In silico assessment of toxicity of heat-generated food contaminants.
Since the discovery of acrylamide in heat-treated carbohydrate-rich foods, many more heat-generated food contaminants have been identified in a variety of foods and models systems. A database of these contaminants, generated as a result of either lipid oxidation or the Maillard reaction, has recently been compiled under the HEATOX project. A large majority of the compounds has not been tested for potential adverse effects on human health, which makes it difficult to carry out adequate assessment of risks to an average consumer. This study used two in silico toxicity Expert Systems (Topkat and Derek for Windows), as a preliminary screening tool to identify potential toxicants among the heat-generated contaminants in foods or model systems. The methodology enabled prioritisation of the compounds on the basis of predicted toxicities, and identification of potential toxicants for targeted testing by standard laboratory procedures. A comparison between the predicted toxicities of selected compounds and the available experimental data indicated that the methodology can be reliably used for assessing toxicity of untested food contaminants.


Carcinoma of the dorsum of the tongue: a rarity or misdiagnosis.
Benign lesions occurring on the dorsum of the tongue have at times been diagnosed as carcinoma. A retrospective investigation into the problem is described and the clinical and histological difficulties that arise in the diagnosis of these lesions are discussed. It is concluded that the occurrence of primary carcinoma on the dorsum of the tongue is a rare entity. It may be erroneously diagnosed in cases of median rhomboid glossitis, granular cell myoblastoma and any other lesion associated with pseudoepitheliomatous hyperplasia. These conditions should always be considered when examining lesions in this location. Histological diagnosis, although difficult, is greatly facilitated by good biopsy technique but, above all, good liaison between surgeon, radiotherapist and pathologist is essential if these mistakes in diagnosis are to be avoided.


[Case of multiple systemic (extrahepatic) manifestations of chronic HCV infection (analysis of the literature and own observations). Case report].
The article presents a description of a patient with chronic HCV infection and multiple extrahepatic manifestations, which manifested in dynamics and were recorded with a different sequence during 15 years of follow-up. In the patient we observed, the most frequently recorded extrahepatic manifestations were verified: porphyria cutanea tarda, mixed cryoglobulenemia, and utoimmune thyroiditis. Chronic HCV infection is often diagnosed in the presence of psoriasis was assessed as a paraneoplastic disease.


Optimization and mechanisms of rapid adsorptive removal of chromium (VI) from wastewater using industrial waste derived nanoparticles.
Nowadays, the existence of metal ions in the environment like chromium (VI) is of significant worry because of its high toxicity to many life forms. Therefore, in this study, an inexpensive and eco-friendly nano-adsorbent was produced from the waste of drinking water industry for effective elimination of Cr (VI) from wastewater. The mineralogical and morphological characterization and compositions of the bulk and nano- adsorbents were performed. The adsorption capabilities of nWTRs for Cr(VI) under different experimental conditions of adsorbent dosage, time, Cr (VI) concentration, solution pH, and competitive ions were investigated. The nWTRs adsorbent exhibits very rapid adsorption potential (92%) for Cr (VI) within the first 15 min. Langmuir model showed high predictive capability for describing Cr (VI) sorption equilibrium data. The estimated maximum sorption capacity (qmax) of nWTRs and bWTRs was found to be 40.65 mg g-1 and 2.78 mg g-1 respectively. The sorption kinetics data of Cr (VI) were perfectly fitted to the model of second-order kinetics. High immobilization capability of nWTRs for sorbed Cr (VI) is evident as most of adsorbed Cr (VI) was associated with the residual fraction. The nWTRs efficiency of Cr (VI) removal from wastewater using batch and column techniques were 98.12 and 96.86% respectively. Electrostatic interactions, outer sphere complexation and pore filling are the main mechanisms suggested for binding of Cr(VI) with functional groups of nWTRs. This study demonstrates that the green low-cost nWTRs have the potential to decontaminate industrial wastewater effluents containing Cr (VI).


Public preferences regarding the priority setting criteria of health interventions for budget allocation: results of a survey of Iranian adults.
Priority setting in health directly impacts the general public as payers and final consumers, so the public preferences must be considered. The present study aimed to provide public preferences about health intervention allocation criteria for the optimal allocation of public health budget in Iran. A choice-based survey method was used to assess the general public's preferences regarding 8 critical criteria with a societal aspect. One thousand sixty-four adult citizens of Tehran, Iran, participated in the study. Participants were asked to allocate a hypothetical budget between the two groups with differences in allocation criteria. Public preferences were inferred from absolute majority responses i.e., more than 50% of participants' allocation for a criterion. The Logistic Regression Model was used to investigate the factors affecting the preferences regarding the importance of allocation criteria. Based on expressed participants' preferences, criteria of disease severity, age, daily care needs, Number of alternative interventions, individual's economic status, and diseases with absence from work were important. Thus, 77, 69, 61, 57, 54, and 51% of participants preferred to allocate the hypothetical budget to the treatment of patients with poor economic status, treatment of patients with diseases leading to absence from work, treating patients with severe diseases, treatment of diseases in need of daily care and treatment of children's diseases, respectively. Findings from the factors affecting participants' preferences regarding allocation criteria also showed that people with different characteristics had different preferences. Iranian general public pays special attention to the criteria of equitable allocation, including patients' economic status, criteria with societal aspects such as absenteeism from work and the need for daily care, as well as criteria with medical aspects such as disease severity and access to alternative interventions which may sometimes be less considered in decision making.


Usefulness of transesophageal echocardiography in diagnosis of hemolytic anemia post total aortic arch replacement using the elephant trunk technique.
We report a rare case of a patient with hemolytic anemia who underwent emergency total arch replacement using the elephant trunk technique for type A acute aortic dissection 3 years earlier. The 78-year-old woman was referred to our hospital for diagnosis of the cause of the hemolytic anemia, which required twice weekly blood transfusion. Although contrast-enhanced computed tomography could not provide sufficient information, transesophageal echocardiography (TEE) revealed graft flection with high velocity. After percutaneous balloon dilatation, the hemolytic anemia improved and follow-up TEE showed no re-stenosis of the dilatation site.


Efficacy and safety of Yunxiangjing derived from Chinese herbal medicine administered as an enema in the management of acute radiation-induced proctitis in patients with pelvic malignancy.
To assess the efficacy and safety of Yunxiangjing (YXJ), derived from Chinese herbal medicine, in the management of acute radiation-induced proctitis (ARIP) in patients with pelvic malignancy. Forty-eight patients with grade 2 ARIP were administered YXJ as an enema (1 : 30 dilution) for 2 weeks and followed up for 2 years. All were assessed for response and ARIP grade. Quality of life (QOL) was assessed with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30. Of the 48 patients, six (12.5%) achieved complete remission of ARIP and 28 (58.3%) showed a decrease from grade 2 to grade 1 ARIP. No patient experienced a grade ≥3 toxicity. At the end of radiotherapy, patients showed significant improvements in QOL (P < 0.05). Two years after treatment, 46 patients showed no late toxicity, with only two experiencing grade 1 late toxicity. YXJ can be used as an enema to manage acute radiation-induced proctitis in cancer patients undergoing radiotherapy. These findings suggest that YXJ enema may be an alternative treatment of ARIP.


Downregulated expression of hepatoma-derived growth factor (HDGF) reduces gallbladder cancer cell proliferation and invasion.
Hepatoma-derived growth factor (HDGF), a heparin-binding growth factor, has a wide range of biological functions, including mitogenic activity and vascular development. Recent studies demonstrated that HDGF also acted as an oncogene with aberrantly increased activity in multiple human cancers; however, little is known about the biological function of HDGF in gallbladder cancer (GBC). In this study, we focused on the clinical significance and biological functions of HDGF in GBC and found that Nuclear HDGF protein overexpression was frequently detected in GBC tissues. Patients with nuclear HDGF-positive tumors had worse overall survival than patients with HDGF-negative tumors. Furthermore, treatment of GBC lines with HDGF-targeting siRNA oligonucleotides (HDGF-siRNA) significantly reduced the proliferation of GBC-SD and SGC-996 cell lines and diminished both anchorage-independent growth on soft agar and cell migration. These data indicate that HDGF acts as a putative oncogene in GBC and could be a novel diagnostic and therapeutic target for GBC.


Relationship of early neural tube appearance to myeloschisis in a chick embryo model.
Myeloschisis, a form of neural tube defect involving the spinal cord, was induced in chicks by creating a window in the eggshell of the fertilized egg at 26 h after placement in an incubator. The embryos were stained and photographed through the window at 48 to 60 h after commencement of incubation and the neural tube was determined to be normal, delayed, irregular, or abnormally open for the developmental stage of the embryo. The eggs were then reincubated until 14 days of age. At that time the chicks were determined to have normal spinal cords or myeloschisis by gross examination, dissection, and histology. The appearance of the neural tube at 48 to 60 h was then correlated with the appearance of the spinal cord at 14 days of age. It was determined that in the chick embryo model of myeloschisis induced by windowing, a normal neural tube at the time of neural tube closure results in a 2.3% incidence of myeloschisis, a widely open neural tube a 47% incidence of myeloschisis, an irregular neural tube a 37% incidence of myeloschisis, and delayed closure of the neural tube a 14% incidence of myeloschisis. Thus, no appearance of an early neural tube can be said to always correlate with myeloschisis or a normal outcome. Additionally, it appears that within a single model there may be multiple mechanisms of production of myeloschisis.


Using Multiplex PCR for Assessing the Quality of Whole Genome Amplified DNA.
This chapter describes a simple and inexpensive multiplex PCR-based method to assess the quality of whole genome amplification (WGA) products generated from heat-induced random fragmented DNA. A set of four primer pairs is used to amplify DNA sequences of WGA products in and downstream of GAPDH gene in yielding 100, 200, 300, and 400 bp fragments. PCR products are analyzed by agarose gel electrophoresis and the respective WGA quality is classified according to the number of obtained PCR bands. WGA products that yield three or four PCR bands are considered to be of high quality and yield good results when analyzed by means of array comparative genome hybridization (CGH).


