Rat intestinal iron transfer capacity and the longitudinal distribution of its adaptation to iron deficiency.
The longitudinal gradient of intestinal iron transfer was investigated in normal and iron-deficient male Sprague-Dawley rats in vitro and in vivo. In normal rats in vitro iron transfer in the duodenum was approximately 3 times higher than in the jejunum and decreased in the ileum to approximately half the jejunal values. Compared to the controls in vitro iron transfer was increased 3-4 times in the duodenum and in the first jejunal segment and 2-3 times in the second jejunal segment. No significant adaptation to iron deficiency was found in the rest of the small intestine. Iron transfer rates showed the same longitudinal pattern when iron was chelated with nitrilotriacetic acid (NTA) or with ascorbate. The absorbed iron quantities, however, were approximately 5 times lower when Fe-ascorbate was used, which might be due to differences in bioavailability. Omission of Fe-NTA and Fe-ascorbate had no impact on the vitality of the segments. Glucose transfer was used as vitality criterion. It was not significantly different between corresponding iron-deficient and control segments. To control these results in vivo mesenteric blood was collected from duodenal and jejunal segments in situ. Corresponding to in vitro findings iron transfer was close to linear over the experimental period. In iron deficient duodenal segments iron transfer increased approximately 3 times as compared to controls while no adaptational changes were found in the distal jejunum. No significant longitudinal gradient was found in the mucosal content of ferritin and nonheme iron. Both parameters were decreased in iron deficiency by about half. The mucosal transferrin content showed no longitudinal gradient in control animals. In iron deficiency transferrin was significantly increased in the duodenum and in the three most proximal jejunal segments. The results indicate that in rats adaptation of iron absorption to the demand can only be expected in the duodenum and in the proximal 20 cm of the jejunum. Because this process shows a steep gradient in the proximal small intestine, studies on the adaptation of intestinal iron transfer to the demand should use short and well-defined segments in order to provide reproducible results.


The role of postsecondary education in welfare reform. Ohio's JOBS Student Retention Program.
The 1996 federal welfare reform legislation encourages quick employment over education and training for the nation's welfare recipients. However, some argue that a one-size-fits-all approach ignores the heterogeneity of this population. This article presents findings from a net impact evaluation of Ohio's JOBS Student Retention Program (JSRP), a program designed to facilitate success for public assistance recipients at 2-year community or technical colleges. The authors evaluate this policy using state administrative data sets. The analyses consist of unadjusted and regression-adjusted comparisons of means for the JSRP group and a constructed comparison group. Outcomes examined include program completion, employment, earnings, and welfare recipiency. Focusing on the most recent 11 of 16 quarters of data available, the average increase in quarterly earnings was 8.45% for program participants and 12.91% for program completers. The results indicate that encouraging postsecondary education for some welfare recipients will boost earnings capacity and therefore long-term self-sufficiency.


[Differentiation between allergic rhinitis and vasomotor rhinitis. Light and electron microscopic studies].
The pathological changes of nasal mucosa from allergic rhinitis and vasomotor rhinitis were observed. The results showed that the general characteristic was vascular dilatation with increased permeability and glandular proliferation with increased secretory activity. The pathological difference between mucous membranes of allergic and vasomotor rhinitis were mainly cellular infiltration and degree of damage on vascular wall. In allergic rhinitis there were more eosinophils, basophils, neutrophils and some mast cells and plasma cells in nasal mucosa. Gap formation in capillary wall was found in allergic nasal mucosa, there were less cellular infiltration and no gap formation in vasomotor rhinitis.


Translating emerging research on the genetics of smoking into clinical practice: ethical and social considerations.
Despite decades of research aimed at improving the effectiveness of smoking treatment, available treatments are only modestly effective, and smoking remains the leading cause of preventable deaths in the United States. Recent research on genetic factors related to smoking behavior eventually may lead to the design of new tobacco dependence treatments and to the individualization of treatment based on genetic factors. Although this research is in its infancy, and data on the analytic and clinical validity of genetic tests to tailor smoking treatment are not yet available, it is not too soon to begin identifying and addressing key ethical issues associated with genetic testing in the context of tobacco dependence treatment. Key concerns include (a) potential harm (e.g., stigmatization, discrimination) to patients related to inappropriate use of genetic information, (b) implications of pleiotropic associations, (c) differential prevalence of risk-conferring genotypes among racial or ethnic subpopulations, (d) preparedness of primary care physicians to incorporate genetic testing into smoking treatment, (e) informed consent, and (f) ensuring an appropriate balance between individually tailored treatment by genotype and broad-based interventions that focus on social and environmental factors affecting smoking behavior. Additional research on these ethical and social issues must be conducted simultaneously with the scientific work currently under way. Failure to address these concerns will likely undermine efforts to translate knowledge emerging from the United States' substantial investment in genetic research on smoking into clinical practice and improved patient outcomes.


Highly enantiomeric reduction of acetophenone and its derivatives by locally isolated Rhodotorula glutinis.
Ninety isolates of microorganisms belonging to different taxonomical groups (30 bacteria, 20 yeast, and 40 fungi) were previously isolated from various samples. These isolates were screened as reducing agents for acetophenone 1a to phenylethanol 2a. It was found that the isolate EBK-10 was the most effective biocatalyst for the enantioselective bioreduction of acetophenone. This isolate was identified as Rhodotorula glutinis by the VITEK 2 Compact system. The various parameters (pH 6.5, temperature 32 degrees C, and agitation 200 rpm) of the bioreduction reaction was optimized, which resulted in conversions up to 100% with >99% enantiomeric excesses (ee) of the S-configuration. The preparative scale bioreduction of acetophenone 1a by R. glutinis EBK-10 gave (S)-1-phenylethanol 2a in 79% yield, complete conversion, and >99% ee. In addition, R.glutinis EBK-10 successfully reduced various substituted acetophenones.


Morphological Characteristics Predict Postoperative Outcomes After Vitrectomy in Myopic Traction Maculopathy Patients.
To provide the surgical indication for patients with myopic traction maculopathy (MTM) by investigating the postoperative outcomes after vitrectomy among different types of morphological characteristic groups. This was a retrospective cohort study that included patients (37 eyes) diagnosed with MTM at a single institution. All 37 eyes from 37 patients with MTMs were classified into three groups: foveal retinoschisis (FS), lamellar macular hole (LMH), and foveal retinal detachment (FRD). The ratios of anatomic recovery, central retinal thickness (CRT), and best-corrected visual acuity (BCVA) were statistically analyzed among the three groups preoperatively and at 1, 3, 6, and 12 months after vitrectomy. Anatomical recovery could be found in all patients of the FS group at 6 months postoperatively and in the LMH group at 12 months postoperatively. Only 83.33% patients in the FRD group showed anatomic recovery until 12 months. The time taken for CRT to reduce to 200 µm was gradually increased between the FS, LMH, and FRD groups. Postoperative BCVA was better in the FS group than the LMH and FRD groups (P < .05), but the LMH and FDR groups had no difference (P ≥ .05) at any point. The visual acuity was significantly improved in the FS group (P < .01) and FRD group (P = .018), but not in the LMH group (P = .196) at 12 months postoperatively. The FS group achieved anatomical recovery in the shortest time and had the best postoperative BCVA. FRD patients could get visual gain but need too much time for the anatomical recovery. LMH patients experienced anatomic success with surgery, but not in BCVA. Early surgery might be considered for eyes at FS prior to the occurrence of LMH or FRD. [Ophthalmic Surg Lasers Imaging Retina. 2020;51:574-582.].


Serum bone alkaline phosphatase is a useful marker to evaluate lumbar bone mineral density in Japanese postmenopausal osteoporotic women during denosumab treatment.
A worldwide health concern, osteoporosis (OP), increases the risk of bone fracture and results in morbidity. This study examined whether the representative bone absorption marker serum tartrate-resistant acid phosphatase 5b (TRACP-5b) or bone formation marker bone alkaline phosphatase (BAP) could estimate primary OP status and denosumab efficacy in a real-world setting. We retrospectively enrolled 114 female postmenopausal primary OP patients in Japan. Values and percent changes in TRACP-5b, BAP, lumbar 1-4 bone mineral density (L-BMD), and total hip BMD (H-BMD) were assessed before treatment and at 4, 8, and 12 months of therapy to identify the correlations between the percent changes in bone metabolic markers and BMD. We also established two sets of subgroups based on the upper limits of reference values in Japan for serum: TRACP-5b (<420 mU/dL) and (≥420 mU/dL) and BAP (<14.5 µg/L) and (≥14.5 µg/L). Negative correlations were observed for the percent changes of TRACP-5b and H-BMD at 4 months (r=-0.3476) and 8 months (r=-0.3880), for the percent changes of BAP and H-BMD at 8 months (r=-0.3354), and for the percent changes of BAP and L-BMD at 12 months (r=-0.3186). We observed a significant difference between the subgroups for the percent changes of L-BMD at 8 months (p=0.013) and 12 months (p=0.004) in BAP values. These results suggest that TRACP-5b and BAP had negative correlations with BMD, and that BAP represented a useful serum marker to evaluate L-BMD during denosumab therapy for OP.


Polyamines in soybeans.
Putrescine, spermidine, and spermine were three main polyamines isolated from soybeans and partially characterized. Occurrence of polyamines in soybeans was established by separating trichloroacetic acid extracts of soybeans by cationic exchange column chromatography, identification with thin layer chromatography, paper electrophoresis, mass spectral analysis, reactions with ninhydrin and Dragendorff reagents, and spectrophotometric characteristics. Soybeans contained a minimum of 29.0 micrograms of polyamines per gram of full-fat flour. The alcohol-soluble fraction of soybeans contained polyamines also. Resting seeds contained spermidine in higher concentration than either putrescine or spermine. Spermine appeared to be present in lowest concentration. Preliminary experiments suggested that some polyamines were possibly in bound forms.


Recycling the Purpose of Old Drugs to Treat Ovarian Cancer.
The main challenge in ovarian cancer treatment is the management of recurrences. Facing this scenario, therapy selection is based on multiple factors to define the best treatment sequence. Target therapies, such as bevacizumab and polymerase (PARP) inhibitors, improved patient survival. However, despite their achievements, ovarian cancer survival remains poor; these therapeutic options are highly costly and can be associated with potential side effects. Recently, it has been shown that the combination of repurposed, conventional, chemotherapeutic drugs could be an alternative, presenting good patient outcomes with few side effects and low costs for healthcare institutions. The main aim of this review is to strengthen the importance of repurposed drugs as therapeutic alternatives, and to propose an in vitro model to assess the therapeutic value. Herein, we compiled the current knowledge on the most promising non-oncological drugs for ovarian cancer treatment, focusing on statins, metformin, bisphosphonates, ivermectin, itraconazole, and ritonavir. We discuss the primary drug use, anticancer mechanisms, and applicability in ovarian cancer. Finally, we propose the use of these therapies to perform drug efficacy tests in ovarian cancer ex vivo cultures. This personalized testing approach could be crucial to validate the existing evidences supporting the use of repurposed drugs for ovarian cancer treatment.


