Neural signatures of inhibitory control in bilingual spoken production.
Bilinguals activate both languages when they intend to speak even one language alone (e.g., Kroll, Bobb, & Wodniekca, 2006). At the same time, they are able to select the language they intend to speak and switch back and forth between languages rapidly, with few production errors. Previous research utilizing behavioral (Linck, Kroll, & Sunderman, 2009) and neuroimaging techniques (ERPs and fMRI; Guo, Liu, Misra, & Kroll, 2011; Misra, Guo, Bobb, & Kroll, 2012) suggest that successful bilingual speech production is enabled by active inhibition of the language not in use. Results showing an asymmetric switching cost for the L1 compared to the L2 (with a larger cost -reflected in longer naming latencies-when switching from the L2 to the L1) have been taken as evidence that the L1 (usually the dominant language for bilinguals who learned their second language later in life) may need to be inhibited when speaking in the L2. However, there is still little research on the scope of this inhibitory process. The goal of this event-related functional magnetic resonance imaging study is to understand how the recruitment of neural areas implicated during bilingual language processing are shaped by the scope of language use. The results show that bilinguals engage a wide functional control network that is hierarchically engaged in local control for single lexical items, but extends further to the broader semantic level, and finally to the whole language. This functional network is modulated by proficiency in the L2.


Association of arterial stiffness in non-hypertensive offspring with parental hypertension: the Hanzhong adolescent hypertension cohort study.
Arterial stiffness may be an early marker for vascular changes associated with hypertension in young adults. Individuals with a family history of hypertension are at high risk of developing hypertension. We investigated whether arterial stiffness measured, such as mean arterial pressure (MAP) and brachial to ankle pulse wave velocity (baPWV), were increased in normotensive offspring with a parental history of hypertension. We compared MAP and baPWV in a sample of 1953 non-hypertensive participants (974 men, mean age 42±3 years) recruited in the previous Hanzhong adolescent hypertension cohort study. Standardized questionnaires, physical examinations and laboratory tests were used to obtain information, with a particular focus on family hypertension history, anthropometric, hemodynamic, and biochemical factors. A total of 1039, 759, 155 participants had 0, 1, and 2 parents with hypertension, respectively. Parental hypertension was associated with elevated offspring MAP (in multivariable-adjusted models, B=1.5 mm Hg, 95% CI 0.8-2.2 for 1 parent with hypertension; B=3.0 mm Hg, 95% CI 1.8-4.3, for 2 parents with hypertension; p<0.001 for each). A significant positive correlation was also observed between MAP and baPWV (r=0.543, p<0.001). BaPWV displayed a similar correlation with parental hypertension in age-adjusted, sex-adjusted and body mass index (BMI)-adjusted models (B=23.1 cm/s, 95% CI 8.0-38.1, for 1 parent with hypertension, p<0.01; B=53.0 cm/s, 95% CI 25.8-80.2, p<0.001 for 2 parents with hypertension), but associations were attenuated in multicovariate models after adjustment for MAP. In multivariable-adjusted models, logistic regression analysis showed that the risk of belonging to the upper quartile of MAP was significantly increased for offspring whose parents had hypertension (OR=1.5, 95% CI 1.2-1.9, for 1 parent with hypertension; OR=2.3, 95% CI 1.6-3.4, for 2 parents with hypertension; p<0.001 for each). Similarly, the odds ratios of belonging to the upper quartile of baPWV increased (OR=1.3, 95% CI 1.1-1.6, for 1 parent with hypertension, p<0.05; OR=2.1, 95% CI 1.5-3.0, for 2 parents with hypertension, p<0.001, in age-sex-BMI-adjusted models), and were then brought down in the fully adjusted models including MAP, but the increase remained significant for 2 parents with hypertension (OR=1.6, 95% CI 1.0-2.3, p<0.05). These findings provide evidence that arterial stiffness is higher in young-to middle-aged normotensive subjects with a family history of hypertension, suggesting that increased arterial stiffness may occur in the early stages during the pathogenesis of hypertension.


Comparative response of platelet fV and plasma fV to activated protein C and relevance to a model of acute traumatic coagulopathy.
Acute traumatic coagulopathy (ATC) has been linked to an increase in activated protein C (aPC) from 40 pM in healthy individuals to 175 pM. aPC exerts its activity primarily through cleavage of active coagulation factor Va (fVa). Platelets reportedly possess fVa which is more resistant to aPC cleavage than plasma fVa; this work examines the hypothesis that normal platelets are sufficient to maintain coagulation in the presence of elevated aPC. Coagulation responses of normal plasma, fV deficient plasma (fVdp), and isolated normal platelets in fVdp were conducted: prothrombin (PT) tests, turbidimetry, and thromboelastography (TEG), including the dose response of aPC on the samples. PT and turbidimetric assays demonstrate that normal plasma is resistant to aPC at doses much higher than those found in ATC. Additionally, an average physiological number of washed normal platelets (200,000 platelets/mm3) was sufficient to eliminate the anti-coagulant effects of aPC up to 10 nM, nearly two orders of magnitude above the ATC concentration and even the steady-state pharmacological concentration of human recombinant aPC, as measured by TEG. aPC also demonstrated no significant effect on clot lysis in normal plasma samples with or without platelets. Although platelet fVa shows slightly superior resistance to aPC's effects compared to plasma fVa in static models, neither fVa is sufficiently cleaved in simulations of ATC or pharmacologically-delivered aPC to diminish coagulation parameters. aPC is likely a correlative indicator of ATC or may play a cooperative role with other activity altering products generated in ATC.


Preoperative Chest Computed Tomography Screening for Coronavirus Disease 2019 in Asymptomatic Patients Undergoing Cardiac Surgery.
Due to the outbreak of Severe Acute Respiratory Syndrome coronavirus (SARS-Cov-2), an efficient COVID-19 screening strategy is required for patients undergoing cardiac surgery. The objective of this prospective observational study was to evaluate the role of preoperative computed tomography (CT) screening for COVID-19 in a population of COVID-19 asymptomatic patients scheduled for cardiac surgery. Between the 29th of March and the 26th of May 2020, patients asymptomatic for COVID-19 underwent a CT-scan the day before surgery, with reverse-transcriptase polymerase-chain reaction (RT-PCR) reserved for abnormal scan results. The primary endpoint was the prevalence of abnormal scans, which was evaluated using the CO-RADS score, a COVID-19 specific grading system. In a secondary analysis, the rate of abnormal scans was compared between the screening cohort and matched historical controls who underwent routine preoperative CT-screening prior to the SARS-Cov-2 outbreak. Of the 109 patients that underwent CT-screening, an abnormal scan result was observed in 7.3% (95% confidence interval: 3.2-14.0%). One patient, with a normal screening CT, was tested positive for COVID-19, with the first positive RT-PCR on the ninth day after surgery. A rate of preoperative CT-scan abnormalities of 8% (n = 8) was found in the unexposed historical controls (P > 0.999). In asymptomatic patients undergoing cardiac surgery, preoperative screening for COVID-19 using computed tomography will identify pulmonary abnormalities in a small percentage of patients that do not seem to have COVID-19. Depending on the prevalence of COVID-19, this results in an unfavorable positive predictive value of CT screening. Care should be taken when considering CT as a screening tool prior to cardiac surgery.


Prevalence of the variant allele rs61764370 T>G in the 3'UTR of KRAS among Dutch BRCA1, BRCA2 and non-BRCA1/BRCA2 breast cancer families.
Recently, a variant allele in the 3'UTR of the KRAS gene (rs61764370 T>G) was shown to be associated with an increased risk for developing non-small cell lung cancer, as well as ovarian cancer, and was most enriched in ovarian cancer patients from hereditary breast and ovarian cancer families. This functional variant has been shown to disrupt a let-7 miRNA binding site leading to increased expression of KRAS in vitro. In the current study, we have genotyped this KRAS-variant in breast cancer index cases from 268 BRCA1 families, 89 BRCA2 families, 685 non-BRCA1/BRCA2 families, and 797 geographically matched controls. The allele frequency of the KRAS-variant was found to be increased among patients with breast cancer from BRCA1, but not BRCA2 or non-BRCA1/BRCA2 families as compared to controls. As BRCA1 carriers mostly develop ER-negative breast cancers, we also examined the variant allele frequency among indexes from non-BRCA1/BRCA2 families with ER-negative breast cancer. The prevalence of the KRAS-variant was, however, not significantly increased as compared to controls, suggesting that the variant allele not just simply associates with ER-negative breast cancer. Subsequent expansion of the number of BRCA1 carriers with breast cancer by including other family members in addition to the index cases resulted in loss of significance for the association between the variant allele and mutant BRCA1 breast cancer. In this same cohort, the KRAS-variant did not appear to modify breast cancer risk for BRCA1 carriers. Importantly, results from the current study suggest that KRAS-variant frequencies might be increased among BRCA1 carriers, but solid proof requires confirmation in a larger cohort of BRCA1 carriers.