The cyclooxygenase-2-selective inhibitors rofecoxib and celecoxib prevent colorectal neoplasia occurrence and recurrence.
Colorectal cancer is one of the leading causes of cancer death. Most colorectal cancers are believed to develop from colorectal adenomas. We examined the effect of the selective cyclooxygenase-2 inhibitors rofecoxib and celecoxib, nonselective nonsteroidal anti-inflammatory drugs, aspirin, and acetaminophen on colorectal neoplasia (colorectal cancer, colorectal adenoma, or both). This was a nested case-control study, which used data from a government insurance database on patients 65 years and older who underwent a diagnostic test or procedure for colorectal neoplasia between January and June 2001. Logistic regression models were used to determine the effect of exposure to the drugs of interest for at least 3 months on the occurrence or recurrence of colorectal neoplasia. The control group included 2568 patients found to be free of colorectal neoplasia; 730 patients were diagnosed with colorectal adenoma, and 179 were diagnosed with colorectal cancer. Patients more likely to have colorectal adenoma (odds ratio, 95% confidence interval) were those diagnosed with colorectal adenoma (4.12, 3.27-5.18) or colorectal cancer (3.74, 2.32-6.03) in the previous 1-3 years and those with hemorrhage of the rectum or unspecified anemia in the prior month (3.19, 2.46-4.12). Exposures to rofecoxib (0.67, 0.46-0.98) and nonselective nonsteroidal anti-inflammatory drugs (0.41, 0.21-0.83) reduced the risk of colorectal adenoma. Rofecoxib, celecoxib, and nonselective nonsteroidal anti-inflammatory drugs were all protective against both neoplasias (0.64, 0.45-0.91; 0.73, 0.54-0.99; and 0.47, 0.26-0.86, respectively). Rofecoxib, celecoxib, and nonselective nonsteroidal anti-inflammatory drugs seem to protect against the development of colorectal neoplasia.


Identification of VRK1 as a New Neuroblastoma Tumor Progression Marker Regulating Cell Proliferation.
Neuroblastoma (NB) is one of the most common pediatric cancers and presents a poor survival rate in affected children. Current pretreatment risk assessment relies on a few known molecular parameters, like the amplification of the oncogene MYCN. However, a better molecular knowledge about the aggressive progression of the disease is needed to provide new therapeutical targets and prognostic markers and to improve patients' outcomes. The human protein kinase VRK1 phosphorylates various signaling molecules and transcription factors to regulate cell cycle progression and other processes in physiological and pathological situations. Using neuroblastoma tumor expression data, tissue microarrays from fresh human samples and patient-derived xenografts (PDXs), we have determined that VRK1 kinase expression stratifies patients according to tumor aggressiveness and survival, allowing the identification of patients with worse outcome among intermediate risk. VRK1 associates with cell cycle signaling pathways in NB and its downregulation abrogates cell proliferation in vitro and in vivo. Through the analysis of ChIP-seq and methylation data from NB tumors, we show that VRK1 is a MYCN gene target, however VRK1 correlates with NB aggressiveness independently of MYCN gene amplification, synergizing with the oncogene to drive NB progression. Our study also suggests that VRK1 inhibition may constitute a novel cell-cycle-targeted strategy for anticancer therapy in neuroblastoma.


Safety of intravenous terbutaline in acute severe asthma: a retrospective study.
(1) To determine the effect of intravenous terbutaline in children with acute severe asthma on parameters like heart rate, blood pressure, electrocardiogram and serum electrolytes; (2) to assess the safety profile and to evaluate the outcome of children treated with intravenous terbutaline for acute severe asthma. Retrospective study of admission records of children admitted with acute severe asthma who needed intravenous terbutaline. Children's Hospital at the Leicester Royal Infirmary, UK. 77 children with acute severe asthma admitted between April 1999 and October 2002. There was a significant increase in heart rate and significant fall in diastolic blood pressure in this cohort. Four patients required inotropic support. None of the patients had cardiac arrhythmias. Potassium supplements were required in 10 patients due to hypokalaemia. All patients improved and none required initiation of ventilation after commencing terbutaline. There was no mortality in this cohort. Terbutaline was found to be safe for use in this patient group in doses ranging between 1 and 5 microg/kg/min. Intravenous terbutaline was found to be a useful adjunct in those who failed to respond to standard initial therapy.


Radial basis collocation method with parameters optimized for estimating pollutant release history.
The identification of pollutant source release history in rivers is important for emergency response of pollution accidents and formulating remediation strategies. Space-time radial basis collocation method (RBCM), as a meshless method with strong applicability, can directly estimate the release history from the concentration data measured at downstream observation sites. However, the uncertainty of specific parameters in space-time RBCM is the main factor affecting the accuracy of estimation. Therefore, a way to solve the parameters efficiently and accurately is essential. For this purpose, a new model which combines space-time RBCM and differential evolution algorithm (DEA) is established to identify the source release history. First of all, efficient parameter optimizer DEA is introduced to search the parameters that affect the estimation accuracy of space-time RBCM. Then, a new loss function considering the imbalance configuration of RBCM nodes is designed to ensure the rationality of the parameters obtained by DEA. The results of numerical cases and real field case show that the proposed method can accurately estimate the real release history with low time consumption. It is also demonstrated that DEA is more efficient than k-fold cross-validation in searching the optimal parameters for space-time RBCM, and the parameters obtained from the new loss function can make the estimated release history more precise.


Pathways to cognitive deficits in Down syndrome.
Major efforts in Down syndrome (DS) research have been directed at the identification and functional characterization of genes encoded by human chromosome 21 (HSA21). In parallel with this, tissue samples and cell lines derived from individuals with DS have been examined for abnormalities in gene expression and cellular morphology, and mouse models of DS have been characterized for abnormalities at the molecular, cellular, electrophysiological, and behavioral level. One goal of such investigations has been the identification of effective targets for pharmacotherapies that can prevent or correct the abnormalities and, by extension to human clinical trials, prevent or lessen aspects of the cognitive deficits seen in people with DS. Because it is caused by an extra copy of an entire chromosome, DS has been considered by some as too complicated a genetic perturbation to be amenable to postnatal pharmacological interventions. However, recent data from experiments with one mouse model, the Ts65Dn, have clearly demonstrated that several pharmacological interventions can indeed rescue DS-relevant learning and memory deficits. Extension of mouse data to successful human clinical trials will be aided by understanding the molecular basis of successful drug treatments, that is, how increased expression of HSA21 genes perturbs molecular mechanisms that are targeted and rescued by specific drugs. Here, we review information on HSA21 genes, their expression and their likely contributions to the DS phenotype. We then describe results of a bioinformatics effort that integrates information on genes known to cause intellectual disability when mutated, the pathways in which these genes function, and how these pathways are impacted by HSA21 encoded proteins. This pathway approach to the molecular basis of ID in DS aids in understanding why some drug therapies have been successful in the Ts65Dn and in predicting whether these same drugs are likely to be successful in treating ID in DS. These data can be used to design new experiments and interpret information for prediction of additional targets for effective drug treatments.


What is the Risk of Having Offspring with Cleft Lip/Palate in Pre-Maternal Obese/Overweight Women When Compared to Pre-Maternal Normal Weight Women? A Systematic Review and Meta-Analysis.
The purpose of the study was to identify the risk of orofacial cleft in the offspring of women with pre-maternal obesity/overweight when compared with pre-maternal normal weight women. MEDLINE and EMBASE were searched from 1980 to July 2014 for cohort, case control and cross sectional studies. BMI were categorized according to WHO recommendation: normal weight (BMI 18.5 - 24.9), overweight (BMI 25 - 29.9) and obese (BMI ≥ 30). Six studies were identified; three case control studies which were used for the meta-analysis and two cross sectional studies and one cohort study. Compared with women of recommended BMI, obese women were at increased odds of pregnancy affected by CLP (OR = 1.16; 95% CI 1, 1.34) and CP (OR = 1.14; 95% CI 0.95, 1.37). Overweight women were also at increased odds of pregnancy affected by CLP (OR = 1.06; 95% CI 0.93, 1.21) but not CP (OR = 0.89; 95% CI 0.75, 1.06). The results of the risk ratios reported in the cross sectional and cohort studies were similar to the results of the meta-analysis. The results of this study reveal that there is an increased risk of having offspring with orofacial cleft in obese/overweight women. The reason for this association is not known. Although, the risk is small, it is important because of the increasing incidence of obesity.


Continuation-like semantics for modeling structural process anomalies.
Biomedical ontologies usually encode knowledge that applies always or at least most of the time, that is in normal circumstances. But for some applications like phenotype ontologies it is becoming increasingly important to represent information about aberrations from a norm. These aberrations may be modifications of physiological structures, but also modifications of biological processes. To facilitate precise definitions of process-related phenotypes, such as delayed eruption of the primary teeth or disrupted ocular pursuit movements, I introduce a modeling approach that draws inspiration from the use of continuations in the analysis of programming languages and apply a similar idea to ontological modeling. This approach characterises processes by describing their outcome up to a certain point and the way they will continue in the canonical case. Definitions of process types are then given in terms of their continuations and anomalous phenotypes are defined by their differences to the canonical definitions. The resulting model is capable of accurately representing structural process anomalies. It allows distinguishing between different anomaly kinds (delays, interruptions), gives identity criteria for interrupted processes, and explains why normal and anomalous process instances can be subsumed under a common type, thus establishing the connection between canonical and anomalous process-related phenotypes. This paper shows how to to give semantically rich definitions of process-related phenotypes. These allow to expand the application areas of phenotype ontologies beyond literature annotation and establishment of genotype-phenotype associations to the detection of anomalies in suitably encoded datasets.


Surgical nuances of giant neurocysticercosis according to intracranial location in the Southwest region of the Dominican Republic, presentation of cases, and literature review.
Neurocysticercosis (NCC) is the most common infestation of the central nervous system, caused by the larval stage of the pig tapeworm Taenia solium. It is prevalent in regions with poor sanitation and underdevelopment, such as Latin America. We present four cases in which they harbored an intraventricular/intraparenchymal, frontal convexity, cerebellomedullary, and intraparenchymal NCC cyst of medium size, respectively. Three of them underwent complete removal of the cyst by craniotomy; the fourth had a shunt for obstructive hydrocephalus first, followed by excision of a suboccipital cyst 8 months later. The intraventricular/intraparenchymal lesion was more complex to treat than its subarachnoid counterparts because the average brain should be transected and dissected away to achieve total removal. Waterjet dissection, arachnoid microdissection, and cyst drainage allowed minor brain damage than capsule coagulation and traction. Populated prospective studies are needed better to understand the surgical nuances of these rare entities.


