Metal Semiconductor Field-Effect Transistor with MoS2/Conducting NiO(x) van der Waals Schottky Interface for Intrinsic High Mobility and Photoswitching Speed.
Molybdenum disulfide (MoS2) nanosheet, one of two-dimensional (2D) semiconductors, has recently been regarded as a promising material to break through the limit of present semiconductors. With an apparent energy band gap, it certainly provides a high carrier mobility, superior subthreshold swing, and ON/OFF ratio in field-effect transistors (FETs). However, its potential in carrier mobility has still been depreciated since the field-effect mobilities have only been measured from metal-insulator-semiconductor (MIS) FETs, where the transport behavior of conducting carriers located at the insulator/MoS2 interface is unavoidably interfered by the interface traps and gate voltage. Moreover, thin MoS2 MISFETs have always shown large hysteresis with unpredictable negative threshold voltages. Here, we for the first time report MoS2-based metal semiconductor field-effect transistors (MESFETs) using NiOx Schottky electrode which makes van der Waals interface with MoS2. We thus expect that the maximum mobilities or carrier transport behavior of the Schottky devices may hardly be interfered by interface traps or an on-state gate field. Our MESFETs with a few and ∼10 layer MoS2 demonstrate intrinsic-like high mobilities of 500-1200 cm(2)/(V s) at a certain low threshold voltage between -1 and -2 V without much hysteresis. Moreover, they work as a high speed and highly sensitive phototransistor with 2 ms switching and ∼5000 A/W, respectively, supporting their high intrinsic mobility results.


DNA methylation profile in diffuse type gastric cancer: evidence for hypermethylation of the BRCA1 promoter region in early-onset gastric carcinogenesis.
Diffuse type gastric carcinoma is the most aggressive type of gastric cancer. This type of tumor is not preceded by precancerous changes and is associated with early-onset and hereditary syndromes. To test the hypothesis that DNA methylation profile would be useful for molecular classification of the diffuse type gastric carcinoma, DNA methylation patterns of the CpG Island of 17 genes were studied in 104 cases and 47 normal adjacent gastric mucosa by Methylation-specific PCR, Immunohistochemistry and Hierarchical clustering analysis. The most frequent methylated genes were FHIT, E-cadherin, BRCA1 and APC (>50%), followed by p14, p16, p15, p73, MGMT and SEMA3B (20-49%). Hierarchical clustering analysis reveals four groups with different clinical features. The first was characterized by hypermethylation of BRCA1 and younger age (<45 years old), and the second by hypermethylation of p14 and p16 genes, male predominance and Epstein-Barr virus infection. The third group was characterized by hypermethylation of FHIT and antrum located tumors and the fourth was not associated with any clinical variables. In normal adjacent mucosa only the p73 gene was significantly less methylated in comparison to tumor mucosa. DNA methylation identified subgroups of diffuse type gastric cancer. Hypermethylation of BRCA1 associated with young age suggests a role in early-onset gastric carcinoma.


Sequence analysis of diamine oxidase gene from fava bean and its expression related to γ-aminobutyric acid accumulation in seeds germinating under hypoxia-NaCl stress.
γ-Aminobutyric acid (GABA) is synthesized via the polyamine degradation pathway in plants, with diamine oxidase (DAO) being the key enzyme. In this study the cDNA of DAO in fava bean was cloned and its expression in seeds germinating under hypoxia-NaCl stress was investigated. Fava bean DAO cDNA is 2199 bp long and contains 2025 bp of open reading frame that encodes 675 amino acid peptides with a calculated molecular weight of 76.31 kDa and a pI of 5.41. Hypoxia and hypoxia-NaCl stress enhanced DAO activity and resulted in GABA accumulation in germinating fava bean. However, DAO gene expression was down-regulated under hypoxia compared with non-stress condition, while its expression in the cotyledon and shoot was up-regulated under hypoxia-NaCl. In addition, DAO expression could be promoted to enhance GABA accumulation after increasing the stress intensity using NaCl. DAO gene expression was significantly inhibited by aminoguanidine treatment under hypoxia but increased under hypoxia-NaCl. Under hypoxia, GABA accumulation due to NaCl was mainly concentrated in the cotyledon. The GABA content increase under hypoxia did not result from DAO gene expression, but DAO existing in seeds was activated under hypoxia. DAO gene expression was up-regulated to enhance GABA accumulation after increasing the stress intensity.


Dose ranging study of the effects of cholecystokinin in healthy volunteers.
The authors determined whether response to cholecystokinin-tetrapeptide (CCK-4) was dose-dependent. Healthy volunteers (n = 36) received double-blind injections of either 9 micrograms, 25 micrograms, or 50 micrograms of CCK-4 and placebo in a randomized sequence of injection. Significant dose-related differences were found for the number of symptoms, sum intensity of symptoms and the time until onset of symptoms, but not for the duration of symptoms. The incidence of panic attacks with CCK-4 was 11%, 17% and 47% for the 9 micrograms, 25 micrograms and 50 micrograms dose, respectively. None of the controls panicked with placebo injections. These results support the notion of a dose-dependent effect of CCK-4-induced panic symptoms. Implications of these findings in the neurobiology of panic attacks are discussed.


Innate and adaptive immune responses are tolerized in chimeras prepared with nonmyeloablative conditioning.
Mixed chimerism is an effective approach for tolerance induction in transplantation. Strategies to achieve mixed chimerism with relatively low toxicity have significantly expanded the clinical use of chimerism. Allogeneic bone marrow transplants were performed between B6 (H2(b)) and BALB/c (H2(d)) mice. Recipient B6 mice were nonmyeloablatively conditioned with anti-αβ-T-cell receptor, anti-CD154, or rapamycin alone or in different combinations. A total of 15 × 10(6) BALB/c bone marrow cells were transplanted after varying doses of cGy of total body irradiation. Pretreatment of recipients with anti-CD154 and rapamycin with or without T-cell lymphodepletion reduced the total body irradiation requirement to 100 cGy for establishing stable mixed chimerism. The mixed chimeras accepted donor islet allografts long term. Lymphocytes from mixed chimeras did not respond to host or donor antigens, yet were reactive to major histocompatibility complex-disparate third-party alloantigens, demonstrating functional donor-specific T-cell tolerance. No antibodies against donor and host were detected in mixed chimeras, suggesting humoral tolerance. Mixed chimeras showed no cytotoxicity to donor cells, but a similar rapid killing rate for major histocompatibility complex disparate third-party B10.BR cells compared with T-cell-deficient and wild-type controls in in vivo cytotoxicity assays, suggesting donor-specific tolerance in the innate immune cells was achieved in mixed chimeras. Mixed chimeras prepared with low-intensity nonmyeloablative conditioning exhibit systemic tolerance in innate immunity and tolerance in adaptive T- and B-cell immune responses.


[Relationship between carbon dioxide combining power and contrast- induced acute kidney injury in patients with ST segment elevation myocardial infarction undergoing emergency percutaneous coronary intervention].
To study the relationship between carbon dioxide combining power(CO₂-CP) and contrast-induced acute kidney injury (CI-AKI) in patients with ST segment elevation myocardial infarction and undergoing percutaneous coronary intervention. We retrospectively analyzed 174 patients admitted to our hospital from March 2012 to August 2013 with ST segment elevation myocardial infarction and underwent emergency percutaneous coronary intervention. Patients were divided into three tertiles according to pre-operative CO₂-CP: T1 (CO₂-CP < 22.62 mmol/L), T2(CO₂-CP 22.62-24.30 mmol/L), T3(CO₂-CP > 24.30 mmol/L). Baseline clinical data, CI-AKI incidence, in-hospital mortality and dialysis rate were compared among groups. An increase in serum creatinine of >26.4 µmol/L and/or >50% from baseline within 48 hours after contrast exposure was defined as CI-AKI. Univariate logistic regression analysis was used to identify the risk factors of CI-AKI. The relationship between CO₂-CP and CI-AKI was assessed by multivariate logistic regression analysis. Receiver operating characteristic curve was used to identify the optimal cutoff of the CO₂-CP for predicting CI-AKI. CI-AKI occurred in 25 (14.4%) patients, and lower CO₂-CP was related to higher incidence of CI-AKI (27.6% (16/58) in group T1, 5.3% (3/57) in group T2, 1.7 % (1/59) in group T3, P = 0.002) and higher in-hospital mortality (10.3% (6/58) vs. 0 and 1.7% (1/59), P = 0.010). Dialysis rate was similar among 3 groups (5.2% (3/58) vs. 0 and 1.7% (1/59), P = 0.168). The incidence of CI-AKI was significantly associated with CO₂-CP < 22.00 mmol/L in univariate analyses (OR = 6.767, 95% CI 2.731-16.768, P < 0.001). After adjusting for potential confounding risk factors, CO₂-CP < 22.00 mmol/L remained significantly associated with the incidence of CI-AKI (OR = 5.835, 95%CI 1.800-18.914, P = 0.003) in multivariate logistic regression. ROC analysis revealed that the optimal cutoff of CO₂-CP to predict CI-AKI was 22.00 mmol/L (sensitivity 64.0%, specificity 79.1%, AUC = 0.714). Pre-percutaneous coronary intervention CO₂-CP in patients with ST segment elevation myocardial infarction undergoing percutaneous coronary intervention is related to CI-AKI. CO₂-CP < 22.00 mmol/L predicts higher risk of CI-AKI in this patient cohort.


Cholesterol biosynthesis from lanosterol: regulation and purification of rat hepatic sterol 14-reductase.
We have previously characterized the membrane-bound sterol 14-reductase (14-reductase) that catalyzes anaerobically NADPH-dependent reduction of the 14-double bond of delta 8,14-diene or delta 7,14-diene sterols that are sterol intermediates in cholesterol biosynthesis in mammals (Paik et al. (1984) J. Biol. Chem. 259, 13413-13423). To elucidate the regulatory mechanism as well as molecular characteristics of the 14-reductase, we extended our investigation on the consequences of alteration of the enzymic activity under various physiological conditions. The enzymic activity of rat hepatic sterol 14-reductase was induced more than 11-fold by feeding 5% cholestyramine plus 0.1% lovastatin (the CL-diet) for 7 days but was severely suppressed by feeding 5% cholesterol or 0.01% AY-9944 (an inhibitor of 14-reductase) for the same period. The increase or decrease in the 14-reductase activity also parallels the same change in the cholesterol synthetic rate in hepatocytes from rats that had been fed either the CL-diet or 0.01% AY-9944. In vitro inhibition studies revealed that AY-9944 acts as a competitive inhibitor of the 14-reductase (Ki = 0.26 microM). A diurnal variation was observed for the 14-reductase with peak activity near the middle of the dark cycle (10 p.m.), which was abolished by administration of cycloheximide. With induced enzyme conditions 14-reductase has been further purified with chromatographic procedures to near homogeneity. Purified 14-reductase appears to be a M(r) = 70,000 protein that is composed of two equally-sized subunits having a M(r) = 38,000. All properties of the purified 14-reductase suggest that the solubilized enzyme is the principal 14-reductase of microsomes. Taken together, our results provide the first evidence in support of a previously unknown regulatory role for the 14-reductase in the overall cholesterol synthetic pathway.