Ventromedial hypothalamic lesions increase gastrointestinal DNA synthesis through vagus nerve in rats.
It was recently reported that ventromedial hypothalamic (VMH) lesions produced an increase in gastrointestinal DNA content in rats. In the present study, the mechanism of this alteration was examined. The DNA content and synthesis after VMH lesioning in rat gastrointestinal tracts were determined. Total content of DNA in stomach and small intestine began to increase at 3 days and continued to increase for 7 days, whereas DNA content in the large intestine began to increase at 3 days and maintained the same level until 7 days after VMH lesioning. DNA synthesis of these organs increased and reached maximum at 3 days and then decreased to the initial level 7 days following the lesions. This increase in DNA content and synthesis in these organs was largely inhibited by bilateral subdiaphragmatic vagotomy or the administration of atropine, a cholinergic blocker, but not by the administration of anti-insulin antibody. VMH lesions induce cell proliferation in the rat gastrointestinal tract by the firing of vagus nerve activity mainly through the cholinergic receptor mechanism.


Positive and negative consequences of HIV disclosure among seropositive injection drug users.
This study examines HIV status disclosure in an ethnically diverse sample of HIV-seropositive injection drug users (IDUs) from New York City and San Francisco. Qualitative interviews were conducted with 158 participants. Analyses revealed a number of negative and positive consequences of disclosing serostatus to sexual partners. Negative consequences included stigma, rejection by sexual partners and others, loss of intimacy, and threats to personal well-being. Positive rewards resulting from disclosure included increased social support and intimacy with partners, reaffirmation of one's sense of self, and the opportunity to share personal experiences and feelings with sexual partners. The role of responsibility in impacting disclosure and nondisclosure revealed varied patterns in terms of how this construct impacts disclosure and resulting behaviors with sexual partners. Some participants used particular strategies, such as getting involved in seroconcordant relationships or minimizing intimacy in relationships, in order to combat potential negative outcomes of disclosure. For others, positive rewards were viewed as important enough to risk negative consequences. Interventions for HIV-positive IDUs are discussed.


Large leaves in warm, moist environments confer an advantage in seedling light interception efficiency.
Leaf size varies conspicuously along environmental gradients. Small leaves help plants cope with drought and frost, because of the effect of leaf size on boundary layer conductance; it is less clear what advantage large leaves confer in benign environments. We asked if large leaves give species of warm climates an advantage in seedling light interception efficiency over small-leaved species from colder environments. We measured seedling leaf, architectural and biomass distribution traits of 18 New Zealand temperate rainforest evergreens; we then used a 3-D digitiser and the Yplant program to model leaf area display and light interception. Species associated with mild climates on average had larger leaves and larger specific leaf areas (SLA) than those from cold climates, and displayed larger effective foliage areas per unit of aboveground biomass, indicating higher light interception efficiency at whole-plant level. This reflected differences in total foliage area, rather than in self-shading. Our findings advance the understanding of leaf size by showing that large leaves enable seedlings of species with highly conductive (but frost-sensitive) xylem to deploy large foliage areas without increasing self-shading. Leaf size variation along temperature gradients in humid forests may therefore reflect a trade-off between seedling light interception efficiency and susceptibility to frost.


Community-Acquired Antimicrobial Resistant Enterobacteriaceae in Central America: A One Health Systematic Review.
Community-acquired antimicrobial resistant Enterobacteriaceae (CA-ARE) are an increasingly important issue around the world. Characterizing the distribution of regionally specific patterns of resistance is important to contextualize and develop locally relevant interventions. This systematic review adopts a One Health framework considering the health of humans, animals, and the environment to describe CA-ARE in Central America. Twenty studies were identified that focused on antimicrobial resistance (AMR) in Enterobacteriaceae. Studies on CA-ARE in Central America characterized resistance from diverse sources, including humans (n = 12), animals (n = 4), the environment (n = 2), and combinations of these categories (n = 2). A limited number of studies assessed prevalence of clinically important AMR, including carbapenem resistance (n = 3), third generation cephalosporin resistance (n = 7), colistin resistance (n = 2), extended spectrum beta-lactamase (ESBL) production (n = 4), or multidrug resistance (n = 4). This review highlights significant gaps in our current understanding of CA-ARE in Central America, most notably a general dearth of research, which requires increased investment and research on CA-ARE as well as AMR more broadly.


Amino acid metabolism in leg muscle after an endotoxin injection in healthy volunteers.
Decreased plasma amino acid concentrations and increased net release of amino acids from skeletal muscle, especially for glutamine, are common features in critically ill patients. A low dose of endotoxin administered to healthy volunteers was used as a human model for the initial phase of sepsis to study the early metabolic response to sepsis. Six healthy male volunteers were studied in the postabsorptive state. Blood samples from the forearm artery and femoral vein were taken during 4 h before and 4 h after an intravenous endotoxin injection (4 ng/kg body wt). In addition, muscle biopsies from the leg muscle were taken. Plasma concentration of the total sum of amino acids decreased by 19% (P = 0.001) and of glutamine by 25% (P = 0.004) the 3rd h after endotoxin administration. At the same time, muscle concentrations of the sum of amino acids and glutamine decreased by 11% (P = 0.05) and 9% (P = 0.09), respectively. In parallel, the efflux from the leg increased by 35% (P = 0.004) for the total sum of amino acids and by 43% (P = 0.05) for glutamine. In conclusion, intravenous endotoxin administration to healthy volunteers, used as a model for the initial phase of sepsis, resulted in a decrease in plasma amino acid concentrations. At the same time, amino acid concentrations in muscle tissue decreased, whereas the efflux of amino acids from leg skeletal muscle increased.


Discovery of small-molecule modulator of heterotrimeric Gi-protein by integrated phenotypic profiling and chemical proteomics.
Discovery of small-molecule inducers of unique phenotypic changes combined with subsequent target identification often provides new insights into cellular functions. Here, we applied integrated profiling based on cellular morphological and proteomic changes to compound screening. We identified an indane derivative, NPD9055, which is mechanistically distinct from reference compounds with known modes of action. Employing a chemical proteomics approach, we then showed that NPD9055 binds subunits of heterotrimeric G-protein Gi. An in vitro [35S]GTPγS-binding assay revealed that NPD9055 inhibited GDP/GTP exchange on a Gαi subunit induced by a G-protein-coupled receptor agonist, but not on another G-protein from the Gαs family. In intact HeLa cells, NPD9055 induced an increase in intracellular Ca2+ levels and ERK/MAPK phosphorylation, both of which are regulated by Gβγ, following its dissociation from Gαi. Our observations suggest that NPD9055 targets Gαi and thus regulates Gβγ-dependent cellular processes, most likely by causing the dissociation of Gβγ from Gαi.


Cranial nuclear magnetic resonance imaging in head trauma.
Nuclear magnetic resonance imaging revealed focal intracranial lesions consisting of extraaxial hematomas or nonhemorrhagic contusions in 3 patients with severe neurological disability following head trauma. In all 3, standard skull radiography and computed tomography had been unremarkable.


Persistent buccopharyngeal membrane: a report of two cases.
Persistent buccopharyngeal membrane is an extremely rare clinical entity that can be diagnosed easily by simple examination of the oral cavity and confirmed by a lateral contrast x-ray. The abnormality can be easily corrected surgically.


Serum FGF-21 levels in type 2 diabetic patients.
Fibroblast growth factor (FGF)-21 has been recently characterized as a potent metabolic regulator, but the physiological role of FGF-21 remains poorly understood. This study was designed to investigate serum FGF-21 levels in type 2 diabetes mellitus (T2DM) patients and explore the correlations between its serum levels and various cardiometabolic parameters in humans. Fifty-four newly diagnosed patients with T2DM (NDDM), 54 subjects with long duration of T2DM (LDDM), that is, more than 5 years, and 35 normal controls participated in this study. Fasting serum FGF-21 levels were measured using ELISA kits. The anthropometric parameters, glucose, glycosylated hemoglobin A1c, lipids, insulin, and high-sensitive C-reactive protein (hsCRP) levels were also measured in fasting status. Serum FGF-21 levels were significantly higher in patients with NDDM and LDDM than in controls (361.80 ± 140.28 pg/mL and 351.17 ± 133.44 pg/mL vs. 185.89 ± 59.29 pg/mL, both p < 0.01), but there was no difference in serum FGF-21 levels between NDDM and LDDM. Fasting serum FGF-21 was found to correlate positively and significantly with age, waist-to-hip ratio, systolic blood pressure, fasting plasma glucose, glycosylated hemoglobin A1c, homeostasis model assessment (HOMA) of insulin resistance, and hsCRP, but negatively with HOMA of β-cell insulin secretion. Furthermore, multiple regression analyses showed that fasting insulin, HOMA of insulin resistance, low-density lipoprotein cholesterol, and hsCRP were independent factors influencing serum FGF-21 levels. Logistic regression analyses demonstrated that serum FGF-21 was significantly associated with T2DM. Serum FGF-21 levels were significantly increased in patients with T2DM. They may play a role in the pathogenesis of T2DM.


Confirmation of an internal hydatid bladder fistula using postoperative methylene blue retrograde injection via urinary catheter: a case report.
Abdominal hydatidosis resulting in an internal hydatid bladder fistula postoperatively is quite rare and might have serious consequences without timely treatment. A 74-year-old Tibetan woman presented with abdominal distension and was diagnosed with hydatid disease. Cyst contents were removed, and the pericyst was partially resected without contraindication. Furthermore, no internal urinary fistula was found before or during the operation, and the presence of an internal fistula was indicated by methylene blue retrograde injection via urinary catheter after the operation. The use of postoperative methylene blue retrograde injection via urinary catheter is recommended to identify internal hydatid bladder fistula formation.