Mobilizable intracellular pool of p55 (type I) tumor necrosis factor receptors in human neutrophils.
The distribution of type I (p55) and type II (p75) tumor necrosis factor receptors (TNF-Rs) in human polymorphonuclear neutrophils (PMNs) was analyzed by Western blotting of subcellular fractions obtained by centrifugation of PMN cavitates on Percoll density gradients. In resting PMNs, the p55 receptor was associated with both gamma and beta fractions, enriched in plasma membranes and specific granules, respectively, whereas the p75 TNF-R was located only in the gamma fraction. Intracellular p55 TNF-R bound 125I-labeled TNF in a ligand blot assay and migrated as a diffuse band of 46-60 kd, similar to the plasma membrane receptor. Activation of PMNs with the chemoattractant N-formyl-methionyl-leucyl-phenylalanine (fMLP), in conditions that induced the selective release of the tertiary granule marker gelatinase, caused the shedding of most of membrane p55 TNF-R as a 28-kd soluble form but had little effect on the distribution of the receptors in beta fractions. By contrast, when specific granule secretion was induced in the presence of cytochalasin B, a marked decrease in reactivity of beta fractions with anti-p55 TNF-R antibody was observed. At the same time, the amount of soluble 28-kd fragment found in the supernatant was increased. Thus, the intracellular pool of p55 TNF-R is associated with functional secretory granules and is redistributed in response to PMN activation.


Z-code documentation to identify social determinants of health among Medicaid beneficiaries.
Social determinants of health (SDoH) are non-medical factors that impact individuals' health. SDoH can be documented in claims data using International Classification of Disease (ICD) 10th revision codes Z55 - Z65. The study objective was to describe the documentation of SDoH Z-codes among Medicaid beneficiaries in Texas. Texas Medicaid medical and enrollment claims data were utilized. Beneficiaries with at least one claim associated with SDoH Z-codes between 2016 and 2019 were identified excluding those 65+ years of age and others dually eligible for Medicare. SDoH Z-code documentation was associated with approximately 1.2 million claims for 181,136 unique beneficiaries. Females (54.3%) and Hispanics (47.9%) comprised a majority of beneficiaries with Z-code documentation, and the average age was 14.2 ± 13.4 years. Nearly 40% had Z-code documentation of "problems related to upbringing" (Z62) (N = 68,478, 37.8%), followed by "problems related to primary support group including family circumstances" (Z63) (N = 42,378, 23.4%), and "problems related to education and literacy" (Z55) (N = 28,848, 15.9%). SDoH Z-code documentation increased slightly over the years from 1% of Medicaid beneficiaries in 2016 to 1.3% in 2019. A steady increase in SDoH Z-code documentation was observed among Medicaid beneficiaries but represented a relatively small proportion of the beneficiaries overall.


Surgical treatment of a patient with a giant choroidal fissure cyst: a case report.
Choroidal fissure cysts (CFC) are usually an incidental finding on imaging and lead to morbidity only in rare cases. The aim of this study was to present the case of a patient with a giant CFC and its treatment. The patient was a male infant of 9 days of life that presented with symptoms of intracranial hypertension. A CFC measuring 56 × 70 × 86 mm was diagnosed. Endoscopic fenestration of the cyst was performed; however, the communication closed thereafter. A reservoir catheter was inserted, which subsequently became infected and was then replaced by a ventriculoperitoneal shunt. The choroidal fissure is a C-shaped cleft located between the fornix and the thalamus separated from the temporal horn by the layer of tela choroidea. The pathophysiology of CFC is still unclear. In our case, initial endoscopic treatment was decided on to avoid shunt-related complications. Currently, there are no guidelines for the best surgical treatment for CFC. We describe an atypical case of CFC and analyze the surgical treatment performed. Although endoscopic treatment is recommended for CFC, currently no guidelines exist regarding the best management of the entity.


Home Discharge Has Increased After Total Hip Arthroplasty, However Rates Vary Between Large Databases.
There have been significant advancements in perioperative total hip arthroplasty (THA) care and it is essential to quantify efforts made to better optimize patients and improve outcomes. The purpose of this study is to assess trends in discharge destination, length of stay (LOS), reoperations, and readmissions following THA. Patients undergoing primary THA were identified using International Statistical Classification of Diseases and Current Procedural Terminology codes in the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) and Humana claims databases. Discharge destinations were assessed and categorized as home or not home. Trends in discharge destination, LOS, readmissions, reoperation, and comorbidity burden were assessed. In ACS NSQIP, 155,637 patients underwent THA and the percentage of patients discharging home increased from 72.2% in 2011 to 87.0% in 2017 (P < .0001). In Humana, 84,832 THA patients were identified, with an increase in home discharge from 56.6% to 72.8% (P < .0001). LOS decreased and proportion of patients with an American Society of Anesthesiologists score ≥3 or Charlson Comorbidity Index ≥2 increased significantly for both home and nonhome going patients. Patients discharged home had a decrease in readmissions in both databases. Patients undergoing THA more often discharged home and had shorter hospital LOS with lower readmission rates, despite an increasingly comorbid patient population. It is likely these changes in disposition and LOS have resulted in significant cost savings for both payers and hospitals. The efforts necessary to maintain improvements should be considered when changes to reimbursement are being evaluated. ACS NSQIP hospitals had a larger proportion of patients discharged home and the source of data used to benchmark hospitals should be considered as findings may differ.


Quality Control of Chemogenomic Library Using LC-MS.
In chemical biology, using compounds with incorrect identity or insufficient purity can lead to misleading biological activity data. Chemical quality control for confirmation of purity and compound identity is thus central to chemogenomics. We have established a medium-throughput LC-MS-based semi-automated quality control (QC) workflow with a minimal requirement for materials suitable for chemogenomics and other small molecule libraries. This rapid method can cover a broad chemical space of small organic compounds with diverse physicochemical properties such as polarity or lipophilicity.


Odontoma-like tumours of squirrel elodont incisors--elodontomas.
Since 2003, nine squirrels were presented at a South African veterinary dental practice with lesions in the maxilla consistent with the clinical, radiological and histological features of odontomas as described in prairie dogs, rats and mice. These odontoma-like masses have not previously been described in squirrels. This report describes the clinico-pathological features and possible pathogenesis of the lesions and proposes the term "elodontoma" for these hamartomatous odontogenic lesions in the jaws of animals with continuously erupting (elodont) teeth.


Rethinking Catatonia: New Insights from the Autism Spectrum.
Initially conceptualized as a subtype of schizophrenia, catatonia has progressively been recognized to occur in a wide variety of conditions as a kind of final common pathway for many severe mental disorders. There is a significant overlap between the fundamental symptoms of autism spectrum disorder (ASD) and catatonia, and ASD can frequently complicate catatonic states. While provocative, the hypothesis that neuroatypicality may represent the submerged structural piece underlying catatonic states is intriguing. Yet, the multifaced relationship between catatonia and ASD may provide new insights into the etiology and treatment of both disorders.


A simplified plan for follow-up of patients with colon and rectal cancer supported by prospective studies of laboratory and radiologic test results.
Reports of prolonged survival in patients with recurrent colon or rectal cancer following a reoperative surgery suggest that early diagnosis of locally persistent or limited metastatic disease may save some patients. To determine which laboratory and radiologic tests were useful, a prospective comparison of all currently available modalities was begun in 1978. Sixty-six patients at high risk for recurrent large-bowel cancer were studied. At present, mean follow-up is at 4 1/2 years. Protocol studies included monthly carcinoembryonic antigen (CEA) assays for 3 years and then at 3-month intervals for 2 more years. A review of symptoms and a physical examination were performed every 4 months for 3 years and then every 6 months for 2 more years. Computerized tomograms of the abdomen, full lung tomograms, and liver/spleen scintigrams were obtained every 4 months for 3 years and then annually for 2 more years. Intravenous pyelography, barium enema, and bone scintigraphy were performed yearly for 5 years. Thirty-three recurrences were observed in 31 patients. A progressive rise in serial CEA values was the first indication of recurrence in 22 of 33 patients (67%), review of symptoms and physical examination in seven of 33 (21%), CT scan in two of 33, and bone scintigraphy and full lung tomography each in one of 33 patients. Serial CEA assays and routine visits to a physician's office were the most useful tests in this study population. Use of a simplified follow-up plan will result in the earliest detection of recurrent colon cancer.


Ixeris dentata and Lactobacillus gasseri media protect against periodontitis through Nrf2-HO-1 signalling pathway.
Periodontitis is an infectious inflammation in the gums characterized by loss of periodontal ligaments and alveolar bone. Its persistent inflammation could result in tooth loss and other health issues. Ixeris dentata (IXD) and Lactobacillus gasseri media (LGM) demonstrated strong antioxidant activity, which may prevent oxidative and inflammatory periodontitis. Here, IXD and LGM extracts were investigated for antioxidative activity against oral discomfort and evaluated for their synergistic effect against oxidative and inflammatory periodontitis in a mouse model. IXD/LGM suppressed pro-inflammatory cytokines like interleukin (IL)-1β, IL-6, and TNF-α. Additionally, it reduced pro-inflammatory mediators, nitric oxide, iNOS (inducible nitric oxide synthase), and COX-2 (cyclooxygenase-2) and enhanced AKT, Nrf2, and HO-1 activation. Similarly, IXD/LGM treatment elevated osteogenic proteins and mRNAs; alkaline phosphatase, collagen type 1 (COL1), osteopontin (OPN), and runt-related transcription factor 2 (RUNX2). Hematoxylin and Eosin (H&E) staining and micro-CT analysis confirm the positive impact of IXD/LGM on the periodontal structure and its associated inflammation. These findings demonstrate that IXD/LGM inhibits oxidative stress, periodontal inflammation, and its resultant alveolar bone loss in which Akt (also known as protein kinase B)-nuclear factor-erythroid 2-related factor 2 (Nrf2)-hemoxygenase-1 (HO-1) signaling is involved. Thus, IXD/LGM is a potential candidate against oxidative/inflammatory stress-associated periodontitis.


Molecular response to phototoxic stress of UVB-irradiated ketoprofen through arresting cell cycle in G2/M phase and inducing apoptosis.
The phototoxicity of ketoprofen (KP), a non-steroidal anti-inflammatory drug, has recently attracted considerable attention, because it is photolabile and undergoes degradation when irradiated by sunlight to induce various skin diseases. The present study shows that combination of UVB irradiation with KP induced the cytotoxicity and suppressed DNA synthesis in HaCaT cells in a concentration-dependent manner. UVB-irradiated KP inhibited the cell growth and induced G2/M cell cycle arrest by modulating the levels of cdc2, cyclin B1, Chk1, Tyr15-phosphorylated cdc2 and p21. It also provoked a striking accumulation of cyclin B1-cdc2-p21 complexes, concomitantly with an increase in the levels of Tyr15-phosphorylated cdc2 and p21 protein. The presence of KP accentuated the apoptotic response to UVB radiation in HaCaT cells as evidenced by DAPI staining. The apoptotic process was associated with activation of caspase-9, caspase-3 and cleavage of PARP, and this activation could be prevented by a specific caspase-3 inhibitor. Taken together, our results suggest that KP-photoinduced apoptosis may be a useful approach to reduce or prevent skin carcinogenesis.


