The use of a work-related asthma screening questionnaire in a primary care asthma program: an intervention trial.
The work-related asthma screening questionnaire (long-version) (WRASQ(L)) is a 14-item tool designed to increase the recognition of work-related asthma (WRA) in primary care. The purpose of this study was to assess whether the WRASQ(L) provided additional information about a patient's likelihood of WRA, beyond what was collected in standard care, and to assess the use of the WRASQ(L) in the primary care setting. This was an intervention study involving two Ontario primary care sites. Standard care for asthma patients in these sites involved completing the Asthma Care Map (ACM), a template for asthma management that includes seven WRA screening items. Participation in this study involved completing an electronic WRASQ(L) at each visit for participants and prompted care providers to record details related to WRA investigations. Ethics approval was obtained from an Institutional Review Board. The study sample (N = 37) was predominantly female (73.0%), with a mean age of 46.3 years (SD, 10.9). The use of WRASQ(L) identified additional work-related symptoms in 38% and exposures in 60% of participants over and above those identified by the ACM. Two participants were newly suspected of WRA during the study period. The WRASQ(L) provided added information about possible WRA over standard care. The use of the questionnaire's results by care providers was limited due to barriers encountered in incorporating the use of electronic version of the WRASQ(L) into clinical practice. Once validated and implemented in practice, the WRASQ(L) has the potential to increase the recognition of WRA.


Studies on fluoride removal using adsorption process.
Batch adsorption studies were undertaken to assess the suitability of commercially available activated charcoal to remediate fluoride-contaminated water. The effects of some of the major parameters of adsorption, viz. pH, dose of adsorbent, rate of stirring, contact time and initial adsorbate concentration on fluoride removal efficiency were studied and optimized. The optimum sorbent dose was found to be 2.0 g/100 mL, equilibrium was achieved in 120 minutes and enhanced adsorption was obtained at pH 2. Maximum fluoride removal was observed to be 94% at optimum conditions. Freudlich as well as Langmuir isotherms were plotted and kinetic constants were determined.


The effects of estradiol on central serotonergic systems and its relationship to mood in women.
Lifetime prevalence rates of depression are higher in women than men. Because this gender disparity appears after the onset of puberty and declines after menopause, gonadal hormones may play a role in women's increased vulnerability to dysphoric states. Estrogens have powerful effects beyond their role in reproduction. Fluctuations in estrogen occur naturally throughout the reproductive years and can be associated with disruptions in mood. Treatment for depression with exogenous estrogen has produced equivocal results. To shed light on the complex interactions among estrogens, serotonin, and mood, we briefly examine (a) central serotonin systems and their relationship to mood and mood disorders, (b) nonreproductive effects of estrogens on those systems, (c) potential points of intersection between serotonin systems and estrogens, and (d) research into the use of exogenous estrogen in depression in women. In conclusion, we reiterate the call for carefully controlled research into the etiology and treatment of depression in women.


Hemopoietic precursors and development of dendritic cell populations.
The antigen presenting dendritic cells (DCs) are bone marrow (BM) derived cells. Despite their common functions of antigen-processing and T-lymphocyte activation, DCs are diverse in surface markers, migratory patterns and cytokine output. These differences can determine the fate of the T cells they activate. Several subsets of mature DCs have been described in both mouse and human, but tracing the origin of these specialised DC subsets has not been a trivial task. The original concept that all DCs were of myeloid origin was questioned by several recent studies, which demonstrated that in addition to the DCs derived from conventional myeloid precursors, some DCs could also be efficiently generated from lymphoid-restricted precursors. Moreover, it has been shown that both myeloid-restricted and lymphoid-restricted precursors were able to generate DC subsets with similar surface phenotype. These observations demonstrate the existence of both myeloid- and lymphoid-derived DC lineages and suggest an early developmental flexibility of DC precursors. The downstream points where the DC sub-lineages branch off from the conventional myeloid and lymphoid precursors, and the cytokines and environmental factors required for inducing their specialised functions are yet to be determined.


Multiple, recurring origins of aposematism and diet specialization in poison frogs.
Aposematism is the association, in a prey organism, of the presence of a warning signal with unprofitability to predators. The origin of aposematism is puzzling, because of its predicted low probability of establishment in a population due to the prey's increased conspicuousness. Aposematism is a widespread trait in invertebrate taxa, but, in vertebrates, it is mostly evident in amphibians, reptiles, and fishes. Poison frogs (Dendrobatidae) are one of the most well known examples of the co-occurrence of warning coloration and toxicity. This monophyletic group of mostly diurnal leaf-litter Neotropical anurans has both toxic/colorful and palatable/cryptic species. Previous studies suggested a single origin of toxicity and warning coloration, dividing the family in two discrete groups of primitively cryptic and more derived aposematic frogs. Recent molecular phylogenetic analyses using mostly aposematic taxa supported this conclusion and proposed a single tandem origin of toxicity and conspicuous warning coloration. By using expanded taxon and character sampling, we reexamined the phylogenetic correlation between the origins of toxicity and warning coloration. At least four or five independent origins of aposematism have occurred within poison frogs; by using simulations, we rejected hypotheses of one, two, or three origins of aposematism (P < 0.002). We also found that diet specialization is linked with the evolution of aposematism. Specialization on prey, such as ants and termites, may have evolved independently at least two times.


[New experimental therapies for type I allergy].
CD4+ T cells play a central role in the development of the immediate-type allergic response. It was shown that T cells from allergic patients exhibit an imbalance on the level of cytokine production which is characterized by increased IL-4- and decreased IFN-gamma production. Different strategies were developed to therapeutically interfere on various levels of the immunological dysregulation. In this article, the use of the immunomodulatory and immunosuppressive drugs methotrexate, cyclosporine, and intravenous immunoglobulin (IVIG) will be discussed. Furthermore, new experimental therapeutic approaches will be presented which are aimed to selectively interfere on the level of cytokine production and regulation. A different approach targets the functional activity of allergen-specific T cells whose functions could be modulated in an animal model system by subcutaneous treatment with peptides.


Anomalous Left-sided Superior Vena Cava with Cephalad Flow.
The case of a 24-year-old male with complaints of migraine headaches was referred for echocardiography. The rest of medical history was unremarkable. Agitated saline contrast bubble study showed evidence of a right to left intracardiac shunt, probably secondary to a patent foramen ovale. Results of a transesophageal echocardiogram suggested the possibility of an anomalous venous circulation and eventually identified as anomalous left-sided superior vena cava with cardiac magnetic resonance imaging.


[Idiopathic pulmonary fibrosis prognostic factors - analysis of the Czech registry].
Idiopathic pulmonary fibrosis (IPF) is a rare, progressive and usually fatal form of idiopathic interstitial pneumonia. IPF is characterized by failure of alveolar re-epithelization, persistence of fibroblasts, deposition of extracellular matrix, and distortion of lung architecture, which ultimately results in respiratory failure.We analysed 202 consecutive patients with IPF diagnosed at the Departments of Pulmonary Diseases and Tuberculosis in the Czech Republic, who they were included in the nationwide Czech IPF registry. Our aim was to determine prognostic factors of IPF and outcome of the disease.There were 129 males and 73 females who were the median age 67 years. IPF was biopsy-proven in 66 (33 %) of patients. Median time from the first symptom to diagnosis was 12 months. Diagnosis was made in 57 patients (28.3 %) within 6 months from the onset of respiratory symptoms. 8 (4 %) patients had an acute exacerbation during the course of the disease.In uniparametric (univariate) analysis as prognostic factors associated with poorer survival were found: higher age, higher degree dyspnea scores, clubbing fingers, comorbidities (arterial hypertension, osteoporosis), patients without histology biopsy, and bronchoalveolar increased neutrophil count. We found these positive prognostic factors: higher levels of VC (vital capacity), TLC (total lung capacity) and DLCO (diffusing capacity for carbon monooxide).In multiparametric (multivariate) analysis as prognostic factors associated with mortality were found: higher age, higher degree of dyspnoe score. Increased lymphocytes in bronchoalveolar fluid, higher level of VC a DLCO were associated with better survival. There was no difference in survival of patients by sex, by smoking status. No significant difference in survival rates was found between IPF with and without emphysema, between the extent of fibrosis on HRCT (high resolution computed tomography) of thorax and mortality. Median survival was 51.6 months. 58 (28.7 %) patients died. The most frequent reason of dead was IPF progression with respiratory failure. Idiopathic pulmonary fibrosis; prognosis; treatment.


[Apoptosis of type II alveolar epithelial cell induced by bleomycin in lung fibrotic rat].
To investigate the effects of bleomycin (BLM) on the apoptosis of type II alveolar epithelial cell (AT II) in lung fibrotic rats and its possible mechanisms. Totally 32 male Sprague-Dawley rats were randomly divided into sham group (n = 8) and BLM group (n = 24). Rats in sham group or BLM group were intratracheally instillated with saline or 5 mg/kg of bleomycin, respectively. One, three, and seven days after the instillation of bleomycin, 8 rats in BLM group were taken for AT II isolation and purification. Rats in sham group were used to isolate and purify AT II on 7 days after the instillation of saline. The cell cycle and apoptosis, intracellular free calcium concentration, and mitochondrial membrane potential (MMP) in AT II were determined by flow cytometry. Immunohistochemistry was performed to observe the expressions of Bax, Bcl-2, and Fas. Caspase-3, Caspase-8, and Caspase-9 activities were measured by Caspase activity detection kit. The ratio of S phase AT II in BLM group was significantly lower than in sham group (P < 0.05). AT II apoptosis rates on day 1 and 3 were significantly higher in BLM group than in sham group (P < 0.01). Intracellular free calcium concentrations in BLM group were significantly higher than in sham group (P < 0.05). However, MMP was significantly lower than sham group (P < 0.05). The positive rates of Bax, Fas and Caspase-3, Caspase-8, and Caspase-9 activities of BLM group were significantly higher than those of sham group (P < 0.05, P < 0.01). The positive rates of Bcl-2 on day 1 and 3 were significantly lower than those of sham group (P < 0.05). Early AT II apoptosis may be induced by bleomycin, which may be explained by the increase of intracellular free calcium concentration, depression of MMP, increased expressions of Fas and Bax, and increase of Caspase-3, Caspase-8, and Caspase-9 activities.