Cisplatin, carboplatin, and cyclophosphamide combination chemotherapy in advanced-stage ovarian carcinoma: an Eastern Cooperative Oncology Group pilot study.
Cyclophosphamide (CTX) 600 mg/m2, carboplatin 280 mg/m2, and cisplatin 50 mg/m2 were administered on day 1 every 4 weeks to 41 previously untreated ovarian cancer patients with residual disease greater than 2.0 cm after primary laparotomy. Of 22 patients with measurable disease treated with up to eight cycles of therapy, the overall clinical response rate was 73% (exact 95% confidence interval [CI], 50% to 89%), with 50% complete response (CR). Six of 11 clinical CR (cCR) patients underwent surgical restaging; three pathologic CRs (pCRs) and three pathologic partial responses (pPRs) with residual disease less than 2.0 cm were documented. Fourteen patients had nonmeasurable but assessable disease; the clinical response rate was 57% (Cl, 29% to 82%) with two (14%) CRs. Second-look surgery was performed in one of the two cCR patients; a pPR was documented. Five patients with nonassessable disease were stable during chemotherapy; two underwent surgery and had pCRs. The median time to treatment failure (TTF) was 14.8 months, and median survival for the 41 patients is 26.7 months. Overall, 37% of the patients had progression-free intervals of at least 2 years, and 27% have survival times in excess of 3 years. Hematologic toxicity was substantial but manageable, with 58% and 66% experiencing a granulocyte nadir less than 500/microL and a platelet nadir less than 50,000/microL, respectively. One treatment-associated fatality occurred as a result of leukopenic sepsis and renal failure in the setting of progressive disease and ureteral obstruction. Mild to moderate nausea and vomiting occurred in most patients, but none experienced severe ototoxicity or peripheral neuropathy. Over all courses, 73% of the projected dose intensity of CTX and carboplatin and 86% of cisplatin were delivered. Since granulocytopenia and thrombocytopenia were dose-limiting, the addition of colony-stimulating factors that support both myeloid and megakaryocyte precursors may permit further dose intensification.


Patient-controlled interscalene analgesia after shoulder surgery: catheter insertion by the posterior approach.
Insertion and maintenance of an interscalene catheter is technically challenging using lateral or anterior approaches. We report a technique to provide continuous brachial plexus blockade through a 48-h infusion of ropivacaine 0.1% (5 mL/h with a 5 mL bolus dose, 20-min lockout interval) using a catheter inserted with cannula-over-needle technique on the posterior side of the neck in 120 patients undergoing shoulder surgery. All catheters were successfully placed. There were no technical complications (impossibility to thread catheter, accidental vascular, epidural or subarachnoid location), catheter dislodgment, or analgesic solution leakage. Dysphonia, Horner's syndrome, and difficulty breathing were observed in 12 patients, four patients, and one patient, respectively. One patient complained of minor paresthesia that spontaneously resolved. Three patients complained of cervical pain. Pain scores as well as ropivacaine requirement via a patient-controlled analgesia device were low. Evaluation of acute and nonacute complications in a large-size study is needed to compare efficacy and safety of this approach with existing techniques.


Bilateral renal oncocytosis with renal failure.
Oncocytosis is a term recently used to describe diffuse renal involvement by numerous oncocytic nodules. We report herein a case of a 53-year-old man with end-stage renal disease requiring hemodialysis. His kidneys were involved by numerous tumors. Histologic examination revealed more than 100 oncocytomas and an associated papillary renal cell carcinoma in the right kidney.


Bilateral central retinal arterial obstruction following head trauma: a very rare case report.
A 30-year-old patient presented at our outpatient department with complaints of severe loss of vision in both eyes following a head injury six days back. He also had a fracture at left side of the mandible and a few bruises over the left cheek. External ocular examination revealed subconjuctival hemorrhage in the left eye and bilateral sluggishly reacting pupils. Fundus examination showed white- out retina and a cherry red spot at the macula in both eyes. A clinical diagnosis of bilateral central retinal arterial obstruction (CRAO) was made which was later confirmed by fundus fluorescence angiography. Bilateral CRAO is a rare disease usually found in patients with cardiac embolic diseases, giant cell arteritis or systemic vascular inflammations. Our case is the second reported case in English literature of bilateral CRAO following head trauma.


Robust Framework for Medical Time Series Classification and Application to Real Scenarios in Modern Bioengineering.
In this study, a novel unsupervised classification framework for time series of medical nature is presented. This framework is based on the intersection of machine learning, Hilbert Spaces algebra, and signal theory. The methodology is illustrated through the resolution of three biomedical engineering problems: neuronal activity tracking, protein functional classification, and non-invasive diagnosis of atrial flutter (AFL). The results indicate that the proposed algorithms exhibit high proficiency in solving these tasks and demonstrate robustness in identifying damaged neuronal units while tracking healthy ones. Moreover, the application of the framework in protein functional classification provides a new perspective for the development of pharmaceutical products and personalised medicine. Additionally, the controlled environment of the framework in AFL simulation problem underscores the algorithm's ability to encode information efficiently. These results offer valuable insights into the potential of this framework and lay the groundwork for future studies.Clinical relevance- The framework proposed in this study has the potential to yield novel insights into the effects of newly implanted electrodes in the brain. Furthermore, the categorization of proteins by function could facilitate the development of personalised and efficient medicines, ultimately reducing both time and cost. The simulation of atrial flutter also demonstrates the framework's ability to encode information for arrhythmia diagnosis and treatment, which has the potential to lead to improved patient outcomes.


Osmotic stress-induced localisation switch of CBR1 from mitochondria to the endoplasmic reticulum triggers ATP production via β-oxidation to respond to osmotic shock.
Drought and high salinity are major environmental factors that reduce plant growth and development, leading to loss of plant productivity in agriculture. Under these stress conditions, photosynthesis is greatly suppressed despite the high cellular energy cost of stress response processes. Currently, the process that allows plants to secure the energy required for osmotic stress responses remains elusive. Here, we provide evidence that cytochrome b5 reductase 1 (CBR1), a cytochrome b5 reductase, plays an important role in ATP production in response to NaCl and dehydration stresses. Overexpression and loss of function of CBR1 led to enhanced resistance and sensitivity, respectively, to osmotic stress. Upon exposure to osmotic stress, CBR1 was localised to the endoplasmic reticulum (ER) instead of to mitochondria, where it was localised under normal conditions. Transgenic plants overexpressing ER-targeted CBR1 showed enhanced resistance to osmotic stress. Moreover, CBR1-ER and CBR1-OX plants, had higher levels of ATP and unsaturated fatty acids under osmotic stress. However, these effects were abrogated by thioridazine and 2-deoxy glucose, inhibitors of β-oxidation and glycolysis, respectively. Based on these results, we propose that ER-localised CBR1 triggers ATP production via the production and β-oxidation of polyunsaturated fatty acids under osmotic stress.


A hybrid learning scheme combining EM and MASMOD algorithms for fuzzy local linearization modeling.
Fuzzy local linearization (FLL) is a useful divide-and-conquer method for coping with complex problems such as modeling unknown nonlinear systems from data for state estimation and control. Based on a probabilistic interpretation of FLL, the paper proposes a hybrid learning scheme for FLL modeling, which uses a modified adaptive spline modeling (MASMOD) algorithm to construct the antecedent parts (membership functions) in the FLL model, and an expectation-maximization (EM) algorithm to parameterize the consequent parts (local linear models). The hybrid method not only has an approximation ability as good as most neuro-fuzzy network models, but also produces a parsimonious network structure (gain from MASMOD) and provides covariance information about the model error (gain from EM) which is valuable in applications such as state estimation and control. Numerical examples on nonlinear time-series analysis and nonlinear trajectory estimation using FLL models are presented to validate the derived algorithm.


Lactate efflux-induced electrical potential in membrane vesicles of Streptococcus cremoris.
We developed a procedure for isolating membrane vesicles from the homolactic fermentative bacterium Streptococcus cremoris. The membrane vesicles were shown to have a right-side-out orientation by freeze-etch electron microscopy and to be free of cytoplasmic constituents. The membrane vesicles retained their functional properties and accumulated the amino acids L-leucine, L-histidine, and L-alanine in response to a valinomycin-induced potassium diffusion gradient. Studies with these membrane vesicles strongly supported the possibility that there was a proton motive force-generating mechanism by end product efflux (Michels et al., FEMS Lett. 5:357-364, 1979). Lactate efflux from membrane vesicles which were loaded with L-lactate and diluted in a lactate-free medium led to the generation of an electrical potential across the membrane. The results indicate that lactate efflux is an electrogenic process by which L-lactate is translocated with more than one proton.


Prescription opioid use in the rural Appalachia: a community-based study.
The purpose of this study is to describe the sample characteristics and methods for a study of rural medical and nonmedical prescription opioid users with a history of OxyContin use. Snowball sampling was used to recruit 221 rural Appalachian residents. Participants included those under medical supervision for pain (n = 101) as well as those self-reporting nonmedical use of prescription opioids (n = 120). Participants were given an intervieuwer-administered questionnaire. Data relating to demographics, illicit and nonmedical prescription drug use, medical, legal, family, and psychiatric status, as well as pain history were collected. The primary outcomes of interest were differences in past 30 day prescription drug use between pain patients and nonmedical opioid users. A significantly greater proportion of those treated for pain reported using oxycodone and hydrocodone prescribed by a physician in the prior 30 days (p < 0.001); however, more than third of pain participants also reported nonmedical use of OxyContin, methadone, hydrocodone, benzodiazepines, and marijuana in the prior 30 days. A large proportion of rural opioid users who reported being treated for pain also reported nonmedical use ofprescription drugs. Similarly, among the nonmedical users, half of those reported experiencing pain that interfered with their daily life. These results suggest that many rural prescription drug users are being either incorrectly or perhaps inadequately treated for chronic nonmalignant pain. Therefore, developing educational materials and training for rural physicians about pain treatment (including drug seeking behavior) is proposed.