Rapid fluorimetric determination of 5-fluorocytosine in serum.
A rapid fluorimetric procedure for the determination of the fungicide 5-fluorocytosine in serum is described. The method is high in precision (S.D. 1.6 mug/ml at 50 mug/ml) and specificity and can be performed in 60-90 minutes. The results obtained for samples from six patients showed excellent agreement with those obtained by traditional microbiological methods.


An essential role for c-FLIP in the efficient development of mature T lymphocytes.
Apoptosis-related genes play important roles in thymocyte maturation. We show that cellular FLICE-like inhibitory protein (c-FLIP), a procaspase-8-like apoptotic regulator, plays an essential role in the efficient development of mature T lymphocytes. Mice conditionally lacking c-FLIP in T lymphocytes display severe defects in the development of mature T cells, as indicated by a dramatically reduced number of CD4+ and CD8+ T cells in the spleen and lymph nodes of mutant mice. The impaired T lymphocyte maturation in c-FLIP conditional knockout mice occurs at the single-positive thymocyte stage and may be caused by enhanced apoptosis in vivo. Moreover, although c-FLIP has been implicated in T cell receptor signaling through nuclear factor (NF)-kappaB and Erk pathways, activation of NF-kappaB and Erk in c-FLIP-deficient thymocytes appears largely intact. Collectively, our data suggest that the primary role of c-FLIP in thymocyte maturation is to protect cells from apoptosis.


The effects of diabetes, hypertension, asthma, heart disease, and stroke on quality-adjusted life expectancy.
Quality-adjusted life expectancy (QALE) is a summary measure that combines mortality and health-related quality of life across different stages of life. The objective of this study was to estimate QALE loss due to five chronic diseases-diabetes mellitus, hypertension, asthma, heart disease, and stroke. Health-related quality of life scores were from the 1993-2009 Behavioral Risk Factor Surveillance System. Using age-specific deaths from the Compressed Mortality File, this study constructed life tables to calculate losses in life expectancy and QALE due to each of the five diseases from 1993 through 2009 and for 50 US states and the District of Columbia. In 2009, the individual-level QALE loss for diabetic people, compared with nondiabetic people, was 11.1 years; for those with hypertension, 6.3 years; for those with asthma, 7.0 years; for those with heart disease, 10.3 years; and for those with stroke, 12.4 years. At the population level, diabetes, hypertension, asthma, heart disease, and stroke contributed 1.9, 2.2, 0.8, 1.2, and 0.8 years of population QALE loss at age 18 years, respectively. Persons with each of the five diseases had significantly lower life expectancy and QALE. Because the prevalence of diabetes and hypertension has increased significantly in the United States in the last two decades, the burdens of these two conditions, measured by population QALE losses, had increased 83% and 29% from 1993 to 2009, respectively. Also, by examining changes in population QALE loss at different ages, policymakers can identify age groups most affected by particular diseases and develop the most cost-effective interventions by focusing on these groups.


Conventional videodefecography: Pathologic findings according to gender and age.
To review the most common disorders depicted with conventional videodefecography, and to compare the defecographic abnormalities between symptomatic patients according to their gender and age. Conventional videodefecography studies of 300 patients (24 men, 266 women; mean age - 57.7) performed in a 32-month period were reviewed for the following parameters: anorectal angle, movement of the pelvic floor, intussusceptions, incontinence and rectocele. The results were analyzed using the chi-square test. Normal findings were observed in 16.7% men and 7.5% women. In women, the most frequent pathological findings were rectocele (62%), descending perineum syndrome (42.8%), intussusceptions (33.8%), incontinence (10.5%), dyskinetic puborectalis syndrome (9.4%) and rectal prolapse (4.5%); in men the most frequent pathology was the dyskinetic puborectalis syndrome (37.5%). This syndrome is more likely in men than in women (p = 0.01; OR 5.78); descending perineum syndrome (p = 0.027; OR 2.8) is more likely to occur in women. Women with perineal descent younger than 50 years frequently present an increased descent during evacuation (81.8%), while those older than 50 years already have a low pelvic floor during rest (60.3%) (p < 0.001; OR 6.8), with little change in evacuation. Videodefecographic findings vary with age and gender.


The effect of experimental haemorrhagic shock on the bacterial content of thoracic duct lymph.
The effect of haemorrhagic shock on the simultaneous appearance of enteric micro-organisms in the central lymph and the portal blood was studied in 30 dogs. Irreversible haemorrhagic shock results in portal bacteraemia but the lymph remains sterile. Thoracic duct drainage is harmful and hastens the onset of irreversibility.


Computed tomography calcium score scan for attenuation correction of N-13 ammonia cardiac positron emission tomography: effect of respiratory phase and registration method.
The use of coronary calcium scoring (CaScCT) for attenuation correction (AC) of (13)N-ammonia PET/CT studies (NH3) is still being debated. We compare standard ACCT to CaScCT using various respiratory phases and co-registration methods for AC. Forty-one patients underwent a stress/rest NH3. Standard ACCT scans and CaScCT acquired during inspiration (CaScCTinsp, 26 patients) or expiration (CaScCTexp, 15 patients) were used to correct PET data for photon attenuation. Resulting images were compared using Pearson's correlation and Bland-Altman (BA) limits of agreement (LA) on segmental relative and absolute coronary blood flow (CBF) using both manual and automatic co-registration methods (rigid-body and deformable). For relative perfusion, CaScCTexp correlates better than CaScCTinsp with ACCT when using manual co-registration (r = 0.870; P < 0.001 and r = 0.732; P < 0.001, respectively). Automatic co-registration provides the best correlation between CaScCTexp and ACCT for relative perfusion (r = 0.956; P < 0.001). Both CaScCTinsp and CaScCTexp yielded excellent correlations with ACCT for CBF when using manual co-registration (r = 0.918; P < 0.001; BA mean bias 0.05 ml/min/g; LA: -0.42 to +0.3 ml/min/g and r = 0.97; P < 0.001; BA mean bias 0.1 ml/min/g; LA: -0.65 to +0.5 ml/min/g, respectively). The use of CaScCTexp and deformable co-registration is best suited for AC to quantify relative perfusion and CBF enabling substantial radiation dose reduction.


An overview of paper and paper based food packaging materials: health safety and environmental concerns.
Pulp and paper industry is one of the major sector in every country of the globe contributing not only to Gross Domestic Product but surprisingly to environmental pollution and health hazards also. Paper and paperboard based material is the one of the earliest and largest used packaging form for food products like milk and milk based products, beverages, dry powders, confectionary, bakery products etc. owing to its eco-friendly hallmark. Various toxic chemicals like printing inks, phthalates, surfactants, bleaching agents, hydrocarbons etc. are incorporated in the paper during its development process which leaches into the food chain during paper production, food consumption and recycling through water discharges. Recycling is considered the best option for replenishing the loss to environment but paper can be recycled maximum six to seven times and paper industry waste is very diverse in nature and composition. Various paper disposal methods like incineration, landfilling, pyrolysis and composting are available but their process optimization becomes a barrier. This review article aims at discussing in detail the use of paper and paper based packaging materials for food applications and painting a wide picture of various health and environmental issues related to the usage of paper and paper based packaging material in food industry. A brief comparison of the environmental aspects of paper production, recycling and its disposal options (incineration and land filling) had also been discussed.


"Grabbing" Autonomy When the Learning Environment Doesn't Support it: An Evidence-based Guide for Medical Learners.
According to self-determination theory (SDT), environments which support the basic psychological needs for autonomy, competence, and relatedness will facilitate autonomous motivation, learning, and wellness. On the other hand, environments which introduce external controls and power dynamics into the equation will do the opposite. Educational studies support these principles, yet most have focused on learners' need satisfaction as a passive process (e.g., via support or hindrance by educators), rather than the agentic pursuit that SDT emphasizes. In this commentary, I draw on my experience as a practicing physician and SDT researcher, and focus on how medical learners can "grab" more autonomy when the learning environment does not support it. I present a hypothetical case of a preceptor whose teaching style is controlling and unfortunately well-known to medical learners. I then unpack the case and outline different strategies that medical learners can use to navigate this type of interpersonal conflict.


The impact of intra-articular methylprednisolone acetate injection on fructosamine levels in diabetic patients with osteoarthritis of the knee, a case-control study.
Fructosamine is a glycated protein that reflects blood glucose control over the last 2-3 weeks. There are no studies that address the impact of intra-articular injection (IAI) of methylprednisolone acetate (MPA) on fructosamine levels among patients with type-2 diabetes and osteoarthritis of the knee (OAK). Non-selected patients attending the rheumatology or orthopedic clinic with type-2 diabetes and painful OAK, who failed non-steroidal anti-inflammatory drugs (NSAIDS) and physical therapy, were asked to participate in our study. After consent blood tests were drown for fructosamine, hemoglobin A1c (HbA1c) level, complete blood count, lipid profile, serum albumin, serum protein, c-reactive protein, and erythrocyte sedimentation rate. Demographic and different clinical parameters were also documented. Immediately after that, patients had IAI of 80 mg of MPA at the knee joint (group 1). Two to three weeks later, the same blood tests were repeated (except for HbA1c). Age- and sex-matched group of patients with type-2 diabetes and painful OAK attending the same clinics, but who were managed by NSAIDS were asked to participate as a control group (group 2) and had the same evaluation at enrollment and 2-3 weeks later, after consent. Eighteen patients from either group completed the study. Mean fructosamine level in group 1 patients was 263.7 ± 31.8 mg% prior to the IAI vs. 274.6 ± 39.3 mg% (p = 0.035), 2-3 weeks later, while mean fructosamine level in the control group (group 2) at enrollments was 274.2 ± 31.2 mg% vs. 269 ± 30.2 mg%, p = 0.509, 2-3 weeks later. There was no significant change in any other parameter tested at enrollment in either group, compared to those obtained 2-3 weeks afterwards. Body mass index was on the edge of significance as a predictor for a significant change in fructosamine level in group 1 patients. IAI of 80 mg of MPA in patients with type-2 diabetes and OAK had resulted in a significant, though mild increase in fructosamine levels 2-3 weeks later.