Screening History in 313 Cases of Invasive Cancer: A Retrospective Review of Cervical Cancer Screening in Alberta, Canada.
To examine the screening history of invasive cervical cancer (ICC) cases in Alberta, Canada to identify areas for improvement of the population-based cervical cancer screening program. Retrospective review of ICC cases diagnosed in 2 cities in Alberta between 2007 and 2012. Cancer morphology and staging were elicited from the Alberta Cancer Registry; cancer screening history and Pap test results were extracted from the Provincial Cervical Cancer Screening database. Women were classified as adequately screened, underscreened, and unscreened depending on time from last screening Pap test to diagnosis. Of the 280 cases that occurred in women eligible for screening, 125 (44.6%) were adequately screened, 18 (6.4%) were underscreened, and 137 (49%) were unscreened. Among the adequately screened, 71 (56.8%) had normal Pap test results, but 48 (38%) had less than 3 previous Pap tests (p = .003). Cancer stages I to II were diagnosed in 48.8% and 44.1% of adequately screened and unscreened women and cancer stages III to IV in 30.6% and 66.1% in each group, respectively (p = .0058). Squamous cell carcinoma (SCC) was diagnosed in 189 women (67.5%). The proportion of SCCs was similar in adequately screened and unscreened women. The proportion of SCCs and advanced stages of ICC seems to be decreased. The results of quality improvement initiatives such as enhanced surveillance of high-grade Pap test results and histology-cytology correlation will be monitored and are expected to result in better outcomes for adequately screened women.


Vascular communications of the hand in patients being considered for transradial coronary angiography: is the Allen's test accurate?
The purpose of this study was to assess the accuracy of the Allen's test (AT) in predicting hand ischemia in patients undergoing transradial coronary angiography. Patients with poor vascular communications between the radial artery (RA) and ulnar artery (UA), as indicated by an abnormal AT, are usually excluded from transradial coronary angiography to avoid ischemic hand complications. Over a four-month period, patients undergoing coronary angiography were screened for AT time. Circulation in the RA, UA, principal artery of the thumb (PAT), and thumb capillary lactate were measured before and after 30 min of RA occlusion. Fifty-five patients were studied (20 normal, 15 intermediate, 20 abnormal). Three patients with an abnormal AT were excluded, owing to absence of detectible flow in the distal UA. Patients with an abnormal AT were all men, had a larger RA (3.4 vs. 2.8 mm; p <0.001), and smaller UA (1.9 vs. 2.5 mm; p <0.001), compared with patients with a normal AT. After 30 min of RA occlusion in patients with abnormal AT, blood flow to the PAT improved (3.2 to 7.7 cm/s; p <0.001) yet remained reduced relative to patients with normal AT (7.7 vs. 21.4 cm/s; p <0.001. Thumb capillary lactate was elevated in patients with an abnormal AT (2.0 vs. 1.5 mmol/l; p = 0.019). After 30 min of RA occlusion, patients with an abnormal AT showed significantly reduced blood flow to the thumb and increased thumb capillary lactate (compared with patients with a normal AT) suggestive of ischemia. Transradial cardiac catheterization should not be performed in patients with an abnormal AT.


From seed to bread: variation in quality in a set of old durum wheat cultivars.
Old durum wheat varieties are being appreciated again because of their interesting genetic diversity and low fertilizer needs. The agronomic and bread-making performances of 14 old Italian durum wheat varieties grown under two low nitrogen (N) inputs (46 and 86 kg ha-1 ) were determined and the relationships among grain, semolina, dough and bread quality parameters were established. The old varieties yielded similarly to the check modern variety Svevo under both N levels. Increasing N fertilization from 46 to 86 kg ha-1 did not increase grain yield or the mg of N in the grain, although grain protein percentage increased as a result of a decrease in grain weight and an increase in gliadin content. Despite the resulting decrease in the gluten index, dough and bread quality improved at the higher N rate, highlighting the influential role of protein percentage and gliadin in bread quality. The genotypic variation in grain protein percentage among old varieties was more strongly associated with glutenin than with gliadin content. Variation in the gluten index was high (4-54); indeed, it was the most variable semolina parameter, and proved to contribute the most to variation in bread quality. This variation was independent of the glutenin alleles (HMW 20, 20*, 7, 13+16, 6+8) and was linked to the quality of the grain in terms of grain weight and the associated mg of N per grain. Remarkably, two old varieties, namely Calabria and Cappelli, were able to produce both a good yield and high-quality bread. Old Italian durum wheats continue to boast significant biodiversity and are worth exploring in low-input production systems. © 2019 Society of Chemical Industry.


Recurrent toxic delirium in a patient treated with SSRIs: is old age a risk factor?
We present the case of a 71-year-old female suffering from bipolar affective disorder type 2 and an old lacunar brain infarct who, under the combined treatment of fluoxetine for depression and low dose trazodone for the accompanying insomnia, developed a toxic delirium. The subject presented with mental state changes (confusion and agitation), hyperreflexia, diaphoresis, nausea, vomiting, fever, and a general tonic-clonic seizure which developed soon after an increase in the trazodone dose. One year prior to the above episode, she was hospitalized for a transient episode of agitated confusion while being treated with fluvoxamine for depression, alprazolam and brotazolam for the accompanying anxiety and insomnia. Both episodes subsided spontaneously when treatment was discontinued. This case reports the possible existence of increased vulnerability to hyperserotonergic states in elderly patients suffering from concomitant psychiatric and neurological disorders.


New therapies for the failing heart: trans-genes versus trans-cells.
During the past 30 years, hundreds of pharmacological agents have been developed for the treatment of heart failure; yet few of them ultimately have been tested in patients. Such a disconcerting debacle has spurred the search for non pharmacological therapies, including those based on cardiac delivery of transgenes and stem cells. Cardiac gene therapy preceded stem cell therapy by approximately 10 years; however, both of them already have known an initial phase of enormous enthusiasm followed by moderate-to-strong skepticism, not necessarily justified. The aim of the present review is to discuss succinctly some key aspects of these 2 biological therapies and to argue that, after a phase of disillusionment, gene therapy for the failing heart likely will have the chance to regain the stage. In fact, discoveries in stem cell biology might revitalize gene therapy and, vice versa, gene therapy might potentiate synergistically the regenerative capacity of stem cells.


Combination of Laparoscopic Salpingectomy and Endometrial Ablation: A Potentially Underused Procedure.
Despite the advantages of a decreased risk of epithelial-cell ovarian cancer and the extremely minimally invasive nature of the procedure, combined salpingectomy and endometrial ablation is a potentially underused procedure in the United States to treat abnormal uterine bleeding and desired sterilization. The lack of utilization of this combined procedure might be based on factors other than clinical considerations, including slow acceptance and adoption of Committee Opinions expressing the value of salpingectomy over sterilization. Committee Opinions and randomized clinical trials have demonstrated the benefit of salpingectomy for sterilization and epithelial-cancer risk reduction, and there could be an additional protection against postablation tubal sterilization syndrome. This Commentary discusses the advantages and rationale for consideration of expanding usage of the combined approach.


Absorption of polyethylene glycol (PEG) polymers: the effect of PEG size on permeability.
Polyethylene glycol (PEG) polymers are large amphiphilic molecules that are highly hydrated in solution. To explore the permeability properties of different sized PEG polymers across epithelial membranes in vivo, we examined the absorption of fluorescently labeled PEG conjugates sized 0.55-20 kDa from the lung, since this system provides a reservoir that limits rapid diffusion of molecules away from the site of delivery and enables permeability over longer times to be examined. Following intratracheal delivery in rats, the PEG polymers underwent absorption with first-order kinetics described by single exponential decay curves. PEG size produced a marked influence on the rate of uptake from the lung, with half-lives ranging from 2.4 to 13 h, although above a size of 5 kDa, no further change in rate was observed. PEG size likewise affected retention in alveolar macrophages and in lung tissue; whereas smaller PEG sizes (<2 kDa) were effectively cleared within 48 h, larger PEG sizes (>5 kDa) remained in lung cells and tissue for up to 7 days. These data demonstrate that PEG polymers can be absorbed across epithelial membranes and that PEG size plays a dominant role in controlling the rate and mechanism of absorption.


Robotic assistance for percutaneous needle insertion in the kidney: preclinical proof on a swine animal model.
We evaluated the accuracy, safety, and feasibility of a computed tomography (CT)-guided robotic assistance system for percutaneous needle placement in the kidney. Fiducials surgically implanted into the kidneys of two pigs were used as targets for subsequent robotically-assisted needle insertion. Robotically-assisted needle insertions and CT acquisitions were coordinated using respiratory monitoring. An initial scan volume data set was used for needle insertion planning defining skin entry and target point. Then, needle insertion was performed according to robot positioning. The accuracy of needle placement was evaluated upon the distance between the needle tip and the predefined target on a post needle insertion scan. A delayed contrast-enhanced CT scan was acquired to assess safety. Eight needle trajectories were performed with a median procedural time measured from turning on the robotic system to post needle insertion CT scan of 21 min (interquartile range 15.5-26.5 min). Blind review of needle placement accuracy was 2.3 ± 1.2 mm (mean ± standard deviation) in lateral deviation, 0.7 ± 1.7 mm in depth deviation, and 2.8 ± 1.3 mm in three-dimensional Euclidian deviation. All needles were inserted on the first attempt, which determined 100% feasibility, without needle readjustment. The angulation and length of the trajectory did not impact on the needle placement accuracy. Two minor procedure-related complications were encountered: 2 subcapsular haematomas (13 × 6 mm and 35 × 6 mm) in the same animal. Robotically-assisted needle insertion was shown feasible, safe and accurate in a swine kidney model. Further larger studies are needed.


Design, Synthesis, and Cytotoxic Activity of Novel Natural Arylsulfonamide-Inspired Molecules.
Primary arylsulfonamide functional groups feature prominently in diverse pharmaceuticals. However, natural arylsulfonamides are relatively infrequent. In this work, two novel arylsulfonamide natural products were first synthesized, and then a series of novel molecules derived from natural arylsulfonamides were designed and synthesized, and their in vitro cytotoxic activities against A875, HepG2, and MARC145 cell lines were systematically evaluated. The results indicate that some of these arylsulfonamide derivatives exhibit significantly good cytotoxic activity against the tested cell lines compared with the control 5-fluorouracil (5-FU), such as compounds 10l, 10p, 10q, and 10r. In particular, the potential molecule 10q, containing a carbazole moiety, exhibited the highest inhibitory activity against all tested cell lines, with IC50 values of 4.19 ± 0.78, 3.55 ± 0.63, and 2.95 ± 0.78 μg/mL, respectively. This will offer the potential to discover novel drug-like compounds from the sparsely populated area of natural products that can lead to effective anticancer agents.


Benign prostatic hyperplasia.
Benign prostatic hyperplasia (BPH) is a common condition, which increases with increasing age. Although not a life-threatening condition, BPH can significantly affect quality of life. BPH manifests clinically with lower urinary tract symptoms (LUTS) and may be associated with sexual dysfunction. As many as 60% of men aged 60 years have some degree of clinical BPH. With the projected increases in the distribution of people over the age of 60, BPH isset to become an even greater problem in men's health.