Agonistic or antagonistic mucosal-associated invariant T (MAIT) cell activity is determined by the 6-alkylamino substituent on uracil MR1 ligands.
Mucosal-associated invariant T (MAIT) are a subset of innate-like T cells that are activated by uracil ligands presented by MR1. For the first time, we demonstrate that changes to the 6-aminoalkyl chain on uracil agonist 5-OP-RU can determine agonistic or antagonistic MAIT cell activity. Insomuch, a simplified agonist with a functional profile similar to 5-OP-RU, and a new structural class of antagonist that exhibits similar activity to known MAIT cell antagonist Ac-6-FP, were identified.


A report on the First International Workshop for Lupus Anticoagulant Identification.
Recognition that the lupus anticoagulant (LA) is associated with an increased risk for arterial and venous thrombosis, recurrent spontaneous abortions and fetal loss has led to increased laboratory requests for identification of LA. It is of interest not only to laboratory medicine and obstetrics but also to rheumatology, neurology and cardiology. Due to the antibody's heterogeneous expression, no single test confirms its presence. Recent criteria for LA identification include the performance of one or more screening tests to demonstrate LA interference with phospholipid-dependent tests, differential studies to determine the presence of an inhibitor, and confirmatory procedures to prove that the inhibitor is phospholipid dependent. An international workshop was conducted to study a panel of tests for LA identification and to select those most helpful for diagnosis.


Congenital nasal dermoid cysts and fistulas.
Eleven patients who underwent surgical excision of nasal dermoid cysts or fistulas are reported. The patients are discussed according to the aetiology, sex distribution, location on the nose, and possible inheritance. Our surgical results are satisfactory with only one case which required reoperation. We found that late diagnosed cysts had a higher frequency of deep involvement and therefore required more extensive surgery.


Students' response to a Massage & Meditation medical school course elective.
This article was migrated. The article was marked as recommended. Objectives: Due to high incidence of medical student and physician burnout, medical education needs to include skills for life-work balance. Patients complain that clinicians depend on technology during clinic visits, and use less touch. To address this educational need, we designed an 18-hour curriculum that combines massage (to reduce anxiety and teach skillful touch) and meditation (for burnout prevention). We explored whether learning basics of massage and meditation could give medical students tools for self-care and skillful touch. Methods: The curriculum was implemented as an elective at the Medical School since 14 years. We collected 181 anonymous student evaluations and conducted pre-post surveys to evaluate the curriculum. We assess mindful bodily awareness (by Multidimensional Assessment of Interoceptive Awareness questionnaire) and conducted thematic analysis of students' comments. Results: Students appeared highly satisfied with the class (4.94 [Range 1-5]) and reported confidence in being able to apply massage and meditation in their personal and professional life. They commented on the importance of skillful touch and gained more confidence in using touch in clinical care. The pre-post survey showed improvements in interoceptive bodily awareness. Students felt that they developed new skills for self-care and stress management, experienced a sense of community among peers, and stated that the class provided necessary teaching complementary to the mandatory medical school curriculum. Conclusions: A course of Meditation and Massage may be a valuable complementary elective to medical school education, supporting self-care and stress management in preparation for a demanding profession, and may improve palpatory examination skills.


The economic and social burden of compulsive hoarding.
The aim of the present study was to determine the economic and social burden of compulsive hoarding in a large sample of individuals with self-identified hoarding, as well as a separate sample of family members of individuals who hoard. Self-identified hoarding participants (N=864, 94% female, 65% met research criteria for clinically relevant compulsive hoarding) and family informants (N=655, 58% described a relative who appeared to meet research criteria for compulsive hoarding), completed an internet survey. Questions were derived in part from those used in the National Comorbidity Survey (NCS), and when possible, hoarding participants were compared to NCS participants. Compulsive hoarding was associated with an average 7.0 work impairment days in the past month, equivalent to that reported by individuals with psychotic disorders and significantly greater than that reported by female NCS participants with all other anxiety, mood, and substance use disorders. Severity of hoarding predicted the degree of work impairment after controlling for age, sex, and non-psychiatric medical conditions. Hoarding participants were nearly three times as likely to be overweight or obese as were family members. Compared to female NCS participants, hoarding participants were significantly more likely to report a broad range of chronic and severe medical concerns and had a five-fold higher rate of mental health service utilization. Eight to 12% had been evicted or threatened with eviction due to hoarding, and 0.1-3.0% had a child or elder removed from the home. These results suggest that compulsive hoarding represents a profound public health burden in terms of occupational impairment, poor physical health, and social service involvement.


Global potential net primary production predicted from vegetation class, precipitation, and temperature.
Net primary production (NPP), the difference between CO2 fixed by photosynthesis and CO2 lost to autotrophic respiration, is one of the most important components of the carbon cycle. Our goal was to develop a simple regression model to estimate global NPP using climate and land cover data. Approximately 5600 global data points with observed mean annual NPP, land cover class, precipitation, and temperature were compiled. Precipitation was better correlated with NPP than temperature, and it explained much more of the variability in mean annual NPP for grass- or shrub-dominated systems (r2 = 0.68) than for tree-dominated systems (r2 = 0.39). For a given precipitation level, tree-dominated systems had significantly higher NPP (approximately 100-150 g C m(-2) yr(-1)) than non-tree-dominated systems. Consequently, previous empirical models developed to predict NPP based on precipitation and temperature (e.g., the Miami model) tended to overestimate NPP for non-tree-dominated systems. Our new model developed at the National Center for Ecological Analysis and Synthesis (the NCEAS model) predicts NPP for tree-dominated systems based on precipitation and temperature; but for non-tree-dominated systems NPP is solely a function of precipitation because including a temperature function increased model error for these systems. Lower NPP in non-tree-dominated systems is likely related to decreased water and nutrient use efficiency and higher nutrient loss rates from more frequent fire disturbances. Late 20th century aboveground and total NPP for global potential native vegetation using the NCEAS model are estimated to be approximately 28 Pg and approximately 46 Pg C/yr, respectively. The NCEAS model estimated an approximately 13% increase in global total NPP for potential vegetation from 1901 to 2000 based on changing precipitation and temperature patterns.


The direction of glycan synthesis in a bacterial peptidoglycan.
A cell-free membrane preparation from a poorly lytic mutant of Bacillus licheniformis was used to synthesize radioactive peptidoglycan. The product was apparently un-cross-linked. When UDP-N-acetyl[(14)C]glucosamine was used and the final peptidoglycan subjected to Smith degradation, no radioactive glycerol was found. On the other hand, when peptidoglycan labelled with meso-diamino[(14)C]pimelic acid was first hydrolysed in 0.1m-HCl at 60 degrees C for 2h and then subjected to alkaline conditions, radioactive lactyl-peptides were eliminated. The proportion of radioactive lactyl-peptide decreased with increasing time of incorporation. It is concluded that the glycan chains grow by extension at their reducing ends while remaining attached by some linkage labile to mild acid, such as a glycosyl link to undecaprenol pyrophosphate.


The tumour-associated carbonic anhydrases CA II, CA IX and CA XII in a group of medulloblastomas and supratentorial primitive neuroectodermal tumours: an association of CA IX with poor prognosis.
Medulloblastomas (MBs) and supratentorial primitive neuroectodermal tumours (PNETs) are the most common highly aggressive paediatric brain tumours. In spite of extensive research on these tumours, there are only few known biomarkers or therapeutic target proteins, and the prognosis of patients with these tumours remains poor. Our aim was to investigate whether carbonic anhydrases (CAs), enzymes commonly overexpressed in various tumours including glioblastomas and oligodendrogliomas, are present in MBs and PNETs, and whether their expression can be correlated with patient prognosis. We determined the expression of the tumour-associated carbonic anhydrases CA II, CA IX and CA XII in a series of MB/PNET specimens (n = 39) using immunohistochemistry. Endothelial CA II, cytoplasmic CA II, CA IX and CA XII were expressed in 49%, 73%, 23% and 11% of the tumours, respectively. CA II was detected in the neovessel endothelium and the tumour cell cytoplasm. CA IX was mainly expressed in the tumour cells located in perinecrotic areas. CA XII showed the most homogenous distribution within the tumours. Importantly, CA IX expression predicted poor prognosis in both univariate (p = 0.041) and multivariate analyses (p = 0.016). We suggest that CA IX should be considered a potential prognostic and therapeutic target in MBs and PNETs.


[Attitude of patients with peptic ulcer and chronic gastritis to their illness].
A clinicopsychological study of 130 patients with peptic ulcer and chronic gastritis with secretory insufficiency at hospital and out-patient stages of rehabilitation made it possible to reveal an inadequate (neurotic) attitude to disease in most of them. The most common types of personal reaction of the patients to disease were described. A psychiatrist should be necessarily involved in therapeutic-prophylactic measures for these patients with peptic ulcer and chronic gastritis.