Autosomal dominant Klippel-Feil anomaly with cleft palate.
Klippel-Feil anomaly is characterized by the fusion of two or more cervical vertebrae. Most cases are sporadic but dominant and recessive inheritance are well described. Associated anomalies such as a cleft palate are common. We describe a unique family with autosomal dominantly inherited Klippel-Feil anomaly in six individuals associated with a cleft palate in four. One patient, a child, has a cleft palate only but may develop radiological cervical fusion with time, as documented in two other family members.


Further studies on the inhibition of Histoplasma capsulatum within macrophages from immunized animals.
Mononuclear phagocytes freshly harvested from immunized animals restrict the intracellular growth of Histoplasma capsulatum. The fate of the inhibited fungus is the subject of this report. Macrophages harvested from mice immunized by sublethal infection were parasitized in vitro with yeast cells of H. capsulatum. The subsequent fate of the fungus was assessed by staining characteristics, viability on subculture, and radioisotopic techniques. No tinctorial distinction could be made between yeasts within normal or immune phagocytes stained by the May Greenwald-Giemsa or by the Gridley techniques. Yeast cells recovered after 24 h of residence within the cytoplasm of immune monocytes excluded the dye eosin-Y, germinated on Casamino Acid agar incubated at 30 C, and initiated growth at a normal rate within phagocytes from normal animals. Thus even though the growth of H. capsulatum was inhibited within macrophages from immunized animals, the fungus was not killed by the encounter. However, autoradiographic studies established that protein synthesis by the fungus in situ was impaired.


Analysis of the effect of integrons on drug-resistant Staphylococcus aureus by multiplex PCR detection.
The aim of this study was to detect class Ⅰ, II and III integrons using multiplex PCR, and to analyze the role that these integrons play in mediating multidrug-resistant Staphylococcus aureus (SA). The sensitivity of SA to 20 types of antibiotics was examined using the K-B method. A genomic DNA extraction kit was used for extracting genomic DNA and a high-purity 96 plasmid extraction kit was used for extracting plasmid DNA. Class Ⅰ, II and III integrons were amplified using multiplex PCR. Agarose gel electrophoresis was used for analysing amplification products. The positive rate of class Ⅰ and II integrons in the plasmid DNA from SA was higher compared to that of the genomic DNA. The positive rate of class Ⅰ integrons was highest in the group with multidrug resistance to amoxicillin/clavulanic acid, piperacillin/tazobactam, ciprofloxacin, tetracycline, rifampin, imipenem, cefazolin, cefuroxime, levofloxacin and gentamicin. As regards integron detection in the plasmids from drug-resistant SA strians obtained from sputum, blood, cerebrospinal fluid, drainage fluid, excretion and urine specimens, the difference in the detection rate of class Ⅰ integrons among the six types of specimens was significant. Multiplex PCR is an effective method to detect class Ⅰ, II and III integrons. The SA plasmid is the main carrier transferring integrons. Integrons mediate the formation of SA multidrug resistance.


DNA single strand breaks in human lens epithelial cells from patients with cataract.
In recent years, there has been renewed interest in the association between DNA damage to the lens epithelium and the development of lens opacities. Although a number of in vitro studies have indicated that lens epithelial cells are susceptible to a variety of DNA damaging insults and that these cells possess the capacity to repair such damage, no previous studies have directly addressed whether DNA damage is associated with human cataract in vivo. Utilizing samples of lens epithelial cells obtained from patients undergoing cataract surgery, the percentage of cells containing DNA single strand breaks was directly determined by the single-cell gel assay (SGA) method. Non-cataractous human Eye Bank lenses of similar ages to the cataractous samples and calf lenses were used as controls. In approximately 50% of the cataractous samples analyzed, the proportion of cells containing DNA single strand breaks was significantly higher than in control lenses. No relationship between age and DNA damage was noted. These findings are consistent with the hypothesis that in some human patients with cataract, DNA damage in the lens epithelial cell population may be related to the development of lens fiber cell opacity.


Meta-analysis of postoperative adjuvant therapy for small bowel adenocarcinoma.
The role of adjuvant therapy in small bowel adenocarcinoma (SBA), a rare malignancy with a poor prognosis, is controversial. The purpose of this article is to investigate the impact of adjuvant therapy on the survival of patients with SBA in a meta-analysis. We performed a comprehensive search of PubMed, EMBASE and the Cochrane Library database between 2010 and 2017. Hazard ratios (HR) with 95% confidence intervals (95%CI) were used to assess the effect of adjuvant chemotherapy and/or radiation treatment after curative surgery in patients with SBA. Moreover, impact of age, sex, stage, differentiation, lymph node involvement, and margin status was also evaluated. We included 15 studies to evaluate the effect of adjuvant therapy on the survival of patients with SBA. The pooled HR of overall survival (OS) involving 5986 patients showed that adjuvant therapy did not have a statistically significant effect on the survival of patients with SBA (pooled HR = 0.89, 95% CI = 0.73-1.09, p = 0.25). Further, 607 patients with duodenal adenocarcinoma (DA) had similar results (pooled HR = 0.96, 95% CI = 0.75-1.23, p = 0.77). Similarly, adjuvant treatment vs. non-adjuvant treatment in terms of disease-free survival (DFS) or relapse-free survival (RFS) showed the same results (pooled HR = 0.89, 95% CI = 0.64-1.23, p = 0.48). However, we found that adjuvant therapy resulted in favorable postoperative survival in Europe according to the subgroup analysis (pooled HR = 0.63, 95% CI = 0.5-0.8, p = 0.0002). In addition, the pooled HR shows that stage, differentiation, lymph node involvement, and margin status were related to the OS of patients with SBA. Patients with SBA who received adjuvant therapy after surgery did not receive a significant survival benefit. Adjuvant therapy may be more useful in advanced cancer or metastatic patients.


Fulminant sepsis caused by Bacillus cereus in patients with hematologic malignancies: analysis of its prognosis and risk factors.
Bacillus cereus is a growing concern as a cause of life-threatening infections in patients with hematologic malignancies. However, the risk factors for patients with unfavorable outcomes have not been fully elucidated. At our institution, we observed the growth of B. cereus in blood culture in 68 patients with (23) or without (45) hematologic malignancies treated from September 2002 to November 2009. We defined a case as having sepsis when more than two blood culture sets were positive for B. cereus or only a single set was positive in the absence of other microorganisms in patients who had definite infectious lesions. We determined 12 of 23 patients with hematologic malignancies as having sepsis, as well as 10 of 45 patients without hematologic malignancies (p = 0.012). Of the 12 patients with hematologic malignancies, four patients with acute leukemia died of B. cereus sepsis within a few days. In our cohort, risk factor analysis demonstrated that a neutrophil count of 0/mm(3), central venous (CV) catheter insertion, and the presence of central nervous system (CNS) symptoms were significantly associated with a fatal prognosis (p = 0.010, 0.010, and 0.010, respectively). Analysis of data from our cohort in conjunction with those from 46 previously reported patients with B. cereus sepsis identified similar risk factors, that is, acute leukemia, extremely low neutrophil count, and CNS symptoms (p = 0.044, 0.004, and 0.002, respectively). These results indicate that appropriate prophylaxis and early therapeutic intervention against possible B. cereus sepsis are crucially important in the treatment of hematologic malignancies.


Cholesterol balance in prion diseases and Alzheimer's disease.
Prion diseases are transmissible and fatal neurodegenerative disorders of humans and animals. They are characterized by the accumulation of PrPSc, an aberrantly folded isoform of the cellular prion protein PrPC, in the brains of affected individuals. PrPC is a cell surface glycoprotein attached to the outer leaflet of the plasma membrane by a glycosyl-phosphatidyl-inositol (GPI) anchor. Specifically, it is associated with lipid rafts, membrane microdomains enriched in cholesterol and sphinoglipids. It has been established that inhibition of endogenous cholesterol synthesis disturbs lipid raft association of PrPC and prevents PrPSc accumulation in neuronal cells. Additionally, prion conversion is reduced upon interference with cellular cholesterol uptake, endosomal export, or complexation at the plasma membrane. Altogether, these results demonstrate on the one hand the importance of cholesterol for prion propagation. On the other hand, growing evidence suggests that prion infection modulates neuronal cholesterol metabolism. Similar results were reported in Alzheimer's disease (AD): whereas amyloid β peptide formation is influenced by cellular cholesterol, levels of cholesterol in the brains of affected individuals increase during the clinical course of the disease. In this review, we summarize commonalities of alterations in cholesterol homeostasis and discuss consequences for neuronal function and therapy of prion diseases and AD.


Thermodynamic characterization of the multivalent interactions underlying rapid and selective translocation through the nuclear pore complex.
Intrinsically disordered proteins (IDPs) play important roles in many biological systems. Given the vast conformational space that IDPs can explore, the thermodynamics of the interactions with their partners is closely linked to their biological functions. Intrinsically disordered regions of Phe-Gly nucleoporins (FG Nups) that contain multiple phenylalanine-glycine repeats are of particular interest, as their interactions with transport factors (TFs) underlie the paradoxically rapid yet also highly selective transport of macromolecules mediated by the nuclear pore complex. Here, we used NMR and isothermal titration calorimetry to thermodynamically characterize these multivalent interactions. These analyses revealed that a combination of low per-FG motif affinity and the enthalpy-entropy balance prevents high-avidity interaction between FG Nups and TFs, whereas the large number of FG motifs promotes frequent FG-TF contacts, resulting in enhanced selectivity. Our thermodynamic model underlines the importance of functional disorder of FG Nups. It helps explain the rapid and selective translocation of TFs through the nuclear pore complex and further expands our understanding of the mechanisms of "fuzzy" interactions involving IDPs.


Biomarkers for early effects of carcinogenic dual-acting PPAR agonists in rat urinary bladder urothelium in vivo.
Small-molecule agonists of the peroxisome proliferator-activated receptor (PPAR) alpha and gamma isoforms (dual-acting PPAR agonists) can cause urothelial cancers in rodents. Rats were dosed orally for 16 days with bladder carcinogenic (ragaglitazar) as well as non-bladder carcinogenic (fenofibrate and rosiglitazone) PPAR agonists and protein changes were assayed in the urinary bladder urothelium by Western blotting. Dose levels reflected 10-20 x human exposure, and the ragaglitazar dose was in the carcinogenic range. Ragaglitazar induced expression of the transcription factor Egr-1, phosphorylation of the c-Jun transcription factor and phosphorylation of the ribosomal S6 protein were observed. These changes were also observed in rats dosed with either rosiglitazone or fenofibrate. However, the protein changes were stronger (Egr-1 induction) or of a longer duration (S6 phosphorylation) in ragaglitazar-treated animals. Animals co-administered fenofibrate (a specific PPARalpha agonist) and rosiglitazone (a specific PPARgamma agonist) exhibited Egr-1 and S6 protein changes more similar to those induced by ragaglitazar (a dual-acting PPARalpha/gamma agonist) than either fenofibrate or rosiglitazone alone. The findings suggest that ragaglitazar causes Egr-1, c-Jun and S6 protein changes in the urothelium by a mechanism involving PPARalpha as well as PPARgamma, and that the Egr-1, c-Jun and S6 protein changes might have potential biomarker value.


