systems with electric charges identical in sign. The non-ionic micelles of polidocanol induce a small negative pK shift. In contrast, the dimerization equilibrium of porphyrins in oppositely charged micellar phases is displaced to lower pH by approximately 2 units. Nitric oxide binding to monomers and micro-oxo-dimers was examined at pH 5.0 and 8.0, respectively. Contrary to nitrosylation by NO gas, SNAP induces reductive nitrosylation. There was no observed NO-Fe(III)porphyrin intermediate. Nitrosylation rates were obtained and compared in aqueous buffer and in micellar systems. Monomers nitrosylate much faster than micro-oxo-dimers. Oppositely charged micelles prevent nitrosylation of the iron-porphyrins or considerably enhance nitrosylation times. Nitrosylation rates are comparable to transnitrosylation rates between several S-nitrosothiols and thiol-containing proteins, suggesting biological relevance for the process.


The role of tissue biomechanics in the implantation and performance of inflatable penile prostheses: current state of the art and future perspective.
Erectile dysfunction (ED) affects to some degree approximately 52% of the male population aged 40-70 years. Many men do not respond to, or are precluded from using, pharmaceutical treatments for ED and are therefore advised to consider penile prostheses. Different types of penile prosthesis are available, such as inflatable penile prostheses (IPPs). IPPs consist of a pair of inflatable cylinders inserted into the corpora cavernosa (CC). During inflation/deflation of these cylinders, the CC and other surrounding tissues such as the tunica albuginea (TA) are highly impacted. Therefore, it is critical to understand the mechanics of penile tissues for successful implantation of IPPs and to reduce tissue damage induced by IPPs. We explored the importance of the biomechanics of penile tissues for successful IPP function and reviewed and summarized the most significant studies on penile biomechanics that have been reported to date. We performed an extensive literature review of publications on penile biomechanics and IPP implantation. Indenters have been used to characterize the mechanical behavior of whole penile tissue; however, this technique applied only local deformation, which limited insights into individual tissue components. Although one reported study addressed the mechanical behavior of TA, this investigation did not consider anisotropy, and there is a notable absence of biomechanical studies on CC and CS. This lack of understanding of penile tissue biomechanics has resulted in computational models that use linear-elastic materials, despite soft tissues generally exhibiting hyperelastic behavior. Furthermore, available benchtop/synthetic models do not have tissue properties matched to those of the human penis, limiting the scope of these models for use as preclinical testbeds for IPP testing. Improved understanding of penile tissue biomechanics would assist the development of realistic benchtop/synthetic and computational models enabling the long-term performance of IPPs to be better assessed.


Circadian variation and seasonal distribution of implantable defibrillator detected new onset atrial fibrillation.
We aimed to characterize the hourly, daily, and seasonally variations in the detection of new atrial fibrillation (AF) in heart failure patients implanted with a defibrillator. In 1309 patients enrolled in MADIT-RIT without AF at baseline, atrial arrhythmia data were analyzed from device interrogations. The circadian, weekly, and seasonal distribution of device detected AF was evaluated. The morning period was defined as 06:00-11:59, afternoon as 12:00-16:59, evening as 17:00-22:59, and the nighttime as 23:00-05:59. During 17 months of follow-up, 66 (5%) patients developed new device-detected AF. AF patients were less likely to have ischemic cardiomyopathy and were more likely to have received an implantable cardioverter defibrillator rather than a cardiac resynchronization therapy with defibrillator. The highest number of AF occurred during the evening hours (25 patients [38%]) followed by a second peak in AF detection during the afternoon hours (21 patients [32%]). Importantly during the nighttime, new AF occurred only in three patients (4%). In comparison with the nighttime period, the odds ratio (OR) of developing AF during the evening time period was 8.5-fold higher (95% CI 7.3-9.7, P < .01). Detection of AF during the spring and winter seasons accounted for 67% of all new device-detected AF. There is diurnal and seasonal variation in new onset AF. A double peak in the incidence of AF is observed during the afternoon and evening hours, and during the spring and winter seasons. This information may be useful when deciding when to screen at-risk patients for new AF.