Cardiotonic potential of Carissa opaca Stapf ex Haines: A study on isolated rabbit heart.
Carissa opaca (C.O) is a wild shrub, belonging to the family Apocynaceae. The medicinal virtues of this plant have long been known. The present study demonstrates the effects of aqueous-methanolic extract and various fractions (n-butanolic and aqueous) of Carissa opaca on cardiovascular parameters. The perfusion pressure (PP), force of contraction (FC) and heart rate (HR) were assessed on isolated heart of rabbit using Langendroff's technique for crude extract and fractions of C.O, followed by the elucidation of the mechanism of action after estimating toxicity of the plant. Negative ionotropic and positive chronotropic effects, with an increase in PP in isolated perfused rabbit heart were observed the with plant extract and fractions. The aqueous-methanolic extract exhibited maximum response at 1mg/ml while the n-butanolic and aqueous fractions showed a maximum response at 1mg/ml and 10μg/ml respectively. Both fractions produced the same response when treated with atropine (10-5 M), however the actions of adrenaline (10-5 M) and calcium chloride (10-5 M) remained unblocked. Acute toxicity studies indicated that the plant was safe up to 2000 mg/kg and sub-chronic studies demonstrated that no significant change in haematological and biochemical parameters observed. In conclusion, this study supports the folkloric claim of C.O extract.


A global research agenda for leptospirosis.
Leptospirosis is a zoonotic spirochetal disease of global importance. This disease continues to have a major impact on people living in urban and rural areas of developing countries with inestimable morbidity and mortality. Funding for research and control efforts is currently haphazard, not organized and not effective for public health efforts, primarily because there are no concerted, ongoing international efforts to assess the impact of leptospirosis on human health. Major issues in the field need to be addressed to develop strategies of control, amelioration and treatment. These include the following: mechanisms of naturally acquired and vaccine-induced protective immunity against clinical leptospirosis; mechanisms of severe leptospirosis pathogenesis; standardized, precise and simplified taxonomy of Leptospira relevant to disease manifestations, transmission and control; effective adjunct treatments in addition to antimicrobials; and environmental assessment for risk of leptospirosis transmission and relevant mammalian reservoirs. Once effective ongoing, collaborative international efforts to assess the impact of leptospirosis on human and veterinary health are underway, appropriate mobilization of clinical and public health research funding will follow.


The intestinal microflora during the first weeks of life.
Bacterial colonization of the neonatal gastrointestinal tract begins during birth when the neonate comes into contact with the maternal cervical and vaginal flora. In infants delivered by Caesarean section, bacteria colonizing the neonate gastrointestinal tract are provided by the environment. The first bacteria encountered in the majority of healthy infants, are facultative anaerobes, which remain predominant during the first 2 weeks of life. Among them, Staphylococcus, Enterobacteriaceae and Streptococcus were the genera most commonly isolated from the newborn faecal flora at birth. Facultative anaerobic bacteria are followed closely by Bifidobacterium sp. Clostridium perfringens is present within 2 days with an increase incidence in newborns delivered by a Caesarean section. Clostridium perfringens seems to be the precursor for installation of other anaerobic putrefactive bacteria, as Bacteroides and other Clostridium sp. The impact of Caesarean section and the period and quality of hospitalization are mainly implicated in changes of the normal newborn flora. Feeding seems to modulate the colonization pattern. In humans, breast milk plays a role in passive immunization of the neonatal intestine, and contains factors that promote the growth of Bifidobacterium bifidum in the intestinal flora. Formula feeding seems to promote implantation and persistence of Clostridium perfringens, and clearly enhances intestinal colonization of C. difficile in newborns.


Neutron diffraction study of aqueous Laponite suspensions at the NIMROD diffractometer.
The process of dynamical arrest, leading to formation of different arrested states such as glasses and gels, along with the closely related process of aging, is central for both basic research and technology. Here we report on a study of the time-dependent structural evolution of two aqueous Laponite clay suspensions at different weight concentrations. Neutron diffraction experiments have been performed with the near and intermediate range order diffractometer (NIMROD) that allows studies of the structure of liquids and disordered materials over a continuous length scale ranging from 1 to 300 Å, i.e., from the atomistic to the mesoscopic scales. NIMROD is presently a unique diffractometer, bridging the length scales traditionally investigated by small angle neutron scattering or small angle x-ray scattering with that accessible by traditional diffractometers for liquids. Interestingly, we have unveiled a signature of aging of both suspensions in the length scale region of NIMROD. This phenomenon, ascribed to sporadic contacts between Laponite platelets at long times, has been observed with the sample arrested as gel or as repulsive glass. Moreover, water molecules within the layers closest to Laponite platelets surface show orientational and translational order, which maps into the crystalline structure of Laponite.


Cardiac microvascular endothelial cells express alpha-smooth muscle actin and show low NOS III activity.
We established a culture system of porcine coronary microvascular endothelial cells (MVEC) with high cellular yield and purity >98%. Endothelial origin was confirmed by immunostaining, immunoblotting and fluorescence-activated cell sorter (FACS) analysis using low-density lipoprotein uptake, CD31, von Willebrand factor, and the lectin Dolichos biflorus agglutinin. MVEC were positive for alpha-smooth muscle actin in culture and in myocardium, as confirmed by FACS. Of the primary MVEC, approximately 30% expressed nitric oxide synthase (NOS) III in numbers decreasing from the first passage (6 +/- 1%) to the second passage (4 +/- 1%; P < 0.001 vs. primary isolates), whereas approximately 100% of aortic endothelial cells (AEC) expressed NOS III. In AEC, NOS III activity (pmol citrulline. mg protein-1. min-1) was 80 +/- 10 and was nearly abolished in the absence of calcium (5 +/- 1, P < 0.001). In primary MVEC, however, NOS III activity in the presence and absence of calcium was 20 +/- 4 and 25 +/- 5, respectively. We conclude that cardiac MVEC, in contrast to AEC, contain alpha-smooth muscle actin, show low-grade NOS III activity, and provide a suitable in vitro system for the study of endothelial pathophysiology.


Psychological morbidity associated with local recurrence of breast cancer.
Twenty-two individuals who had suffered from local recurrence of breast cancer were interviewed to determine psychosocial morbidity. Psychometric assessment using the Hamilton Anxiety Scale, the Eysenck Personality Questionnaire and the Montgomery Asberg Depression Rating Scale was conducted prior to clinical evaluation including a structured interview, the Composite International Diagnostic Interview. Lifetime and current psychiatric diagnoses were established. Ten (45%) of the recurrence group had current psychiatric illness (anxiety and depression) at the time of local recurrence, a similar prevalence to that described by others at mastectomy. Previous psychiatric illness and trait neuroticism are predictive of vulnerability to psychiatric morbidity at local recurrence. These results suggest that a significant proportion of patients with local recurrence suffer from major depressive illness.


Random assembly of SUR subunits in K(ATP) channel complexes.
Sulfonylurea receptors (SURs) associate with Kir6.x subunits to form tetradimeric K(ATP) channel complexes. SUR1 and SUR2 confer differential channel sensitivities to nucleotides and pharmacological agents, and are expressed in specific, but overlapping, tissues. This raises the question of whether these different SUR subtypes can assemble in the same channel complex and generate channels with hybrid properties. To test this, we engineered dimeric constructs of wild type or N160D mutant Kir6.2 fused to SUR1 or SUR2A. Dimeric fusions formed functional, ATP-sensitive, channels. Coexpression of weakly rectifying SUR1-Kir6.2 (WTF-1) with strongly rectifying SUR1-Kir6.2[N160D] (NDF-1) in COSm6 cells results in mixed subunit complexes that exhibit unique rectification properties. Coexpression of NDF-1 and SUR2A-Kir6.2 (WTF-2) results in similar complex rectification, reflecting the presence of SUR1- and SUR2A-containing dimers in the same channel. The data demonstrate clearly that SUR1 and SUR2A subunits associate randomly, and suggest that heteromeric channels will occur in native tissues.


Hemodynamic characterization of transient blood flow in right coronary arteries with varying curvature and side-branch bifurcation angles.
Hemodynamics plays a critical role in the development and progression of plaques that are prone to sites of arterial curvatures and branch bifurcations. The occurrence of atherosclerosis at curvatures of coronary arteries and at the bifurcation sites of their branches are of medical importance. In this study, we have employed computer simulation coupled with a parametric analysis to rigorously quantify the transient wall shear stress (WSS) and wall pressure gradient (WPG) in idealized and image-based right coronary artery (RCA) models with side-branches, in order to explore the effects of curvature and bifurcation on blood flow characteristics and its hemodynamic variables. Upon establishing and implementing this parametric analysis framework, it is found that the relatively lower wall shear stress and WPG regions at the curvature and branch bifurcation sites of arteries coincide with the plaques prone points of the three investigated image-based arteries, to thereby confirm the correlation of the fluid mechanical properties with the arterial geometry variation in consistence with the data from existing literatures. Moreover, the average WSS and Pressure drop (from inlet to outlet) are significantly increased with the more complex geometry of realistic arteries in comparison with idealized arterial models. It can hence be concluded that the geometry of curvature and angulation of the side branches has a significant effect on the WSS and WPG in hemodynamics analysis of RCAs and its correlation with atherosclerotic lesions.


Small-angle neutron scattering studies of phospholipid-NSAID adducts.
Nonsteroidal anti-inflammatory drugs (NSAIDs) are known to have strong interactions with lipid membranes. Using small-angle neutron scattering, the effect of ibuprofen, a prominent NSAID, on the radius of small unilamellar vesicles of 1,2-dimyristoyl-sn-glycero-3-phosphatidylcholine (DMPC) and their bilayer structure was studied systematically as a function of pH (ranging from 2 to 8) and drug-to-lipid mole ratio (from 0/1 to 0.62/1 mol/mol). Ibuprofen with a pK(a) of approximately 4.6 was found to significantly affect the bilayer structure at all pH values, irrespective of the charge state of the drug. At low pH values, the drug reduces the bilayer thickness, induces fluid-like behavior, and changes headgroup hydration. The incorporation of the drug in the lipid bilayer while affecting the local bilayer structure and hydration of the lipid does not affect the overall stability of the vesicle dispersions over the pH range studied.