Performance analysis of AL amyloidosis cardiac biomarker staging systems with special focus on renal failure and atrial arrhythmia.
Systemic light chain amyloidosis is a rare and life-threatening disorder, for which accurate risk stratification is crucial. Current cardiac staging systems (MAYO2004, MAYO3b, and MAYO2012) are mainly based on biomarkers, which have uncertain reliability in the context of atrial fibrillation, arrhythmia or pacemaker stimulation as well as renal insufficiency. We compared the performance of the established staging systems with particular regard to these comorbidities in 1,224 patients with systemic light chain amyloidosis diagnosed at our center from July 2002 until March 2017. We first characterized the subsets with an estimated glomerular filtration rate <50 mL/min/1.73 m2 (415 patients) and any kind of atrial arrhythmia (183 patients) as unique high-risk subgroups with similarly increased cardiac biomarkers (χ2-test, all P<0.001). This resulted in a shift towards higher risk stages and reduced median overall survival compared to those of patients with better kidney function or without atrial arrhythmia in univariate analyses (13 vs 46 months and 17 vs 53 months, respectively; both P<0.001). Performance analysis revealed that predictions in the entire cohort were least precise with the MAYO2004 staging system and most precise with the MAYO3b system. This performance pattern was almost preserved for patients with an estimated glomerular filtration rate <50 mL/min/1.73 m2, but less so for those with atrial arrhythmias. The MAYO3b staging system was most robust. Importantly, atrial arrhythmia retained its prognostic value in multivariable analysis including age, difference between involved and uninvolved free light chains, and any staging system, while estimated glomerular filtration rate <50 mL/min/1.73 m2 was not statistically significant in multivariable analysis with the MAYO3b staging system. In conclusion, our results favor the MAYO3b staging system due to its consistently best performance and retained applicability in the subgroups with atrial arrhythmia and estimated glomerular filtration rate <50 mL/min/1.73 m2.


Mammary growth patterns in guinea pigs during puberty, pregnancy and lactation.
Mammary gland growth patterns were studied in 110 guinea pigs during the growth phase, pregnancy and lactation. Body weight changes were studied and, in addition, mammary indices were wet weight, dry fat-free tissue (DFFT), deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). Statistical analyses were mathematical regression models to best fit the actual data. These included linear, quadratic, cubic, and several forms of exponential regression models. Data were separated into growth phase (60 guinea pigs in 10 age groups), pregnancy (20 guinea pigs in 4 groups), and lactation (30 guinea pigs in 6 groups). Data during pregnancy and the first 5 days of lactation were pooled and analyzed also because mammary growth continued beyond pregnancy to Day 5 of lactation. Mammary wet weight increased according to a cubic expression in the growth phase, while mammary DFFT, DNA and RNA were rectilinear through 200 days of age. During pregnancy and the first 5 days of lactation, mammary growth parameters followed the pattern of an exponential equation. Daily rates of increase for mammary DFFT and DNA were twice the rate for mammary wet weight. During lactation, mammary gland indices increased to Day 5 and then decreased gradually from Day 10 to Day 20. The best mathematical models for these change were those which are used to describe lactation curves, but all mammary gland indices decreased later and more gradually than milk production. Comparisons in growth rates of guinea pig mammary glands were made with those published for dairy goats and dairy cows. Rates of mammary DNA changed inversely to lengths of gestation in these 3 species.


Influence of the Therapeutic Alliance on the Rehabilitation of Stroke: A Systematic Review of Qualitative Studies.
The therapeutic alliance is a fundamental component of rehabilitation in order to achieve effective outcomes. However, what develops, maintains or hinders this relationship has not been sufficiently explored. The aim of this systematic review is to recognize the role of the therapeutic alliance in the neurological rehabilitation process. A search for articles was carried out in the databases PubMed, Web of Science, SCOPUS, CINAHL, APA PsycInfo, OTseeker and Dialnet. They were selected according to the eligibility criteria. Internal quality assessment of the articles was measured with the Consolidated Criteria for Reporting Qualitative Research (COREQ). The systematic review was registered in PROSPERO (ID 346523). The search in the databases identified 1596 articles, from which 9 different studies were finally included in the systematic review, reflecting the limitations of studies in this field. All studies are qualitative, from the point of view of the patients themselves, their relatives and healthcare professionals. The total sample of the included studies is 182 participants (96 health professionals, 76 users and 10 relatives). Semi-structured interviews, focus group discussions and written reflections were mainly used to collect the data. In conclusion, the therapeutic alliance can be an active component in the post-stroke rehabilitation process. Being recognized as a person, collaboration with the therapeutic team, empathy, empowerment, confidence, professional skills, maintenance of hope and the role of the family have been identified as aspects that can have an influence on the therapeutic alliance.


Impact of class attendance upon examination results of students in basic medical sciences.
A number of studies have shown the impact of attending the classes during the session on examination results of students. Students with good lecture attendance show good results while those with poor lecture attendance are at risk for poor performance in the examinations. In this study we wanted to test this in students of basic medical sciences in our set up. All the students in Basic Medical Sciences of Gomal Medical College, D.I. Khan, Pakistan, during the session 1999-2000 were enrolled for this study. Performance of these students in one of their three annual term tests, which covered duration of studies for four months, from February 2000 to May 2000, was analyzed. Students were grouped into two, Group-A with > or = 75% attendance and Group-B with < 75% attendance. The frequency of failure in the two groups was compared using the chi square test. Results of the term test showed that the percentage of failure in students of Group-B with less than 75%, attendance was significantly higher when compared to Group-A with equal or more than 75% attendance. Our results supported the previous studies showing that attendance in the classes during teaching sessions had a direct impact on performance of students in the examinations. Students with good attendance show good results while those with poor attendance are at risk for poor performance during examinations in basic medical sciences.


Personalized treatment approach to gastroenteropancreatic neuroendocrine tumors: a medical oncologist's perspective.
The medical management of gastroenteropancreatic neuroendocrine tumors involves treatment of symptomatic disease related to hormone secretions or bulky unresectable metastatic disease. Combining gallium DOTA with fluorine-18 fluorodeoxyglucose-PET along with histopathological grading helps to determine tumor heterogeneity and seek reasons for poor response to therapy. In the light of adding chemotherapy in selected patients with intermediate-grade tumors, the newer scan helps in personalization of the therapy along with the biopsy. The tumor dedifferentiation over the particular time period leading to aggressive behavior, a well-known entity, is contrasted with the redifferentiation phenomenon in some patients as a result of chemotherapy or targeted drug therapy. This may support the basis for combining peptide receptor-targeted radiotherapy/octreotide therapy with chemotherapy or mTOR inhibitors such as everolimus.


SVD for imaging systems with discrete rotational symmetry.
The singular value decomposition (SVD) of an imaging system is a computationally intensive calculation for tomographic imaging systems due to the large dimensionality of the system matrix. The computation often involves memory and storage requirements beyond those available to most end users. We have developed a method that reduces the dimension of the SVD problem towards the goal of making the calculation tractable for a standard desktop computer. In the presence of discrete rotational symmetry we show that the dimension of the SVD computation can be reduced by a factor equal to the number of collection angles for the tomographic system. In this paper we present the mathematical theory for our method, validate that our method produces the same results as standard SVD analysis, and finally apply our technique to the sensitivity matrix for a clinical CT system. The ability to compute the full singular value spectra and singular vectors will augment future work in system characterization, image-quality assessment and reconstruction techniques for tomographic imaging systems.


Expression and immunogenicity of NY-ESO-1 in colorectal cancer.
Serum assays of NY-ESO-1 antibodies provide a guide to discriminate between patients who suffer from different types of cancer. In the present study, the expression of NY-ESO-1 was detected with the aim to identify a novel tumor antigen in colorectal cancer (CRC). Sera were obtained from 89 healthy individuals and 236 patients with CRC with stage I, II, III and IV tumors. The NY-ESO-1 autoantibody levels were determined using an enzyme-linked immunosorbent assay. The mRNA and protein expression levels of NY-ESO-1 were detected using reverse transcription-polymerase chain reaction and immunohistochemistry, respectively, in 60 CRC and paired adjacent non-tumor tissues. NY-ESO-1 antibody was detected in 40 of the 236 (16.9%) patients with CRC. The NY-ESO-1 antibody combined with carcinoembryonic antigen enhanced the sensitivity, from 52.1 to 62.7%, of the diagnosis of CRC. The frequency of antibody positivity increased with the TNM cancer stage (8.8 vs. 28.3% in stages I+II and III+IV, respectively). The mRNA and protein expression levels of NY-ESO-1 were significantly higher in CRC tissue than in adjacent non-tumor tissue. In conclusion, NY-ESO-1 is frequently expressed in CRC with the capacity of inducing a humoral immune response in CRC patients, exhibiting the potential to be a promising biomarker for CRC.


Combination of biochar amendment and mycoremediation for polycyclic aromatic hydrocarbons immobilization and biodegradation in creosote-contaminated soil.
Soils impregnated with creosote contain high concentrations of polycyclic aromatic hydrocarbons (PAH). To bioremediate these soils and avoid PAH spread, different bioremediation strategies were tested, based on natural attenuation, biochar application, wheat straw biostimulation, Pleurotus ostreatus mycoremediation, and the novel sequential application of biochar for 21 days and P. ostreatus 21 days more. Soil was sampled after 21 and 42 days after the remediation application. The efficiency and effectiveness of each remediation treatment were assessed according to PAH degradation and immobilization, fungal and bacterial development, soil eco-toxicity and legal considerations. Natural attenuation and biochar treatments did not achieve adequate PAH removal and soil eco-toxicity reduction. Biostimulation showed the highest bacterial development but low PAH degradation rate. Mycoremediation achieved the best PAH degradation rate and the lowest bioavailable fraction and soil eco-toxicity. This bioremediation strategy achieved PAH concentrations below Spanish legislation for contaminated soils (RD 9/2005). Sequential application of biochar and P. ostreatus was the second treatment most effective for PAH biodegradation and immobilization. However, the activity of P. ostreatus was increased by previous biochar application and PAH degradation efficiency was increased. Therefore, the combined strategy for PAH degradation have high potential to increase remediation efficiency.