Switching behavior, coexistence and diversification: comparing empirical community-wide evidence with theoretical predictions.
Theory shows that the presence of behavioural switching between alternative resources can contribute to coexistence when competitors differ in trophic-related traits. In addition, switching can generate disruptive selection on such traits in a low-diversity community, increasing the number of species. Both of these processes should produce communities in which species differ in their values of the trophic trait, and display corresponding differences in the time-course of their switching from one resource to another. Here we present evidence for widespread switching behaviour for a diverse Mediterranean scrubland bird community. We show that species differ in a beak character related to their relative use of insect and fruit resource channels, and that the timing of switching is correlated with the relative use of resources. These patterns are consistent with theoretical predictions, suggesting a possible role of switching behaviour in promoting avian coexistence and diversification.


Potentially Inappropriate Prescribing in Long-Term Care and its Relationship With Probable Delirium.
This study examined potentially inappropriate prescribing (PIP) of medication and its association with probable delirium among long-term care (LTC) residents in Ontario, Canada. Population-based cross-sectional study using provincial health administrative data, including LTC assessment data via the Resident Assessment Instrument-Minimum Dataset version 2.0 (RAI-MDS 2.0). LTC residents in Ontario between January 1, 2016, and December 31, 2019. We used residents' first RAI-MDS 2.0 assessment in the study period as the index assessment. Probable delirium was identified via the delirium Clinical Assessment Protocol. Medication use in the 2 weeks preceding assessment was captured using medication claims data. PIP was measured using the STOPP/START criteria and 2015 Beers criteria, with residents classified as having 0, 1, 2, or 3+ instances of PIP. Relationships between PIP and probable delirium was assessed via bivariate and multivariable logistic regression models. The study population included 171,190 LTC residents (mean age 84.5 years, 66.8% female, 62.9% with dementia). More than half (51.8%) of residents had 1+ instances of PIP and 21% had 3+ instances of PIP according to the STOPP/START criteria; PIP prevalence was slightly lower when assessed using Beers criteria (36.5% with 1+, 11.1% with 3+). Overall, 3.7% of residents had probable delirium. The prevalence of probable delirium increased as the number of instances of PIP increased, with residents with 3+ instances of STOPP/START PIP being 1.66 times more likely (95% CI 1.56-1.77) to have probable delirium compared to those with no instances of PIP. Similar findings were observed when PIP was measured using the Beers criteria. Central nervous system (CNS)-related PIP criteria showed a stronger association with probable delirium than non-CNS-related PIP criteria. This population-based study highlighted that PIP was highly prevalent in long-term care residents and was associated with an increased prevalence of probable delirium.


Effect of testicular capsulotomy on secretion of testosterone and gonadotrophins in rats.
In order to clarify further the mechanisms underlying the effect of capsulotomy on testicular function, the levels of testosterone, LH and FSH were observed. Intratesticular testosterone levels and LH, FSH levels in the peripheral blood of normal, sham-operated and capsulotomized rats were detected by RIA. After testicular capsulotomy, there was a progressive reduction in the testosterone level in the testicular venous blood together with a progressive increase in the LH and FSH levels in the peripheral blood from approximately 30 days post-capsulotomy. Morphological changes were observed at 5-10 days after capsulotomy, i.e., far ahead of the hormonal changes. The seminiferous tubular damage after testicular capsulotomy was not caused by the reduction in testosterone, and on the contrary, the hormonal change might be secondary to the morphological alterations. The increase in LH level most likely resulted from a negative feedback influence from the lowered testosterone level, while the increase in FSH secretion may be a feedback signal of the damaged seminiferous tubules.


Inheritance of resistance to Aphis glycines in soybean P746 from China.
The soybean aphid (Aphis glycines Matsumura) is one of the most serious pests of soybean (Glycine max [L.] Merrill) worldwide. Aphid resistance genes have been identified. However, little is known about genes for resistance to Chinese soybean aphid strains. The objective of this study was to identify the type of aphid resistance in the soybean cultivar P746 and to determine the inheritance of the resistance. In choice and no-choice tests, significant differences in the average number of aphids and the damage index were observed between P746 and the susceptible cultivar Dongnong 47 11 d and 21 d after aphid infestation. F2 plants and their F2:3 families were tested to identify the mode of inheritance of resistance. The 240 F2 plants segregated into 178 resistant and 62 susceptible plants, which matched an expected 3:1 ratio for inheritance of a single dominant trait. Segregation among F2:3 families also matched a 1:2:1 ratio. These results indicated that a single, dominant gene mediated aphid resistance in P746. This information will be useful to soybean breeders developing antibiosis-resistant soybean cultivars.


Stellar Representation of Non-Gaussian Quantum States.
The so-called stellar formalism allows us to represent the non-Gaussian properties of single-mode quantum states by the distribution of the zeros of their Husimi Q function in phase space. We use this representation in order to derive an infinite hierarchy of single-mode states based on the number of zeros of the Husimi Q function: the stellar hierarchy. We give an operational characterization of the states in this hierarchy with the minimal number of single-photon additions needed to engineer them, and derive equivalence classes under Gaussian unitary operations. We study in detail the topological properties of this hierarchy with respect to the trace norm, and discuss implications for non-Gaussian state engineering, and continuous variable quantum computing.


Comparative localization of Dax-1 and Ad4BP/SF-1 during development of the hypothalamic-pituitary-gonadal axis suggests their closely related and distinct functions.
Two nuclear receptors, Ad4BP/SF-1 and Dax-1, are essential regulators for development and function of the mammalian reproductive system. Similarity in expression sites, such as adrenal glands, gonads, pituitary, and hypothalamus, suggests a functional interaction, and the phenotype similarities were manifested in Ad4BP/SF-1-deficient mice and in cases of natural human mutations of Dax-1. In this study, quantitative reverse transcriptase polymerase chain reaction analyses revealed that expression profiles of Dax-1 in embryonic gonads are different between the two sexes and also from those of Ad4BP/SF-1. Immunohistochemical analyses clarified the spatial and temporal expressions of the Dax-1 protein during development of tissues composing the hypothalamic-pituitary-gonadal axis. During gonadal development, Dax-1 occurred after Ad4BP/SF-1 exhibiting a sexually dimorphic expression pattern at indifferent stages, indicating a possibility of Dax-1 involvement in earliest sex differentiation. When cord formation begins in the testis at embryonic day 12.5 (E12.5), Dax-1 was expressed strongly in Sertoli cells, but its expression level markedly decreased in Sertoli cells and increased in interstitial cells between E13.5 and E17.5. In the female, Dax-1 was strongly expressed in the entire ovarian primordium from E12.5 until E14.5, and then its expression level was decreased and limited to cells near the surface epithelium between E17.5 and postnatal day 0 (P0). During postnatal development of the testis, the variable staining of Dax-1 in Sertoli cells was detected as early as P7 and Dax-1-expressing Leydig cells became rare. In the postnatal ovary, Dax-1 expression was detected in granulosa cells with variable staining intensity, and occasionally in interstitial cells. During pituitary organogenesis, Dax-1 but not Ad4BP/SF-1 was expressed in the dorsal part of Rathke's pouch from E9.5. Later in development after E14.5, the distribution of Dax-1 overlapped with that of Ad4BP/SF-1, being restricted to gonadotropic cells in the anterior pituitary. In the ventromedial hypothalamus (VMH), Dax-1 and Ad4BP/SF-1 were mostly colocalized throughout the embryonic and postnatal development. Thus, the coexpression of Dax-1 and Ad4BP/SF-1 indicates their closely related functions in the development of the reproductive system. Furthermore, we noticed the presence of cells that express Dax-1 but not Ad4BP/SF-1, further indicating additional functions of Dax-1 in an Ad4BP/SF-1-independent molecular mechanism.


Diversity of Evoked Astrocyte Ca2+ Dynamics Quantified through Experimental Measurements and Mathematical Modeling.
Astrocytes are a major cell type in the mammalian brain. They are not electrically excitable, but generate prominent Ca2+ signals related to a wide variety of critical functions. The mechanisms driving these Ca2+ events remain incompletely understood. In this study, we integrate Ca2+ imaging, quantitative data analysis, and mechanistic computational modeling to study the spatial and temporal heterogeneity of cortical astrocyte Ca2+ transients evoked by focal application of ATP in mouse brain slices. Based on experimental results, we tune a single-compartment mathematical model of IP3-dependent Ca2+ responses in astrocytes and use that model to study response heterogeneity. Using information from the experimental data and the underlying bifurcation structure of our mathematical model, we categorize all astrocyte Ca2+ responses into four general types based on their temporal characteristics: Single-Peak, Multi-Peak, Plateau, and Long-Lasting responses. We find that the distribution of experimentally-recorded response types depends on the location within an astrocyte, with somatic responses dominated by Single-Peak (SP) responses and large and small processes generating more Multi-Peak responses. On the other hand, response kinetics differ more between cells and trials than with location within a given astrocyte. We use the computational model to elucidate possible sources of Ca2+ response variability: (1) temporal dynamics of IP3, and (2) relative flux rates through Ca2+ channels and pumps. Our model also predicts the effects of blocking Ca2+ channels/pumps; for example, blocking store-operated Ca2+ (SOC) channels in the model eliminates Plateau and Long-Lasting responses (consistent with previous experimental observations). Finally, we propose that observed differences in response type distributions between astrocyte somas and processes can be attributed to systematic differences in IP3 rise durations and Ca2+ flux rates.