Physical mapping of ribosomal RNA genes in peonies (Paeonia, Paeoniaceae) by fluorescent in situ hybridization: implications for phylogeny and concerted evolution.
Physical maps of the 18S-5.8S-26S ribosomal RNA genes (rDNA) were generated by fluorescent in situ hybridization for five diploid Paeonia species, P. delavayi and P. rockii of section Moutan, and P. emodi, P. tenuifolia, and P. veitchii of section Paeonia. Of five pairs of mitotic chromosomes, rDNA loci were mapped near the telomeres of chromosomes 3, 4, and 5 of P. rockii and P. tenuifolia, chromosomes 2, 3, 4, and 5 of P. delavayi, and all five pairs of chromosomes of P. emodi and P. veitchii. Combining this information with the previously obtained rDNA maps of P. brownii and P. californica of section Oneapia, we hypothesized that the most recent common ancestor of extant peony species had three rDNA loci located on chromosomes 3, 4, and 5. Increase in number of rDNA loci occurred later in each of the three sections, and the increase from three to four loci represents a parallel gain of an rDNA locus on chromosome 2 in P. delavayi of section Moutan and P. brownii of section Oneapia. The increase in number of rDNA loci likely resulted from the translocation of rDNA repeats from chromosomes bearing rDNA loci to chromosomes without them; such translocation is probably facilitated by the telomeric location of rDNA loci. For allotetraploid peony species lacking polymorphism in sequences of the internal transcribed spacers (ITS) of rDNA, the rDNAs derived from divergent diploid parents may have been homogenized through concerted evolution among at least six rDNA loci in the allotetraploids. Chromosomal location of rDNA loci has a more substantial impact on the tempo of concerted evolution than the number of loci.


Evidence for a pathophysiological role of keratinocyte-derived type III interferon (IFNλ) in cutaneous lupus erythematosus.
Type I IFNs (IFNα/β) have been shown to have a central role in the pathophysiology of lupus erythematosus (LE). The recently discovered type III IFNs (IFNλ1/IL29, IFNλ2/IL28a, IFNλ3/IL28b) share several functional similarities with type I IFNs, particularly in antiviral immunity. As IFNλs act primarily on epithelial cells, we investigated whether type III IFNs might also have a role in the pathogenesis of cutaneous LE (CLE). Our investigations demonstrate that IFNλ and the IFNλ receptor were strongly expressed in the epidermis of CLE skin lesions and related autoimmune diseases (lichen planus and dermatomyositis). Significantly enhanced IFNλ1 could be measured in the serum of CLE patients with active skin lesions. Functional analyses revealed that human keratinocytes are able to produce high levels of IFNλ1 but only low amounts of IFNα/β/γ in response to immunostimulatory nuclear acids, suggesting that IFNλ is a major IFN produced by these cells. Exposure of human keratinocytes to IFNλ1 induced the expression of several proinflammatory cytokines, including CXCL9 (CXC-motiv ligand 9), which drive the recruitment of immune cells and are associated with the formation of CLE skin lesions. Our results provide evidence for a role of type III IFNs in not only antiviral immunity but also autoimmune diseases of the skin.


A highly-enhanced electrochemiluminescence luminophore generated by a metal-organic framework-linked perylene derivative and its application for ractopamine assay.
In this study, a sensitive and effective monitoring method for ractopamine (RAC) was developed based on a sensitive electrochemiluminescence (ECL) aptasensor. Here, we employed a perylene derivative (PTC-PEI) with a Cu-based metal-organic framework (HKUST-1), which could accelerate the electron-transfer (ET) rate and strengthen interactions by the amido bond, resulting in enhanced ECL sensitivity and stability. Astonishingly, compared with the response of PTC-PEI and complex, the ECL signal of the MOF-based ECL material was noticeably raised by 6 times higher than that of PTC-PEI. HKUST-1 exhibited an excellent catalytic effect towards the electrochemical reduction process of S2O82-, thus allowing more sulfate radical anions (SO4˙-) to be generated. The strong ECL intensity of HKUST-1/PTC-PEI not only stemmed from the fixation of PTC-PEI that utilized its excellent film-forming abilities but also originated from the high porosity of HKUST-1 that carried more luminophores able to be excited. Satisfyingly, in the presence of the target molecule RAC, we observed an obvious quenching effect of signal, which could be attributed to aptamer recognition resulting in RAC being specifically captured on the electrode. Under optimal conditions, the developed sensor for the RAC assay displayed a desired linear range of 1.0 × 10-12-1.0 × 10-6 M and a low detection limit of 6.17 × 10-13 M (S/N = 3). This ECL sensor showed high sensitivity, good stability and excellent selectivity. More importantly, the proposed aptasensor exhibited excellent determination towards RAC detection and potential practical utility for real samples.


LEP, LDLR and APOA4 gene polymorphisms and their relationship with the risk of overweight, obesity and chronic diseases in adults of the State of Sucre, Venezuela.
Overweight, obesity and some chronic diseases have become more prevalent recently. It is well known that their causes may be genetic, epigenetic, environmental, or a mixture of these. To analyze the relationship between nine single nucleotide polymorphisms of genes LEP (rs2167270), LDLR (rs885765, rs688, rs5925, rs55903358, rs5742911) and APOA4 (rs5095, rs675, rs5110) with obesity-related phenotypes and other comorbidities. We recruited 144 adults (76 males and 68 females, with average ages of 29.93±8.29 and 32.49±11.15 years, respectively) in the State of Sucre, Venezuela. Clinical and anthropometric parameters were obtained. Genotype-risk associations were studied. We then compared the averages registered for anthropometric and biochemical variables previously adjusted for biological and environmental factors. According to the body mass index, 38.9% of the individuals in the sample were overweight (25≤BMI≤29.9 kg/m2) and 20.1% were obese (BMI≥30 kg/m2). Genotype and allele frequencies did not differ statistically for groups with normal and high body mass index (overweight plus obesity). The association between LDLR rs5742911 ancestral genotype A/A and high risk condition related to HDL-cholesterol was the only one found to be significant (OR=2.944, 95% CI: 1.446-5.996; p=0.003). The difference in adjusted mean HDL-cholesterol for LDLR rs5742911 genotypes was statistically significant (p=0.005) (A/A: 41.50±14.81 mg/dL; A/G: 45.00±12.07 mg/dL; G/G: 47.17±9.43 mg/dL). For most of the genetic variants studied, there was an association with the presence of overweight and obesity among ancestral genotype carriers, although this was not statistically significant. The rs5742911 polymorphism may be useful as an indicator of a risk of chronic diseases.


Abnormal urinary protein excretion in HIV-infected patients.
HIV infection has been associated with a variety of renal diseases, although the pathogenesis of such dysfunction is unknown. To determine whether HIV-infection is associated with glomerular permeability defects, and if so, the prevalence of the finding, we studied patients with various stages of HIV infection. Urine samples from 505 outpatients with HIV infection (without hypertension, azotemia, or dipstick proteinuria), 41 normal controls and 40 febrile non-HIV positive, hospitalized patients with infectious diseases were analyzed for the urinary microalbumin/creatinine ratio (U microA/Cr), a sensitive indicator of incipient renal disease in diabetes mellitus and hypertension, and the urinary beta 2-microglobulin/creatinine ratio (U beta 2/Cr), an indicator of renal tubular function. Microalbumin concentration was measured by ELISA. Beta 2-microglobulin concentration was measured by an enzyme immunoassay. HIV-infected outpatients had higher mean U microA/Cr than normal subjects, but not febrile hospitalized controls. The prevalence of an increased U microA/Cr was 29.8% in the HIV-infected outpatient population. There was no difference in the ratio between Black and White HIV-infected outpatients, HIV-infected outpatients treated or untreated with zidovudine (AZT), or HIV infected outpatients untreated with any drug. There was no difference between U microA/Cr in stage II, III or IV HIV-infected patients when assessed by analysis of variance. A similar pattern was noted with U beta 2/Cr. The prevalence of an increased U beta 2/Cr ratio was 37.7% in HIV-infected outpatients. Increased urinary albumin and beta 2-microglobulin excretion, not associated with drug therapy, is present in patients with early HIV infection.(ABSTRACT TRUNCATED AT 250 WORDS)


Mass spectrometry-based metabolomics for irritable bowel syndrome biomarkers.
Irritable bowel syndrome (IBS) is a common gastrointestinal disorder without obvious structural abnormalities or consistent associated biomarkers, making its diagnosis difficult. In the present study, we used a urine-based metabolomics approach to identify IBS biomarkers. We used an ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) on urine samples from patients suffering from IBS and healthy controls. Data were coupled for multivariate statistical analysis methods. We selected 30 differential metabolites associated with IBS and found steroid hormone biosynthesis and histidine metabolism alterations in patients with IBS that may be involved in the pathogenesis of the disease. In addition, we identified a panel of five metabolite markers composed of cortisone, citric acid, tiglylcarnitine, N6,-N6,-N6-trimethyl-L-lysine and L-histidine that could be used to discriminate between patients and healthy controls and may be appropriate as IBS diagnosis biomarkers. Our findings indicate that metabolomics combined with pattern recognition can be useful to identify disease diagnostic IBS markers. ChiCTR1800020072.


Hematologic variables and venous thrombosis: red cell distribution width and blood monocyte count are associated with an increased risk.
Recent studies suggest that leukocytes and erythrocytes play a role in coagulation. However, whether leukocytes, erythrocytes and other hematologic variables are associated with risk of venous thrombosis is not well known. To study this, we used data from 2473 patients with venous thrombosis and 2935 controls. The variables assessed were: total leukocytes, granulocytes, lymphocytes, monocytes, hematocrit, hemoglobin, erythrocytes and red cell indices (mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration and red cell distribution width). We found a strong dose-response relation for higher red cell distribution width and monocyte count with risk of venous thrombosis, with odds ratios of 3.1 (95% confidence interval, 2.0-4.8) and 2.8 (95% confidence interval, 1.3-5.8), respectively, after adjustment for age, sex, C-reactive protein level, malignancy and co-morbidities. Monocyte count and red cell distribution width were associated with venous thrombosis even within reference ranges. A low monocyte count (<0.12 × 10(9)/L) was associated with a lower risk of venous thrombosis after full adjustment (odds ratios 0.6; 95% confidence interval, 0.4-0.8). In summary, high red cell distribution width and blood monocyte count, two parameters that are inexpensive and easily obtainable, were clearly associated with an increased risk of venous thrombosis. Future studies should evaluate the underlying mechanism and the use of these variables in prediction models for first and recurrent thrombosis.