Spatial distribution and the prevalence of speech disorders in the provinces of Iran.
Objective: To identify the spatial distribution and prevalence of speech disorder in Iran. Materials and methods: First, the prevalence of speech disorder in 2006 and 2011 was mapped via GIS for each province. Moreover, the prevalence of this disorder was calculated and classified according to age, sex, and residential area. Results: The prevalence in the majority of provinces indicated an overall decrease. Furthermore, its prevalence among the whole population of Iran in 2006 and 2011 was 2.2 and 2 per 1000 people, respectively. The highest prevalence was observed among people aged 75 years and older. Results showed that speech disorders are more prevalent among men compared to women and also among rural residents compared to those in urban areas. Conclusion: It is necessary to identify the high-risk areas in order to well organize the limited facilities to meet the actual needs of patients with speech disorder.


First Report of Root-Knot Nematode (Meloidogyne incognita) on Dioscorea opposita in Henan Province, China.
Dioscorea opposita is an annual twining plant in China that is used for consumption and medicinal purposes. The planting area of D. opposita is near 500,000 hectares in China, mainly in Shangdong, Hebei, Henan, Jiangxi and Yunnan provinces. In August 2021, we observed that some D. opposita plants grew poorly with smaller and chlorotic leaves in Changyuan (35°8'12"N; 114°43'52"E), Henan Province, China. Galls with hook-shaped roots and tuber damage were also observed, typical of root-knot nematode. Thirty tubers were randomly collected and 60% were infested with root-knot nematodes. During a disease survey in Changyuan, the incidences of root-knot nematode damage were 31.5%, 21%, and 18% in three fields (0.33, 0.67, and 4 ha, respectively) at harvest. The average tuber length of infected plants was decreased by 65.8%, and the average weight was decreased by 70.1% compared to the healthy plants. Males, females, second-stage juveniles (J2s), and eggs were extracted from individual diseased tubers from the three fields for morphological identification. Females were white, pear-shaped with a projecting neck. Males showed a trapezoidal labial region with prominent stylet knobs, including a high head cap which had a stepped outline and was centrally concave in lateral view. Morphological measurements are described in the supplementary material. All data and descriptions conformed to the morphological characteristics of Meloidogyne incognita. Genomic DNA was extracted from J2s (n=9) using PCR lysis buffer, and used for PCR amplification of the sequence characterized amplified region (SCAR) markers specific for M. incognita. Two pairs of the SCAR primers, Mi-F/Mi-R, and Inc-K14-F/Inc-K14-R, were used to diagnose whether these nematodes from D. opposita were M. incognita (Meng et al. 2004; Randig et al. 2002). The PCR produced expected amplification products of 955 and 399 bp, confirming the nematode to be M. incognita. Primers specific for M. arenaria (Far/Rar) and M. javanica (Fjav/Rjav) were used but failed to amplify fragments (Randig et al. 2002; Zijlstra et al. 2000). The obtained PCR fragments were sequenced and deposited in GenBank (accession no. OQ420602.1, OQ427638.1). They showed 99.9 and 100% identity to the available GenBank M. incognita sequence (accession no. MK410954.1, ON861825.1), respectively. A pathogenicity test was conducted in greenhouse conditions. Bulbils of D. opposita were sown in the pots filled with 2,000 ml of autoclaved soil mixture (loamy soil/sand, 1:1). One month later, 15 seedlings (five to six leaf stage) were inoculated with 1,000 M. incognita J2s individually. Five plants without nematode inoculation were used as the control. Two months after inoculation, all of the inoculated roots had galling symptoms similar to those observed in the field, and 100% of root system tissues had galls. The root gall index was ~6 according to a 0 to 10 RKN damage rating scale (Poudyal et al. 2005). No symptoms were found on the control plants. The nematodes were reisolated from root tissue and identified. M. incognita has a broad host range in many species of economic importance including Salvia miltiorrhiza (Wen et al. 2023), Ipomoea batatas (Maleita et al. 2022), and Zea mays (López-Robles et al. 2013). So far, M. incognita has been reported in D. alata and D. rotundata in Africa (Onkendi et al. 2014). To our best knowledge, this is the first record of M. incognita on D. opposita in Henan Province, China. With the increased planting area of D. opposita in China, root-knot nematodes are becoming more serious and reducing tuber production, with yield losses more than 60%. This identification is a preliminary step in developing effective disease management schemes. Declaration of interest The authors declare no conflict of interest. Funding This work was financially supported by the Key Scientific Research Projects of Higher Education Institutions of Henan Province (21A180013), China Agriculture Research System (CARS-21), The Zhongyuan high level talents special support plan-Science and Technology Innovation Leading Talents (224200510011) and Science and Technology Research Project of Henan Province (222102310211). References López-Robles, J., et al. 2013. Plant Dis. 97:694. https://doi.org/10.1094/PDIS-07-12-0674-PDN. Maleita, C., et al. 2022. Plant Dis. 106:2536. https://doi.org/10.1094/PDIS-12-21-2680-PDN. Meng, Q. P., et al. 2004. Acta Phytopathol. Sinica 34:204. https://doi.org/10.13926/j.cnki.apps.2004.03.003. Onkendi, E. M., et al. 2014. Plant Pathol. 63:727. https://doi.org/10.1111/ppa.12202. Poudyal, D. S., et al. 2005. Australas. Plant Pathol. 34:181. https://doi.org/10.1071/AP05011. Randig, O., et al. 2002. Genome 45:862. https://doi.org/10.1139/g02-054. Wen, Y., et al. 2023. Plant Dis. Accepted. https://doi.org/10.1094/PDIS-05-22-0997-PDN. Zijlstra, C., et al. 2000. Nematology 2:847. https://doi.org/10.1163/156854100750112798.


Effect of zwitterionic polymers on wound healing.
The effect of a thin film of a zwitterionic random copolymer composed of carboxybetaine [1-carboxy-N,N-dimethyl-N-(2'-methacryloyloxyethyl)methanaminium inner salt] (CMB) and n-butyl methacrylate (BMA), poly(CMB-r-BMA) (CMB, 30 mol%), on the healing of a full-thickness excisional and incisional wound in hairless rats was examined. The poly(CMB-r-BMA) film significantly enhanced wound closure and complete healing of a full-thickness excisional wound compared with the effect of the poly(n-butyl methacrylate) (PBMA) and the poly(ethylene terephthalate) (PET) films. However, the poly(CMB-r-BMA) film did not enhance healing of a full-thickness incisional wound in hairless rats. The amount of proteins adsorbed and that of neutrophiles adhered onto the poly(CMB-r-BMA) film were significantly smaller than those onto the PBMA and PET films. The results suggested that various cells and growth factors in the wound exudate are utilized effectively by covering an excisional wound with the poly(CMB-r-BMA) film, resulting in acceleration of healing. In addition, the poly(CMB-r-BMA) film significantly enhanced healing of a full-thickness excisional wound in hairless rats compared with the effect of Tegaderm as wound dressings. The poly(CMB-r-BMA) film has potential as a new wound dressing.


Prevention of Escherichia coli respiratory infection in broiler chickens with bacteriophage (SPR02).
Bacteriophages are viruses that can infect and kill bacteria. Three studies were conducted to determine the efficacy of bacteriophage to prevent an Escherichia coli respiratory infection in broiler chickens. In the first study 3-d-old-birds were challenged with an air sac inoculation of 10(3) cfu of E. coli per mL mixed with either 10(3) or 10(6) pfu of bacteriophage, or 10(4) cfu E. coli mixed with 10(4) or 10(8) pfu of bacteriophage. In the second study, drinking water of birds to 1 wk of age was treated with 10(3) or 10(4) pfu of bacteriophage per mL and birds were air sac challenged with 10(3) cfu of E. coli, or water was treated with 10(4) or 10(6) pfu of bacteriophage per milliliter and birds were challenged with 10(4) cfu of E. coli. In the third study, birds were air sac challenged at 1 wk of age with 10(4) cfu of E. coli and given 10(5) or 10(6) pfu of bacteriophage per mL of water from 1 d of age to 2 wk of age. In Studies 1 and 2, there were two replicate pens per treatment with 10 birds per pen, and in Study 3, there were four replicate pens per treatment with 10 birds per pen. The studies were all concluded when the birds were 3 wk of age. In Study 1, BW was decreased at 1 and 2 wk of age in the birds that were challenged with 10(3) or 10(4) cfu of E. coli and was decreased at 2 wk of age in the birds challenged with 10(4) cfu of E. coli mixed with 10(4) pfu of the bacteriophage. Mortality was decreased from 80% in the birds challenged with 10(3) cfu of E. coli to 25 and 5% when mixed with 10(3) or 10(6) pfu of the bacteriophage, respectively. Mortality was decreased from 85% in birds challenged with 10(4) cfu of E. coli to 35% when mixed with 10(4) pfu of the bacteriophage, and no mortality occurred when mixed with 10(8) pfu of bacteriophage. There was essentially no protection observed in Studies 2 and 3 when the birds were challenged with 10(3) or 10(4) cfu of E. coli with bacteriophage present in their drinking water at any level. These data suggest that bacteriophage can protect birds from a respiratory challenge with E. coli, but that adding the bacteriophage to the drinking water offered no protection to the birds. The complete protection of the birds observed in Study 1 suggests that bacteriophage may possibly be developed as an alternative to antibiotic use in poultry.


Electron pair localization function: a practical tool to visualize electron localization in molecules from quantum Monte Carlo data.
In this work we introduce an electron localization function describing the pairing of electrons in a molecular system. This function, called "electron pair localization function," is constructed to be particularly simple to evaluate within a quantum Monte Carlo framework. Two major advantages of this function are the following: (i) the simplicity and generality of its definition; and (ii) the possibility of calculating it with quantum Monte Carlo at various levels of accuracy (Hartree-Fock, multiconfigurational wave functions, valence bond, density functional theory, variational Monte Carlo with explicitly correlated trial wave functions, fixed-node diffusion Monte Carlo, etc). A number of applications of the electron pair localization function to simple atomic and molecular systems are presented and systematic comparisons with the more standard electron localization function of Becke and Edgecombe are done. Results illustrate that the electron pair localization function is a simple and practical tool for visualizing electronic localization in molecular systems.