How safe is minimally invasive pedicle screw placement for treatment of thoracolumbar spine fractures?
Prospective analysis of patients who underwent minimally invasive posterior instrumentation. The purpose of this study was to evaluate the safety of minimally invasive pedicle screw placement in patients with unstable thoracic and lumbar spine fractures using the conventional fluoroscopy technique. Although wound infection, haematoma, and new neurological deficit due to screw malplacement remain a common source of morbidity, estimates of their rates of occurrence remain relatively limited. 2052 percutaneous pedicle screws in 433 consecutive patients were evaluated. The accuracy of pedicle screw placement was based on evaluation of axial 3-mm slice computed tomography scans. Morbidity and mortality data were collected prospectively. A total of 2029 of 2052 screws (99%) had a good or excellent position. 5 screws (0.2%) showed a higher grade violation of the medial pedicle wall. Seven patients (1.8%) needed revision due to screw malposition (3 pat.), surgical site infection, postoperative haematoma, implant failure (2 pat.), and technical difficulties. Minimally invasive transpedicular instrumentation is an accurate, reliable, and safe procedure to treat thoracic and lumbar spine fractures.


[Features of the surgical treatment of postbulbar ulcers of the duodenum].
The article describes main principles of the operative treatment of 42 patients with postbulbar ulcers. Choice of the surgical method was individualized: resection for the "exclusion" was used in 25 patients, gastric resection with the excision of the ulcer--in 11 patients, organ preserving operations--in 5 patients. The operations made for the "exclusion" gave most favourable immediate and long-term results. Technical details of the operations are described.


Secreted metalloproteases ADAMTS9 and ADAMTS20 have a non-canonical role in ciliary vesicle growth during ciliogenesis.
Although hundreds of cytosolic or transmembrane molecules form the primary cilium, few secreted molecules are known to contribute to ciliogenesis. Here, homologous secreted metalloproteases ADAMTS9 and ADAMTS20 are identified as ciliogenesis regulators that act intracellularly. Secreted and furin-processed ADAMTS9 bound heparan sulfate and was internalized by LRP1, LRP2 and clathrin-mediated endocytosis to be gathered in Rab11 vesicles with a unique periciliary localization defined by super-resolution microscopy. CRISPR-Cas9 inactivation of ADAMTS9 impaired ciliogenesis in RPE-1 cells, which was restored by catalytically active ADAMTS9 or ADAMTS20 acting in trans, but not by their proteolytically inactive mutants. Their mutagenesis in mice impaired neural and yolk sac ciliogenesis, leading to morphogenetic anomalies resulting from impaired hedgehog signaling, which is transduced by primary cilia. In addition to their cognate extracellular proteolytic activity, ADAMTS9 and ADAMTS20 thus have an additional proteolytic role intracellularly, revealing an unexpected regulatory dimension in ciliogenesis.


A seasonal variation in the onset of postoperative adhesive small bowel obstruction is related to changes in the climate.
Postoperative small bowel obstruction following abdominal procedures is more common in patients who have undergone laparotomy. However, little is known about the influence of climate on the incidence of postoperative small bowel obstruction. To evaluate whether seasonal climatic variations are a risk factor for postoperative small bowel obstruction, hospital-based, retrospective case series was designed from medical records of 230 patients suffering from postoperative small bowel obstruction admitted to the Tokyo University Branch Hospital. Detailed analysis of weather charts from the Japanese Meteorological Agency and review of medical records for selected patients who were diagnosed with postoperative small bowel obstruction. The obstruction was diagnosed by abdominal X-ray imaging, clinical examination, and patient interviews. A total of 233 patients diagnosed with postoperative small bowel obstruction were identified. Analysis of the medical records of these 233 patients revealed that the variables associated with an increased risk of postoperative small bowel obstruction included low ambient temperatures of 5-10 degrees C, an increase in air humidity by 40-50% and air pressure of 1010-1015 hPa. The typical winter weather in Tokyo is characterised by low temperatures, low humidity and moderate air pressure. These winter climate conditions could be correlated with an increased incidence of postoperative small bowel obstruction in Tokyo during our period.