A Historical Perspective on the Reversal of Anticoagulants.
There has been a landmark shift in the last several decades in the management and prevention of thromboembolic events. From the discovery of parenteral and oral agents requiring frequent monitoring as early as 1914, to the development of direct oral anticoagulants (DOACs) that do not require monitoring or dose adjustment in the late 20th century, great advances have been achieved. Despite the advent of these newer agents, bleeding continues to be a key complication, affecting 2 to 4% of DOAC-treated patients per year. Bleeding is associated with substantial morbidity and mortality. Although specific reversal agents for DOACs have lagged the release of these agents, idarucizumab and andexanet alfa are now available as antagonists. However, the efficacy of these reversal agents is uncertain, and complications, including thrombosis, have not been adequately explored. As such, guidelines continue to advise the use of nonspecific prohemostatic agents for patients requiring reversal of the anticoagulant effect of these drugs. As the indications for DOACs and the overall prevalence of their use expand, there is an unmet need for further studies to determine the efficacy of specific compared with nonspecific pro-hemostatic reversal agents. In this review, we will discuss the evidence behind specific and nonspecific reversal agents for both parenteral and oral anticoagulants.


Translation and cross-cultural adaptation of the Wheelchair Skills Test (WST) version 4.3 form from English to Colombian Spanish.
Introduction: The World Health Organization estimates that in 2010, 15% of the world's population lived with some form of disability and 10% of these people required wheelchairs. Colombia and other Spanish-speaking countries lack reliable scales, and ones that are in Spanish, to assess wheelchair handling skills such as that provided by the Wheelchair Skills Test 4.3.Objective: To translate and cross-culturally adapt the Wheelchair Skills Test 4.3 form to Spanish, to be used with the Colombian population that uses a wheelchair.Materials and method: The design of this research uses a methodology that centres on validation studies and transcultural adaptation following the stages of translation, back translation and evaluation of translations by the author and expert judgement.Results: The adaptation had a global agreement index of 93.3 (Total Agreement Level). The three indicators were 92% relevance, 93.3% coherence and 94.5% sufficiency; and 22 of the 51 items evaluated (43.1%) had a 100% agreement level.Conclusions: The outcome of this transcultural adaptation was the Colombian Spanish version of the Wheelchair Skills Test (WST) 4.3 Form.Implications for rehabilitationFifteen per cent of the world's population (2010), and 10% of people with disabilities need wheelchairs.The Colombian population requiring the use of a manual wheelchair, 51% are limited in terms of "walking, running, jumping" and permanently limited in their movement for walk (29.32%).The use of reliable and cross-culturally adapted scales, such as the Wheelchair Wheelchair Skills Test (WST), is essential for rehabilitation personnel.The assessment of wheelchair user skills is fundamental to identify the level of participation in their respective communities as well as the development of their basic activities.


Activation of mitogen activated protein kinase in human platelets by genistein.
Genistein, a putative tyrosine kinase inhibitor, stimulated human platelet mitogen activated protein kinase (MAPK) activity in a dose- and time-dependent manner. When MAPK was maximally stimulated by phorbol 12-myristate 13-acetate (PMA), genistein still elicited the increase in MAPK activity. Staurosporine (50 nm), significantly decreased the PMA-induced MAPK activity, but had little inhibitory effect on the genistein-induced MAPK activity. Both these observations indicated a protein kinase C (PKC) independent pathway for the genistein-stimulated MAPK activity. When other tyrosine kinase inhibitors (methyl-2,5-dihydroxycinnamate, and tyrphostin) were employed, similar increases in the MAPK activity were observed. Addition of genistein to cytosolic fraction of platelets had no effect on the MAPK activity and indicated that this effect is not due to direct physical interaction between genistein and MAPK and that intact platelets are required for it. MAPK activity of platelets from rabbit and pig was also stimulated by genistein. This effect of genistein was not observed in other cell types tested (BNLCL2, HEL and U937 cells). Forskolin, which increases cyclic AMP had little effect on the basal platelet MAPK activity or the genistein activated MAPK, while it decreased by half the PMA-induced MAPK activity. The inactive analog of genistein, daidzein, which does not inhibit tyrosine kinase had little effect on MAPK. Genistein caused a decrease in basal tyrosine phosphorylation of pp60(c-src) protein as detected with anti-phosphotyrosine (anti-PTyr) Ab. Thus, inhibition of basal tyrosine kinase results in an increase in MAPK activity. This study demonstrates for the first time a novel mechanism for regulation of MAPK in platelets in which inhibition of tyrosine kinase results in activation of MAPK, independent of PKC and cAMP pathways.


Barbiturate and picrotoxin-sensitive chloride efflux in rat cerebral cortical synaptoneurosomes.
The effects of various barbiturates and picrotoxin in modifying the efflux of chloride (36Cl-) was studied in a novel subcellular preparation from rat cerebral cortex, the 'synaptoneurosome'. Dilution of synaptoneurosomes pre-loaded with 36Cl- resulted in rapid efflux of 36Cl- that could be measured as early as 10 s following dilution. In the presence of barbiturates such as pentobarbital and hexobarbital there was a significant increase in 36Cl- efflux which was not observed with the pharmacologically-inactive barbiturate, barbital. The effect of barbiturates in enhancing 36Cl- efflux was also stereospecific [(-)-DMBB greater than (+)-DMBB] and reversed by picrotoxin. By contrast, picrotoxin alone significantly inhibited 36Cl- efflux. These data demonstrate pharmacologically relevant Cl- transport for the first time in a subcellular brain preparation.


COVID-19 Is Straining Mental Health-Could Technology Be the Answer?
One of the most pernicious side effects of the COVID-19 pandemic is a steep rise in stress and mental health problems. According to a poll by the Kaiser Family Foundation, nearly half of American adults say that worry and stress about the pandemic is hurting their mental health [1]. There are plenty of factors feeding into this phenomenon. People are anxious about getting sick, grieving lost loved ones, and experiencing financial stress, parental stress, and loneliness. The pandemic places additional burdens on essential workers and people of color, both of whom are at greater risk of dying from the disease. COVID-19 itself has been linked to neurological problems as well as anxiety, depression, and sleep disorders [2].


Self-report measures for assessing treatment outcomes in cardiac surgery patients.
Patient self-report measures are increasingly valued as outcome variables in health services research studies. In this article, the authors describe the Functional Status, Health Related Quality of Life, Life Satisfaction, and Patient Satisfaction scales included in the Processes, Structures, and Outcomes of Cardiac Surgery (PSOCS) cooperative study underway within the Department of Veterans Affairs health care system. In addition to reporting on the baseline psychometric characteristics of these instruments, the authors compared preoperative Medical Outcomes Study SF-36 data from the study patients with survey data from a probability sample of the US population and with preoperative data on cardiac surgery patients from a high volume private sector surgical practice. Descriptive analyses indicate that the SF-36 profiles for all of the cardiac patients are highly similar. The Veterans Affairs and private sector patients report diminished physical functioning, physical role functioning, and emotional role functioning as well as reduced energy relative to an age-matched comparison sample. At the same time, however, the Veterans Affairs patients evidenced lower levels of capacity on most of the SF-36 dimensions relative to the private sector patients.


Immunohistochemical and morphological studies on the human fetal cochlea: a comparative view on methods.
The preservation of morphology and antigenicity can vary uncontrollably with human fetuses since these rely heavily on immediate fixation of the temporal bone following spontaneous abortion. Once good fixation is established, there is the question of the approach taken for morphologic and immunohistochemical studies. To achieve maximal preservation for the purpose of studying normal and pathologic fetal cochleae, commonly used preparation methods for analyzing the cochlea were reviewed and compared for both immunohistochemical and morphologic studies. Cochleae obtained after spontaneous abortion ranged from the 9th gestational week to birth. Four different methods were compared for morphologic study: the block surface method; a microslicing technique; paraffin; and celloidin sectioning. For immunohistochemical study, three methods were compared: pre-embedding; paraffin; and frozen sectioning. For morphologic preservation, the block surface method gave best overall results, showing good representation of the fetal cochlea for surface preparation, light, and electron microscopy. Celloidin sectioning was also found to show good light microscopic results for both the middle and inner ear. To achieve optimal results, preservation quality, fixation procedures, and antibody all contribute to the efficacy of a methods choice.


Portopulmonary hypertension: Still an appropriate consideration for liver transplantation?
Liver transplantation (LT) in patients with portopulmonary hypertension (PoPH) has historically resulted in unpredictable and often poor outcomes. The United Kingdom experience for the period 1992-2012 is reported in this article. A retrospective analysis of patients, preoperatively fulfilling the PoPH European Respiratory Society Task Force on Pulmonary-Hepatic Vascular Disorders diagnostic criteria was conducted across all UK LT centers. Data collection included comorbidities, use of preoperative and postoperative pharmacotherapy, patient survival, and cause of death. To enable survival stratification, PoPH was classified as mild, moderate, or severe based on mean pulmonary pressure of <35 mm Hg, 35-49 mm Hg, and ≥50 mm Hg, respectively. Of 127 patients reported to have PoPH, just 28 fulfilled the diagnostic criteria (14 mild, 9 moderate, 5 severe). Twenty (71.4%) patients were male with median age and Model for End-Stage Liver Disease of 50 years (range, 23-62 years) and 18 (range, 6-43), respectively. Twelve (42.9%) patients died within 5 years of LT. The majority of deaths (10 of 12; 83%) occurred within the first 6 months after LT, aetiologies of which included right heart failure (n = 3), progressive PoPH (n = 2), and sepsis (n = 2). Of those receiving preoperative pharmacotherapy (n = 8), 5 are currently alive and were classified as mild to moderate PoPH. Both severe PoPH patients optimized preoperatively with pharmacotherapy died within a year of LT. Development of effective vasodilatory therapies in the setting of pulmonary arterial hypertension has led to a dramatic improvement in patient survival. The available data indicate that in this era of pharmacotherapy, PoPH in isolation no longer represents a valid consideration to transplant. Liver Transplantation 22 1637-1642 2016 AASLD.