Dialysis headache: characteristics, impact and cerebrovascular evaluation.
Headache is one of the most frequent symptoms that occur during hemodialysis sessions. Despite the high prevalence of dialysis headache, it has been little studied. To evaluate the characteristics, impact and factors associated with dialysis headache. The behavior of the cerebral vasculature was also compared between patients with and without dialysis headache. This was a cross-sectional study. Consecutive patients who underwent hemodialysis were assessed through a semi-structured questionnaire, the Headache Impact Test (HIT-6), the Hospital Anxiety and Depression Scale and the Short Form-36 Health Survey (SF-36). Transcranial Doppler ultrasonography was performed in the first and fourth hours of hemodialysis. A total of 100 patients were included; 49 of them had dialysis headache. Women (OR=5.04; 95%CI 1.95-13.04), younger individuals (OR=1.05; 95%CI 1.01-1.08), individuals with higher schooling levels (OR=3.86; 95%CI 1.4-10.7) and individuals who had spent longer times on dialysis programs (OR=0.99; 95%CI 0.98-1) had more dialysis headache (logistic regression). Individuals with dialysis headache had worse quality of life in the domains of pain and general state of health (56.9 versus 76.4, p=0.01; 49.7 versus 60.2, p=0.03, respectively). Dialysis headache was associated with significantly greater impact on life (OR=24.4; 95%CI 2.6-226.6; logistic regression). The pulsatility index (transcranial Doppler ultrasonography) was lower among patients with dialysis headache than among those without them. Dialysis headaches occur frequently and are associated with worse quality of life and patterns of cerebral vasodilatation.


Synthesis and characterization of a fluorescent water-soluble paclitaxel prodrug.
A fluorescence susceptible water-soluble paclitaxel was synthesized by a condensation reaction between PEGylated paclitaxel (namely, PP7) and 1-pyrene butyric acid (PBA) in order to obtain a better understanding of the mechanism of action of paclitaxel as well as of the environment of the paclitaxel-binding site. The reaction was performed successfully and the resulting paclitaxel was characterized by FT-NMR, analytical-HPLC, UV spectro photometry, and fluorescence spectrometry. The synthesized paclitaxel analogue showed a high susceptibility to fluorescence in both excitation and emission spectra. And we have investigated the time-resolved fluorescence behavior of them in different solvents and at different excitation wavelengths.


Menstrual Hygiene Problems and Challenges Faced by Adolescent Females in Rural Areas: A Narrative Review.
Menstruation is a vital sign of reproductive health and development. Menstrual hygiene practices are consequently a significant public health issue. However, menstrual practices are still tainted by taboos and other sociocultural constraints, which adversely affect health since adolescent females in rural areas are unaware of the scientific facts regarding menstrual hygiene practices. The Indian government has recognized the significance of menstrual hygiene and developed and implemented several programs and schemes for menstrual hygiene management (MHM). But due to a lack of, little, or inaccurate knowledge and cultural practices and socio-economic status, adolescent females face many obstacles and suffer from health issues. A comprehensive literature and data search was done using key databases such as PubMed and Google Scholar and other sources such as the Ministry of Health and Family Welfare (MoHFW), the United Nations International Children's Emergency Fund (UNICEF), the World Health Organization (WHO), and Google to identify the relevant articles and reviewed publications using full-text search. A total of 40 articles out of 1,461 were selected for review after the screening and elimination of repeated articles. The objective of this literature review is to assess the awareness and knowledge of the importance of menstruation, the understanding of safe menstruation practices, the significance of properly disposing of menstrual products, and the knowledge of how to guard against reproductive system infection and its consequences and also to identify the problems and challenges faced by adolescent females during their menstrual hygiene practices or management. The core of many health issues is misinformation, myths, erroneous beliefs, lack of awareness, and incomplete or incorrect knowledge about menstruation. Therefore, it is essential to teach adolescent females about hygienic behavior and safe menstrual practices.


Quantitative autoradiography of tyrosine hydroxylase immunoreactivity in the rat brain.
Levels of tyrosine hydroxylase (TH) were quantified in discrete areas of unfixed rat brain tissue sections using a rapid and sensitive radioimmunohistochemical method. The immunological reaction with the TH monoclonal antibody was revealed by a 35S-labelled secondary antibody and thus permitted autoradiographic detection of the enzyme. Autoradiograms were generated by apposition of tissue sections to high-sensitivity films or by dipping into autoradiographic emulsion. A detailed analysis of antibody concentration, incubation time, tissue section thickness, and exposure time of the film was undertaken to determine optimal conditions to produce a linear radiolabelling intensity with respect to the amount of antigen. Quantification of the antigen at regional levels was assessed by computer-assisted image analysis. Autoradiographic optical density of radiolabelling in brain areas was converted to enzyme concentrations by interpolation with a constructed TH calibration curve processed in parallel with tissue sections. The specificity of the labelling and the validity and reproducibility of the quantification were investigated. The distribution of TH radiolabelling was comparable to that described using immunofluorescence histochemistry or measuring TH enzymatic activity on homogenates. Using a 35S-labelled antibody, the detection of TH could be performed at the cellular level.


Accuracy of Intraocular Lens Power Calculation in Eyes Filled with Silicone Oil.
Silicone oil (SO) is used mainly when managing complex retinal detachments, commonly with proliferative vitreoretinopathy, as well as a hemostatic agent in proliferative diabetic retinopathy. Combined lens exchange and pars plana vitrectomy remains preferred by many surgeons; however, sequential surgery might be advantageous to minimize the postoperative anterior chamber inflammatory response, particularly in proliferative diabetic retinopathy or retinal detachment. The aim of the study was to evaluate the optimal method of intraocular lens (IOL) calculation in eyes filled with SO. Different techniques are employed for axial length assessment in eyes filled with SO, including preoperative A-scan applanation or immersion biometry, partial coherence interferometry (PCI), or less commonly computed tomography, magnetic resonance imaging, or intraoperative retinoscopy/biometry after SO removal. PCI might provide better refractive outcomes compared to ultrasound measurements, however, the quality of presented evidence is low. Bias in calculation may be a result of limited vitreous base removal during vitrectomy, partial filling of the vitreous chamber with SO and measurements in supine position, macular edema or detachment, selection of an inappropriate IOL calculation formulas and sulcus IOL placement. Clinicians should consider that even when employing optical biometry and correct calculation formulas only a third of eyes filled with silicone oil might achieve ± 1.0 D of target refraction, compared to 97.2% of normal eyes. We would recommend performing optical biometry before the application of SO; if this is impossible, measurement of the second eye or biometry after SO removal is an alternative. Implantation of a convex-plano monofocal polymethyl methacrylate or foldable hydrophobic acrylic IOL with large optic diameter is advised in these patients.


[Dynamics of hexachlorobenzene residues in meat and eggs from chickens].
In a feeding experiment with poultry a more than twofold cumulation of hexachlorobenzene (HCB) in eggs and in meat and a 7.5-fold cumulation in fat, in comparison with the concentration in the feed, have been demonstrated. With the aid of a combined identification by gas chromatography (before and after a conversion into anisole derivatives) and by thin layer chromatography the presence of pentachlorophenol in the liver, in fat and in muscles after feeding the birds with HCB as well as BHC-isomers has been proved. 2,4,6-trichlorophenol and 2,4-dichlorophenol were found by thin layer chromtography (without derivatisation). While 2,4,6-trichlorophenol was found after feeding with HCB only, 1,2,4,5-tetrachlorobenzene has been demonstrated by gas chromatography after feeding with HCB as well as with BHC-isomers.


Novel synthesis of macroporous poly(N-isopropylacrylamide) hydrogels using oil-in-water emulsions.
Porous N-isopropylacrylamide (NIPA) hydrogels having a unique structure, that is, spherelike cavities distributed randomly and a homogeneous network in the gel phase, were successfully synthesized by means of an emulsion templating method; this method involves the synthesis of NIPA gels in an oil-in-water (O/W) emulsion by free radical copolymerization with a cross-linker, followed by washing (removal) of the dispersed oil as a pore template (porogen). The synthesis conditions, O/W volume ratio, amount of added surfactant, and monomer concentration affect the internal pore structure, equilibrium swelling, and swelling/shrinking kinetics. A porous hydrogel swollen at 10 degrees C has a pore diameter distribution in the range of 1-40 microm, which was observed with a scanning electron microscope. Scanning electron micrographs and swelling degree reveal that the pore size and porosity can be adjusted by varying the O/W volume ratios and surfactant amounts. The porous hydrogels show very rapid swelling/shrinking in accordance with the temperature swing. The fast response is attributed to the convection flow of water through the macropores. In addition to a faster response gel, the emulsion templating method can yield potentially intelligent gels in which the pores function as spaces for reaction, separation, and storage.


Effects of the bisphosphonate, alendronate, on parturition in the rat.
Alendronate is a bisphosphonate which inhibits bone resorption. In female fertility studies in rats, dosages of 10 and 15 mg/kg/day produced physical signs of toxicity at parturition, including tremors, dystocia, and death in the dams and these were associated with neonatal deaths. These effects were associated with hypocalcemia in the dams but the fetuses were normocalcemic. There was no one critical period of treatment during gestation for these effects; they were instead proportional to length of treatment. Neonatal deaths were due to protracted deliveries rather than a direct effect of alendronate on the pups. Intravenous calcium supplementation (9.3 mg/dam) prevented the above-described adverse effects on dams and pups. In rats, fetal skeletal ossification is at its greatest rate in late gestation, and during this period free calcium is preferentially transported to the fetal compartment. The females meet this increased demand by calcium mobilization via increased bone resorption. We conclude that the maternotoxicity of alendronate in rats is due to the designed pharmacologic activity of this bisphosphonate; the drug prevents bone resorption and thereby denies the dam an important source of calcium at a time when fetal demand for this mineral is at its peak. The alendronate-induced hypocalcemia adversely affects parturition because uterine muscle contraction is a calcium-dependent process.


Activation of AKT induces EZH2-mediated β-catenin trimethylation in colorectal cancer.
Colorectal cancer (CRC) develops in part through the deregulation of different signaling pathways, including activation of the WNT/β-catenin and PI3K/AKT pathways. Additionally, the lysine methyltransferase enhancer of zeste homologue 2 (EZH2) is commonly overexpressed in CRC. EZH2 canonically represses gene transcription by trimethylating lysine 27 of histone H3, but also has non-histone substrates. Here, we demonstrated that in CRC, active AKT phosphorylated EZH2 on serine 21. Phosphorylation of EZH2 by AKT induced EZH2 to interact with and methylate β-catenin at lysine 49, which increased β-catenin's binding to the chromatin. Additionally, EZH2-mediated β-catenin trimethylation induced β-catenin to interact with TCF1 and RNA polymerase II and resulted in dramatic gains in genomic regions with β-catenin occupancy. EZH2 catalytic inhibition decreased stemness but increased migratory phenotypes of CRC cells with active AKT. Overall, we demonstrated that EZH2 modulates AKT-induced changes in gene expression through the AKT/EZH2/β-catenin axis in CRC.