[¹²⁵I]YP20: a novel radioligand specific for the extracellular domain of the CRF₁ receptor.
The peptide corticotropin-releasing factor (CRF) binds to the CRF₁ receptor via a two-domain mechanism such that the extracellular domain (ECD) of the receptor captures the CRF's C-terminus to facilitate the binding of CRF's N-terminus to the juxta-membrane or "J"-site. Known small molecule antagonists bind to the J-site while known CRF₁ receptor peptide radioligands bind to both sites. We report here the in vitro binding properties of the first radioligand that binds exclusively to the ECD of the CRF₁ receptor. This ligand, which we named [¹²⁵I]Yamada peptide 20 ([¹²⁵I]YP20), is a radiolabeled analog of a synthetic peptide first reported by Yamada et al. (2004). We confirmed its high affinity for the [¹²⁵I]CRF binding site on the hCRF₁ receptor and also found it to potently antagonize CRF-stimulated cAMP production in hCRF₁-CHO cells. Under optimized conditions, 20 pM [¹²⁵I]YP20 reproducibly bound to hCRF₁-CHO membranes with a pharmacology consistent with binding specific to the ECD of the CRF₁ receptor. Saturation binding studies revealed the presence of a high affinity site with an estimated K(d) of ≈0.9 nM. The kinetic association of 20 pM [¹²⁵I]YP20 binding best fit to a rapid component (t(1/2)=0.69 min) and a sluggish component (t(1/2)=42 min). [¹²⁵I]YP20's specific binding was rapidly reversible with dissociation kinetics also best described by two phases (t(1/2)=0.92 min and t(1/2)=11.7 min). While [¹²⁵I]YP20's binding kinetics are complex, its high affinity and pharmacological specificity indicate that it is an excellent radioligand for probing the ECD site of the CRF₁ receptor.


Adverse events during and after per-oral endoscopic myotomy: prevention, diagnosis, and management.
Per-oral endoscopic myotomy (POEM) has surfaced as an effective endoscopic treatment modality for achalasia cardia (AC). Promising results in short- and mid-term follow-up studies have increased the use of POEM for the management of AC. POEM can be safely performed in an endoscopy suit, and major adverse events (AEs) are uncommon. AEs encountered during POEM or during the perioperative period principally include insufflation-related AEs, mucosal injuries, bleeding, pain, and aspiration pneumonia. Most insufflation-related AEs do not require an active intervention and therefore should not be considered as AEs in the true sense. When management of AEs is required, most intraoperative AEs can be managed at the same time without untoward consequences. Occurrences of AEs lessen after completion of the learning curve. However, experience alone does not ensure "zero" incidence of AEs, and early recognition remains essential. Postoperative AEs, like leaks, delayed bleeding, and delayed mucosal perforations, may pose special challenges for diagnosis and management. There is no standardized classification system for grading the severity of AEs associated with POEM, resulting in wide variation in their reported occurrences. Uniform reporting of AEs is not only crucial to comprehensively analyze the safety of POEM but also for comparison with other established treatment modalities like Heller's myotomy. GERD is an important long-term AE after POEM. Unlike the perioperative AEs, little is known regarding the intraoperative or patient-related factors that influence the occurrence of post-POEM GERD. Large prospective studies with long-term follow-up are required to determine the procedural factors associated with GERD after POEM.


Ectopic opening of the vas deferens into a Müllerian duct cyst.
Two consecutive cases of ectopic opening of the vas deferens into Müllerian duct cysts are presented, with descriptions of the presentation, physical examination, radiographic and ultrasonographic images, surgical findings and treatment undertaken. In both cases, ablation of the cyst and ligature of the vas deferens was the technique employed. Both patients are currently well, with normal urinary flow and no urinary tract infections, 3 years after surgery. Ectopic opening of the vas deferens into Müllerian duct cysts is a rare entity but should always be considered when a child presents with purulent urinary discharge and abdominal tumor. Surgery is the only treatment recommended.


A neoceratopsian dinosaur from the early Cretaceous of Mongolia and the early evolution of ceratopsia.
Ceratopsia is a diverse dinosaur clade from the Middle Jurassic to Late Cretaceous with early diversification in East Asia. However, the phylogeny of basal ceratopsians remains unclear. Here we report a new basal neoceratopsian dinosaur Beg tse based on a partial skull from Baruunbayan, Ömnögovi aimag, Mongolia. Beg is diagnosed by a unique combination of primitive and derived characters including a primitively deep premaxilla with four premaxillary teeth, a trapezoidal antorbital fossa with a poorly delineated anterior margin, very short dentary with an expanded and shallow groove on lateral surface, the derived presence of a robust jugal having a foramen on its anteromedial surface, and five equally spaced tubercles on the lateral ridge of the surangular. This is to our knowledge the earliest known occurrence of basal neoceratopsian in Mongolia, where this group was previously only known from Late Cretaceous strata. Phylogenetic analysis indicates that it is sister to all other neoceratopsian dinosaurs.


The Idiographic Approach in Psychological Research. The Challenge of Overcoming Old Distinctions Without Risking to Homogenize.
In this paper I discuss the relevance of the single-case approach in psychological research. Based upon work by Hurtado-Parrado and López-López (Integrative Psychological and Behavioral Science, 2015), who outlined the possibility that Single-Case Methods (SCMs) could be a valid alternative to Null Hypothesis Significance Testing (NHST), I introduce the idiographic approach (Salvatore and Valsiner Theory & Psychology, 20(6), 817-833, 2010; Valsiner Cultural & Psychology, 20(2), 147-159, 2014; Salvatore Culture & Psychology, 20(4), 477-500, 2014) based on the logic of abductive generalization, rather than the logic of inductive generalization. I present the theoretical, epistemological and methodological assumptions that this approach proposes; in particular, I discuss the re-conceptualization of some now obsolete rigid opposition, the inconsistency of sample use in psychological research, the relationship between uniqueness and general, the relationship between theory and phenomena, and finally the validation process.


Discovery of phenylpyrrolidine derivatives as a novel class of retinol binding protein 4 (RBP4) reducers.
Retinol-binding protein 4 (RBP4) is a potential drug target for metabolic and ophthalmologic diseases. A high-throughput screening of our compound library has identified a small-molecule RBP4 reducer 7a, as a hit compound. Aiming to provide a suitable tool for investigating the pharmacological effects of RBP4 reducers, we conducted a structure-activity relationship study of 7a. Exploration of the aryl head, oxazole core, and propanoic acid tail of 7a resulted in the discovery of novel, potent, and orally available phenylpyrrolidine derivatives 43b and 43c. Compound 43b had a potent and long-lasting blood RBP4-level-reducing effect when orally administered to mice at a dose as low as 0.3 mg/kg.


Some hemodynamic determinants of immune complex trapping by the kidney.
This study was undertaken to help clarify the relationship between capillary hemodynamic events and the tissue uptake of circulating immune complexes (IC). In each of 23 dogs, bovine serum albumin (BSA) and rabbit antiBSA soluble IC labeled with 125I were given by constant i.v. infusion, and IC uptake by a normally perfused kidney was compared to that of the contralateral kidney in which renal blood flow (RBF) was changed by renal artery constriction or raised ureteral pressure. In these same animals, IC uptake in 15 other major organ systems was also measured simultaneously. During IC infusion microspheres of 85Sr were injected to measure cardiac output and tissue blood flow, and red cells labeled with 51Cr were infused to mark tissue vascular volume. At completion of the IC infusion, tissue samples were taken from the kidneys and the 15 other major organs systems. From the isotope content of each tissue, we determined IC content, blood flow rate, vascular transit time, and fractional uptake of IC (FIC). In addition, glomeruli were isolated from renal cortex to assess IC uptake in glomerular versus renal nonglomerular tissue. We found that 1) for kidney, IC delivery rate, capillary hydrostatic pressure, and capillary ultrafiltration rate are less important than the plasma IC concentration in determining IC uptake; 2) for each organ studied, the principal determinant of IC uptake per gram of tissue, at any given PIC, is vascular volume per gram of tissue; 3) tissue vascular volume per gram of tissue may determine IC uptake per gram of tissue because tissue vascular volume determines the capillary surface area in contact with circulating IC or because tissue vascular volume determines tissue vascular transit time, at any given tissue blood flow rate.


Clinical course and prognosis of one hundred and two patients with hepatic coma 1958 through 1975.
The clinical course and prognosis of hepatic coma were examined in 102 patients treated in the period from 1958 to 1975. The diagnoses included 9 fulminant hepatitis, 7 subacute hepatitis, 53 liver cirrhosis without liver carcinoma (40 cases of the acute type, 10 cases of the chronic type and 3 cases of another type, according to Sherlock's classification of hepatic coma) and 33 liver cirrhosis with primary liver carcinoma. Four of 9 fulminant hepatitis patients gained consciousness within 1 week and recovered completely. Seven subacute hepatitis patients died within 2 weeks after onset of hepatic coma. In the period from 1958 to 1969, 20% of liver cirrhosis patients with the acute type of coma recovered from coma, and in the period from 1970 to 1975, 45% of patients recovered. Seven of 10 patients with the chronic type of coma died between 4 months and 9 years after the onset of coma. Three other patients are presently still alive. The median survival time was 2.5 years. Nine primary liver carcinoma patients with coma were hospitalized from 1958 to 1969 and 24 from 1970 to 1975. Hepatorenal syndrome was present in 31 of 71 examined patients. Twenty-three patients with hepatorenal syndrome were in the period from 1970 to 1975.


The Moore's Law of microbiology - towards bacterial culture miniaturization with the micro-Petri chip.
A recent publication has reported the fabrication of a new microbial culture device containing an array of unprecedented density - a million growth chambers. This micro-Petri chip should impact on various fields, including biotechnology, ecology, food microbiology and drug development, by enabling high-throughput screens and therefore the detection of rare phenotypes within a large population of microorganisms.


Haemodynamics in a patient-specific intracranial aneurysm according to experimental and numerical approaches: A comparison of PIV, CFD and PC-MRI.
The haemodynamics determined by different approaches for studying fluid dynamics - i.e. computational fluid dynamics (CFD), particle image velocimetry (PIV), and phase-contrast magnetic resonance imaging (PC-MRI) - have rarely been thoroughly compared; nor have the factors that affect accuracy and precision in each method. As each method has its own advantages and limitations, this knowledge is important for future studies to be able to achieve valid analyses of fluid flows. To gauge the capacity of these methods for analysing aneurysmal flows, we compared the haemodynamic behaviours determined by each method within a patient-specific aneurysm model. An in vitro silicone aneurysm model was fabricated for PIV and PC-MRI, and an in silico aneurysm model with the same geometry was reconstructed for CFD. With the same fluid model prepared numerically and physically, CFD, PIV and PC-MRI were performed to study aneurysmal haemodynamics. 2D velocity vectors and magnitudes show good agreement between PIV and CFD, and 3D flow patterns show good similarity between PC-MRI and CFD. These findings give confidence to future haemodynamic studies using CFD technology. For the first time, the morphological inconsistency between the PCMRI model and others is found to affect the measurement of local flow patterns.