First and efficient synthesis of phosphonodifluoromethylene analogues of nucleoside 3'-phosphates: crucial role played by sulfur in construction of the target molecules.
Phosphoric esters of secondary alcohols are ubiquitous in biological systems. However, despite the obvious interest of the corresponding difluoromethylene phosphonates as isopolar mimics, a single example of such an analogue featuring this particular substitution pattern has so far been reported in the literature, due to synthetic problems associated with their preparation. The lithium salt of diethyl difluoromethylphosphonothioate 28d provides a solution to this problem, as demonstrated by an 8-step synthesis of all five fully protected analogues of nucleoside 3'-phosphates in 9-18% overall yield, from readily available ketones. Sulfur is shown to play a crucial role in the introduction of the phosphorus-substituted difluoromethylene unit onto the furanose ring. Complete diastereoselectivity is observed in the three steps of the process requiring stereocontrol. The key conversion of the P=S bond into its oxygenated analogue is simply achieved by use of m-chloroperoxybenzoic acid. It is noteworthy that the synthesis can be carried out on large scale: a 31-g batch of compound 26b has been prepared. The deprotected nucleoside 3'-phosphate analogues can be liberated from their precursors as exemplified by the conversion of 7b, 8b, and 9b into the corresponding difluorophosphonic acids, isolated in the form of their disodium salts.


Homeostatic competition drives tumor growth and metastasis nucleation.
We propose a mechanism for tumor growth emphasizing the role of homeostatic regulation and tissue stability. We show that competition between surface and bulk effects leads to the existence of a critical size that must be overcome by metastases to reach macroscopic sizes. This property can qualitatively explain the observed size distributions of metastases, while size-independent growth rates cannot account for clinical and experimental data. In addition, it potentially explains the observed preferential growth of metastases on tissue surfaces and membranes such as the pleural and peritoneal layers, suggests a mechanism underlying the seed and soil hypothesis introduced by Stephen Paget in 1889, and yields realistic values for metastatic inefficiency. We propose a number of key experiments to test these concepts. The homeostatic pressure as introduced in this work could constitute a quantitative, experimentally accessible measure for the metastatic potential of early malignant growths.


Assignment of aluminum corroles absorption bands to electronic transitions by femtosecond polarization resolved VIS-pump IR-probe spectroscopy.
We combine femtosecond polarization resolved VIS-pump IR-probe spectroscopy with DFT and TD-DFT calculations to identify and assign absorption bands to electronic transitions for corroles. These macrocycles and their corresponding metal complexes are receiving great attention because of their utility in many fields, while many of their spectroscopic features have not yet been fully described. Analysis of the perturbed free induction decay provides information about the bleaching signal at time zero and allows for determination of overlapping excited state and bleaching signal amplitudes. The S(0) → S(1) and S(0) → S(2) transitions in the Q-band of the hexacoordinated Al(tpfc)(py)(2) and Br(8)Al(tpfc)(py)(2) absorption spectra are explicitly assigned. Angles between these electronic transition dipole moments (tdms) with a single vibrational transition dipole moment of (53 ± 2)° and (34 ± 2)° when excited at 580 and 620 nm for hexacoordinated Al(tpfc)(py)(2) and (51 ± 2)° and (43 ± 2)° when excited at 590 and 640 nm for hexacoordinated Br(8)Al(tpfc)(py)(2) were determined. The relative angles between the two lowest electronic tdms are (90 ± 8)° and (94 ± 3)° for Al(tpfc)(py)(2) and Br(8)Al(tpfc)(py)(2), respectively. Angles are determined before time zero by polarization resolved perturbed free induction decay and after time zero by polarization resolved transients. Comparison of corrole's wave functions with those of porphine show that the reduced symmetry in the corrole molecules results in lifting of Q-band degeneracy and major reorientation of the electronic transition dipole moments within the molecular scaffold. This information is necessary in designing optimal corrole-based electron and energy transfer complexes.


Selection of Cashmere Fineness Functional Genes by Translatomics.
Cashmere fineness is an important index to evaluate cashmere quality. Liaoning Cashmere Goat (LCG) has a large cashmere production and long cashmere fiber, but its fineness is not ideal. Therefore, it is important to find genes involved in cashmere fineness that can be used in future endeavors aiming to improve this phenotype. With the continuous advancement of research, the regulation of cashmere fineness has made new developments through high-throughput sequencing and genome-wide association analysis. It has been found that translatomics can identify genes associated with phenotypic traits. Through translatomic analysis, the skin tissue of LCG sample groups differing in cashmere fineness was sequenced by Ribo-seq. With these data, we identified 529 differentially expressed genes between the sample groups among the 27197 expressed genes. From these, 343 genes were upregulated in the fine LCG group in relation to the coarse LCG group, and 186 were downregulated in the same relationship. Through GO enrichment analysis and KEGG enrichment analysis of differential genes, the biological functions and pathways of differential genes can be found. In the GO enrichment analysis, 491 genes were significantly enriched, and the functional region was mainly in the extracellular region. In the KEGG enrichment analysis, the enrichment of the human papillomavirus infection pathway was seen the most. We found that the COL6A5 gene may affect cashmere fineness.


Attempts to detect cyclic adenosine 3':5'-monophosphate in higher plants by three assay methods.
Endogenous levels of cyclic adenosine-3':5'-monophosphate in coleoptile first leaf segments of oat (Avena sativa L.), potato (Solanum tuberosum L.) tubers, tobacco (Nicotiana tabacum L.) callus, and germinating seeds of lettuce (Lactuca sativa L.) were measured with a modified Gilman binding assay and a protein kinase activation assay. The incorporation of adenosine-8-(14)C into compounds with properties similar to those of cyclic AMP was also measured in studies with germinating lettuce seeds. The binding assay proved reliable for mouse and rat liver analyses, but was nonspecific for plant tissues. It responded to various components from lettuce and potato tissues chromatographically similar to but not identical with cyclic AMP. The protein kinase activation assay was much more specific, but it also exhibited positive responses in the presence of compounds not chromatographically identical to cyclic AMP. The concentrations of cyclic AMP in the plant tissues tested were at the lower limits of detection and characterization obtainable with these assays. The estimates of maximal levels were much lower than reported in many previous studies.


In vitro evaluations of U-76,252 (CS-807): antimicrobial spectrum, beta-lactamase stability, and enzyme inhibition.
Compound U-76,252 (Upjohn) is a cephalosporin ester that enhances oral absorption of the active free acid cephem, U-76,253. The active form structurally resembles parenteral aminothiazolyl-methoxyimino cephalosporins such as cefotaxime and its desacetyl metabolite. The g-negative antimicrobial activity of U-76,253 A (sodium salt of U-76,253) was most similar to that of cefixime and more potent than that of cefaclor or cefuroxime among the orally administered cephalosporins. Against g-positive bacteria, U-76,253 A was more active than cefixime. U-76,253 A was relatively stable to hydrolysis by five beta-lactamases (Type Ia, TEM-1, K1, CARB-2, and OXA-1), a stability most similar to cefotaxime and superior to that of cefaclor. Only the Type Ia (P99) enzyme was significantly inhibited by U-76,253 (IC 50 = 2.0 microM).


Assessment of endometrial differentiation and function.
The failure to produce an endometrium which is receptive and able to support implantation may underlie some cases of infertility and represent a contributory factor preventing higher pregnancy rates in IVF. This is of direct relevance to ovarian hyperstimulation protocols which may affect the pattern of endometrial differentiation and function and to patients possessing intrinsic defects in their endometrial response. It is apparent that markers of endometrial differentiation are required, particularly those defining the ability of the tissue to support implantation. The common method of assessing endometrial differentiation by histological evaluation, which has been substantially improved by techniques of morphometric analysis, depend upon alterations in endometrial structure. However, the production of monoclonal antibodies to proteins and epitope-bearing mucins which exhibit specific patterns of expression during the luteal phase now also enables immunohistological assessment of endometrial differentiation. Whether these proteins mediate essential functions is not known but as they represent end-points of hormone action this would suggest that their measurement may form the basis of tests of endometrial function and supplement morphometric analyses.


Spatio-temporal clustering of Baylisascaris procyonis, a zoonotic parasite, in raccoons across different landscapes in southern Ontario.
Baylisascaris procyonis, the raccoon roundworm, is a parasite found throughout North America and parts of Europe. More than 150 species of mammals and birds including humans can develop neurological disease following infection with the larval stage of this parasite. To investigate whether B. procyonis infections in raccoons cluster in space, time, or space-time, we used data from 1353 Ontario raccoons submitted to the Canadian Wildlife Health Cooperative between 2013 and 2016. We identified a significant spatial cluster of increased infection prevalence in southern Ontario centered over a major metropolitan area, as well as a significant cluster of decreased infection prevalence in a primarily agricultural region in southwestern Ontario. Furthermore, we identified statistically significant temporal clusters in the fall in annual scans of data from 2014, 2015 and 2016. Examination of both Bernoulli and space-time permutation models for space-time analysis suggested that the purely spatial and temporal clusters were not explained by relatively short and spatially discrete events in space-time. The identified annual temporal clusters are consistent with previous research on the seasonality of B. procyonis infection in raccoons. Recognition of the spatial infection clusters will help identify potential geographic and anthropogenic factors associated with the occurrence of B. procyonis infection in raccoons. Given the zoonotic potential of this parasite, identification of a cluster of high infection prevalence in a major metropolitan area has implications for public education and risk management strategies.


Social participation and employment status after kidney transplantation: a systematic review.
To summarize and assess literature regarding social participation of recipients after successful kidney transplantation. A systematic review including a literature search in Medline (1980-2003) and five other databases, and assessment of methodological quality of selected studies by two reviewers applying a checklist of twelve criteria. Seventeen studies out of 1443 identified references were selected. Quality scores for internal validity ranged from 0% to 50% (median 20%). Employment was the most used indicator of social participation and two studies briefly reported on vacation and recreation. Employment rate ranged from 18% to 82%, however differences in defining categories of employment or lack of description were present. Study populations were heterogeneous with regard to demographic and clinical characteristics. Three studies identified pre-transplant employment status as predictor of post-transplant employment. Other potential risk factors were not consistent across studies. Measurement of social participation focuses mainly on employment status. Quality assessment revealed shortcomings in reporting and validity of studies, whereby valid conclusions regarding the degree of social participation after kidney transplantation cannot be drawn. Future research should supplement the focus on employment status by examining other aspects of social participation as well as potential risk factors.