Response of butterflies to structural and resource boundaries.
1. Two aspects of landscape composition shape the behavioural response of animals to habitat heterogeneity: physical habitat structure and abundance of key resources. In general, within-habitat movement behaviour has been investigated in relation to resources, and preference at boundaries has been quantified in response to physical structure. 2. Habitat preference studies suggest that responses to resources vs. structure should differ, e.g. between male and female animals, and effects of responses to structure and resources may also interact. However, most studies of animal movement combine various aspects of behavioural responses to 'habitat', implicitly assuming that resources and structure are broadly equivalent. 3. We conducted a large-scale experiment of the movement of Fender's blue (Icaricia icarioides fenderi), an endangered butterfly, to investigate butterfly response to physical structure of the landscape (prairie, open woods and dense woods) and to resources [presence or absence of Kincaid's lupine, Lupinus oreganus (larval hostplant patches)]. The experiment included 606 butterfly flight paths across four habitat types and nine ecotones. 4. Responses to physical structure and resource patches were not congruent. Butterflies were attracted to resource patches within both prairies and open woods and moved more slowly when in resource patches. Butterflies tended to prefer prairie at prairie-forest edges but tended to move faster in prairies than in open woods. Physical structure and resources also interacted; butterflies did not respond to physical habitat structure when resource patches spanned prairie - open woods ecotones. 5. Even dense woods were not perfect barriers, in contrast to a large body of literature that assumes insects from open habitats will not enter dense forests. 6. Movement of both males and females responded to resources and structure. However, female butterflies had stronger responses to both resources and structure in most cases. Females had strongest response to resource (hostplant) patches at patch edges, whereas the strongest preference of males was to return to prairie from open forest. 7. If other species behave like Fender's blue, then combining different definitions of 'habitat' (physical structure vs. resources), different aspects of movement (edge preference vs. within-habitat movement) and/or males and females within species could all lead to misleading conclusions. Our results highlight the importance of investigating these responses, and our study provides a framework for separating them in other systems.


The cell wall architecture of Enterococcus faecium: from resistance to pathogenesis.
The cell wall of Gram-positive bacteria functions as a surface organelle that continuously interacts with its environment through a plethora of cell wall-associated molecules. Enterococcus faecium is a normal inhabitant of the GI tract of mammals, but has recently become an important etiological agent of hospital-acquired infections in debilitated patients. Insights into the assembly and function of enterococcal cell wall components and their interactions with the host during colonization and infection are essential to explain the worldwide emergence of E. faecium as an important multiantibiotic-resistant nosocomial pathogen. Understanding the biochemistry of cell wall biogenesis and principles of antibiotic resistance at the molecular level may open up new frontiers in research on enterococci, particularly for the development of novel antimicrobial strategies. In this article, we outline the current knowledge on the most important antimicrobial resistance mechanisms that involve peptidoglycan synthesis and the role of cell wall constituents, including lipoteichoic acid, wall teichoic acid, capsular polysaccharides, LPxTG cell wall-anchored surface proteins, WxL-type surface proteins and pili, in the pathogenesis of E. faecium.


Physical inactivity during adolescence heightens risk for cannabis use disorder in adulthood.
The association between physical inactivity and substance use throughout adolescence was prospectively investigated in relation to developing cannabis use disorder (CUD). Physical inactivity and substance use in males (N = 462) and females (N = 178) were measured at 12-14, 16, 19, and 22 years of age in a repeated measures design. A structured diagnostic interview was administered to formulate current CUD diagnosis at 22 years of age. Mixture modeling path analysis evaluated the association between physical inactivity, substance use, and CUD. Males: Slope of physical inactivity increase spanning 12-22 years of age mediates the association between number of parents with substance use disorder (SUD) and rate of increase in substance use frequency (prodrome) which mediates the association between physical inactivity (hypothesized vulnerability) and CUD. Females: Number of SUD parents predicts slope of physical inactivity increase in daughters throughout adolescence which covaries with slope of increasing substance use frequency culminating in CUD. The association between parental SUD load (number of SUD affected parents) and CUD was found to not be mediated by physical inactivity. Rate of increase in physical inactivity during adolescence in males and females is a facet of the vulnerability for CUD. These results have ramifications for prevention considering that numerous cognitive, behavior, and emotion features of CUD vulnerability are attenuated by exercise. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Pilot testing of a mindfulness- and acceptance-based intervention for increasing cardiorespiratory fitness in sedentary adults: A feasibility study.
Vigorous physical activity (PA) has been promoted for improving cardiorespiratory fitness (CRF). However, therapeutic techniques designed to engage participants in vigorous PA have fallen short; one reason for this may be the unpleasant physical sensations associated with vigorous exercise (e.g., temporary shortness of breath and mild muscle soreness). Mindfulness and acceptance-based therapies such as Acceptance and Commitment Therapy (ACT) may be helpful at improving adherence to vigorous PA levels. In this open clinical trial, we sought to demonstrate the feasibility and acceptability of a mindfulness- and acceptance-based intervention for increasing CRF in sedentary adults and to generate initial outcomes data. Participants (N=24) engaged in a 10-week fitness walking program while attending regular group sessions based on ACT. The feasibility and acceptability of the intervention were demonstrated through high levels of walking adherence (89.30%) and group session attendance (85.50%). A large significant decrease in total 1-mile walk test time [t(18)=4.61, p=.0002, d=.64] and a moderate significant increase in estimated VO2max [t(18)=-4.05, p=.0007, d=-.43] were observed. Analyses indicated a large significant increase in exercise-related experiential acceptance [t(18)=-9.19, p <.0001, d=-2.09]. This study demonstrates the feasibility and acceptability of an ACT-based intervention for supporting participation in vigorous PA in sedentary individuals.


The Relationship Between Heart Rate Variability, Psychological Flexibility, and Pain in Neurofibromatosis Type 1.
Individuals with neurofibromatosis type 1 (NF1) and plexiform neurofibromas (PNs) can experience chronic pain. Previous research has examined the relationship between heart rate variability (HRV) and persistent pain. HRV is an index of autonomic nervous system functioning, and reflects the variability in time elapsed between heartbeats. Patients with chronic pain tend to exhibit lower HRV, which has been associated with poor adaptability, or psychological flexibility, to stress. The aim of the current study was to examine relationships between HRV, psychological flexibility, and pain in a sample of adolescents and young adults (AYAs) with NF1 and PNs. AYA participants (n = 40) 16 to 34 years of age with NF1 completed baseline measures of pain and psychological functioning, and underwent a 5-minute electrocardiogram (ECG). A subset of 20 participants completed follow-up questionnaires and a second ECG 8 weeks later. Spectral analyses of ECGs yielded a measure of high-frequency heart rate variability (HF-HRV). Baseline correlations revealed that lower HF-HRV is related to greater inflexibility and more pain interference, but not pain intensity. Moreover, psychological inflexibility significantly mediated the relationship between HF-HRV and pain interference. Finally, regression models indicated that baseline psychological inflexibility is a significant predictor of HF-HRV at follow-up and, separately, that baseline HF-HRV significantly predicted pain intensity at follow-up. These findings suggest complex mind-body processes in the experience of pain in NF1, which have not been studied previously. Implications for pain-related interventions and future research are discussed.


Synthetic applications of Pd(II)-catalyzed C-H carboxylation and mechanistic insights: expedient routes to anthranilic acids, oxazolinones, and quinazolinones.
A Pd(II)-catalyzed reaction protocol for the carboxylation of ortho-C-H bonds in anilides to form N-acyl anthranilic acids has been developed. This reaction procedure provides a novel and efficient strategy for the rapid assembly of biologically and pharmaceutically significant molecules, such as benzoxazinones and quinazolinones, from simple anilides without installing and removing an external directing group. The reaction conditions are also amenable to the carboxylation of N-phenyl pyrrolidinones. A monomeric palladacycle containing p-toluenesulfonate as an anionic ligand has been characterized by X-ray crystallography, and the crucial role of p-toluenesulfonic acid in the activation of C-H bonds in the presence of carbon monoxide is discussed. Identification of two key intermediates, a mixed anhydride and benzoxazinone formed by reductive elimination from organometallic Ar(CO)Pd(II)-OTs species, provides mechanistic evidence for a dual-reaction pathway.


Effectiveness of high-throughput miniaturized sorbent- and solid phase microextraction techniques combined with gas chromatography-mass spectrometry analysis for a rapid screening of volatile and semi-volatile composition of wines--a comparative study.
In this study the feasibility of different extraction procedures was evaluated in order to test their potential for the extraction of the volatile (VOCs) and semi-volatile constituents (SVOCs) from wines. In this sense, and before they could be analysed by gas chromatography-quadrupole first stage masss spectrometry (GC-qMS), three different high-throughput miniaturized (ad)sorptive extraction techniques, based on solid phase extraction (SPE), microextraction by packed sorbents (MEPS) and solid phase microextraction (SPME), were studied for the first time together, for the extraction step. To achieve the most complete volatile and semi-volatile signature, distinct SPE (LiChrolut EN, Poropak Q, Styrene-Divinylbenzene and Amberlite XAD-2) and MEPS (C(2), C(8), C(18), Silica and M1 (mixed C(8)-SCX)) sorbent materials, and different SPME fibre coatings (PA, PDMS, PEG, DVB/CAR/PDMS, PDMS/DVB, and CAR/PDMS), were tested and compared. All the extraction techniques were followed by GC-qMS analysis, which allowed the identification of up to 103 VOCs and SVOCs, distributed by distinct chemical families: higher alcohols, esters, fatty acids, carbonyl compounds and furan compounds. Mass spectra, standard compounds and retention index were used for identification purposes. SPE technique, using LiChrolut EN as sorbent (SPE(LiChrolut EN)), was the most efficient method allowing for the identification of 78 VOCs and SVOCs, 63 and 19 more than MEPS and SPME techniques, respectively. In MEPS technique the best results in terms of number of extractable/identified compounds and total peak areas of volatile and semi-volatile fraction, were obtained by using C(8) resin whereas DVB/CAR/PDMS was revealed the most efficient SPME coating to extract VOCs and SVOCs from Bual wine. Diethyl malate (18.8±3.2%) was the main component found in wine SPE(LiChrolut EN) extracts followed by ethyl succinate (13.5±5.3%), 3-methyl-1-butanol (13.2±1.7%), and 2-phenylethanol (11.2±9.9%), while in SPME(DVB/CAR/PDMS) technique 3-methyl-1-butanol (43.3±0.6%) followed by diethyl succinate (18.9±1.6%), and 2-furfural (10.4±0.4%), are the major compounds. The major VOCs and SVOCs isolated by MEPS(C8) were 3-methyl-1-butanol (26.8±0.6%, from wine total volatile fraction), diethyl succinate (24.9±0.8%), and diethyl malate (16.3±0.9%). Regardless of the extraction technique, the highest extraction efficiency corresponds to esters and higher alcohols and the lowest to fatty acids. Despite some drawbacks associated with the SPE procedure such as the use of organic solvents, the time-consuming and tedious sampling procedure, it was observed that SPE(LiChrolut EN), revealed to be the most effective technique allowing the extraction of a higher number of compounds (78) rather than the other extraction techniques studied.