Macrophage reporter cell assay for screening immunopharmacological activity of cell wall-active antifungals.
Antifungal exposure can elicit immunological effects that contribute to activity in vivo, but this activity is rarely screened in vitro in a fashion analogous to MIC testing. We used RAW 264.7 murine macrophages that express a secreted embryonic alkaline phosphatase (SEAP) gene induced by transcriptional activation of NF-κB and activator protein 1 (AP-1) to develop a screen for immunopharmacological activity of cell wall-active antifungal agents. Isolates of Candida albicans and Aspergillus fumigatus that conditionally express genes involved in cell wall synthesis were also tested with the reporter macrophages. We found that growth of fungi in subinhibitory concentrations of glucan synthesis inhibitors (caspofungin and enfumafungin A) or repression of the β-glucan catalytic subunit of glucan synthase, FKS1, increased macrophage NF-κB/AP-1 activation in a dectin-1-dependent manner. This pattern of activation was also transiently observed with repression of chitin synthesis in C. albicans or when yeast cells were incubated in low concentrations of the chitin synthesis inhibitor nikkomycin Z.


Whipple's disease: morphologic and immunofluorescence characterization of bacterial antigens.
The bacterial etiology of Whipple's disease is generally accepted. However, the exact identity of the "Whipple bug" has remained elusive. Indeed, the isolation of several types of bacteria from different patients with Whipple's disease has caused some to speculate that Whipple's disease may have polymicrobial etiology. Our light and electron microscopic studies document the presence of bacilliform organisms lying free in the lamina propria of the duodenal mucosa. Intact and partially degraded bacterial organisms were seen in the phagosomes of macrophages. Indirect immunofluorescence studies demonstrated the presence of multiple bacterial antigens in the lamina propria as well as the macrophage granules. This profile of antigens is similar to the profile demonstrated in four other patients in two previous studies. The occurrence of similar profiles of bacterial antigens in the tissues of different patients with Whipple's disease suggests a single microorganism in the etiology of Whipple's disease. Because of the overlapping features of muciphages and Whipple's cells in the rectal biopsy material, the superiority and reliability of proximal small intestinal biopsy in preference to rectal biopsy are re-emphasized.


Deep Vein Thrombosis Interventions in Cancer Patients.
The presence of cancer increases the risk of deep vein thrombosis (DVT), DVT recurrence, and treatment-related bleeding, and therefore offers distinctive clinical considerations when planning treatment. Anticoagulation with a low-molecular-weight heparin is the preferred initial and long-term therapy in cancer patients. Inferior vena cava filters may be used judiciously for patients with cancer-related DVT who have contraindications to anticoagulation or who exhibit breakthrough pulmonary embolism (PE) despite anticoagulation, but should be removed when the PE risk is felt to subside. Because moderate-quality evidence suggests that the use of catheter-directed thrombolysis (CDT) can prevent the postthrombotic syndrome, cancer patients with acute iliofemoral DVT, low expected bleeding risk, and good functional status may reasonably be considered for CDT if DVT-related sequelae are likely to be a dominant contributor to the patient's clinical condition, functional status, and quality of life. In selected patients who have chronic venous symptoms from mass/nodal compression of the pelvic veins, endovascular stent placement may provide symptom relief. As current recommendations are based on very limited data, further studies would be welcome to better delineate the most appropriate use of endovascular therapies in patients with cancer.


A protein with an inactive pterin-4a-carbinolamine dehydratase domain is required for Rubisco biogenesis in plants.
Ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) plays a critical role in sustaining life by catalysis of carbon fixation in the Calvin-Benson pathway. Incomplete knowledge of the assembly pathway of chloroplast Rubisco has hampered efforts to fully delineate the enzyme's properties, or seek improved catalytic characteristics via directed evolution. Here we report that a Mu transposon insertion in the Zea mays (maize) gene encoding a chloroplast dimerization co-factor of hepatocyte nuclear factor 1 (DCoH)/pterin-4α-carbinolamine dehydratases (PCD)-like protein is the causative mutation in a seedling-lethal, Rubisco-deficient mutant named Rubisco accumulation factor 2 (raf2-1). In raf2 mutants newly synthesized Rubisco large subunit accumulates in a high-molecular weight complex, the formation of which requires a specific chaperonin 60-kDa isoform. Analogous observations had been made previously with maize mutants lacking the Rubisco biogenesis proteins RAF1 and BSD2. Chemical cross-linking of maize leaves followed by immunoprecipitation with antibodies to RAF2, RAF1 or BSD2 demonstrated co-immunoprecipitation of each with Rubisco small subunit, and to a lesser extent, co-immunoprecipitation with Rubisco large subunit. We propose that RAF2, RAF1 and BSD2 form transient complexes with the Rubisco small subunit, which in turn assembles with the large subunit as it is released from chaperonins.


Evolution of dry patches in evaporating liquid films.
We investigate evolution of dry patches in a thin film of a volatile liquid on a heated plate in the framework of a model that accounts for the effects of surface tension, evaporation, thermocapillarity, and disjoining pressure. Dry areas on the plate are modeled by isothermal microscopic films which are in thermodynamic equilibrium with the vapor. For nonpolar liquids such equilibrium is achieved due to van der Waals forces, well-defined capillary ridges are formed around growing dry patches, contact line speed increases with time. For polar liquids the microscopic film is formed by combined action of van der Waals and electrical double layer forces, capillary ridge is small, and contact line speed quickly approaches a constant value. Thermocapillary stresses tend to increase the height of the capillary ridges formed around expanding patches. Numerical simulations demonstrate that the proposed model is capable of describing a number of complicated phenomena observed in experimental studies of evaporating films including fingering instabilities and merger of growing dry patches.


Managing invasive fungal disease in immunocompromised patients.
Celebrating its 30th anniversary in Budapest this year, the International Immunocompromised Host Society (ICHS) was established to advance the understanding of interactions between host defenses and microbial agents in order to improve the prevention and management of human disease in patients with compromised immune function. Much has been achieved in the intervening years, and presentations on the challenges of invasive fungal disease at this year's ICHS congress reflected the changing nature of the population at risk of fungal disease, the growing range of fungal pathogens, and evolving approaches to the prevention, diagnosis and treatment of fungal infection.


Efforts to Improve the Safety Culture of the Elderly in Nursing Homes: A Qualitative Study.
The attention to building a safety culture in nursing homes is relatively less when compared to hospitals. Good patient safety will improve the quality of health services and minimize incidents related to patient safety. This study aims to look at efforts that can be made to improve safety culture in nursing homes. The research design uses phenomenological qualitative with in-depth interviews. Purposive sampling was used with interpretive phenomenological analysis. Participants were 29 staff from four government and private institutions in East Java, Indonesia. The sub-themes resulting from the research efforts to improve the safety culture of the elderly in nursing homes are the provision of new staff orientation, training, improvement of infrastructure, and procurement of security staff. The analysis shows that efforts to improve safety culture can be carried out with various strategies by paying attention to risk assessment steps, patient risk identification, and management, incident reporting, and analysis, the ability to learn from incidents and their follow-up, as well as implementing solutions to minimize risks and prevent them from occurring injury. Safety culture plays an essential role in improving the quality of care.


Guiding across the generations: rediscovering nursing's promise.
This report describes the parallels between guiding and nursing. The principles of guiding, safety, discovery, integrity, and intention are reviewed and tied to specific skills. Nursing guides integrate these principles and skills to show the way to people for whom they care. The safety that guiding provides serves multiple generations and their unique needs.


[Quality criteria of phlebography examination methods. Technically conditioned possibilities of error prediction (author's transl)].
The article describes the technical and anatomical limitations of information supplied by phlebography. Injection of contrast medium into the v. mediana hallucis enables optimal contrast medium distribution. The more proximal the site of injection, the greater the uncertainty of achieving continuous filling of the deep veins with contrast medium. Obstructions during compression (ulcer, oedema) may prove an obstacle to the assessment of insufficient v. perforantes due to overfilling of superficial veins with contrast medium. Even without any abnormal finding it is not possible to stain muscle veins and the v. femoris profunda in about 50% of the examinations. Muscular traction can result in deformation of mainly the v. poplitea and hence results in discontinuous filling with contrast medium if the musculature is not properly relaxed. The veins of the thigh and pelvis must be stained with high contrast in a continuous manner, since otherwise occlusions and collaterals are overlooked in an otherwise normal distal phlebogram. Valve motility can be assessed without additional examination measures directly after ascending phlebography during recumbency of the patient.


[AIDS in childhood].
1% of registered AIDS cases are children, 80% have been perinatally infected. Special diagnostic criteria have to be applied for infants. Intrauterine infection can produce a specific malformation syndrome. Chronic pulmonary illness can be caused by pulmonary lymphoid hyperplasia and-less frequently-by Pneumocystis carinii pneumonia. Pulmonary lymphoid hyperplasia is responsive to corticoids. HIV infected mothers should refrain from breast feeding. Teenagers have to be informed adequately about the risks of and how to avoid HIV infection.


Detection of bluetongue virus RNA in field-collected Culicoides spp. (Diptera: Ceratopogonidae) following the discovery of bluetongue virus serotype 1 in white-tailed deer and cattle in Louisiana.
In November 2004, bluetongue virus (family Reoviridae, genus Orbivirus, BTV) serotype 1 (BTV-1) was detected for the first time in the United States from a hunter-killed deer in St. Mary Parish, LA. In 2005, sera surveys were conducted on three cattle farms near the area where the deer was found, and BTV-1-seropositive cattle were found on two of the three farms; in 2006, sera surveys from the cattle on the three farms did not detect any BTV-1-positive animals. The purpose of this study was to survey ceratopogonid populations at the three farms and test field-collected specimens for the presence of BTV and epizootic hemorrhagic disease virus (family Reoviridae, genus Orbivirus, EHDV). Miniature CDC light traps and New Jersey traps were used to capture ceratopogonids on the three farms from January 2006 through November 2007. In total, 3,319 ceratopogonids were captured, including 1,790 specimens of 10 different species of Culicoides. IR-RT-polymerase chain reaction (PCR) was performed to screen for BTV and EHDV in 264 pools representing 2,309 specimens collected at the farms. All positive samples were sequenced for serotype determination. Five pools of 275 (1.8%) were positive for BTV. Pools of four species of Culicoides were found to be positive: Culicoides crepuscularis (Malloch), Culicoides debilipalpis Lutz (two pools), Culicoides haematopotus Malloch, and Gulicoidesfurens (Poey). The amplicons of the positive specimens were sequenced and found to be identical to both BTV-17 and BTV-13. During our study, no BTV-1 transmission was detected in cattle, and no BTV-1 was detected in specimens of ceratopogonids.