A simple protocol for identification of helical and mobile residues in membrane proteins.
A simple molecular dynamics (MD) simulations is protocol shown to predict whether a residue is in a structured alpha-helical segment or in a mobile loop or terminal segment of a membrane protein. The results are verified by comparisons with experimental NMR data. The protocol consists of performing several independent MD simulations on a polypeptide sequence of interest in a dielectric continuum with a relative permittivity epsilon = 2. The time histories of the individual angles between NH bond vectors at time 0 and time t later are calculated, and then Gaussian smoothing of typically 50 ps is applied. The smoothed data are subtracted from the original data to yield the short time fluctuations of the NH bond vectors, and then the rms deviations of the angles are calculated and compared to experimental NMR results. Pf1 coat protein and the c subunit of the E. coli F1F0 ATP synthase are used as examples of membrane proteins. The calculated NH bond rms fluctuations are in qualitative agreement with experimental NMR data in showing that each of these proteins has a mobile segment connecting two helices, as well as mobile N and C-terminal regions. This MD simulations protocol can demonstrate the presence of both the amphipathic and hydrophobic helices while hydropathy plots are able to detect only the hydrophobic helices present in membrane proteins.


Review on Approved and Inprogress COVID-19 Vaccines.
The last generation of Coronavirus named COVID-19 is responsible for the recent worldwide outbreak. Concerning the widespread and quick predominance, there is a critical requirement for designing appropriate vaccines to surmount this grave problem. Correspondingly, in this revision, COVID-19 vaccines (which are being developed until March 29th, 2021) are classified into specific and non-specific categories. Specific vaccines comprise genetic-based vaccines (mRNA, DNA), vector-based, protein/recombinant protein vaccines, inactivated viruses, live-attenuated vaccines, and novel strategies including microneedle arrays (MNAs), and nanoparticles vaccines. Moreover, specific vaccines such as BCG, MRR, and a few other vaccines are considered Non-specific. What is more, according to the significance of Bioinformatic sciences in the cutting-edge vaccine design and rapid outbreak of COVID-19, herein, Bioinformatic principles including reverse vaccinology, epitopes prediction/selection and, their further applications in the design of vaccines are discussed. Last but not least, safety, challenges, advantages, and future prospects of COVID-19 vaccines are highlighted.


Supervised Classification of Operator Functional State Based on Physiological Data: Application to Drones Swarm Piloting.
To improve the safety and the performance of operators involved in risky and demanding missions (like drone operators), human-machine cooperation should be dynamically adapted, in terms of dialogue or function allocation. To support this reconfigurable cooperation, a crucial point is to assess online the operator's ability to keep performing the mission. The article explores the concept of Operator Functional State (OFS), then it proposes to operationalize this concept (combining context and physiological indicators) on the specific activity of drone swarm monitoring, carried out by 22 participants on simulator SUSIE. With the aid of supervised learning methods (Support Vector Machine, k-Nearest Neighbors, and Random Forest), physiological and contextual are classified into three classes, corresponding to different levels of OFS. This classification would help for adapting the countermeasures to the situation faced by operators.


EEG source estimation accuracy in presence of simulated cortical lesions.
Methods to reconstruct the neuroelectrical activity in the brain source space can be used to improve the spatial resolution of scalp-recorded EEG and to estimate the locations of electrical sources in the brain. This procedure can improve the investigation of the functional organization of the human brain, exploiting the high temporal resolution of EEG to follow the temporal dynamics of information processing. As for today, the uncertainties about the effects of inhomogeneities due to brain lesions preclude the adoption of EEG functional mapping on patients with lesioned brain. The aim of this work is to quantify the accuracy of a distributed source localization method in recovering extended sources of activated cortex when cortical lesions of different dimensions are introduced in simulated data. For this purpose, EEG source-distributed activity estimated from real data was modified including silent lesion areas. Then, for each simulated lesion, forward and inverse calculations were carried out to localize the produced scalp activity and the reconstructed cortical activity. Finally, the error induced in the reconstruction by the presence of the lesion was computed and analyzed in relation to the number of electrodes and to the size of the simulated lesion. Results returned values of global error in the whole cortex and of error in the non-lesioned area which are strongly dependent on the number of recorded scalp sensors, as they increase when a lower spatial sampling is performed on the scalp (64 versus 32 EEG channels). For increasing spatial sampling frequencies, the accuracy of the source reconstruction improves and even the presence of small lesions induces significantly higher error levels with respect to the lesion-free condition.


[Clinical efficacy evaluation of needle-knife for lumber disc herniation based on surface electromyography signals].
To apply needle-knife to treat lumber disc herniation (LDH) and surface electromyography were used to analyze biomechanical characteristic of patient's lumber muscle to make a comprehensive evaluation on its efficacy. Thirty patients who met the inclusive criteria were selected and treated with needle-knife, once a week for 2 weeks. Visual analogue scale (VAS), ASLR and JOA score before and after treatment were observed. Surface electromyography was applied to test the surface electromyography signals. AEMG, MFs and MPF were calculated before and after the treatment. After treatment, VAS was significantly reduced, ASLR, JOA, AEMG and MPF were obviously increased, and the absolute value of MFs was lowed (all P < 0.01). The needle-knife could significantly relieve lumbar muscle strength, muscle tone and muscle fatigue, improve in the imbalance of lumbar extensor muscle group, leading to the recovery of biomechanical characteristic, and the clinical efficacy is superior.


Environmental, maternal, and child factors which contribute to early childhood caries: a unifying conceptual model.
Although the general pathways connecting the external social environment and child risk factors of early childhood caries (ECC) have been previously identified, the maternal and other links to ECC are not well understood. The aim of this paper is to propose a unifying conceptual model that ties together the broad social environmental, maternal, and child factors that are commonly associated with ECC. The aetiological factors of ECC are first reviewed individually to demonstrate their connections with ECC risk followed by presentation of the unifying conceptual model. In severe ECC cases, there is usually a background of social disadvantage associated with low socioeconomic status, ethnicity or immigrant status, and low maternal educational level. These factors are commonly associated with economic and familial stresses which may in turn result in maternal psychological distress. The distress may be compounded by difficult temperaments of the children and can lead to dysfunctional parenting behaviours that place a child at risk for ECC. The proposed conceptual model provides a framework that connects the social, psychological, and behavioural mediating factors involved in ECC. It demonstrates that the causative pathways involved are best explored using a combination of quantitative and qualitative research.


Prevalence and associated factors of suicidal behavior among pregnant mothers in southern Ethiopia: a cross-sectional study.
Suicidal behavior among pregnant mothers is one of the most common psychiatric emergencies that require a major public health concern by researchers and mental health task forces. Pregnant mothers experience suicidal attempt, which is a fatal problem to end life. Therefore, there was a need to assess the prevalence and associated factors of suicidal behavior among pregnant mothers to integrate mental health care, particularly suicide, with maternal management. A cross-sectional study was conducted among 504 pregnant mothers in the Gedeo zone, southern Ethiopia. Suicidal behavior was assessed using revised suicidal behavior questionnaire (SBQ-R) with a total score of 3-18; those scoring ≥7 were considered as having Suicidal behavior. Data were entered into Epi-data 3.1 and analyzed using SPSS version 20. Bivariate and multivariate binary logistic regression analysis was performed to identify associated factors of suicidal behavior. Variables with a P-value less than 0.05 with 95% CI were considered statistically significant. In this study, the overall prevalence of suicidal behavior among pregnant mothers was 47(9.3%) with 95% CI (7.1- 11.9). Regarding the factors; being unmarried [AOR = 5.69, 95% CI, (1.19, 27.23)], gestation age greater than 27 weeks, [AOR = 4.92, 95% CI (1.67, 14.53)], history of having chronic medical illness [AOR = 4.47, 95% CI (1.35, 14.85)], depression [AOR = 4.20, 95% CI (1.90, 9.28], and intimate partner violence [AOR = 7.60, 95% CI (3.27, 17.67)] were significantly associated with suicidal behavior at P value less than 0.05 and corresponding 95% CI. Pregnant mothers in the community had a high prevalence of suicidal behavior compared to studies conducted among general populations. It is better to include and implement the assessment of suicidal risk factors as a primary treatment package for pregnant mothers, training of health extension workers and other primary health workers on how to assess the risk of suicide among pregnant mothers is warranted.


Development of a multicomponent implementation strategy to reduce upper gastrointestinal bleeding risk in patients using warfarin and antiplatelet therapy, and protocol for a pragmatic multilevel randomized factorial pilot implementation trial.
The concomitant use of anticoagulant and antiplatelet medications increases the risk of upper gastrointestinal (GI) bleeding. Two underused evidence-based practices (EBPs) can reduce the risk: de-prescribe unnecessary antiplatelet therapy or initiate a proton pump inhibitor. We describe the development of a multicomponent intervention to increase use of these EBPs in patients treated with warfarin and followed by an anticoagulation monitoring service (AMS), and the design of a pilot pragmatic implementation trial. A participatory planning group iteratively used Implementation Mapping and the Multiphase Optimization Strategy to develop implementation strategies and plan the trial. Informed by qualitative interviews with patients and clinicians, we drew on several implementation science theories, as well as self-determination theory, to design interventions. For patients, we developed an activation guide to help patients discuss the EBPs with their clinicians. For clinicians, we developed two electronic health record (EHR)-based interventions: (1) clinician notification (CN) consists of a templated message that identifies a patient as high risk, summarizes the EBPs, and links to a guidance statement on appropriate use of antiplatelet therapy. (2) Clinician notification with nurse facilitation (CN+NF) consists of a similar notification message but includes additional measures by nursing staff to support appropriate and timely decision-making: the nurse performs a chart review to identify any history of vascular disease, embeds indication-specific guidance on antiplatelet therapy in the message, and offers to assist with medication order entry and patient education. We will conduct a pilot factorial cluster- and individual-level randomized controlled trial with a primary objective of evaluating feasibility. Twelve clinicians will be randomized to receive either CN or CN+NF for all their patients managed by the AMS while 50 patients will be individually randomized to receive either the activation guide or usual care. We will explore implementation outcomes using patient and clinician interviews along with EHR review. This pilot study will prepare us to conduct a larger optimization study to identify the most potent and resource conscious multicomponent implementation strategy to help AMSs increase the use of best practices for upper GI bleeding risk reduction. ClinicalTrials.gov NCT05085405 . Registered on October 19, 2021-retrospectively registered.