Significance of smoking in patients receiving thrombolytic therapy for acute myocardial infarction. Experience gleaned from the International Tissue Plasminogen Activator/Streptokinase Mortality Trial.
Despite the fact that smoking is a well-established risk factor for the development of coronary artery disease, some investigators have noted that hospital mortality after acute myocardial infarction is lower in patients who smoke than in nonsmoking patients. To evaluate the association of smoking with mortality during hospitalization after thrombolytic therapy and 6 months afterward, we analyzed the results of the International Tissue Plasminogen Activator/Streptokinase Mortality Trial. Patients were divided into three groups: nonsmokers (those who never smoked), ex-smokers, and active smokers. Multivariate and univariate comparisons were made with respect to baseline characteristics and clinical outcome. There were 2,366 nonsmokers, 2,244 ex-smokers, and 3,649 active smokers. The baseline characteristics of nonsmoking patients differed significantly from the ex-smokers and active smokers. The nonsmoking group included more women than the ex-smokers or active smokers (45% versus 10.6% and 17.6%, respectively), was older (67 +/- 10 years versus 64 +/- 10 years and 58 +/- 11 years), had a higher rate of diabetes mellitus (16.3% versus 11.1% and 7.5%), and had a worse Killip class at admission. Nonsmoking patients and ex-smokers experienced more in-hospital reinfarction than active smokers (4.7% and 5% versus 2.7%, p < 0.0001, respectively). Nonsmokers experienced more in-hospital shock than the ex-smokers or active smokers (9.2% versus 6.4% and 5.8%, p < 0.0001), stroke (1.9% versus 1.8% and 0.8%, p < 0.0001), and bleeding (7.2% versus 6.5% and 4.4%, p < 0.0001). They also experienced a higher in-hospital and 6-month mortality (12.8% and 17.6%) than ex-smokers (8.2% and 12.1%) or active smokers (5.4% and 7.8%) (p < 0.0001). A multivariate analysis accounting for all baseline characteristics demonstrated a significant association between nonsmoking and increased hospital mortality, with an odds ratio of 1.42 (confidence limits, 1.15-1.72). Among active smokers, there was a nonsignificant trend for mortality rates to decrease with increasing numbers of cigarettes smoked per day. This retrospective analysis indicates that smokers receiving thrombolytic therapy after acute myocardial infarction have significantly better hospital and 6-month outcome than nonsmokers or ex-smokers. However, smokers sustained their infarction at a significantly earlier age than nonsmokers, and strenuous efforts should continue to be made to decrease the incidence of new and continued smoking.


99mTc-mercaptoacetyltriglycine camera-based measurement of renal clearance: should the result be normalized for body surface area?
Testing the rate of creatinine clearance by measuring the level of creatinine in the blood and in a 24-h urine collection is a common method of evaluating renal function. The result is routinely normalized for body surface area (BSA). Alternatively, renal clearance can be measured by (99m)Tc-mercaptoacetyltriglycine (MAG3) renal imaging without the need for urine collection. Frequently, the (99m)Tc-MAG3 camera-based result is also normalized for BSA. I evaluated the need for BSA normalization of renal clearance measurements in (99m)Tc-MAG3 imaging studies from both a conceptual and a mathematic point of view. Both approaches involved analyzing the effect of patient size, that is, BSA, on the factors blood volume, renal blood flow, and amount of test substance present in the blood in the creatinine clearance method compared with the (99m)Tc-MAG3 camera-based method. Both the conceptual and the mathematic analyses were consistent with a significant difference between the creatinine and (99m)Tc-MAG3 approaches to measuring renal clearance. Larger patients have larger kidneys, greater renal blood flow, higher renal clearances, larger blood volumes, more muscle mass, and higher BSAs than smaller patients. However, the concentration of creatinine in the blood of patients of any size with normal renal function is similar because the amount of creatinine released into the blood varies with patient muscle mass, which varies with blood volume. Because normalization for BSA is needed for creatinine clearance, a single reference range can be used for all patients. In the case of measurement of renal clearance with (99m)Tc-MAG3 imaging (assuming a constant dose), the concentration of tracer in the blood will vary inversely with patient size because blood volume varies with patient size. Thus, as patient size increases, the blood concentration of tracer will go down and compensate for the increase in renal blood flow and renal clearance, and conversely. Consequently, the (99m)Tc-MAG3 renal imaging study is self-correcting for BSA and no additional correction is needed. A conceptual and mathematic analysis suggests that, although normalization for BSA is necessary in the measurement of renal clearance by the standard creatinine clearance test, such normalization is inappropriate in the (99m)Tc-MAG3 camera-based imaging study because the (99m)Tc-MAG3 method is inherently self-normalizing for BSA.


[Effectiveness of trazodone in the treatment of sexual dysfunctions].
Sexual dysfunctions may be main cause of social disability. The knowledge of the rates of occurrence of sexual dysfunctions in the general population and the primary risk factors for these conditions is very important to assist in assessing the risk and planning treatment. Sexual dysfunctions are highly prevalent in our society worldwide, and that the occurrence of sexual dysfunctions increases directly with age for both men and women. Specific medical conditions and health behaviors represent major risk factors for sexual disorders. Trazodone is sedative antidepressant drug, which is effective, safe, fast acting, with a few side effects, with proved efficiency in the treatment of sexual dysfunction.


Reductive Alkylation of Tertiary Lactams via Addition of Organocopper (RCu) Reagents to Thioiminium Ions.
A simple procedure for the conversion of tertiary lactams to 2-monoalkylated cyclic amines is described. The reaction sequence involves conversion of a lactam to a thioiminium ion followed by reaction with an organocopper (RCu) reagent and final reduction with triacetoxyborohydride. The reaction is high yielding and shows an excellent functional group tolerance. Its utility is demonstrated by a rapid synthesis of indolizidine 167B. The excellent chemoselectivity of the process, where only monoalkylation products are formed, is rationalized by a mechanism involving the formation of a transient enamine.


[Double localization of intracranial germinoma. Apropos of a case].
The authors report a case of a double localization of an intracranial germinoma in the pineal and suprasellar regions, which represents only 2 to 7% of all germinomas. Reviewing the literature, they discuss the pathogenesis, histopathology, biology and treatment of these tumours.


Deep anterior lamellar keratoplasty for keratoconus: a review.
Deep anterior lamellar keratoplasty (DALK) is a surgical technique that involves the removal of pathological corneal stroma down to Descemet membrane and replacing it with a donor cornea. Over the last decade, there has been a paradigm shift in the surgical techniques of DALK, which has made it safer with visual outcomes comparable with penetrating keratoplasty. This review aims to discuss the existing popular techniques of DALK, their advantages and limitations. We will also describe techniques of DALK that are useful in special situations.


Identification of Secretory Proteins in Mycobacterium tuberculosis Using Pseudo Amino Acid Composition.
Tuberculosis is killing millions of lives every year and on the blacklist of the most appalling public health problems. Recent findings suggest that secretory protein of Mycobacterium tuberculosis may serve the purpose of developing specific vaccines and drugs due to their antigenicity. Responding to global infectious disease, we focused on the identification of secretory proteins in Mycobacterium tuberculosis. A novel method called MycoSec was designed by incorporating g-gap dipeptide compositions into pseudo amino acid composition. Analysis of variance-based technique was applied in the process of feature selection and a total of 374 optimal features were obtained and used for constructing the final predicting model. In the jackknife test, MycoSec yielded a good performance with the area under the receiver operating characteristic curve of 0.93, demonstrating that the proposed system is powerful and robust. For user's convenience, the web server MycoSec was established and an obliging manual on how to use it was provided for getting around any trouble unnecessary.


Differential expression of genes related to drug responsiveness between sparsely and densely granulated somatotroph adenomas.
There are two main subtypes of GH-producing pituitary adenoma: densely granulated (DG-type) and sparsely granulated (SG-type). Despite the difference in drug responsiveness between the two subtypes, their molecular mechanisms remain unknown. The aim of this study is to evaluate the differential expression of genes related to drug responsiveness between the two subtypes of somatotroph adenoma, and their relationship to the clinical characteristics. Eighty-two acromegaly patients (44 DG-type, 38 SG-type) were studied retrospectively. Clinical characteristics were compared between the two subtypes. Among them, 36 tumor tissue specimens (19 DG-type, 17 SG-type) were available for investigation of the expression of SSTR2, SSTR5 and D2R that are reported to be involved in drug responsiveness by realtime RT-PCR. Protein level was evaluated by immunohistochemical study. Patients with SG-type adenomas were younger in age and showed greater GH suppression by octreotide, but not by bromocriptin, and bigger in size and more invasiveness than DG-type adenomas. The mRNA expression of SSTR2 in DG-type adenomas were greater than those in SG-type adenomas and showed significantly positive correlation with GH suppression by octreotide. There was positive correlation between mRNA and protein levels of SSTR2. These data suggested that the differences of responsiveness to octreotide between DG- and SG-type adenomas are based on the expression levels of SSTR2.


Quantitative study of reflection of sunlight by a glass curtain wall resulting in a visual masking effect.
Because of the complexity of the shapes of the structures of buildings, the glass curtain walls of such buildings have different geometries; some of these glass curtain walls have high reflectivity and can strongly focus incident solar light. Under ideal conditions, the solar radiation flux incident onto the glass curtain wall and the solar flux reflected from the glass curtain wall can be theoretically determined. When exposed to an intense light source, human eyes exhibit a visual masking effect when processing an image; the resulting noise level and signal-to-noise ratio in the image are studied. Using field measurements to measure the reflected sunlight of two types of glass curtain walls, the energy distributions of the light reflected from these two different glass curtain walls are determined. This paper focuses on analysis of the experimental results and the cause of the visual masking effect due to the reflection of sunlight from a glass curtain wall and on the method of quantitative calculation of the visual masking effect.


Medical examinations under the Americans with Disabilities Act.
Title I of the Americans with Disabilities Act, effective July 26, 1992, established new guidelines for physicians who perform medical examinations of job applicants and existing employees with confidentiality requirements. These guidelines have a broad impact on physicians and employers.