Metabolic Syndrome-Role of Dietary Fat Type and Quantity.
Metabolic syndrome increases the risk of cardiovascular disease (CVD) over and above that related to type 2 diabetes. The optimal diet for the treatment of metabolic syndrome is not clear. A review of dietary interventions in volunteers with metabolic syndrome as well as studies examining the impact of dietary fat on the separate components of metabolic syndrome was undertaken using only recent meta-analyses, if available. Most of the data suggest that replacing carbohydrates with any fat, but particularly polyunsaturated fat, will lower triglyceride(TG), increase high density lipoprotein (HDL) cholesterol, and lower blood pressure, but have no effects on fasting glucose in normal volunteers or insulin sensitivity, as assessed by euglycemic hyperinsulinemic clamps. Fasting insulin may be lowered by fat. Monounsaturated fat (MUFA) is preferable to polyunsaturated fat (PUFA) for fasting insulin and glucose lowering. The addition of 3-4 g of N3 fats will lower TG and blood pressure (BP) and reduce the proportion of subjects with metabolic syndrome. Dairy fat (50% saturated fat) is also related to a lower incidence of metabolic syndrome in cohort studies.


Intra-operative correction of volar tilt of distal radius fractures using volar locking plate as reduction tool: review of 24 cases.
In surgical fixation of distal radius fractures with metaphyseal comminution, volar tilt can be restored using an anatomical volar locking plate as a reduction tool. The purpose of our study is to assess the degree of over or under correction of volar tilt that can result with our 'lift' technique and to determine the ratio between theoretical and actual angular correction. We retrospectively reviewed 24 patients who underwent distal radius fracture fixation using this technique and assessed intra-operative radiographs for parameters including pre-'lift' and post-'lift' volar tilt and pre-'lift' plate-shaft angles. The ratio between actual angular correction and theoretical angular correction was calculated. The 'lift' technique is found to be reliable in restoring volar tilt in most fractures. Over- or under-correction does occur due to errors in visual estimation and actual angular correction is generally less than the theoretical angular correction.


Asymmetric Synthesis of Amino-Bis-Pyrazolone Derivatives via an Organocatalytic Mannich Reaction.
A new series of N-Boc ketimines derived from pyrazolin-5-ones have been used as electrophiles in asymmetric Mannich reactions with pyrazolones. The amino-bis-pyrazolone products are obtained in excellent yields and stereoselectivities by employing a very low loading of 1 mol % of a bifunctional squaramide organocatalyst. Depending on the substitution at position 4 of the pyrazolones, the new protocol allows for the generation of one or two tetrasubstituted stereocenters, including a one-pot version combing the Mannich reaction with a base-mediated halogenation.


[Anaerobic bacteria, the unknown members of the lung microbiota].
Lungs were considered as sterile for a long time. However, it is now evident that the lungs of healthy people are colonized by microorganisms. Among the bacteria present in the pulmonary microbiota, a significant proportion is anaerobic (strict or facultative). Even though interest in the pulmonary microbiota is increasing, few studies have focused on these unknowns that represent the lung resident anaerobic bacteria. This review describes the biodiversity of anaerobes in physiological conditions, and in different chronic respiratory diseases (cystic fibrosis, COPD, asthma). It also explains anaerobes' roles in the barrier flora effect, in inflammation, or as potential biomarkers in disease progression.


Phagocytosis of degenerating germ cells by follicle cells in fetal guinea pig ovaries.
Virus-like particles (80 mmu to 100 mmu in diameter) occur in the endoplasmic reticulum of germ cells in the ovaries of fetal guinea pigs, and are confined to this population of cells. Using these particles as a marker, the phagocytosis of degenerating germ cells by somatic cells in the cortex of the ovary was traced.


Cryopreservation of platelets: an in-vitro comparison of four methods.
Platelets were cryopreserved in four different cryoprotectives-two intracellular (dimethylsulphoxide, glycerol) and two extracellular (hydroxyethyl starch, dextran). The platelets were evaluated according to their yields, hypotonic shock response, and serotonin uptake, which are useful parameters for establishing optimum storage conditions. Hydroxyethyl starch and dextran were found to be poor cryoprotectives while 5% dimethylsulphoxide was the most suitable.


Prevalence and incidence data in the assessment of the risk of coronary heart disease.
Estimates of risk of coronary heart disease (CHD) derived from two prevalence survey examinations and from a 7- to 9-year incidence study were compared using data from the Evans County Cardiovascular study. Four risk factors were studied: sex, blood pressure, age and serum cholesterol; relative risks and morbidity ratios were used as estimators of the risk of CHD. Considerable agreement was found between the estimates of risk derived from the incidence and prevalence data.


Evidence for the Propositions of the Interpersonal Theory of Suicide Among a Military Sample.
Although the interpersonal theory of suicide may explain the elevated suicide risk among military service members, past explorations have been equivocal. This study aimed to investigate the propositions of the interpersonal theory in a sample of U.S. Army recruiters. Participants (N = 3,428) completed self-report measures assessing the interpersonal theory's constructs (i.e., thwarted belongingness (TB), perceived burdensomeness (PB), acquired capability for suicide), current suicidal ideation, agitation, and insomnia. History of depression was obtained from medical records. Hierarchical multiple regression analyses revealed that the interaction between TB and PB was associated with current suicidal ideation, controlling for depression, agitation, and insomnia. This effect was especially notable among those with high capability for suicide. Findings provide support for the interpersonal theory in a large, diverse military sample. It may be advantageous to assess and therapeutically address TB and PB among at-risk service members.


Winding number constrained contour detection.
Salient contour detection can benefit from the integration of both contour cues and region cues. However, this task is difficult due to different nature of region representations and contour representations. To solve this problem, this paper proposes an energy minimization framework based on winding number constraints. In this framework, both region cues, such as color/texture homogeneity, and contour cues, such as local contrast and continuity, are represented in a joint objective function, which has both region and contour labels. The key problem is how to design constraints that ensure the topological consistency of the two kinds of labels. Our technique is based on the topological concept of winding number. Using a fast method for winding number computation, a small number of linear constraints are derived to ensure label consistency. Our method is instantiated by ratio-based energy functions. By successfully integrating both region and contour cues, our method shows advantages over competitive methods. Our method is extended to incorporate user interaction, which leads to further improvements.


Interactions between the Translation Machinery and Microtubules.
Microtubules are components of eukaryotic cytoskeleton that are involved in the transport of various components from the nucleus to the cell periphery and back. They also act as a platform for assembly of complex molecular ensembles. Ribonucleoprotein (RNP) complexes, such as ribosomes and mRNPs, are transported over significant distances (e.g. to neuronal processes) along microtubules. The association of RNPs with microtubules and their transport along these structures are essential for compartmentalization of protein biosynthesis in cells. Microtubules greatly facilitate assembly of stress RNP granules formed by accumulation of translation machinery components during cell stress response. Microtubules are necessary for the cytoplasm-to-nucleus transport of proteins, including ribosomal proteins. At the same time, ribosomal proteins and RNA-binding proteins can influence cell mobility and cytoplasm organization by regulating microtubule dynamics. The molecular mechanisms underlying the association between the translation machinery components and microtubules have not been studied systematically; the results of such studies are mostly fragmentary. In this review, we attempt to fill this gap by summarizing and discussing the data on protein and RNA components of the translation machinery that directly interact with microtubules or microtubule motor proteins.


The polymorphic apocrine nevus: a study of a unique tumor including carcinoembryonic antigen staining.
The apocrine nevus is a rare tumor. We report a 32-year-old man with a neck nodule, histologically an apocrine nevus displaying mature and immature apocrine structures in a distinctive pattern. The carcinoembryonic antigen staining was positive intracellularly only in the smaller luminal structures. We have named this unique tumor a polymorphic apocrine nevus.


Ambient particulate matter air pollution exposure and ovarian cancer incidence in the USA: An ecological study.
To investigate associations between air particulate matter of ≤2.5 μm in diameter (PM2.5 ) and ovarian cancer. County-level ecological study. Surveillance, epidemiology, and end results from a collection of state-level cancer registries across 744 counties. Data from the Environmental Protection Agency's network for PM2.5 monitoring was used to calculate trailing 5- and 10-year PM2.5 county-level values. County-level data on demographic characteristics were obtained from the American Community Survey. A total of 98 751 patients with histologically confirmed ovarian cancer as a primary malignancy from 2000 to 2016. Generalised linear regression models were developed to estimate the association between PM2.5 and PM10 levels, over 5- and 10-year periods of exposure, and ovarian cancer risk, after accounting for county-level covariates. Risk ratios for associations between ovarian cancer (both overall and specifically epithelial ovarian cancer) and PM2.5 levels. For the 744 counties included, the average PM2.5 level from 1990 through 2018 was 11.75 μg/m3 (SD = 3.7) and the average PM10 level was 22.7 μg/m3 (SD = 5.7). After adjusting for county-level covariates, the overall annualised ovarian cancer incidence was significantly associated with increases in 5-year PM2.5 (RR = 1.11 per 10 units (μg/m3 ) increase, 95% CI 1.06-1.16). Similarly, when the analysis was limited to epithelial cell tumours and adjusted for county-level covariates there was a significant association with trailing 5-year PM2.5 exposure models (RR = 1.12 per 10 units increase, 95% CI 1.08-1.17). Likewise, 10-year PM2.5 exposure was associated with ovarian cancer overall and with epithelial ovarian cancer. Higher county-level ambient PM2.5 levels are associated with 5- and 10-year incidences of ovarian cancer, as measurable in an ecological study.