Tumor markers in patients with advanced breast cancer as prognosticators: a preliminary study.
A retrospective study was performed on 69 breast cancer patients (stage II, N = 18; advanced disease, N = 51) in order to assess the prognostic value of circulating prolactin (PRL), CEA, CA 15-3, insulin-like growth factor-1 (IGF-1), and epidermal growth factor (EGF) by RIA/IRMA. These markers were compared with short-term prognosis (two years). Significant difference was observed only for PRL ( < 20.0 ng/ml vs. > 20.0 ng/ml), which provide an independent predictor of short-term prognosis in advanced breast cancer.


[Reimbursement of patients with high costs in a department of otorhinolaryngology of maximum care and refinancing by the German DRG system].
With the introduction of a diagnosis related groups (DRG)-system in Germany, the medical analysis of the total costs of caring for a given patient is of significance. The medical identification of cost intensive patients becomes of increasing importance for the financial perspective of a department, because the averaged lump sum system might not break even these treatments. In the Department of Otorhinolaryngology, University Ulm, a tertiary referral center, the 56 most expensive patients from 3131 inpatients which were treated in 2002 were retrospectively identified and expenses for diagnostic tests, therapy and post-operative complications were analyzed. All patients' related costs, including all costs for personnel, were assigned to a DRG (Version 1.0 G-DRG and G-DRG 2004). The most expensive treatments included extensive tumor surgeries, surgery of the trachea, emergency procedures and reconstructive surgery. Costs increased with complications, prolonged stay in the intensive care unit and simultaneous internal diseases. The cost at our institution for an pharynocutaneous fistula added 3000 Euro. The assignment of treatment costs to a DRG is complex. Based on our data extensive surgeries for head and neck malignancies showed a homogeneous cost distribution in the DRG group of G-DRG 2004 which was however inadequately reimbursed. Detailed prospective analyses from multiple centers to identify expensive treatments in the field of otorhinolaryngology are necessary to incorporate modifications into the German DRG-system.


(+/-)-cis-(6-Ethyl-tetrahydropyran-2-yl)-formic acid: a novel substance with antinociceptive properties.
We described in this paper the first synthesis to the (+/-) cis (6-ethyl-tetrahydropyran-2-yl) formic acid (1) using the very efficient Prins cyclization reaction as strategy to construction of its tetrahydropyran skeleton. This new compound presented a significant antinociceptive property by the tail-flick model.


Models of schizophrenia in humans and animals based on inhibition of NMDA receptors.
The research of the glutamatergic system in schizophrenia has advanced with the use of non-competitive antagonists of glutamate NMDA receptors (phencyclidine, ketamine, and dizocilpine), which change both human and animal behaviour and induce schizophrenia-like manifestations. Models based on both acute and chronic administration of these substances in humans and rats show phenomenological validity and are suitable for searching for new substances with antipsychotic effects. Nevertheless, pathophysiology of schizophrenia remains unexplained. In the light of the neurodevelopmental model of schizophrenia based on early administration of NMDA receptor antagonists it seems that increased cellular destruction by apoptosis or changes in function of glutamatergic NMDA receptors in the early development of central nervous system are decisive for subsequent development of psychosis, which often does not manifest itself until adulthood. Chronic administration of antagonists initializes a number of adaptation mechanisms, which correlate with findings obtained in patients with schizophrenia; therefore, this model is also suitable for research into pathophysiology of this disease.


Autologous platelet-rich plasma in the treatment of refractory corneal ulcers: A case report.
To evaluate the efficacy of a low-cost preparation of platelet-rich plasma (PRP) eye drops in the treatment of persistent non-infectious corneal ulcer. A 67-year-old female presented to our clinic with a wide corneal ulcer and severe paracentral corneal thinning refractory to medical therapy with antibiotics, lubricant and contact lens bandage. The patient received a novel preparation of PRP solution. After 15 days of therapy, we observed complete resolution of the corneal ulcer with regrowth of the epithelium and a reduction in corneal opacity. Although the low-cost PRP preparation gives a lower platelet concentration than standard procedures, our work shows this preparation to be effective in the treatment of refractory non-infectious corneal ulcer.


Combined therapy affects outcomes differentially after mild traumatic brain injury and secondary forebrain ischemia in rats.
Muscarinic and NMDA receptors contribute to post-traumatic hypersensitivity to secondary ischemia. However, the effect of these receptor antagonists on behavior and CA1 neuronal death after traumatic brain injury (TBI) with acute (1 h after TBI) forebrain ischemia has not been systematically assessed. We examined cognitive and motor dysfunction and the relationship of behavior deficits to neuronal death in this model using muscarinic and NMDA antagonists. Three behavioral groups (n=10/group) of Wistar rats were subjected to mild TBI and 6 min of forebrain ischemia imposed 1 h after TBI with 45 days survival. Motor and spatial memory performance were assessed using the rotarod task and Morris water maze. Seven additional groups (n=6/group) were evaluated only for CA1 death after 7 days survival following sham, individual or combined injury with and without drug treatments. Rats were given 0.3 mg/kg MK-801 (M) and 1.0 mg/kg scopolamine (S) alone or combined (M-S) before or 45 min after TBI. Rotarod performance was tested at days 1-5 and maze performance on days 11-15 and 40-44 after M-S treatment. The 7-day studies showed M-S treatment (p<0.01) reduced CA1 neuronal death better than either S or M alone. Behavioral groups had inadvertent post-ischemic hypothermia that decreased CA1 death and likely influenced behavioral morbidity. M-S given before TBI (p<0.01) decreased memory deficits on day 15, while M-S treatment given after TBI was ineffective. Unexpectedly, M-S treatment before or after TBI produced transient motor deficits (p<0. 01). Memory improvement occurred independent of CA1 death.


High-CO2 Modified Atmosphere Packaging with Superchilling (-1.3 °C) Inhibit Biochemical and Flavor Changes in Turbot (Scophthalmus maximus) during Storage.
The effects of modified atmosphere packaging (MAP) in combination with superchilling (-1.3 °C) on the physicochemical properties, flavor retention, and organoleptic evaluation of turbot samples were investigated during 27 days storage. Results showed that high-CO2 packaging (70% or 60% CO2) combined with superchilling could reduce the productions of off-flavor compounds, including total volatile basic nitrogen (TVB-N) and ATP-related compounds. Twenty-four volatile organic compounds were determined by gas chromatography-mass spectrometry (GC/MS) during storage, including eight alcohols, 11 aldehydes, and five ketones. The relative content of off-odor volatiles, such as 1-octen-3-ol, 1-penten-3-ol, (E)-2-octenal, octanal, and 2,3-octanedione, was also reduced by high-CO2 packaging during superchilling storage. Further, 60% CO2/10% O2/30% N2 with superchilling (-1.3 °C) could retard the water migration on the basis of the water holding capacity, low field NMR, and MRI results, and maintain the quality of turbot according to organoleptic evaluation results during storage.


Use of the oxygen cost of breathing as an index of weaning ability from mechanical ventilation.
The oxygen cost of breathing (which is the difference in oxygen consumption measured during controlled ventilation and again during spontaneous ventilation) was measured in 30 patients between the ages of 17 and 96 years at the time of commencement of weaning from mechanical ventilation. There was a significant exponential correlation between the oxygen cost of breathing in ml/m2/min and the oxygen cost of breathing as a percentage of total oxygen consumption during spontaneous ventilation (OCB/VO2SV%) and the duration of weaning in days.


Macrophage chemotaxis in anti-tubular basement membrane-induced interstitial nephritis in guinea pigs.
Interstitial renal lesions containing T cells and macrophages develop after 14 days in guinea pigs immunized to produce anti-tubular basement membrane-induced interstitial nephritis. We serially examined the renal venous and systemic arterial sera from such animals to determine if chemotactic factors were released across their kidneys. Our findings demonstrated the presence of a macrophage-specific renal chemoattractant with peak detectability on Days 10-14, just subsequent to the deposition of alpha TBM-Ab, but prior to the development of significant renal injury. We propose that such factors may provide important communication signals in the immunopathogenesis of this form of interstitial injury.


Lysosomal activity maintains glycolysis and cyclin E1 expression by mediating Ad4BP/SF-1 stability for proper steroidogenic cell growth.
The development and differentiation of steroidogenic organs are controlled by Ad4BP/SF-1 (adrenal 4 binding protein/steroidogenic factor 1). Besides, lysosomal activity is required for steroidogenesis and also enables adrenocortical cell to survive during stress. However, the role of lysosomal activity on steroidogenic cell growth is as yet unknown. Here, we showed that lysosomal activity maintained Ad4BP/SF-1 protein stability for proper steroidogenic cell growth. Treatment of cells with lysosomal inhibitors reduced steroidogenic cell growth in vitro. Suppression of autophagy did not affect cell growth indicating that autophagy was dispensable for steroidogenic cell growth. When lysosomal activity was inhibited, the protein stability of Ad4BP/SF-1 was reduced leading to reduced S phase entry. Interestingly, treatment of cells with lysosomal inhibitors reduced glycolytic gene expression and supplying the cells with pyruvate alleviated the growth defect. ChIP-sequence/ChIP studies indicated that Ad4BP/SF-1 binds to the upstream region of Ccne1 (cyclin E1) gene during G1/S phase. In addition, treatment of zebrafish embryo with lysosomal inhibitor reduced the levels of the interrenal (adrenal) gland markers. Thus lysosomal activity maintains steroidogenic cell growth via stabilizing Ad4BP/SF-1 protein.


Development of an electrochemical detector for high-performance liquid chromatographic assay of brain catecholamines.
An electrochemical detector that utilizes the reduction-oxidation phenomena of electrochemically active substances has been developed for high-performance liquid chromatography. The construction and application of the detector to brain catecholamines, particularly for norepinephrine and dopamine analysis, are described. The differences between this detector and those reported previously are discussed.


Cyclic 3',5'-adenosine monophosphate (cAMP) in a 42-month-old child with clinical evidence of multiple hormonal disturbances.
In a boy aged 42 months, small stature, retarded psychomotor development, dry skin, excessive thirst, polyuria, cryptorchidism, and rickets were signs of multihormonal disturbances. Contrary to the clinical manifestations, laboratory investigations showed normal or raised levels of hormones (hGH, insulin, T3RU, T4, TSH, PTH). The cAMP level in the plasma was low and its urinary excretion was reduced. After administration of hGH, adrenaline, T3, T4, pitressin, vitamin D3 and aminophylline there was no rise in the cAMP concentration in plasma and urine. In the light of these results it may be assumed that deficient function of the adenyl cyclase system led to development of a clinical syndrome of tissue insensitivity to multiple hormonal factors in this case.