Mutational uncoupling of the transcriptional activation function of the TyrR protein of Escherichia coli K-12 from the repression function.
The tyrosine repressor (TyrR) protein of Escherichia coli can function either as a transcriptional enhancer or as a repressor. The structural basis for these opposite effects was analyzed in specific tyrR deletion mutants constructed in vitro. The functional behavior of the mutant TyrR proteins was evaluated in vivo by using single-copy lacZ reporter systems based on the mtr promoter (10-fold activation by wild-type TyrR protein, mediated by phenylalanine or tyrosine) or the aroF promoter (over 20-fold repression by wild-type TyrR protein, mediated by tyrosine). A mutant TyrR protein lacking amino acids 2 to 9 was completely devoid of transcriptional activation function. Five additional mutant TyrR proteins lacking progressively greater numbers of N-terminal amino acids were likewise activation defective. The mutant TyrR proteins lacking amino acid residues 2 to 9 or 2 to 19 were essentially identical to the wild-type TyrR protein in their ability to repress the aroF promoter. Three other TyrR mutant proteins, lacking up to 143 amino acid residues from the N-terminal end of the protein, retained the ability to repress the aroF promoter, to different extents, in a tyrosine-dependent manner.


[Studies on the existence of renin in the human testis].
Recent reports have shown the existence of renin in Leydig cells of the rat testis and immunoreactive renin activity in the human testis. But we could not rule out the possibility that the renin found in the testis is contamination of plasma components by endocytosis. In the present study we tried to demonstrate the renin production in the human testis by the following experiments. At first, we measured the plasma renin activity and testosterone in the internal spermatic vein simultaneously after treatment with hCG and obtained the results that suggested hCG-induced renin secretion in the human testis. Next, we showed the hCG-dependent renin production from the cultured human Leydig cell tumors in vitro. Thirdly, we demonstrated the existence of renin mRNA in the human testisusing reverse transcriptase-polymerase chain reaction (RT-PCR). Fourthly, we detected significant signals of human renin mRNA in the human testicular tissues by in situ hybridization. From the above results, it was demonstrated that the human renin gene was hCG-dependently expressed in the human testis.


Assessment of Movement Skill Performance in Preschool Children: Convergent Validity Between MOT 4-6 and M-ABC.
The purpose was to determine the level of agreement between the Motoriktest für Vier- bis Sechsjährige Kinder [MOT 4-6] and the Movement Assessment Battery for Children [M-ABC]. 48 preschool children participated in the study (Mean age = 5 years, 6 months, SD = 3 months). There was high classification agreement (90%) between both tests. A Kappa correlation coefficient (0.67) provided moderately strong support for convergent validity. Less agreement was shown in identification of motor difficulties (58%). This was reflected by lower correlation coefficients on the fine movement cluster and test item level. The MOT 4-6 showed values within the range of similar movement skill performance assessment protocols. Because of its specific focus it may be of meaningful value to assess movement skill competence in typically developing preschool children (ages 4 to 6). Key pointsThe Motoriktest für Vier- bis Sechsjährige Kinder (MOT 4-6) showed values within the range of similar motor performance tests. Because of its specific focus it may be of great value to assess movement skill competence in typically developing preschool children (ages 4 to 6).Children's movement skill competence can be expressed as a single composite score. The results from this study also support the use of composite scores that include functional categorization (e.g. locomotion, object control and stability).


Post-traumatic cubitus varus: long-term follow-up of corrective osteotomy using the Ilizarov method of compression distraction osteogenesis.
The term cubitus varus describes the inward inclination of the supinated forearm on the extended elbow. The deformity manifests clinically as a decreased carrying angle, decreased range of motion (ROM) along with a cosmetically unsightly appearance. The aim of the present study was to evaluate the technique of compression-distraction osteogenesis using the Ilizarov apparatus in the management of patients with post-traumatic cubitus varus deformity. The objectives were to study the impact of this method on the ROM, the Humerus Elbow Wrist (HEW) angle as well as the Lateral Prominence Index. A total of 32 patients who presented with a cubitus varus deformity of ≥10° at the elbow were retrospectively analyzed using data retrieved from a computerized hospital database. All patients had undergone a mini-incision subperiosteal osteotomy followed by application of an Ilizarov frame. Cinico-radiological follow-up was carried out at regular intervals until union was achieved and yearly thereafter. The mean time to union was 11 weeks. The mean follow-up period ranged from 2 to 12 years (mean 4.0 years). Results were graded as excellent in 25 cases (78.1%), good in 2 (6.3%) and poor in 5 case (15.6%) using the grading system of Oppenheim. The mean HEW angle at final follow-up improved from 20° of varus to 6° of valgus. The mean flexion/extension improved from 121°/-3° preoperatively to 125°/-4° at final follow-up. The Mayo Elbow Performance scores at final follow-up were excellent in 23 cases, good in 7 and fair in 2. Complications encountered included superficial pintract infections in three cases, lateral condylar prominence in one case, loss of terminal flexion in three cases and valgus over-correction in one case.


Intrapleural palliative treatment of malignant pleural effusions with mitoxantrone versus placebo (pleural tube alone).
From 11/87 until 7/90 103 patients entered a prospective randomized trial on the treatment of malignant pleural effusions (MPE) with intrapleural mitoxantrone versus placebo (pleural tube alone with instillation of isotonic NaCl). Our data suggest no statistically significant difference between the two arms with respect to response and response duration. There is no influence on survival time. The toxicity is moderate, with only fever occurring more often in the mitoxantrone arm. We recommend performance of pleurodesis in patients with MPE first by sufficient drainage with a tube of 16-20 char. Only in instances of failure it is necessary to add sclerosing agents such as tetracycline, etc.


Household projection methods.
"The role of household projections as a basis for forecasts of households at [the] national and sub-national level is discussed and a number of criteria for such projections are outlined. The projection method used by the Department of the Environment [in the United Kingdom] is examined in the context of these criteria and it is concluded that it is both practical and robust. However, it is open to criticism, first because of its failure to make the best use of the available data and of theoretical knowledge, and secondly because of its 'black box' nature. An alternative two-stage strategy is developed. The first stage involves constructing projections using a new curve-fitting method which takes account of within cohort life-cycle headship rate changes. The second is a method of analysing the resulting projections by modelling transition rates between different household states. Worked examples of both methods are presented."


Clinical Neuropsychological Profile and Quality of Life in Women Who Have Suffered Gender-Based Violence.
This research characterizes the clinical and neuropsychological profiles and the quality of life in a group of Ecuadorian women who suffered physical violence, psychological violence, or sexual violence, exploring their relationships with sociodemographic factors. A battery of tests were used to explore the clinical and neuropsychological functions and quality of life in 120 participants who were selected from a population affected by violence. Sixty percent of the participants showed clinical anxiety, 26.7% clinical depression, 40% post-traumatic stress disorder symptoms, 15% moderate personality disorder, and 51.7% a low quality-of-life index. Their Z-scores in the neuropsychological domains evaluated were verbal memory (Rey Auditory Verbal Learning Test = -1.35), working memory (Digits = -1.67), attention (D2 = -1.24), processing speed (Coding = -1.33; Trail Making Test A = 1.81), and executive function (Trail Making Test B = -1.15; Stroop = -0.20; verbal-semantic fluency test = 0.05; verbal fluency test = -1.23). The majority of women who suffered gender-based violence presented clinical levels of anxiety, depression, and post-traumatic symptoms. The cognitive functions with lower scores (Z < -1.5) were working memory and processing speed, mediated by education factor.


[Effect of carbon disulfide on mitochondrial respiratory chain in spermatogenic cells in male rats].
To investigate the effect of carbon disulfide (CS(2)) on the mitochondrial respiratory chain in testicular spermatogenic cells in male rats and to explore the possible mechanism of reproductive system damage caused by CS(2) in male rats. Twenty-four male Sprague-Dawley rats (clean grade) were randomly divided into four groups: three CS(2) exposure groups (CS(2) concentrations: 50, 250, and 1250 mg/m(3)) and a control group. The rats in CS(2) exposure groups were exposed to CS(2) by static inhalation for 10 weeks (2 h/d, 5 d/w), while the rats in control group were exposed to air. Then, all rats were sacrificed by decapitation; testicular tissues were collected, and mitochondrial protein in spermatogenic cells were extracted; the levels of mitochondrial respiratory chain enzyme complex I∼V were measured by enzyme-linked immunosorbent assay. Compared with the control group, all CS(2) exposure groups had significantly increased levels of mitochondrial respiratory chain enzyme complex I∼V in spermatogenic cells (P < 0.05). There were no significant differences in the levels of respiratory chain enzyme complex I∼IV between the CS(2) exposure groups (P < 0.05), but the level of respiratory chain enzyme complex V rose significantly as the concentration of CS(2) increased (P<0.05). Various levels of CS(2) exposure may increase the levels of mitochondrial respiratory chain enzyme complex in testicular spermatogenic cells among male rats, thus affecting the normal oxidative phosphorylation in mitochondria.


Randomized trial of effects of continuous combined HRT on markers of lipids and coagulation in women with acute coronary syndromes: WHISP Pilot Study.
Randomized trials have not demonstrated coronary heart disease benefit from hormone replacement therapy (HRT). We hypothesized that low-dose HRT may avoid harm. We studied the effects of HRT on lipids and coagulation in women with acute coronary syndromes. A total of 100 post-menopausal women >55 years were enrolled between 2 and 28 days after an acute coronary syndrome and randomized to oral oestradiol-17beta 1 mg plus norethisterone acetate 0.5 mg daily, or matching placebo, and followed for up to 12 months. Levels of lipids, lipoproteins, and haemostasis markers were measured at baseline, 3, and 6 months. There were no significant differences in lipid levels between the two groups, probably due to concomitant statin use. Antithrombin and factor VII levels were significantly lower in the HRT group, whereas fibrinogen was significantly decreased in the placebo group. No evidence of increased coagulation activation was observed, nor of adverse cardiovascular outcomes [odds ratio (OR) 0.63 (95% confidence intervals 0.31-1.31)]. Low-dose HRT may give cardiovascular benefit. These findings require confirmation in a full clinical trial with evaluation of cardiovascular outcomes as the primary objective.