Primary Central Nervous System Lymphoma.
Primary central nervous system lymphoma (PCNSL) is an extranodal non-Hodgkin lymphoma limited to the brain, spinal cord, leptomeninges, and eyes. The majority of patients are immunocompetent, with a median age of 65 years at diagnosis. Historically, whole-brain radiation therapy (WBRT) was the first and sole treatment for PCNSL. Today, due to the recognized neurotoxicity of WBRT, this modality is usually avoided in the treatment. Most chemotherapy regimens are based on high-dose methotrexate plus the anti-CD20 monoclonal antibody rituximab, leading to high response rates, but 5-year survival is still poor at approximately 30% compared with other extranodal lymphomas. New treatment strategies including high-dose chemotherapy/autologous stem cell transplantation, targeted therapies focusing on, for example, genetic alterations in B cells or mammalian target of rapamycin signaling, and immunotherapy with inhibitors of the programmed cell death 1 receptor are only a few options to improve the armamentarium against PCNSL.


Gulf war syndrome: could it be triggered by biological warfare-vaccines using pertussis as an adjuvant?
Several recent epidemiological studies have shown that vaccinations against biological warfare using pertussis as an adjuvant were associated with the Gulf war syndrome. If such epidemiological findings are confirmed, we propose that the use of pertussis as an adjuvant could trigger neurodegeneration through induction of interleukin-1beta secretion in the brain. In turn, neuronal lesions may be sustained by stress or neurotoxic chemical combinations. Particular susceptibility for IL-1beta secretion and potential distant neuronal damage could provide an explanation for the diversity of the symptoms observed on veterans.


Testing the tools for revealing and characterizing the iodine-iodine halogen bond in crystals.
To understand what tools are really suitable to identify and classify the iodine-iodine non-covalent interactions in solid organic polyiodides, we have examined the anisotropy of the electron density within the iodine atomic basin along and across the iodine-iodine halogen bond using the Laplacian of electron density, one-electron potential and electron localization function produced by Kohn-Sham calculations with periodic boundary conditions. The Laplacian of electron density exhibits the smallest anisotropy and yields a vague picture of the outermost electronic shells. The one-electron potential does not show such a deficiency and reveals that the valence electron shell for the halogen-bond acceptor iodine is always wider than that for the halogen-bond donor iodine along its σ-hole direction. We have concluded that the one-electron potential is the most suitable for classification of the iodine-iodine bonds and interactions in complicated cases, while the electron localization function allows to distinguish the diiodine molecule bonded with the monoiodide anion from the typical triiodide anion.


The Proteome of Equine Oviductal Fluid Varies Before and After Ovulation: A Comparative Study.
Equine fertilization cannot be performed in the laboratory as equine spermatozoa do not cross the oocyte's zona pellucida in vitro. Hence, a more profound study of equine oviductal fluid (OF) composition at the pre-ovulatory and post-ovulatory stages could help in understanding what components are required to achieve fertilization in horses. Our work aimed to elucidate the proteomic composition of equine OF at both stages. To do this, OF was obtained postmortem from oviducts of slaughtered mares ipsilateral to a pre-ovulatory follicle (n = 4) or a recent ovulation (n = 4); the samples were kept at -80°C until analysis. After protein extraction and isobaric tags for relative and absolute quantification (iTRAQ) labeling, the samples were analyzed by nano-liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). The analysis of the spectra resulted in the identification of a total of 1,173 proteins present in pre-ovulatory and post-ovulatory samples; among these, 691 were unique for Equus caballus. Proteins from post-ovulatory oviductal fluid were compared with the proteins from pre-ovulatory oviductal fluid and were categorized as upregulated (positive log fold change) or downregulated (negative log fold change). Fifteen proteins were found to be downregulated in the post-ovulatory fluid and 156 were upregulated in the post-ovulatory OF compared to the pre-ovulatory fluid; among the upregulated proteins, 87 were included in the metabolism of proteins pathway. The identified proteins were related to sperm-oviduct interaction, fertilization, and metabolism, among others. Our data reveal consistent differences in the proteome of equine OF prior to and after ovulation, helping to increase our understanding in the factors that promote fertilization and early embryo development in horses.


Review of Experimental Modelling in Vascular Access for Hemodialysis.
This paper reviews applications of experimental modelling in vascular access for hemodialysis. Different techniques that are used in in-vitro experiments are bulk pressure and flow rate measurements, Laser Doppler Velocimetry and Vector Doppler Ultrasound point velocity measurements, and whole-field measurements such as Particle Image Velocimetry, Ultrasound Imaging Velocimetry, Colour Doppler Ultrasound, and Planar Laser Induced Fluorescence. Of these methods, the ultrasound techniques can also be used in-vivo, to provide realistic boundary conditions to in-vitro experiments or numerical simulations. In the reviewed work, experimental modelling is mainly used to support computational models, but also in some cases as a tool on its own. It is concluded that, to further advance the utility of computational modelling in vascular access research, a rigorous verification and validation procedure should be adopted. Experimental modelling can play an important role in both in-vitro validation, and the quantification of the accuracy, uncertainty, and reproducibility of in-vivo measurement methods.


Expression Level and Significance of Tim-3 in CD4+ T Lymphocytes in Peripheral Blood of Patients with Coronary Heart Disease.
To investigate the expression level and significance of T cell immunoglobulin and mucin-domain containing molecules-3 (Tim-3) and interleukin-7 (IL-7) in CD4+ T lymphocytes in peripheral blood of patients with coronary heart disease (CHD). 75 patients with CHD treated at our hospital were selected and classified as mild group (25 cases), moderate group (25 cases) and severe group (25 cases), according to the severity of illness. Twenty-five healthy volunteers who underwent a physical examination at our hospital during the same period were selected as the control group. The expression level of Tim-3 in CD4+ T lymphocytes in peripheral blood of patients in four groups was detected by flow cytometry and quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). The expression level of IL-7 in peripheral blood serum was measured by enzymelinked immunosorbent assay (ELISA). Correlation analyses of Tim-3 and IL-7, Tim-3 and disease severity and IL-7 and disease severity were performed, respectively. Flow cytometry and qRT-PCR demonstrated that the expression of Tim-3 in CD4+ T lymphocytes in peripheral blood of patients with CHD increased with the aggravation of the disease. ELISA showed that the tendency of IL-7 expression in peripheral blood serum was consistent with the expression of Tim-3, and the expression of Tim-3 had a positive correlation with IL-7. The expression levels of both Tim-3 and IL-7 were positively correlated with the Gensini score. The expression of Tim-3 and IL-7 in peripheral blood of patients with CHD was upregulated and increased with the aggravation of CHD.


Effect of pore size in substrate and diffusion of enzyme on hydrolysis of cellulosic materials with cellulases.
The effect of cellulase size on hydrolysis was studied by comparing the behavior of crosslinked cellulase (CC) with normal cellulase (FC). The average molecular weight of the CC was at least three times the molecular weight of the FC. The amounts of each enzyme were adjusted so that the degree of solubilization after 2 h was the same. The degree of solubilization of Avicel with CC was higher than that with FC in the late stage of reaction. The degree of solubilization of pretreated lignocelluloses was much greater than that of Avicel, but the degree of solubilization with CC was lower than that with FC at all times during the reaction. The degree of solubilization of artificial lignified Avicel was higher with FC than with CC, but the degree of solubilization of de-lignified the artificial lignified Avicel was lower with FC than with CC. The degree of solubilization of amorphous cellulose with FC was the same as that with CC at all times during the reaction. These behaviors are examined by the hypothesis that when small pores dominate, the smaller enzyme components diffuse into the pores and become inactive since synergism with the larger components is no longer possible, whereas, when larger pores dominate, the entire enzyme can diffuse in and therefore the available surface area is increased. This hypothesis is supported by direct measurement of the pore size in two of the substrates and by diffusion inside Avicel of only smaller molecular cellulase component.


The sphenoid sinus, foramen rotundum and vidian canal: a radiological study of anatomical relationships.
The sphenoid sinus is an important structure in ventral skull base surgeries that is surrounded by several vital anatomical structures including the internal carotid arteries, optic nerve and cranial nerves inside the cavernous sinus. In addition, the foramen rotundum is a small canal deeply situated in the base of the skull, which represents the way for exit of the maxillary nerve. Understanding of the sphenoid bone anatomical relationships is central to the expanded endonasal approaches to the skull base. To record and analyze the measurement indexes of the sphenoid sinus and foramen rotundum in the coronal plane of normal computer tomography scans. Patients underwent paranasal sinuses computer tomography scan from June 2014 to November 2015 were retrospectively entered this cross-sectional study. We obtained several morphometric measurements from both the right and left sides using computer software. We also classified foramen rotundum and vidian canal types and determined position of the foramen rotundum regarding to base of lateral pterygoid plate. One-hundred patients with the mean age of 38.56±18.51 years entered this study. Mean bilateral FR distances were 38.48±3.87mm. Average right and left FRs distances to midline were 19.00±2.07 and 19.34±2.17mm, respectively (p=0.03). Twenty-eight cases (28%) had type I vidian canal, 48% and 24% had type II and III vidian canals, respectively. Four patients (4%) had type I rotundum foramen, 28% and 44% had type IIa and IIb, respectively and 24% had type III rotundum foramen. The position of foramen rotundums regarding to the base of lateral pterygoid plate was online in 50% of cases, medially placed in 47% and laterally placed in 3% of cases. The results of this study can be used to provide a better anatomical understanding of the area, which is necessary for endoscopic skull base surgeons.


Differential expression of c-jun, c-fos and hsp 70 mRNAs after folic acid and ischemia-reperfusion injury: effect of antioxidant treatment.
The regenerative repair response to folic acid and ischemia-reperfusion injury is characterized by different patterns of renal tubular cell proliferation. The purpose of this study was to examine the time course of the expression of two early growth response genes, c-jun and c-fos, and of the stress response gene hsp70 after such renal injuries and to determine the role played by reactive oxygen species generated during reperfusion, on gene induction. Ischemic injury caused an almost immediate increase of c-jun, c-fos and hsp70 mRNA expression, that reached a maximum at 1 h of reperfusion. Folic acid treatment increased c-fos and hsp70 mRNAs at 2 h, while c-jun accumulated at 1 h, although to a lesser extent. The intravenous administration of two antioxidant drugs, allopurinol or dimethyl sulfoxide (DMSO), 20 min before ischemia, to prevent the generation of oxygen free radicals during reperfusion, did not cause any change in gene expression. In contrast, the combined administration of allopurinol and DMSO reduced c-jun and c-fos mRNA expression as well as tubular cell damage at 1 h of reperfusion, although not at earlier times while hsp70 mRNA expression remained almost unchanged. Taken together, the results suggest that these scavengers, by reducing reactive oxygen species and renal damage during reperfusion, may affect the expression and/or persistence of transcripts involved in the control of epithelial cell proliferation.