Nickel phytomining from industrial wastes: Growing nickel hyperaccumulator plants on galvanic sludges.
Nickel (Ni) is used in numerous industrial processes, with large amounts of Ni-rich industrial wastes produced, which are largely sent to landfill. Nickel recovery from waste materials that would otherwise be disposed is of particular interest. Nickel phytomining represents a new technology in which hyperaccumulator plants are cultivated on Ni-rich substrates for commercial metal recovery. The aim of this study was to investigate the possibility of Ni transfer from industrial waste into plant biomass, to support recovery processes from bio-ores. Different industrial galvanic sludges (containing 85-150 g kg-1 Ni) were converted into artificial substrates (i.e. technosols) and the Ni hyperaccumulator Odontarrhena chalcidica (formerly Alyssum murale) was cultivated on these Ni-rich matrices. A greenhouse pot experiment was conducted for three months including an ultramafic soil control and testing fertilized (NPK) and unfertilized replicates. The results showed that fertilization was effective in improving plant biomass for all the substrates and that O. chalcidica was capable of viably growing on technosols, producing a comparable biomass to O. chalcidica on the control (ultramafic soil). On all technosols, O. chalcidica achieved Ni shoot concentrations of more than >1000 mg Ni kg -1 and maximum Ni uptake was obtained from one of the technosols (26.8 g kg -1 Ni, unfertilized; 20.2 g kg -1 Ni, fertilized). Nickel accumulation from three of the technosols resulted to be comparable with the control ultramafic soil. This study demonstrated the feasibility of transferring Ni from toxic waste into the biomass of Odontarrhena chalcidica and that phytomining from galvanic sludge-derived technosols can provide similar Ni yields as from natural ultramafic soils.


Maintenance of complex neural function during perfusion of the mammalian brain.
A perfused brain preparation was developed utilizing non-pulsatile flow of artificial blood. Cortical electrical activity and respiratory motor output were maintained for as long as 7-8 h. This preparation permits stable intracellular recordings from CNS neurons displaying ongoing respiratory activity, and should permit analysis of synaptic and intrinsic cellular mechanisms involved in producing the respiratory output. A similar approach may be useful for electrophysiology throughout the CNS, and for other fields in which control of the blood composition and/or mechanical stability are required.


Cloning and molecular characterization of a human recombinant IgG Fab binding to the Tat protein of human immunodeficiency virus type 1 (HIV-1) derived from the repertoire of a seronegative patient.
A study aiming at cloning and characterizing natural antibodies to human immunodeficiency virus type 1 (HIV-1) targets is described. In particular, we report the molecular cloning of a Fab molecule binding the HIV-1/Tat protein from a seronegative patient. The Fab was characterized for its binding specificity and investigated in regards to its molecular structure. Furthermore, to evaluate the role played by the heavy and light chains in the binding to the antigen, hybrid Fabs were constructed combining the heavy and the light chain of the natural anti-Tat clone with a control high-affinity Fab derived from the repertoire of the same patient. The results indicate that the natural immunoglobulin under study: (i) is a polyreactive antibody of IgG1 isotype, and not an IgM as usually described for anti-HIV natural clones, (ii) shows a pattern of mutations compatible with an antigen-driven mechanisms, (iii) its heavy chain derives from a V-gene subfamily (V3-23) highly represented in fetal life, and (iv) its heavy chain variable region exhibits several characteristics, including an extremely long, hydrophilic CDR3, that are unusual and theoretically important in determining the polyreactive capacity of the molecule.


Comparative effectiveness of peer leaders and community health workers in diabetes self-management support: results of a randomized controlled trial.
To compare a peer leader (PL) versus a community health worker (CHW) telephone outreach intervention in sustaining improvements in HbA1c over 12 months after a 6-month diabetes self-management education (DSME) program. One hundred and sixteen Latino adults with type 2 diabetes were recruited from a federally qualified health center and randomized to (1) a 6-month DSME program followed by 12 months of weekly group sessions delivered by PLs with telephone outreach to those unable to attend or (2) a 6-month DSME program followed by 12 months of monthly telephone outreach delivered by CHWs. The primary outcome was HbA1c. Secondary outcomes were cardiovascular disease risk factors, diabetes distress, and diabetes social support. Assessments were conducted at baseline, 6, 12, and 18 months. After DSME, the PL group achieved a reduction in mean HbA1c (8.2-7.5% or 66-58 mmol/mol, P < 0.0001) that was maintained at 18 months (-0.6% or -6.6 mmol/mol from baseline [P = 0.009]). The CHW group also showed a reduction in HbA1c (7.8 vs. 7.3% or 62 vs. 56 mmol/mol, P = 0.0004) post-6 month DSME; however, it was attenuated at 18 months (-0.3% or -3.3 mmol/mol from baseline, within-group P = 0.234). Only the PL group maintained improvements achieved in blood pressure at 18 months. At the 18-month follow-up, both groups maintained improvements in waist circumference, diabetes support, and diabetes distress, with no significant differences between groups. Both low-cost maintenance programs led by either a PL or a CHW maintained improvements in key patient-reported diabetes outcomes, but the PL intervention may have additional benefit in sustaining clinical improvements beyond 12 months.


Clinical and Visual Outcomes of Dysthyroid Optic Neuropathy After Surgical Orbital Decompression.
Background: Current guidelines suggest high-dose steroids as first-line treatment for dysthyroid optic neuropathy (DON). When steroids fail, decompressive surgery is mandatory. Methods: We conducted a single-center, retrospective cohort study in a tertiary care combined Thyroid-Eye clinic in Milan, Italy. We studied 88 orbits of 56 patients that were submitted to surgical orbital decompression to treat DON from 2005 to 2020. Of these, 33 orbits (37.5%) underwent surgery as first-line treatment for DON whereas the other 55 (62.5%) were decompressed after being unresponsive to very high-dose steroids. Previous orbital surgery, concurrent neurological or ophthalmologic diseases, or incomplete follow-up were considered as exclusion criteria from this study. Surgery was considered successful if no further decompression was needed to preserve vision. Pinhole best corrected visual acuity (p-BCVA), color sensitivity, automated visual field, pupil reflexes, optic disk and fundus appearance, exophtalmometry, and ocular motility were studied before and after surgery (1 week, 1, 3, 6, and 12 months). Activity of Graves' Orbitopathy (GO) was graded using a clinical activity score (CAS). Results: Surgery was successful in 77 orbits (87.5%). The remaining 11 orbits (12.5%) needed further surgery to treat DON definitively. All parameters of visual function improved significantly at follow-up and GO inactivated (CAS <3) within 1 month. At 3 months, all 77 responding orbits had p-BCVA >0.63 whereas all of the 11 non-responding orbits had p-BCVA ≤0.63. Visual field parameters and color sensitivity were not associated with response to surgery. High-dose steroid treatment before surgery was associated with a better response rate (96% vs. 73%; p = 0.004). Balanced decompression was associated with a higher response rate compared with medial wall decompression (96% vs. 80%; p = 0.04). A significant inverse correlation was observed between final p-BCVA and the patient's age (r = -0.42; p = 0.0003). Conclusions: Surgical decompression was found to be a very effective treatment for DON. In this study, all clinical parameters improved after surgery and further intervention was rarely needed.


Reduction in road fatalities and injuries after legislation for compulsory wearing of seat belts: experience in Victoria and the rest of Australia.
In 1970 the Government of the State of Victoria became the first in the 'western' world to introduce legislation for compulsory wearing of seat belts. Within 14 months the other Australian states followed. Seat belt wearing rates increased to attain 90 per cent in 1977. This paper presents an evaluation of changes during the period 1955--77 in the incidence of road crash fatalities and injuries for vehicle occupants in Victoria and the rest of Australia. The introduction of the legislation in Victoria and subsequently in the other Australian states coincided with significant and marked decreases in driver and passenger fatality and injury rates (numbers per 10 000 registered vehicles). The decreases were enough to reduce the total numbers of vehicle occupant fatalities and injuries for all post-legislation years in Victoria. The improvements have been maintained throughout the entire post-legislation period. The legislation did not apply to child passengers of less than 8 years of age and the frequency of seat belt or harness wearing among them remained low. These children did not share in the overall improvement for passengers. The Australian experience supports the view that legislation for compulsory wearing of seat belts is the single most effective method available for the protection of vehicle occupants in road crashes.


ALIX binds a YPX(3)L motif of the GPCR PAR1 and mediates ubiquitin-independent ESCRT-III/MVB sorting.
The sorting of signaling receptors to lysosomes is an essential regulatory process in mammalian cells. During degradation, receptors are modified with ubiquitin and sorted by endosomal sorting complex required for transport (ESCRT)-0, -I, -II, and -III complexes into intraluminal vesicles (ILVs) of multivesicular bodies (MVBs). However, it remains unclear whether a single universal mechanism mediates MVB sorting of all receptors. We previously showed that protease-activated receptor 1 (PAR1), a G protein-coupled receptor (GPCR) for thrombin, is internalized after activation and sorted to lysosomes independent of ubiquitination and the ubiquitin-binding ESCRT components hepatocyte growth factor-regulated tyrosine kinase substrate and Tsg101. In this paper, we report that PAR1 sorted to ILVs of MVBs through an ESCRT-III-dependent pathway independent of ubiquitination. We further demonstrate that ALIX, a charged MVB protein 4-ESCRT-III interacting protein, bound to a YPX(3)L motif of PAR1 via its central V domain to mediate lysosomal degradation. This study reveals a novel MVB/lysosomal sorting pathway for signaling receptors that bypasses the requirement for ubiquitination and ubiquitin-binding ESCRTs and may be applicable to a subset of GPCRs containing YPX(n)L motifs.


Age-related changes in the microcirculation of skeletal muscle.
The age-related reduction in exercise capacity is associated with a reduction in cardiac output and maximal oxygen consumption (VO2max). The loss of muscle mass explains a large portion of the age-related decline in VO2max. The capillary supply to a muscle fibre is primarily determined by its size, but also by its metabolic profile and the metabolic profile of surrounding fibres. Thus the age-related fibre atrophy and changes in the fibre type composition are expected to be accompanied by changes in the capillarisation. The exchange of oxygen, blood-borne energy sources, metabolites and heat between the blood and muscle tissue takes place in the microcirculation. Changes in the microcirculation may thus affect the functioning and viability of the muscle. The resting blood flow is minimally affected by age, but blood flow during or following exercise is generally reduced. This may in part be due to a reduced vasodilatory capacity and a decreased capillarisation. However, the coupling between capillary supply to a fibre and its metabolic profile or the profile of the surrounding fibres is maintained. There are some changes in ultrastructure of the endothelium. The age-related changes in the microcirculation are associated with a reduced VO2max and exercise capacity. The adaptability of the microcirculation is maintained at old age.