Degradation of 3-hydroxy-3-methylglutaryl-CoA reductase in endoplasmic reticulum membranes is accelerated as a result of increased susceptibility to proteolysis.
The endoplasmic reticulum (ER) membrane protein 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase is subject to regulated degradation when cells are presented with an excess of sterols or mevalonate. In this report, we demonstrate the degradation of HMG-CoA reductase in ER membranes prepared from cells which have been pretreated with mevalonate or sterols prior to membrane purification. Degradation of HMG-CoA reductase in membranes prepared from pretreated cells is more rapid than in membranes prepared from cells which have received no regulatory molecules. In vitro degradation is blocked by protease inhibitors previously shown to inhibit reductase degradation in vivo and is specific for intact HMG-CoA reductase. The lumenal contents of the ER membranes are dispensible for the regulated proteolysis and the proteases responsible for reductase degradation are stably associated with the ER membrane. Regulated proteolysis of HMG-CoA reductase is inhibited by lactacystin, a newly defined inhibitor of the multicatalytic protease, the proteasome, and in vitro degradation of reductase correlates with the presence of proteasome subunits in purified ER membranes. The ubiquitin system for protein degradation, which has recently been shown to be required for the degradation of several ER membrane proteins, is not required for the degradation of HMG-CoA reductase. Finally, we conclude that the regulated proteolysis of HMG-CoA reductase in response to regulatory molecules such as mevalonate or sterols is mediated by increased susceptibility of the reductase to ER proteases, rather than the induction of a new proteolytic activity.


Occurrence of thrombosis and haemorrhage, relationship with anti-Xa, anti-IIa activities, and D-dimer plasma levels in patients receiving a low molecular weight heparin, enoxaparin or tinzaparin, to prevent deep vein thrombosis after hip surgery.
Studies in experimental animal models and in patients receiving low molecular weight heparin (LMWH) to prevent thromboembolic events after surgery have not demonstrated a clear relationship between anti-Xa and anti-IIa activities in plasma and either bleeding or prevention of thrombosis. The relationship between these clinical outcomes and ex vivo anti-Xa and anti-IIa activities, activated partial thromboplastin time (APTT) and D-dimers were evaluated in 440 patients undergoing total hip replacement and given prophylaxis once daily with a LMWH (tinzaparin or enoxaparin) in a multicentre double-blind randomized study. 221 patients received 4500 anti-Xa IU of tinzaparin; 219 patients received 40 mg (4000 anti-Xa IU) of enoxaparin. Both regimens were administered subcutaneously once daily. Blood samples for anti-IIa, anti-Xa, D-dimers levels and APTT were taken at baseline, on day 1, day 5 and on the day of discharge (days 8-14) and clinical assessments were performed dafly until day 14. All patients had bilateral venography between days 8 and 14. All coagulation tests were performed in central laboratories. A significant correlation was observed between anti-IIa activity and anti-Xa activity and the dose of each LMWH injected. The anti-Xa activity was significantly higher with enoxaparin and the anti-IIa activity was significantly higher with tinzaparin. No clear relationship between these two activities and the clinical outcomes was observed. This was also true with regards to APTT. Before and after surgery, D-dimers were significantly higher in patients with deep vein thrombosis (DVT) than in those without DVT but had no predictive value. Interestingly, a significant post-operative increase of D-dimers persisted in both groups of patients during the whole observation period, possibly suggesting that a longer duration of prophylactic treatment may be appropriate.


Neonatal exposure to di(n-butyl) phthalate (DBP) alters male reproductive-tract development.
The purpose of this study was to evaluate male reproductive-organ development in early postnatal male rats following neonatal exposure to di(n-butyl) phthalate (DBP) and identify a mechanism of action. Neonatal male rats were injected subcutaneously from d 5 to 14 after birth with corn oil (control) and DBP (5, 10, or 20 mg/animal). Animals were killed at postnatal day (PND) 31 and PND 42, respectively, and testes, epididymis, seminal vesicles, ventral prostate, levator ani plus bulbocavernosus muscles (LABC), and Cowper's glands were weighed. In addition, the expressions of androgen receptor (AR), estrogen receptors (ERs), and steroidogenic factor-1 (SF-1) were also examined in the testes. Total body weights gains were significantly reduced at PND 29-31, but gradually recovered on PND 42. However, DBP (20 mg/animal) significantly reduced the weights of testes and accessory sex organs (seminal vesicles, LABC, and Cowper's glands), but not of the epididymis. These adverse effects persisted through puberty at PND 42. Serum testosterone levels did not show any significant changes in the control and DBP treatment groups. Histomorphological examination showed mild diffuse Leydig-cell hyperplasia in the interstitium of severely affected tubules on PND 31. Only a few multinuclear germ cells were observed. DBP (20 mg/animal) significantly decreased the expression of AR, whereas ER expression and SF-1 expression were increased in a dose-dependent manner on PND 31 in the rat testes. On PND 42, DBP (20 mg/animal) significantly inhibited ER expression in the testes, but not AR, ER, and SF-1. These results demonstrate that neonatal exposure to DBP produces permanent changes in the endocrine system and leads to abnormal male reproductive-tract development until puberty. Thus our data suggest that DBP is likely to exert its antiandrogenic actions through disruption of AR or ER expression during the early neonatal stage.


Formation of very stable and selective Cu(II) complexes with a non-macrocyclic ligand: can basicity rival pre-organization?
The synthesis of ligand L based on a 2,6-bis[(N,N-bis(methylene phosphonic acid)aminomethyl] pyridine scaffold is described. Potentiometry combined with UV-Vis absorption spectrophotometric titrations were used to determine the protonation constants of the ligand and the stability constants of its corresponding Cu(II), Ni(II), Zn(II) and Ga(III) cations (0.1 M NaClO(4), 25.0 °C). The physico-chemical approach revealed very large stability constants for Cu(II) complexation (logK(CuL) = 22.71(7)) reflected in a very high pCu(II) value of ∼ 15.5 (pH = 7.4, [L](tot) = 10(-5) M, [Cu](tot) = 10(-6) M), close to those measured for the strong methylphosphonate functionalized cyclen chelators. Based on a literature survey, a correlation is proposed between the pK values of branched polyamine ligands and their stability constants for Cu(II) complexation, allowing for an estimation of the latter on the basis of the protonation constants of L. Ligand L was also shown to be very selective towards Cu(II) compared to the other cations studied (ΔlogK > 4). UV-Vis spectroscopy and kinetic measurements indicated that the formation of the cupric complexes with L is very fast, which, in combination with all other properties, makes it an excellent non-cyclic target for Cu(II) radiopharmaceutical within the frame of (64)Cu positron emission tomography imaging and radiotherapy.


Associating school doctor interventions with the benefit of the health check: an observational study.
The benefits of school doctor interventions conducted at routine general health checks remain insufficiently studied. This study explored the associations of school doctor interventions with the doctor-evaluated and parent-evaluated benefits of routine health checks. Between August 2017 and August 2018, we recruited a random sample of 1341 children from grades 1 and 5 from 21 Finnish elementary schools in 4 municipalities. Doctors routinely examined all children, who were accompanied by parents. The doctor-reported interventions were categorised into six groups: instructions and/or significant discussions, prescriptions, laboratory tests and/or medical imaging, scheduling of follow-up appointments, referrals to other professionals and referrals to specialised care. Doctors evaluated the benefit of the appointment using predetermined criteria, and parents provided their subjective perceptions of benefit. Interventions and reported benefit were compared using multilevel logistic regression. Doctors reported 52% and parents 87% of the appointments with interventions beneficial. All interventions were independently associated with doctor-evaluated benefit (ORs: 1.91-17.26). Receiving any intervention during the appointment was associated with parent-evaluated benefit (OR: 3.25, 95% CI 2.22 to 4.75). In analyses of different interventions, instructions and/or significant discussions (OR: 1.71, 95% CI 1.20 to 2.44), prescriptions (OR: 7.44, 95% CI 2.32 to 23.91) and laboratory tests and/or medical imaging (OR: 3.38, 95% CI 1.34 to 8.55) were associated with parent-evaluated benefit. Scheduled follow-up appointments and referrals to other professionals showed no significant association with parent-evaluated benefit. Doctors and parents valued the appointments with interventions. Parents especially appreciated immediate help and testing from the doctor. NCT03178331.


Leukocytes from diabetic patients kill retinal endothelial cells: effects of berberine.
Accumulating evidence in animals suggests that leukocytes are involved in the pathogenesis of diabetic retinopathy. The present study was designed to investigate whether leukocytes from diabetic patients could kill retinal endothelial cells and whether that cytotoxicity could be inhibited in vivo by administration of berberine. Human retinal endothelial cells (HRECs) were cocultured (24 h) with leukocytes freshly isolated from nondiabetic and diabetic patients, and leukocyte-mediated death of HRECs was analyzed with flow cytometry. HRECs or leukocytes were incubated with antibodies against intercellular adhesion molecule-1(ICAM-1) or integrin beta-2, or with various concentrations of berberine. The protein expression levels of inflammatory factors were investigated using western blots, and activities of antioxidant enzymes and malondialdehyde content were examined as markers of oxidative stress. In addition, leukocytes were isolated from 28 diabetic patients with retinopathy and nondiabetic patients before and after 1 month in vivo therapy with berberine. The effects of the berberine on leukocyte-mediated killing of endothelial cells was again assessed. Leukocytes from diabetic patients induced more apoptosis of HRECs in a coculture system than did cells from nondiabetic patients, and this killing occurred primarily via direct cell-cell contact. Berberine inhibited the leukocyte-mediated killing of HRECs in vitro, the decrease in antioxidant enzyme activities, the nuclear translocation of nuclear factor kappa B, and the increase in intercellular adhesion molecule-1 and inducible nitric oxide synthase expression and malondialdehyde content in HRECs cultured in high glucose. Berberine also decreased integrin beta-2 expression of leukocytes in vitro and in vivo. Oral consumption of berberine for 1 month likewise inhibited the diabetes-induced increase in leukocyte-mediated killing of HRECs. Our findings suggest that leukocytes from diabetic patients kill retinal endothelial cells, and that berberine can inhibit this leukocyte-mediated killing of vascular endothelium. Coculture of leukocytes with HRECs might serve as a biomarker to study the role of leukocytes in the development of diabetic retinopathy, and the data are consistent with berberine being a therapy against diabetic retinopathy.