Characterization of New Allergens from the Venom of the European Paper Wasp Polistes dominula.
Discriminating Polistes dominula and Vespula spp. venom allergy is of growing importance worldwide, as systemic reactions to either species' sting can lead to severe outcomes. Administering the correct allergen-specific immunotherapy is therefore a prerequisite to ensure the safety and health of venom-allergic patients. Component-resolved diagnostics of Hymenoptera venom allergy might be improved by adding additional allergens to the diagnostic allergen panel. Therefore, three potential new allergens from P. dominula venom-immune responsive protein 30 (IRP30), vascular endothelial growth factor C (VEGF C) and phospholipase A2 (PLA2)-were cloned, recombinantly produced and biochemically characterized. Sera sIgE titers of Hymenoptera venom-allergic patients were measured in vitro to assess the allergenicity and potential cross-reactivity of the venom proteins. IRP30 and VEGF C were classified as minor allergens, as sensitization rates lay around 20-40%. About 50% of P. dominula venom-allergic patients had measurable sIgE titers directed against PLA2 from P. dominula venom. Interestingly, PLA2 was unable to activate basophils of allergic patients, questioning its role in the context of clinically relevant sensitization. Although the obtained results hint to a questionable benefit of the characterized P. dominula venom proteins for improved diagnosis of venom-allergic patients, they can contribute to a deeper understanding of the molecular mechanisms of Hymenoptera venoms and to the identification of factors that determine the allergenic potential of proteins.


New mutations in MID1 provide support for loss of function as the cause of X-linked Opitz syndrome.
Opitz syndrome (OS) is a genetically heterogeneous malformation disorder. Patients with OS may present with a variable array of malformations that are indicative of a disturbance of the primary midline developmental field. Mutations in the C-terminal half of MID1, an RBCC (RING, B-box and coiled-coil) protein, have recently been shown to underlie the X-linked form of OS. Here we show that the MID1 gene spans at least 400 kb, almost twice the distance originally reported and has a minimum of six mRNA isoforms as a result of the alternative use of 5' untranslated exons. In addition, our detailed mutational analysis of MID1 in a cohort of 15 patients with OS has resulted in the identification of seven novel mutations, two of which disrupt the N-terminus of the protein. The most severe of these (E115X) is predicted to truncate the protein before the B-box motifs. In a separate patient, a missense change (L626P) was found that also represents the most C-terminal alteration reported to date. As noted with other C-terminal mutations, GFP fusion constructs demonstrated that the L626P mutant formed cytoplasmic clumps in contrast to the microtubular distribution seen with the wild-type sequence. Notably, however, both N-terminal mutants showed no evidence of cytoplasmic aggregation, inferring that this feature is not pathognomonic for X-linked OS. These new data and the finding of linkage to MID1 in the absence of a demonstrable open reading frame mutation in a further family support the conclusion that X-linked OS results from loss of function of MID1.


Association of Chorioamnionitis with Cerebral Palsy at Two Years after Spontaneous Very Preterm Birth: The EPIPAGE-2 Cohort Study.
To assess whether chorioamnionitis is associated with cerebral palsy (CP) or death at 2 years' corrected age in infants born before 32 weeks of gestation after spontaneous birth. EPIPAGE-2 is a national, prospective, population-based cohort study of children born preterm in France in 2011; recruitment periods varied by gestational age. This analysis includes infants born alive after preterm labor or preterm premature rupture of membranes from 240/7 to 316/7 weeks of gestation. We compared the outcomes of CP, death at 2 years' corrected age, and "CP or death at age 2" according to the presence of either clinical chorioamnionitis or histologic chorioamnionitis. All percentages were weighted by the duration of the recruitment period. Among 2252 infants born alive spontaneously before 32 weeks of gestation, 116 (5.2%) were exposed to clinical chorioamnionitis. Among 1470 with placental examination data available, 639 (43.5%) had histologic chorioamnionitis. In total, 346 infants died before 2 years and 1586 (83.2% of the survivors) were evaluated for CP at age 2 years. CP rates were 11.1% with and 5.0% without clinical chorioamnionitis (P = .03) and 6.1% with and 5.3% without histologic chorioamnionitis (P = .49). After adjustment for confounding factors, CP risk rose with clinical chorioamnionitis (aOR 2.13, 95% CI 1.12-4.05) but not histologic chorioamnionitis (aOR 1.21, 95% 0.75-1.93). Neither form was associated with the composite outcome "CP or death at age 2." Among infants very preterm born spontaneously, the risk of CP at a corrected age of 2 years was associated with exposure to clinical chorioamnionitis but not histologic chorioamnionitis.


Association between heme oxygenase-1 gene promoter polymorphisms and type 2 diabetes mellitus: a HuGE review and meta-analysis.
Several studies have recently focused on the association between heme oxygenase-1 (HMOX1) gene promoter polymorphisms and susceptibility to type 2 diabetes mellitus; however, results have been conflicting. This systematic Human Genome Epidemiology review and meta-analysis was undertaken to integrate previous findings and summarize the effect size of the association of HMOX1 gene promoter polymorphisms with susceptibility to type 2 diabetes. The authors retrieved all studies matched to search terms from the PubMed/MEDLINE, EMBASE, and ISI Web of Science databases that had been published through December 31, 2009. The articles were then checked independently by 2 investigators according to the eligibility and exclusion criteria. For all alleles and genotypes, odds ratios were pooled using either fixed-effects or random-effects models. An increased odds ratio for type 2 diabetes was observed in persons with the (GT)(n) L (long) allele as compared with those with the (GT)(n) S (short) allele (odds ratio = 1.12, 95% confidence interval: 1.02, 1.24; P = 0.02). Furthermore, the diabetes odds ratio for persons with the LL genotype, versus those with the SS genotype, was significantly increased (odds ratio = 1.25, 95% confidence interval: 1.04, 1.50; P = 0.02). Persons carrying longer (GT)(n) repeats in the HMOX1 gene promoter may have a higher risk of type 2 diabetes.


Myelin-specific CD8+ T cells exacerbate brain inflammation in CNS autoimmunity.
Multiple sclerosis (MS) is an inflammatory, demyelinating disease of the CNS. Although CD4+ T cells are implicated in MS pathogenesis and have been the main focus of MS research using the animal model experimental autoimmune encephalomyelitis (EAE), substantial evidence from patients with MS points to a role for CD8+ T cells in disease pathogenesis. We previously showed that an MHC class I-restricted epitope of myelin basic protein (MBP) is presented in the CNS during CD4+ T cell-initiated EAE. Here, we investigated whether naive MBP-specific CD8+ T cells recruited to the CNS during CD4+ T cell-initiated EAE engaged in determinant spreading and influenced disease. We found that the MBP-specific CD8+ T cells exacerbated brain but not spinal cord inflammation. We show that a higher frequency of monocytes and monocyte-derived cells presented the MHC class I-restricted MBP ligand in the brain compared with the spinal cord. Infiltration of MBP-specific CD8+ T cells enhanced ROS production in the brain only in these cell types and only when the MBP-specific CD8+ T cells expressed Fas ligand (FasL). These results suggest that myelin-specific CD8+ T cells may contribute to disease pathogenesis via a FasL-dependent mechanism that preferentially promotes lesion formation in the brain.


Tensile failure of C2 pedicles and of subsequent direct repair in a porcine model.
This repeated-measures biomechanical study evaluated the tensile force required to cause bipedicular (hangman's) fractures in isolated porcine C2 specimens, and the subsequent force to failure after direct fracture repair with bipedicular lag screws. To assess the pullout strength of direct lag screw fixation of hangman's fracture, relative to the strength of the intact specimens. Clinical studies have reported successful treatment of hangman's fractures by direct screw repair followed by a collar after surgery. However, to the authors' best knowledge, there has not yet been a biomechanical analysis of the force required for screw pullout after direct repair. Of 60 mounted porcine C2 specimens subjected to tensile anteroposterior force, hangman's fracture occurred in 15 cases, 12 of which were fixed with bipedicular 4.0-mm lag screws. These fixed specimens were retested to failure in the same manner. Most specimens had laminar fractures after the application of tensile force, with 15 of 60 (25%) showing bipedicular fractures. The force to bipedicular failure was 3259.1 +/- 148.5 N (mean +/- standard error of the mean). After screw fixation, the force to failure of the same specimens was 882.0 +/- 108.5 N (mean +/- standard error of the mean), or 27.3% of the intact bone. The pullout strength was substantial (882 N), although the relative strength of fixation was only 27.3% of the fracture strength shown by the intact specimens. The findings are discussed in relation to previous studies. To the authors' best knowledge, this is the first study to examine screw pullout forces after direct repair of hangman's fracture.