Hints on the Lateralization of Dopamine Binding to D1 Receptors in Rat Striatum.
Dopamine receptors in striatum are important for healthy brain functioning and are the target of levodopa-based therapy in Parkinson's disease. Lateralization of dopaminergic neurotransmission in striata from different hemispheres occurs in patients, but also in healthy individuals. Our data show that the affinity of dopamine binding to dopamine D1 receptors is significantly higher in left than in right striatum. Analysis of data from radioligand binding to striatal samples from naïve, 6-hydroxydopamine lesioned, levodopa-treated and levodopa-induced dyskinetic rats shows differential receptor structure and gives hints on the causes of right/left lateralization of dopamine binding to striatal D1 receptors. Moreover, binding data showed loss of lateralization in levodopa (L-DOPA)-induced dyskinetic rats.


Depression in early adulthood: prevalence and psychosocial correlates among young Swiss men.
Depression in young adults is common, but data from Switzerland are scarce. Our study gives a point prevalence estimate of depression in young Swiss men, and describes the association between depression and education, material and social resources, and job/school satisfaction. We used data from the cross-sectional Swiss Federal Surveys of Adolescents (ch-x) from 2010 to 2011 comprising 9,066 males aged between 18 and 25 years. Depression was assessed by means of self-reports using the Patient Health Questionnaire (PHQ-9). Persons were categorised into three groups: depression, subthreshold depression, and no depression. We assessed the relationship between depression and education, material and social resources, and satisfaction with job/school. Differences according to depression status were tested with chi-square tests for categorical variables and one-way analyses of variance for continuous variables. Point prevalence of depression (3.60%) and subthreshold depression (3.62%) was high. Poor mental health was associated with lower education in young adults (p <0.001), and with their parents' education (p = 0.024). Social resources in persons with depression and subthreshold depression were substantially reduced (i.e., social support and satisfaction with social relations; both p <0.001). Young men with depression and subthreshold depression also reported a current lack of satisfaction with job/school (p <0.001). Prevalence of (subthreshold) depression is high in young Swiss men. Depression at this age might result in a bad long-term prognosis owing to its association with low satisfaction with job/school and low self-efficacy. Interventions should especially consider the lower social resources of young men with depression.


Spatial Distribution of Vulnerable Plaques: Comprehensive In Vivo Coronary Plaque Mapping.
The authors performed a comprehensive analysis on the distribution of coronary plaques with different phenotypes from our 3-vessel optical coherence tomography (OCT) database. Previous pathology studies demonstrated that thin-cap fibroatheroma (TCFA) is localized in specific segments of the epicardial coronary arteries. A detailed description of in vivo coronary plaques of various phenotypes has not been reported. OCT images of all 3 coronary arteries in 131 patients were analyzed every 1 mm to assess plaque phenotype and features of vulnerability. In addition, plaques were divided into tertiles according to percent area stenosis (%AS). Among 534 plaques identified in 393 coronary arteries, 27.0% were fibrous plaques, 13.3% were fibrocalcific plaques, 40.8% were thick-cap fibroatheromas, and 18.9% were TCFAs. TCFAs showed clustering in the proximal segment, particularly in the left anterior descending artery. On the other hand, fibrous plaques were relatively evenly distributed throughout the entire length of the coronary arteries. In patients with acute coronary syndromes (ACS), TCFAs showed stronger proximal clustering in the left anterior descending, 2 clustering peaks in the right coronary artery, and 1 clustering peak in the circumflex artery. The pattern of TCFA distribution was less obvious in patients without ACS. The prevalence of TCFA was higher in the highest %AS tertile, compared with the lowest %AS tertile (30% vs. 9%; p < 0.001). The present 3-vessel OCT study showed that TCFAs cluster at specific locations in the epicardial coronary arteries, especially in patients with ACS. TCFA was more prevalent in segments with tight stenosis. (The Massachusetts General Hospital Optical Coherence Tomography Registry; NCT01110538).


The metNPQ operon of Bacillus subtilis encodes an ABC permease transporting methionine sulfoxide, D- and L-methionine.
The Bacillus subtilis yusCBA operon, which encodes an ABC-type transporter, contains an S-box motif in its promoter region. We showed that the expression of these genes is repressed via the S-box system when methionine is available. The YusCB proteins are involved in the transport of both d- and l-methionine but also methionine sulfoxide. A yusCB mutant is unable to grow in the presence of 5 microM l-methionine or 100 microM methionine sulfoxide, while it grows similarly to the wild type with 100 microM l-methionine and 1 mM methionine sulfoxide. Other uptake systems are therefore present for these two compounds. In contrast, the Yus ABC transporter corresponds to the sole d-methionine uptake system. We propose to rename yusC, yusB and yusA as metN, metP and metQ, respectively.


Evaluation of Changes in Sexual Function Related to Uterine Fibroid Embolization (UFE): Results of the EFUZEN Study.
The main goal of the study was to evaluate sexual function before and one year after UFE. The secondary goals were to evaluate the quality of life before and one year after UFE and to determine the relation of imaging findings (MRI data) before and 3-6 months after UFE to changes in sexual function and quality of life. Study design: a prospective, multicenter (25 centers) observational study was conducted. a total of 264 consecutive symptomatic women undergoing UFE using Embozene® (Celonova) from March 2012 to May 2013 were enrolled. Clinical data: the sexual function score and the quality of life score were calculated using the previously validated Female Sexual Function Index (FSFI) by Rosen and UFS-QOL by Spies, respectively, before and one year after UFE. Imaging data: MRI were performed before and 3-6 months after UFE. Data recorded were uterine and main fibroid volume, percentage of fibroid enhancement after injection of gadolinium. Impact of imaging data before and after UFE FSFS scores and QOL scores after UFE was searched. Complete FSFI study and QOL study were obtained in 170 and 192 women, respectively. At 1 year post-UFE, improvement of FSFI score was seen in 134/170 women (78.8%), QOL scores were improved in 183/203 women (90.2%) and symptoms severity in 163/192 (84.9%). The relation between main fibroid reduction, decrease of fibroid enhancement and global UFS-QOL and FSFI scores was not established. At one year post-embolization, UFE significantly improves all aspects of sexual function and quality of life.


The identity and distribution of striped bagrid catfish, Mystus tengara (Hamilton 1822) revealed through integrative taxonomy.
The taxonomic status and geographical distribution of M. tengara are vague. No genetic diversity and phylogenetic study have been done till now to resolve its identity and distribution. In the present study, an integrated taxonomic approach has been applied to clarify the taxonomic status, identity, and distribution of bagrid catfish, Mystus tengara. Comparative morphometric evaluation of M. tengara identified in the present study from distant geographical locations revealed variations of the traits in response to body length and environment, without significant genetic distance. The observed morphometric traits of M. tengara were found to be overlapping with available morphometric traits of M. tengara, M. carcio and M. vittatus. Maximum likelihood and Bayesian phylogenetic analysis based on mitochondrial cytochrome c oxidase (COI) gene also could not resolve their identity, and five paraphyletic clades comprising of M. tengara, M. vittatus, and M. carcio from India, Nepal, and Bangladesh were observed. Morphological and genetic evidence along with comparative evaluation of M. tengara, from its type locality, we consider M. tengara identified in the present study to be true, with its distribution extending from North East India to West Bengal, North India, Central India, Northern peninsular India, and Bangladesh. The observation of paraphyletic subclades and evaluation of genetic distance between subclades reveals the presence of four cryptic species. Further confirmation on the identity of M. vittatus and M. carcio, by an integrated taxonomic approach based on fresh specimens collected from the type locality, is required.


Entamoeba histolytica infections in flight personnel of an international airline.
A cohort of 99 subjects, members of the flight staff of Lufthansa German airlines, all infected with Entamoeba histolytica, were followed over a period of 2.5 years to monitor their clinical and parasitological status. All but 4 of the subjects were infected with non-pathogenic zymodemes of E. histolytica and had negative amoebic serology, and most were clinically well. One male heterosexual carrying a pathogenic zymodeme was found, despite massive treatment regimes, to carry the infection persistently for 12 months. Most non-pathogenic infections were left untreated.


Overexpression of a rice OsDREB1F gene increases salt, drought, and low temperature tolerance in both Arabidopsis and rice.
DREB transcription factors play key roles in plant stress signalling transduction pathway, they can specifically bind to DRE/CRT element (G/ACCGAC) and activate the expression of many stress inducible genes. Here, a novel rice DREB transcription factor, OsDREB1F, was cloned and characterised via subtractive suppression hybridisation (SSH) from upland rice. Expression analysis revealed that OsDREB1F gene was induced by salt, drought, cold stresses, and also ABA application, but not by pathogen, wound, and H2O2. Subcellular localization results indicated that OsDREB1F localizes in nucleus. Yeast activity assay demonstrated that OsDREB1F gene encodes a transcription activator, and can specifically bind to DRE/CRT but not to ABRE element. Transgenic plants harbouring OsDREB1F gene led to enhanced tolerance to salt, drought, and low temperature in both rice and Arabidopsis. The further characterisation of OsDREB1F-overexpressing Arabidopsis showed that, besides activating the expression of COR genes which contain DRE/CRT element in their upstream promoter regions, the expression of rd29B and RAB18 genes were also activated, suggested that OsDREB1F may also participate in ABA-dependent pathway.


The novel function of OCT4B isoform-265 in genotoxic stress.
OCT4 is a key transcription factor in maintaining the pluripotency and self-renewal of embryonic stem cells (ESCs). Human OCT4 gene can generate three mRNA isoforms (OCT4A, OCT4B, and OCT4B1) by alternative splicing and four protein isoforms (OCT4A, OCT4B-265, OCT4B-190, and OCT4B-164) by alternative splicing or alternative translation initiation. OCT4A is a transcription factor responsible for the stemness of ESCs, while the function of OCT4B protein isoforms is still not clear. We have previously reported that OCT4B-190 functioned in cell stress response. Here, we present another product of OCT4 gene, OCT4B-265, which is upregulated under genotoxic stress in stem cells, and it may function in stress response through p53 signaling pathway. This work gives an insight into the novel function of OCT4B protein isoforms and helps us to understand the complex expression patterns and biological functions of OCT4 gene.