Epidemiology of hyperhidrosis in 2 population-based health care databases.
Population-based and clinical case reports of hyperhidrosis (HH) provide prevalence estimates that vary widely across reported studies because of differences in case ascertainment. In this study, we specify diagnostic, symptom, and prescription codes for HH to estimate incidence and prevalence for the United Kingdom and the United States. Data from UK and US health care databases were analyzed to ascertain HH cases and estimate incidence and prevalence from health care records during calendar years 2011 through 2013. On the basis of 2013 data for the United States and United Kingdom, between 1.0% and 1.6% of these populations have health care records indicating diagnosis or treatment of HH. Women accounted for approximately 60% of incident and prevalent cases in both databases. Because the case ascertainment methods rely on available data for those seeking health care, we may have underestimated the number of HH cases in both countries. The findings represent a plausible estimate for incidence and prevalence of HH among persons seeking medical care for excessive sweating. Improved practices for identifying HH in clinical settings may increase the sensitivity and specificity of future studies and improve characterization and quantification of the population burden of this significant disease.


A comparison of family of origin factors between children of alcoholics and children of non-alcoholics in a longitudinal panel.
Secondary analysis of longitudinal panel data reveals minimal differences in family of origin factors between children of alcoholics (COAs) and children of non-alcoholics (non-COAs). From 220 subjects, 37 parents were identified as alcoholic. The COA subjects' retrospective reports about family of origin factors were compared to those of non-COAs. Contrary to the assertions of the COA clinical literature, few differences were found between the two groups. However, these differences are congruent with the findings of other panel studies which have investigated family of origin factors and adult outcome among COAs.


Neighborhood Socioeconomic Characteristics and Utilization of ADHD Medication in Schoolchildren: A Population Multilevel Study in Stockholm County.
Objective: To examine the effects of neighborhood socioeconomic disadvantage and ethnic composition on the utilization of ADHD medication in schoolchildren after accounting for individual- and family-level characteristics. Method: A cohort of all schoolchildren living in Stockholm County was prospectively followed for new prescriptions of ADHD medication (N = 276,955). Three-level logistic regression models were used with individual/family characteristics (e.g., immigrant background) at the first level and small area market statistics (SAMS) and municipality characteristics (i.e., socioeconomic disadvantage and ethnic composition) at the second and third level. Results: SAMS socioeconomic disadvantage was associated with increased utilization of ADHD medication. The utilization of ADHD medication was lower among immigrant children as compared with natives, and their odds of not utilizing medication increased as the degree of concentration of foreign-born increased. Conclusion: These results suggest that interventions at the neighborhood level may offer an additional route for the prevention of the disorder and/or alleviation of its consequences.


p53-independent regulation of p21Waf1/Cip1 expression and senescence by Chk2.
The Chk2 kinase is a tumor suppressor and key component of the DNA damage checkpoint response that encompasses cell cycle arrest, apoptosis, and DNA repair. It has also been shown to have a role in replicative senescence resulting from dysfunctional telomeres. Some of these functions are at least partially exerted through activation of the p53 transcription factor. High-level expression of virally transduced Chk2 in A549 human lung carcinoma cells led to arrested proliferation, apoptosis, and senescence. These were accompanied by various molecular events, including p21(Waf1/Cip1) (p21) transcriptional induction, consistent with p53 activation. However, Chk2-dependent senescence and p21 transcriptional induction also occurred in p53-defective SK-BR-3 (breast carcinoma) and HaCaT (immortalized keratinocyte) cells. Small interfering RNA-mediated knockdown of p21 in p53-defective cells expressing Chk2 resulted in a decrease in senescent cells. These results revealed a p53-independent role for Chk2 in p21 induction and senescence that may contribute to tumor suppression and genotoxic treatment outcome.


Regulation of protein O-glycosylation by the endoplasmic reticulum-localized molecular chaperone Cosmc.
Regulatory pathways for protein glycosylation are poorly understood, but expression of branchpoint enzymes is critical. A key branchpoint enzyme is the T-synthase, which directs synthesis of the common core 1 O-glycan structure (T-antigen), the precursor structure for most mucin-type O-glycans in a wide variety of glycoproteins. Formation of active T-synthase, which resides in the Golgi apparatus, requires a unique molecular chaperone, Cosmc, encoded on Xq24. Cosmc is the only molecular chaperone known to be lost through somatic acquired mutations in cells. We show that Cosmc is an endoplasmic reticulum (ER)-localized adenosine triphosphate binding chaperone that binds directly to human T-synthase. Cosmc prevents the aggregation and ubiquitin-mediated degradation of the T-synthase. These results demonstrate that Cosmc is a molecular chaperone in the ER required for this branchpoint glycosyltransferase function and show that expression of the disease-related Tn antigen can result from deregulation or loss of Cosmc function.


Ion Selectivity in P2X Receptors: A Comparison between hP2X3 and zfP2X4.
Charge discrimination in P2X receptors occurs in two stages. The first stage takes place in the extracellular vestibule. The second one happens as the ions travel across the pore. The search of the amino acids required to achieve these goals has focused on negatively charged residues conserved among the family members. This strategy, however, has afforded baffling results since residues that strongly influence ion selectivity in a given member are not present in others. This finding suggests that alternative family members could achieve the same goal using different molecular approaches. We have compared the mechanisms of charge discrimination in the extracellular vestibule of zebrafish P2X4 (zfP2X4) and human P2X3 (hP2X3), employing molecular dynamics simulations. In particular, we have analyzed how the mutation of residues D59 and D61 of zfP2X4 and residues E46, D53, and E57 of hP2X3 influence ion behavior. The results indicate that both D59 and D61 are required to confer the extracellular vestibule of zfP2X4 a preference for cations. In contrast, the presence of D53 suffices to provide that capacity to hP2X3. We also computed the potentials of mean force for the passage of Na+ and Cl- through the pore of hP2X3. These profiles were compared against those already available for zfP2X4. Altogether, the results provide a detailed description of the mechanisms employed by these receptors to discriminate between cations and anions.


A simple GC method for determination of cryoprotector diols 1,4-butanediol or 2,3-butanediol in isolated rat hepatocytes.
We devised a simple method for determining the cryoprotectant agents 1,4-butanediol or 2,3-butanediol in isolated rat hepatocytes. After extraction of of hepatocytes with water (containing internal standard - ethylene glycol 1.25 mg/mL) the diol content was analyzed by gas chromatography. The method shows a linear response in the range 0.125 to 2.50 mg/mL for 1,4-butanediol and 0.25 to 3.75 mg/mL for 2,3-butanediol. The accuracy and precision of the method were evaluated and the coefficients of variation were found to be within = 6.0 %. The recoveries from hepatocyte samples containing 0.50, 1.00 and 2.00 mg/mL were 91.0 to 108 % for 1,4-butanediol and 80.6 to 100.3 % for 2,3-butanediol, respectively. This method allowed the determination of the intracellular concentration of diols in hepatocytes preserved for up to 120 hours at - 4 (C in UW solution + 8 % w/v 1,4-butanediol (or 2,3-butanediol).


Acute abdominal pain: computer aided diagnosis by non-medically qualified staff.
This report explores the role of computer aided diagnosis in acute abdominal pain when applied by non-medically qualified personnel. Clinical features of 153 patients (75 males, 78 females, aged range 6-92 years, median 35 years) suffering from less than one weeks' abdominal pain were recorded. Junior doctors' diagnostic accuracy with (65 cases) and without (70 cases) structured computer history sheets were compared with first year clinical medical students using the computer system (46 cases: 28 also seen by doctor, 18 cases student only). These students had no previous surgical training or experience. Doctors' diagnostic accuracy of 51% rose significantly to 69% with the use of structured history forms (chi 2 = 4.53, P = less than 0.05). Computer assisted clinical students' diagnostic accuracy matched the improved doctors' accuracy (69.5%). These results have implications not only for medical education but also for isolated paramedical personnel who should be supplied with structured diagnostic forms and, where appropriate, a microcomputer.


Laser-Assisted Uvulopalatoplasty for Obstructive Sleep Apnea: A Systematic Review and Meta-Analysis.
Laser-assisted uvulopalatoplasty (LAUP) has been used as treatment for obstructive sleep apnea (OSA). The objective of this study was to perform a systematic review and meta-analysis for LAUP alone as treatment for OSA in adults. Three authors searched five databases (including PubMed/MEDLINE) from inception through October 30, 2016 for peer-reviewed studies, with any design/language. A study quality assessment tool was used. The PRISMA statement was followed. A meta-analysis was performed. Twenty-three adult studies (717 patients) reported outcomes (age: 50 ± 9 years, body mass index: 29 ± 4 kg/m2). The pre- and post-LAUP means (M) ± standard deviations (SDs) for apnea-hypopnea index (AHI) were 28 ± 13 and 19 ± 12 events/h (32% reduction). Random effects modeling for 519 patients demonstrated an AHI mean difference (MD) of -6.56 [95% CI -10.14, -2.97] events/h. Individual patient data analyses demonstrate a 23% success rate (≥50% reduction in AHI and <20 events/h) and an 8% cure rate. Additionally, 44% of patients had worsening of their AHI after LAUP. Lowest oxygen saturation (LSAT) improved from a M ± SD of 80 ± 8% to 82 ± 7%. A limitation is that most studies were case series studies and only two were randomized controlled trials. In this meta-analysis, LAUP reduced AHI by 32% among all patients; while the LSAT only changed minimally. Individual data demonstrated a success rate of 23%, cure rate of 8%, and worsening of the AHI among 44% of patients. We recommend that LAUP be performed with caution or not performed at all given the unfavorable results of currently published studies.


Does the Person-of-the-Therapist Training (POTT) Promote Self-Care? Personal Gains of MFT Trainees Following POTT: A Retrospective Thematic Analysis.
As we recognize how taxing our profession can be, therapist's self-care has become a salient topic in mental health. However, we are still discerning how to promote self-care in our practice and in training. In this paper, we present a study on the personal gains that MFT students experienced after participating in the Person-of-the-Therapist Training (POTT). We propose that the reported changes (better understanding of self, change to self, relational changes, and change as a process) constitute improvements in the trainees' well-being, and can therefore be considered self-caring behaviors and practices. We state that models like POTT, that focus on embracing our vulnerability, can help clinicians be more caring toward ourselves. We conclude this paper by presenting clinical and training recommendations.