Surgical Treatment of Distal Biceps Tendon Ruptures: An Analysis of Complications in 784 Surgical Repairs.
Distal biceps brachii tendon ruptures lead to substantial deficits in elbow flexion and supination; surgical repair restores muscle strength and endurance. To examine clinical and surgical outcomes for distal biceps tendon repairs in a large, multispecialty, integrated health care system. Cohort study; Level of evidence, 3. Retrospective cohort study of distal biceps tendon repairs performed between January 1, 2008, and December 31, 2015. The repair methods were classified as double-incision approach using bone tunnel-suture fixation or anterior single-incision approach. Anterior single incisions were further classified according to the fixation method: cortical button alone, cortical button and interference screw, or suture anchors alone. Patient demographics, surgeon characteristics, range of motion, and complications were analyzed for all repair types. Of the 784 repairs that met the inclusion criteria, 639 (81.5%) were single-incision approaches. When comparing double-incision and single-incision repairs, there was a significantly higher rate of posterior interosseous nerve palsy (3.4% vs 0.8%, P = .010), heterotopic bone formation (7.6% vs 2.7%, P = .004), and reoperation (8.3% vs 2.3%, P < .001). The most common nerve complication encountered was a lateral antebrachial cutaneous nerve palsy (n = 162), which was significantly more common in the single-incision repairs than in the double-incision repairs (24.4% vs 4.1%, P < .001). When excluding lateral antebrachial cutaneous nerve palsies, there was no significant difference in the overall nerve palsies between single-incision and double-incision (5.8% vs 6.9%, P = .612). The overall rate of tendon rerupture was 1.9% (single incision, 1.6%; double incision, 2.8%; P = .327). The overall rate of postoperative wound infection was 1.5% (single incision, 1.3%; double incision, 2.8%; P = .182). The average time from surgery to release from medical care was 14.4 weeks (single incision, 14 weeks; double incision, 16 weeks; P = .286). Patients treated with cortical button plus interference screw were released significantly sooner than were patients with other single-incision repair types (13.1 ± 8.01 weeks, P = .011). There were no significant differences in rates of motor neurapraxia, infection, rerupture, and reoperation with regard to surgeon's years of practice, fellowship training, or case volume. The surgical repair of distal biceps tendon ruptures has an overall low rate of serious complications, regardless of approach or technique. However, the double-incision technique has a higher rate of posterior interosseous nerve palsy, heterotopic bone formation, and reoperation rate. Surgeon's years of practice, fellowship training, and case volume do not affect the rate of major complications.


[In vitro comparative study of the sensitivity of Aspergillus to antifungal agents].
Minimum inhibitory concentrations (MIC) of amphotericin B, 5-fluorocytosine, miconazole, tioconazole, econazole and ketoconazole were determined for 310 Aspergillus strains belonging to four different species isolated from clinical specimens. Econazole exhibited the best in vitro activity with MIC less than or equal to 3.12 micrograms/ml for 96% of strains and less than or equal to 1.56 micrograms/ml for 68%. For amphotericin B, 69% of strains were less than or equal to 1.56 micrograms/ml and, for 5-fluorocytosine, 50% were less than or equal to 25 micrograms/ml. Miconazole and ticonazole exhibited comparable in vitro activities with MIC less than or equal to 6.25 micrograms/ml for 66% and 58% of strains respectively. Ketoconazole was the less active agent in vitro, with MIC less than or equal to 6.25 micrograms/ml for only 27% of strains. Moreover, this study demonstrated significant differences in susceptibility from species to species. A. fumigatus was susceptible to amphotericin B (75%) and 47% of strains were susceptible to 5-fluorocytosine. A. niger showed high susceptibility to amphotericin B (82%) and 5-fluorocytosine (82%). A. flavus exhibited the highest resistance to 5-fluorocytosine (14%), the highest susceptibility to ketoconazole (72%), and average susceptibility to amphotericin B (41%). A. nidulans was rarely susceptible to amphotericin B (21%) or 5-fluorocytosine (29%) and 46% of strains were susceptible to miconazole and ketoconazole. These results provide useful guidelines for the choice of antifungal agents in the difficult treatment of aspergillosis.


Tracking of proton flow during transition from anaerobiosis to steady state. 2. Effect of cation uptake on the response of a hydrophobic membrane bound pH indicator.
1. During aerobic cation uptake in liver mitochondria, the hydrophobic pH indicator bromothymol blue undergoes a multiphase response: phase 1 (rapid acidification), phase 2 (slow alkalinization), phase 3 (rapid alkalinization) and phase 4 (reacidification). 2. Titrations with ruthenium red and malonate indicate that the various phases depend on the relative rates of cation uptake and proton translocation: at high rates of cation uptake, phase 1 disappears and phases 2 and 3 are transformed in a monotonic process of alkalinization. 3. The comparison of the bromothymol blue response with the arsenazo III, 2',7'-bis(carboxyethyl)-5(6)carboxyfluorescein (BCECF) and safranine responses indicates that: (a) phase 2 (slow alkalinization) corresponds to a slow rise of matrix pH and a parallel decline of membrane potential; (b) phase 3 (rapid alkalinization) corresponds to termination of proton translocation and initiation of the processes of cation efflux and proton reuptake. All the above processes reach completion during phase 4. 4. Although bromothymol blue always behaves as a membrane-bound indicator, the extent to which it reflects the matrix or the cytosolic pH is a function of the membrane-potential-determined asymmetric distribution: in parallel with the lowering of the membrane potential, the dye chromophore is shifted from the cytosolic to the matrix side membrane layer. 5. A model is discussed which describes the behaviour of bromothymol blue as pH indicator recording the changes in membrane layers facing either the matrix or the cytosolic side. The complex response of the dye during cation uptake is due to two independent processes, one of pH change and another of dye intramembrane shift. Computer simulations of the dye response, based on the conversion of a kinetic model into an electrical network and closely reproducing the experimental observations, are reported.


Utilizing carbon nanotube electrodes to improve charge injection and transport in bis(trifluoromethyl)-dimethyl-rubrene ambipolar single crystal transistors.
We have examined the significant enhancement of ambipolar charge injection and transport properties of bottom-contact single crystal field-effect transistors (SC-FETs) based on a new rubrene derivative, bis(trifluoromethyl)-dimethyl-rubrene (fm-rubrene), by employing carbon nanotube (CNT) electrodes. The fundamental challenge associated with fm-rubrene crystals is their deep-lying HOMO and LUMO energy levels, resulting in inefficient hole injection and suboptimal electron injection from conventional Au electrodes due to large Schottky barriers. Applying thin layers of CNT network at the charge injection interface of fm-rubrene crystals substantially reduces the contact resistance for both holes and electrons; consequently, benchmark ambipolar mobilities have been achieved, reaching 4.8 cm(2) V(-1) s(-1) for hole transport and 4.2 cm(2) V(-1) s(-1) for electron transport. We find that such improved injection efficiency in fm-rubrene is beneficial for ultimately unveiling its intrinsic charge transport properties so as to exceed those of its parent molecule, rubrene, in the current device architecture. Our studies suggest that CNT electrodes may provide a universal approach to ameliorate the charge injection obstacles in organic electronic devices regardless of charge carrier type, likely due to the electric field enhancement along the nanotube located at the crystal/electrode interface.


The Palestinian primary ciliary dyskinesia population: first results of the diagnostic and genetic spectrum.
Diagnostic testing for primary ciliary dyskinesia (PCD) started in 2013 in Palestine. We aimed to describe the diagnostic, genetic and clinical spectrum of the Palestinian PCD population. Individuals with symptoms suggestive of PCD were opportunistically considered for diagnostic testing: nasal nitric oxide (nNO) measurement, transmission electron microscopy (TEM) and/or PCD genetic panel or whole-exome testing. Clinical characteristics of those with a positive diagnosis were collected close to testing including forced expiratory volume in 1 s (FEV1) Global Lung Index z-scores and body mass index z-scores. 68 individuals had a definite positive PCD diagnosis, 31 confirmed by genetic and TEM results, 23 by TEM results alone, and 14 by genetic variants alone. 45 individuals from 40 families had 17 clinically actionable variants and four had variants of unknown significance in 14 PCD genes. CCDC39, DNAH11 and DNAAF11 were the most commonly mutated genes. 100% of variants were homozygous. Patients had a median age of 10.0 years at diagnosis, were highly consanguineous (93%) and 100% were of Arabic descent. Clinical features included persistent wet cough (99%), neonatal respiratory distress (84%) and situs inversus (43%). Lung function at diagnosis was already impaired (FEV1 z-score median -1.90 (-5.0-1.32)) and growth was mostly within the normal range (z-score mean -0.36 (-3.03-2.57). 19% individuals had finger clubbing. Despite limited local resources in Palestine, detailed geno- and phenotyping forms the basis of one of the largest national PCD populations globally. There was notable familial homozygosity within the context of significant population heterogeneity.


New Tools for Measuring and Improving Patient Safety in Canadian Hospitals.
The Canadian Institute for Health Information (CIHI) and the Canadian Patient Safety Institute (CPSI) have collaborated on a new measure of patient safety, along with a resource of evidence-informed practices. This measure captures four broad categories of harm in acute care hospitals, consisting of 31 clinical groups selected by clinicians. Analysis showed that harm was experienced in 1 of 18 hospital stays in Canada in 2014ߝ2015 and that no single category accounted for the majority of harmful events. Although CIHI and CPSI continue to work with hospitals and experts to further refine the methodology, the measure and associated Improvement Resource are useful new tools for monitoring and identifying harm, and have the potential to improve patient safety.


PNIPAM-MAPOSS Hybrid Hydrogels with Excellent Swelling Behavior and Enhanced Mechanical Performance: Preparation and Drug Release of 5-Fluorouracil.
Poly(N-isopropylacrylamide) (PNIPAM) is a widely-studied polymers due to its excellent temperature sensitivity. PNIPAM-MAPOSS hybrid hydrogel, based on the introduction of acrylolsobutyl polyhedral oligomeric silsesquioxane (MAPOSS) into the PNIPAM matrix in the presence of polyethylene glycol, was prepared via radical polymerization. The modified hydrogels exhibited a thick, heterogeneous porous structure. PEG was used as a pore-forming agent to adjust the pore size. MAPOSS reduced the swelling ratios of gels, and decreased the LCST, causing the hydrogels to shrink at lower temperatures. However, its hydrophobicity helped to improve the temperature response rate. The incorporation of rigid MAPOSS into the polymer network greatly increased the compressive modulus of the hydrogel. It is worth noting that, by adjusting the amount of MAPOSS and PEG, the hydrogel could have both ideal mechanical properties and swelling behavior. In addition, hydrogel containing 8.33 wt % MAPOSS could achieve stable and sustained drug release. Thus, the prepared PNIPAM-MAPOSS hybrid hydrogel can serve as drug carrier for 5-fluorouracil and may have potential application in other biomedical fields.