Acceptability and appropriateness of a perinatal depression preventive group intervention: a qualitative analysis.
Perinatal depression is a prevalent public health concern. Although preventive interventions exist, there is limited literature on the acceptability and appropriateness of these interventions, especially those delivered by paraprofessionals. The Mothers and Babies Program (MB) is a group-based perinatal depression preventive intervention delivered prenatally. A cluster-randomized controlled trial examined the acceptability, appropriateness, and effectiveness of MB delivered by mental health professionals compared to paraprofessional staff from home visiting programs. The full study enrolled 874 pregnant women. Fifty-three facilitators were trained and delivered the MB intervention to women in one of seven states in the United States. Semi-structured interviews were attempted with a randomly-selected subset of the full sample of pregnant women who received the MB intervention and with all facilitators. Specifically, interviews were conducted with 88 women who received the MB group intervention (45 in the paraprofessional-led arm and 43 in the mental health professional-led arm) and 46 women who facilitated the groups (27 home visiting staff and 19 mental health professionals). Interviews were conducted over the phone in English or Spanish and audio recorded. The recordings were translated into English, as needed, and transcribed. Thematic analysis was conducted using NVIVO to identify key themes related to intervention acceptability and appropriateness. Similarities and differences between study arms were explored. Clients and facilitators found the MB content and group format acceptable. Challenges included maintaining group attendance, transportation issues, and managing group discussion. Overall, facilitators found the intervention appropriate for pregnant clients with some challenges presented for clients in crisis situations, experiencing housing instability, and with literacy and learning challenges. Participants provided suggestions for improvement, both for the course content and implementation. There were no significant differences found between study arms. Overall, clients and facilitators enjoyed MB irrespective of study arm, and facilitators found the intervention appropriate for the population. These findings add to the qualitative literature on perinatal depression preventive interventions, specifically those delivered by paraprofessionals. This trial is registered on ClinicalTrials.gov (Initial post: December 1, 2016; identifier: NCT02979444).


Mavrilimumab, a human monoclonal antibody targeting GM-CSF receptor-α, in subjects with rheumatoid arthritis: a randomised, double-blind, placebo-controlled, phase I, first-in-human study.
To evaluate the safety, tolerability, pharmacokinetic and pharmacodynamic profiles of mavrilimumab, a human monoclonal antibody targeting the granulocyte-macrophage colony-stimulating factor receptor-α, in subjects with rheumatoid arthritis (RA). A randomised, double-blind, placebo-controlled, dose-escalating phase I study in subjects with RA who received stable methotrexate treatment for ≥3 months before enrolment. received single intravenous escalating doses of mavrilimumab (0.01-10.0 mg/kg) or placebo. 32 subjects were enrolled in this study (1 unblinded subject at 0.01 mg/kg and another at 0.03 mg/kg were followed by five sequential double-blinded cohorts, n=6 each, treated with 0.1, 0.3, 1.0, 3.0 and 10.0 mg/kg, respectively). Adverse events were mild or moderate and were reported with similar frequency across all treatment cohorts. One subject (10.0 mg/kg) experienced moderate face and neck urticaria during infusion that resolved with symptomatic treatment. Systemic clearance of mavrilimumab approached that of endogenous IgG at doses >1.0 mg/kg; pharmacodynamic activity was confirmed in the 1.0 and 3.0 mg/kg cohorts by suppression of suppressor of cytokine signalling 3 mRNA transcripts. In exploratory analyses, reductions of acute phase reactants were observed in subjects with elevated C-reactive protein (>5 mg/l) and erythrocyte sedimentation rate (≥20.0 mm/h) at baseline. No significant change in Disease Activity Score 28-joint assessment (DAS28) was seen in any of the cohorts. In mavrilimumab-treated subjects (n=15) with baseline DAS28 >3.2, mean disease activity (DAS28) was significantly reduced at 4 weeks. In this first-in-human study, mavrilimumab showed preliminary evidence of pharmacodynamic activity. Importantly, the safety and pharmacokinetic profiles of mavrilimumab support further clinical studies in RA. NCT00771420.


[Use of the Decatron gamma therapeutic apparatus in treating cervical cancer].
Since August 1974 to November 1978 95 patients with cancer of the uterine servix were given high-dose-rate afterloading therapy which was carried out on a "Decatron" machine with a distant control. The dosage regimes in high-dose-rate afterloading therapy and in the routine intracavitary gamma therapy are reported. The immediate results of the treatment are shown comparatively as well as variations in the incidence of early and late radiation reactions.


Aeromonas-related diarrhoea in Nasarawa, Nigeria.
Two hundred and fifty volunteer patients attending 5 major hospitals in Nasarawa town, Nasarawa State, Nigeria were involved in this study to determine the prevalence of Aeromonas spp in persons with diarrhoea. The study population consisted of 133 males and 117 females between the ages of 0-70 years. Stool samples (148 diarrhoeal and 102 non-diarrhoeal) were analysed for the presence of Aeromonas spp. using standard bacteriological methods. The isolates were also subjected to antimicrobial susceptibility testing using the disc diffusion method. Four (1.60%) of the 250 stool samples were positive for Aeromonas spp. Three (2.03%) of the isolates were recovered from diarrhoeal specimens and 1 (0.98%) from non-diarrhoeal (control) samples. The difference was statistically significant (P < 0.05). The highest numbers of isolates 3 (3.66%) were recovered from age group 0-10 years while age group 61-70 years yielded 1 (14.29%). All isolates were found to be Aeromonas hydrophilia. The isolates were all sensitive to tetracycline, gentamicin, chloramphenicol, cotrimoxazole and streptomycin but resistant to penicillin and ampicillin. Other enteropathogens isolated were Shigella spp 5 (2.0%) and Salmonella spp 2 (0.8%). This study has shown that a small percentage of gastroenteritis can be attributed to Aeromonas hydrophilia.


Autonomic function, postprandial hypotension and falls in older adults at one year after critical illness.
Postprandial hypotension occurs frequently in older survivors of critical illness at 3 months after discharge. We aimed to determine whether postprandial hypotension and its predictors - gastric dysmotility and cardiovascular autonomic dysfunction - persist or resolve as older survivors of critical illness recover, and whether postprandial hypotension after intensive care unit (ICU) discharge is associated with adverse outcomes at 12 months. Prospective observational study. Tertiary medical-surgical ICU. Older adults (aged ≥ 65 years) who had been studied 3 months after ICU discharge and who returned for a follow-up study at 12 months after discharge. On both occasions after fasting overnight, participants consumed a 300 mL drink containing 75 g glucose, radiolabelled with 20 MBq 99mTcphytate. Blood pressure, heart rate, blood glucose concentration and gastric emptying rate were measured concurrently before and after ingestion of the drink. Falls, quality of life, hospitalisation and mortality rates were also quantified. Out of 35 older adults studied at 3 months, 22 returned for the follow-up study at 12 months. Postprandial hypotension was evident in 29% of participants (95% CI, 14-44%) at 3 months and 10% of participants (95% CI, 1-30%) at 12 months. Postprandial hypotension at 3 months was associated with a more than threefold increase in the risk of falls in the year after ICU discharge (relative risk, 3.7 [95% CI, 1.6-8.8]; P = 0.003). At 12 months, gastric emptying was normal (mean time taken for 50% of gastric contents to empty, 101.6 [SD, 33.3] min) and cardiovascular autonomic dysfunction prevalence was low (9% [95% CI, 1-29%]). In older adults who were evaluated 3 and 12 months after ICU discharge, postprandial hypotension at 3 months was associated with an increased risk of subsequent falls, but the prevalence of postprandial hypotension decreased with time.


Attendance at day care centers increases the risk of childhood pneumonia among the urban poor in Fortaleza, Brazil.
We carried out a case-control study to investigate risk factors for childhood pneumonia in two groups of 650 children aged under two years in the city of Fortaleza, Ceará, Brazil. The cases were children recruited at the main pediatric hospital with a radiological diagnosis of pneumonia, and controls were children of the same age group recruited from the neighbourhood of the cases. In this paper we focus on variables related to childcare practices. Working mothers, proportion of time the mother had worked since the child was born, and use of day care centers emerged as important risk factors with estimated relative risks of 1.58, 1.76 and 5.22, respectively. Also important were the number of children living in the house and presence of grandparents. However, the presence of siblings under two years and the birth order were not associated with pneumonia. All analysis included adjustment for confounding by income, parents' education, and other risk factors as appropriate. This is the first study from a developing country to identify attendance at day care centers as a risk factor for increased childhood morbidity, in this case pneumonia. This finding is of significant public health importance for countries such as Brazil with growing urban populations and an increasing need by mothers to find work outside the home.


Immunological responses to protein, carbohydrate and lipid fractions of Nocardia asteroides in mice.
The protein, polysaccharide and phospholipid constituents of Nocardia asteroides have been partially purified and their immunogenicity studied in mice. Humoral and cellular immune responses were demonstrated against a crude cytoplasmic protein fraction (CPF). Two fractions of CPF were prepared on a Sephadex G-200 column; a high mol. wt fraction, fraction-1(F1) was capable of eliciting both types of immune responses, whereas fraction-2(F2) behaved more like a hapten. Phosphatides elicited only humoral responses whereas polysaccharides were non-immunogenic.


A large response range reflectometric urea biosensor made from silica-gel nanoparticles.
A new silica-gel nanospheres (SiO2NPs) composition was formulated, followed by biochemical surface functionalization to examine its potential in urea biosensor development. The SiO2NPs were basically synthesized based on sol-gel chemistry using a modified Stober method. The SiO2NPs surfaces were modified with amine (-NH2) functional groups for urease immobilization in the presence of glutaric acid (GA) cross-linker. The chromoionophore pH-sensitive dye ETH 5294 was physically adsorbed on the functionalized SiO2NPs as pH transducer. The immobilized urease determined urea concentration reflectometrically based on the colour change of the immobilized chromoionophore as a result of the enzymatic hydrolysis of urea. The pH changes on the biosensor due to the catalytic enzyme reaction of immobilized urease were found to correlate with the urea concentrations over a linear response range of 50-500 mM (R2 = 0.96) with a detection limit of 10 mM urea. The biosensor response time was 9 min with reproducibility of less than 10% relative standard deviation (RSD). This optical urea biosensor did not show interferences by Na+, K+, Mg2+ and NH4+ ions. The biosensor performance has been validated using urine samples in comparison with a non-enzymatic method based on the use of p-dimethylaminobenzaldehyde (DMAB) reagent and demonstrated a good correlation between the two different methods (R2 = 0.996 and regression slope of 1.0307). The SiO2NPs-based reflectometric urea biosensor showed improved dynamic linear response range when compared to other nanoparticle-based optical urea biosensors.