User satisfaction with computerized order entry system and its effect on workplace level of stress.
To evaluate the impact of Computerized Provider Order Entry (CPOE) on workplace stress and overall job performance, as perceived by medical students, housestaff, attending physicians and nurses, after CPOE implementation at Penn State-Milton S. Hershey Medical Center, an academic tertiary care facility, in 2005. Using an online survey, the authors studied attitudes towards CPOE among 862 health care professionals. The main outcome measures were job performance and perceived stress levels. Statistical analyses were conducted using the Statistical Analytical Software (SAS Inc, Carey, NC). A total of413 respondents completed the entire survey (47.9 % response rate). Respondents in the younger age group were more familiar with the system, used it more frequently, and were more satisfied with it. Interns and residents were the most satisfied groups with the system, while attending physicians expressed the least satisfaction. Attending physicians and fellows found the system least user friendly compared with other groups, and also tended to express more stress and frustration with the system. Participants with previous CPOE experience were more familiar with the system, would use the system more frequently and were more likely to perceive the system as user friendly. User satisfaction with CPOE increases by familiarity and frequent use of the system. Improvement in system characteristics and avoidance of confusing terminology and inconsistent display of data is expected to enhance user satisfaction. Training in the use of CPOE should start early, ideally integrated into medical and nursing school curricula and form a continuous, long-term and user-specific process. This is expected to increase familiarity with the system, reducing stress and leading to improved user satisfaction and to subsequent enhanced safety and efficiency.


Description and outcomes of a custom Web-based patient occurrence reporting system developed for Baylor University Medical Center and other system entities.
To improve the timeliness, efficiency, and effectiveness of occurrence reporting. Baylor University Medical Center, a 1000-bed tertiary facility, and other components of the Baylor Health Care System, all located in Dallas and the surrounding area. Designing a custom Web-based patient occurrence reporting system through the efforts of the Center for Quality and Care Coordination and Information Services and training staff not only in using the system but also in viewing reporting as a key element for quality and safety rather than as an individual performance or disciplinary measure. Both the number of occurrences reported and the timeliness of reports improved: prior to implementation of the Web forms, an average of 128 paper patient occurrence reports were received per month an average of 7.6 days after the occurrence; in the 12 months afterwards, an average of 175 patient occurrence reports were submitted, with 82% reported within 24 hours of the occurrence. Anecdotal comments about the system from end users have been positive. Paperless Web-based systems are timely, efficient, and effective. The system developed at Baylor met its goals, including being secure, offering online helps and formal education, creating a risk stratification model, remaining adaptable for system needs, and serving as a tool for data analysis. Efforts to change the culture around patient occurrence reporting are ongoing and an essential element for success.


Four additional members of the ras gene superfamily isolated by an oligonucleotide strategy: molecular cloning of YPT-related cDNAs from a rat brain library.
Several oligonucleotide mixtures corresponding to a 6-amino acid sequence that is strictly conserved in all the ras and ras-related proteins (from various organisms) were tested for their ability to hybridize to 11 cloned members of the ras gene superfamily. Among these mixtures, a combination of two sets of partially complementary oligomers were able to hybridize to all the tested sequences. To identify members of the ras superfamily, we screened a rat brain cDNA library with these probes and isolated four genes, denoted rab1, -2, -3, and -4, encoding proteins homologous to the yeast YPT protein. Amino acid homology scores with YPT range from 75% for rab1 to 37% for rab4, whereas the homologies with p21 ras and other ras-related proteins are approximately equal to 30%, and homologous residues were clustered in the regions involved in GTP/GDP binding. Another striking similarity shared by the rab and the other ras-related proteins is the conservation of at least one cysteine residue near the carboxyl-terminal end involved in the membrane binding of the ras proteins. rab1 is a mammalian homolog of the yeast YPT gene, and the four rab genes constitute an additional branch of the ras gene superfamily that to our knowledge has not been described in higher eukaryotes.


Schistosoma mansoni: excretory-secretory polypeptides exhibit selective binding to plasma components of the snail Biomphalaria glabrata.
Previous studies have shown that Schistosoma mansoni excretory-secretory polypeptides (ESP) inhibit various internal defense functions of hemocytes from Biomphalaria glabrata and that plasma also may exert a modulatory effect on hemocyte activity. To better understand how plasma may influence hemocyte-schistosome interactions in inbred strains of snails, biotinylated ESP (b-ESP) were used as probes to identify ESP-reactive plasma components and partially characterize the nature of their binding interactions. In a plasma binding assay, b-ESP bound in a dose-dependent fashion to immobilized snail plasma, although no quantitative differences in ESP reactivity to plasma of schistosome-susceptible (M-line) and -resistant (13-16-R1) snail strains were detected. Moreover, co-incubation of b-ESP with homologous plasma or pretreatment of plasma with nonbiotinylated ESP in the plate assay significantly reduced b-ESP binding to immobilized plasma, indicating a specific interaction between ESP and plasma. Pretreatment of b-ESP with mannose, porcine stomach mucin, fetuin, and asialofetuin resulted in a significant inhibition of b-ESP binding to plasma, whereas pretreatment of immobilized plasma with a cocktail of monosaccharides (including mannose), porcine stomach mucin, and fetuin had no inhibitory effect. These data suggest the presence of a carbohydrate-binding protein(s) in sporocyst ESP that is targeted to plasma glycoconjugates. Based on the carbohydrate content of the major inhibitory glycoproteins, galactosyl and n-acetyl-galactosaminyl sugars may represent putative determinants for the lectin-like ESP molecule(s). However, ESP binding to plasma from M-line and 13-16-R1 B. glabrata strains exhibited similar sugar and glycoprotein inhibition patterns. SDS-PAGE and electroblot analyses further demonstrated that ESP bound to a subset of separated plasma polypeptides, most prominently to a doublet of 52 and 54 kDa, and a complex of proteins with molecular masses greater than 150 kDa. Other polypeptides exhibiting weaker binding interactions included components of 34, 60, 64, 86, and 125 kDa. Although both M-line and 13-16-R1 snail strains contained a similar complement of ESP-binding plasma proteins, ESP binding to the 34- and 86-kDa proteins occurred at higher frequencies in susceptible M-line plasma. It is concluded that ESP, released during in vitro transformation of S. mansoni miracidia, contain carbohydrate-reactive proteins capable of selectively binding to components of snail plasma. Quantitative differences between snail strains in the occurrence of ESP-binding plasma molecules was documented.


[The surgical procedure in treating vascular thrombosis after performing aortofemoral reconstruction].
Experience of vascular thrombosis prophylaxis and treatment after reconstructive operation conduction on abdominal aorta and peripheral arteries in 244 patients, including 112 of them immediately after the operation, 32-up to one year time, 100-in long-term follow-up period was summarized. Main aetiological cause for thrombosis occurrence immediately after the operation were technical and tactical failures committed during its conduction, in the early postoperative period-the neointima hyperplasia in the anastomosis area, in late terms-the blood outflow disorder from the reconstructed segment due to the atherosclerosis progression. Original methods of reoperation conduction for the transplant thrombosis and the outflow arteries reconstruction were proposed. Mortality lowering from 8.8 to 5.3% and the extremity revascularization occurrence, in 75% of patients immediately after the operation and in 84%-in long-term period was promoted owing to tactics of postoperative thrombosis treatment elaborated.


Which endoscopic treatment is the best for small rectal carcinoid tumors?
The incidence of rectal carcinoids is rising because of the widespread use of screening colonoscopy. Rectal carcinoids detected incidentally are usually in earlier stages at diagnosis. Rectal carcinoids estimated endoscopically as < 10 mm in diameter without atypical features and confined to the submucosal layer can be removed endoscopically. Here, we review the efficacy and safety of various endoscopic treatments for small rectal carcinoid tumors, including conventional polypectomy, endoscopic mucosal resection (EMR), cap-assisted EMR (or aspiration lumpectomy), endoscopic submucosal resection with ligating device, endoscopic submucosal dissection, and transanal endoscopic microsurgery. It is necessary to carefully choose an effective and safe primary resection method for complete histological resection.


Epidemiological characteristics and in-hospital management of acute coronary syndrome patients in Greece: results from the TARGET study.
Conduction of national surveys is needed to depict temporal trends in the risk profile, type of implemented treatment strategy and outcome of patients with acute coronary syndromes (ACS). The TARGET study is a multicenter, observational study that aimed to evaluate the epidemiological characteristics, management pattern and outcome of ACS patients in Greece. A total of 418 consecutive patients with ACS (44.7% STEMI, 34.2% NSTEMI, 21.1% unstable angina) from 17 centers (52.9% with catheterization facilities) were enrolled in the study (78.0% males, 63.9 ± 12.9 years). Overall, 67.9% of the patients had hypertension, 27.5% were diabetics and 57.4% had dyslipidemia. Thrombolytic therapy (60.7% tenecteplase, 38.2% reteplase) was administered in 22.7% of the study population, while invasive management was performed in 40.2% of patients (27.0% PCI and 1.0% CABG) during the index hospitalization. In-hospital all-cause mortality was 1.9%, with 12.2% of patients experiencing adverse clinical events. Evidence-based medications were prescribed to the majority of enrolled patients during hospitalization and upon discharge (97% and 94% received aspirin, 93% and 84% clopidogrel, 87% and 86% beta-blockers, 96% and 93% statins, respectively). The prevalence of modifiable risk factors exhibits an increasing trend among ACS patients in Greece. The prescription pattern of evidence-based medications has improved considerably, while there remains considerable room for improvement in expanding the implementation of invasive management in realworld clinical practice.


Preparation of Polypropylene Spin Tips Filled with Immobilized Titanium(IV) Ion Monolithic Adsorbent for Robust Phosphoproteome Analysis.
In this study, we developed a Ti(IV) monolithic spin tip for phosphoproteome analysis of a minute amount of biological sample for the first time. The surface of polypropylene pipet tip was activated by the photoinitiator benzophenone under UV light radiation followed by polymerization of ethylene glycol methacrylate phosphate and bis-acrylamide in the tip to form a porous monolith with reactive phosphate groups. The as-prepared tips grafted with monolithic adsorbent were then chelated with titanium(IV) ion for phosphopeptide enrichment. It was found that the tips enabled fast and efficient capture of phosphopeptides from microscale complex samples. The monolithic tip was demonstrated to have a detection limit as low as 5 fmol β-casein tryptic digest, along with an exceptionally high specificity to capture phosphopeptides from complex tryptic digest mixed with an unphosphorylated protein and a phosphorylated protein at a molar ratio up to 1000:1. When the tip was applied to enrich phosphopeptides from 5 μg of tryptic digest of complex HeLa cell proteins, 1185 high confidence of phosphorylated sites were successfully identified with the specificity as high as 92.5%. So far, this is the most sensitive phosphoproteomics analysis using a standard liquid chromatography-tandem mass spectrometry (LC-MS/MS) system for proteome-wide phosphorylation analysis in mammalian cells.