Dynamic real-time microscopy of the urinary tract using confocal laser endomicroscopy.
To develop the diagnostic criteria for benign and neoplastic conditions of the urinary tract using probe-based confocal laser endomicroscopy (pCLE), a new technology for dynamic, in vivo imaging with micron-scale resolution. The suggested diagnostic criteria will formulate a guide for pCLE image interpretation in urology. Patients scheduled for transurethral resection of bladder tumor (TURBT) or nephrectomy were recruited. After white-light cystoscopy (WLC), fluorescein was administered as contrast. Different areas of the urinary tract were imaged with pCLE via direct contact between the confocal probe and the area of interest. Confocal images were subsequently compared with standard hematoxylin and eosin analysis. pCLE images were collected from 66 participants, including 2 patients who underwent nephrectomy. We identified key features associated with different anatomic landmarks of the urinary tract, including the kidney, ureter, bladder, prostate, and urethra. In vivo pCLE of the bladder demonstrated distinct differences between normal mucosa and neoplastic tissue. Using mosaicing, a post hoc image-processing algorithm, individual image frames were juxtaposed to form wide-angle views to better evaluate tissue microarchitecture. In contrast to standard pathologic analysis of fixed tissue with hematoxylin and eosin, pCLE provides real time microscopy of the urinary tract to enable dynamic interrogation of benign and neoplastic tissues in vivo. The diagnostic criteria developed in this study will facilitate adaptation of pCLE for use in conjunction with WLC to expedite diagnosis of urinary tract pathology, particularly bladder cancer.


Sex-specific quantitative trait loci govern susceptibility to Theiler's murine encephalomyelitis virus-induced demyelination.
Susceptibility to Theiler's murine encephalomyelitis virus-induced demyelination (TMEVD), a mouse model for multiple sclerosis (MS), is genetically controlled. Through a mouse-human comparative mapping approach, identification of candidate susceptibility loci for MS based on the location of TMEVD susceptibility loci may be possible. Composite interval mapping (CIM) identified quantitative trait loci (QTL) controlling TMEVD severity in male and female backcross populations derived from susceptible DBA/2J and resistant BALBc/ByJ mice. We report QTL on chromosomes 1, 5, 15, and 16 affecting male mice. In addition, we identified two QTL in female mice located on chromosome 1. Our results support the existence of three linked sex-specific QTL on chromosome 1 with opposing effects on the severity of the clinical signs of TMEV-induced disease in male and female mice.


Metabolomics of World Trade Center-Lung Injury: a machine learning approach.
Biomarkers of metabolic syndrome expressed soon after World Trade Center (WTC) exposure predict development of WTC Lung Injury (WTC-LI). The metabolome remains an untapped resource with potential to comprehensively characterise many aspects of WTC-LI. This case-control study identified a clinically relevant, robust subset of metabolic contributors of WTC-LI through comprehensive high-dimensional metabolic profiling and integration of machine learning techniques. Never-smoking, male, WTC-exposed firefighters with normal pre-9/11 lung function were segregated by post-9/11 lung function. Cases of WTC-LI (forced expiratory volume in 1s <lower limit of normal, n=15) and controls (n=15) were identified from previous cohorts. The metabolome of serum drawn within 6 months of 9/11 was quantified. Machine learning was used for dimension reduction to identify metabolites associated with WTC-LI. 580 metabolites qualified for random forests (RF) analysis to identify a refined metabolite profile that yielded maximal class separation. RF of the refined profile correctly classified subjects with a 93.3% estimated success rate. 5 clusters of metabolites emerged within the refined profile. Prominent subpathways include known mediators of lung disease such as sphingolipids (elevated in cases of WTC-LI), and branched-chain amino acids (reduced in cases of WTC-LI). Principal component analysis of the refined profile explained 68.3% of variance in five components, demonstrating class separation. Analysis of the metabolome of WTC-exposed 9/11 rescue workers has identified biologically plausible pathways associated with loss of lung function. Since metabolites are proximal markers of disease processes, metabolites could capture the complexity of past exposures and better inform treatment. These pathways warrant further mechanistic research.


The temporal association of excessive health expenditure with suicidal ideation among primary income earners: a cross-sectional design using the Korean Welfare Panel Survey (KoWePS).
Excessive health expenditure (EHE) is a global issue for households suffering from high-cost medical conditions, low incomes and limited insurance coverage. After the international financial crisis of 2008, EHE became a social problem in developed countries. Such economic crisis might induce severe mental stress, resulting in suicidal ideation. We used the Korean Welfare Panel Study (KoWePS) from 2011 to 2013 and selected primary income earners, who were defined as practical and economic representatives of households; the total number of analysed samples was 4247 of 5717 households in the database. We only included households that had never experienced EHE before 2011. To examine the temporal relationship between EHE and suicidal ideation, we conducted a logistic regression analysis. Among 4247 participants, 146 (3.4%) experienced suicidal ideation, whereas 4101 (96.6%) did not. One scale of depression score (OR=1.28, CI 1.23 to 1.34, p<0.001) was associated with increased suicidal ideation. Such ideation was influenced to a greater extent by a recent EHE above 10% of disposable income (OR=1.91, CI 1.16 to 3.15, p=0.012) than by either a remote EHE (OR=1.29, CI 0.71 to 2.32) or one in 2011 and 2012 (OR=1.67, CI 1.01 to 2.78, p=0.048). In this study, more recent EHE resulted in more suicidal ideation. In conclusion, we suggest that recent household EHE might be considered as an important factor to prevent suicidal ideation and to improve the mental health of individuals.


β-Diketiminate calcium hydride complexes: the importance of solvent effects.
A series of (DIPPnacnac)CaN(SiMe3)2·S complexes (DIPPnacnac = HC[C(Me)N(2,6-iPr-C6H3)]2; S = solvent) could be obtained by the addition of S = THF, DME or N-Me-morpholine (Morph) to (DIPPnacnac)CaN(SiMe3)2·OEt2 or (DIPPnacnac)CaN(SiMe3)2. Crystal structures for complexes with S = DME and Morph are compared to literature-known structures with S = none, THF or Et2O. Bulkier and weaker Lewis bases like the tertiary amines Et3N, TMEDA and DABCO did not interact with (DIPPnacnac)CaN(SiMe3)2. The reaction of (DIPPnacnac)CaN(SiMe3)2 with PhSiH3 gave conversion to a calcium hydride complex that dismutated in (DIPPnacnac)2Ca and CaH2. The reaction of (DIPPnacnac)CaN(SiMe3)2·S with PhSiH3 gave [(DIPPnacnac)CaH·S]2 for S = THF, Et2O or N-Me-morpholine (Morph). For S = DME, high reaction temperatures were needed and dismutation into (DIPPnacnac)2Ca and CaH2 was observed. Extensive NMR investigations (VT-NMR and PGSE) confirm the dimeric nature of [(DIPPnacnac)CaH·THF]2 in aromatic solvents or in THF. Thermal decomposition of [(DIPPnacnac)CaH·THF]2 (release of H2 at 200 °C) is compared to that of Mg and Zn analogues. Weakly coordinating Et2O in [(DIPPnacnac)CaH·OEt2]2 could be replaced by THF, Morph or DABCO but not with Et3N. The addition of TMEDA led to the formation of CaH2 and unidentified products. The addition of DME led to the decomposition of Et2O and complex [(DIPPnacnac)CaOEt]2 was obtained. Crystal structures of the following compounds are presented: (DIPPnacnac)CaN(SiMe3)2·S (S = Morph, DME), [(DIPPnacnac)CaH·S]2 (S = Et2O, Morph and DABCO) and [(DIPPnacnac)CaOEt]2. Although bulky ligands have long been thought to be the key to the stabilization of calcium hydride complexes, the presence of a polar, strongly coordinating, co-solvent is also crucial.


A representation of an NTCP function for local complication mechanisms.
A mathematical formalism was tailored for the description of mechanisms complicating radiation therapy with a predominantly local component. The functional representation of an NTCP function was developed based on the notion that it has to be robust against population averages in order to be applicable to experimental data. The model was required to be invariant under scaling operations of the dose and the irradiated volume. The NTCP function was derived from the model assumptions that the complication is a consequence of local tissue damage and that the probability of local damage in a small reference volume is independent of the neighbouring volumes. The performance of the model was demonstrated with an animal model which has been published previously (Powers et al 1998 Radiother. Oncol. 46 297-306).


Efficient and Stable Dye-Sensitized Solar Cells Based on a Tetradentate Copper(II/I) Redox Mediator.
The identification of an efficient and stable redox mediator is of paramount importance for commercialization of dye-sensitized solar cells (DSCs). Herein, we report a new class of copper complexes containing diamine-dipyridine tetradentate ligands (L1 = N, N'-dibenzyl- N, N'-bis(pyridin-2-ylmethyl)ethylenediamine; L2 = N, N'-dibenzyl- N, N'-bis(6-methylpyridin-2-ylmethyl)ethylenediamine) as redox mediators in DSCs. Devices constructed with [Cu(L2)]2+/+ redox couple afford an impressive power conversion efficiency (PCE) of 9.2% measured under simulated one sun irradiation (100 mW cm-2, AM 1.5G), which is among the top efficiencies reported thus far for DSCs with copper complex-based redox mediators. Remarkably, the excellent air, photo, and electrochemical stability of the [Cu(L2)]2+/+ complexes renders an outstanding long-term stability of the whole DSC device, maintaining ∼90% of the initial efficiency over 500 h under continuous full sun irradiation. This work unfolds a new platform for developing highly efficient and stable redox mediators for large-scale application of DSCs.


Hepatic metastases of granulosa cells tumour of the ovary.
A case of metastatic granulosa cell tumour of the ovary is reported. Investigations revealed a secondary tumour in segment VI and VII of the liver. Right hepatic resection was performed. Microscopic findings revealed a tumour with histological features identical to that removed eleven years before.


[Role of interprotein interactions in the regulation of the sarcoplasmic reticulum Ca-pump].
The data on the structural state of sarcoplasmic reticulum membranes in skeletal muscles of rabbit were obtained by EPR-spectroscopy, fluorescent analysis and flash-photolysis and discussed in the paper. Comparison of the functional state of Ca-pump and variations in hydrophobic volume and membrane microviscosity permits concluding that thermoinduced anomalies of the enzymic activity are due to changes in the phase state of lipids. It is shown that changes in the physiochemical state of lipids affect the interprotein interactions in the oligomeric Ca-pump structure. In this case ATP weakens the interaction between Ca-pump globules, while a decrease in the hydrophobic membrane volume intensifies it. An assumption is advanced that the modifying ATP effect on Ca-pump is based on an increase in the functional independence of Ca2+-ATPase monomers, and therefore it is under the control of the membrane lipid phase.


Possible involvement of a tetrahydrobiopterin in photoreception for UV-B-induced anthocyanin synthesis in carrot.
Our previous studies of action spectra for UV-B-induced anthocyanin accumulation in cultured carrot cells indicated that a reduced form of pterin, possibly tetrahydrobiopterin, contributes to UV-B photoreception. In this report, we provide additional evidence for the involvement of pterin in UV-B light sensing. UV-B-induced phenylalanine ammonia-lyase (PAL) activity was considerably suppressed by N-acetylserotonin (an inhibitor of tetrahydrobiopterin biosynthesis), and this suppression was partially recovered by adding biopterin or tetrahydrobiobiopterin. In addition, protein(s) specifically bound to biopterin were detected by radiolabeling experiments in N-acetylserotonin-treated cells. Furthermore, diphenyleneiodonium, a potent inhibitor of electron transfer, completely suppressed UV-B-induced PAL activity. These results suggest the occurrence of an unidentified UV-B photoreceptor (other than UVR8, the tryptophan-based UV-B sensor originally identified in Arabidopsis) with reduced pterin in carrot cells. After reexamining published action spectra, we suggest that anthocyanin synthesis is coordinately regulated by these two UV-B sensors.


Evaluation of fibronectin and C-reactive protein levels in patients with sepsis: a case-control study.
Sepsis is a significant health problem with an estimated 750,000 new cases in the USA annually. It is also the third leading cause of death in developed countries, equaling the number of fatalities from acute myocardial infarction. The high sepsis-related mortalities mean there is an urgent need to improve the diagnosis and management of sepsis patients. The aim of this study was the evaluation of fibronectin and C-reactive protein (CRP) plasma levels in patients with sepsis and other infectious diseases without sepsis. In a case-control study, 90 patients with sepsis and 90 patients with other infectious diseases without sepsis were studied. Serum levels of fibronectin and CRP were measured. The data were analyzed by SPSS version 15. The mean levels of fibronectin in the cases and controls were 288.97±89.10 mg/l and 341.24±110.53 mg/l respectively (P=0.001). The mean levels of CRP in the cases and controls were 89.42±54.05 µg/ml and 27.42±25.89 µg/ml respectively (P<0.001). Concerning the source of infection, the mean CRP levels were significantly higher in septic patients with urinary tract infection, pneumonia, and soft tissue infection (P<0.001). Decreased levels of fibronectin and increased levels of CRP may be considered as reliable diagnostic markers for sepsis. Also, CRP could be a better predictive factor for sepsis than fibronectin.


Neuronal mechanisms of voice control are affected by implicit expectancy of externally triggered perturbations in auditory feedback.
Accurate vocal production relies on several factors including sensory feedback and the ability to predict future challenges to the control processes. Repetitive patterns of perturbations in sensory feedback by themselves elicit implicit expectations in the vocal control system regarding the timing, quality and direction of perturbations. In the present study, the predictability of voice pitch-shifted auditory feedback was experimentally manipulated. A block of trials where all pitch-shift stimuli were upward, and therefore predictable was contrasted against an unpredictable block of trials in which the stimulus direction was randomized between upward and downward pitch-shifts. It was found that predictable perturbations in voice auditory feedback led to a reduction in the proportion of compensatory vocal responses, which might be indicative of a reduction in vocal control. The predictable perturbations also led to a reduction in the magnitude of the N1 component of cortical Event Related Potentials (ERP) that was associated with the reflexive compensations to the perturbations. We hypothesize that formation of expectancy in our study is accompanied by involuntary allocation of attentional resources occurring as a result of habituation or learning, that in turn trigger limited and controlled exploration-related motor variability in the vocal control system.


120-W GreenLight laser photoselective vaporization of prostate for benign prostatic hyperplasia: midterm outcomes.
To evaluate the safety and efficacy of 120-W high-performance system (HPS) laser photoselective vaporization of the prostate (PVP) in the treatment of patients with lower urinary tract symptoms secondary to benign prostatic hyperplasia. Two experienced surgeons performed 120-W HPS laser PVP. The baseline characteristics, perioperative data, complications, and postoperative outcomes were evaluated at 3, 6, 12, 24, and 36 months postoperatively. A total of 550 consecutive patients, with a mean age of 67.6 years, underwent PVP with a 120-W HPS laser. The mean prostate volume was 72.93 cm3, with a mean prostate-specific antigen level of 3.57 ng/mL. The mean operative duration and the mean applied energy was 61.3 minutes and 164.06 kJ, respectively. No major complication occurred intraoperatively or postoperatively. The mean follow-up was 17.80 months. Significant improvements were observed postoperatively in the mean International Prostate Symptom Score, quality of life score, maximal urinary flow rate, and postvoid residual urine volume. The mean catheterization time was 18.5 hours. The complications included delayed hematuria in 26 (4.8%), recatheterization in 24 (4.4%), reoperation owing to residual prostatic adenoma in 46 (8.5%), urethral stricture in 19 (3.5%), and bladder neck contracture in 6 (1.1%) patients. PVP with a 120-W HPS laser for benign prostatic hyperplasia has been proved to be a safe and effective procedure for our patients, including those treated with oral anticoagulants. The functional outcome in larger prostates was similar to that in smaller glands.


Intron Length Coevolution across Mammalian Genomes.
Although they do not contribute directly to the proteome, introns frequently contain regulatory elements and can extend the protein coding potential of the genome through alternative splicing. For some genes, the contribution of introns to the time required for transcription can also be functionally significant. We have previously shown that intron length in genes associated with developmental patterning is often highly conserved. In general, sets of genes that require precise coordination in the timing of their expression may be sensitive to changes in transcript length. A prediction of this hypothesis is that evolutionary changes in intron length, when they occur, may be correlated between sets of coordinately expressed genes. To test this hypothesis, we analyzed intron length coevolution in alignments from nine eutherian mammals. Overall, genes that belong to the same protein complex or that are coexpressed were significantly more likely to show evidence of intron length coevolution than matched, randomly sampled genes. Individually, protein complexes involved in the cell cycle showed the strongest evidence of coevolution of intron lengths and clusters of coexpressed genes enriched for cell cycle genes also showed significant evidence of intron length coevolution. Our results reveal a novel aspect of gene coevolution and provide a means to identify genes, protein complexes and biological processes that may be particularly sensitive to changes in transcriptional dynamics.


Efficacy of various naturally occurring caffeic acid derivatives in preventing post-harvest protein losses in forages.
In red clover, oxidation of endogenous o-diphenols by polyphenol oxidase (PPO) inhibits post-harvest proteolyis. This system is transferable to alfalfa by providing PPO (via a transgene) and o-diphenol PPO substrates (via exogenous application). To exploit the PPO system for protein protection, it would be advantageous to produce PPO substrates in alfalfa, which lacks them. We assessed the extent of PPO-mediated proteolytic inhibition by phenolic compounds, especially those whose biosynthesis could be engineered into alfalfa. Tested compounds included o-diphenols (caffeic acid, phaselic acid, chlorogenic acid, clovamide) and monophenols (p-coumaric acid, p-coumaroyl-malic acid). In the presence of PPO, 2 mmol o-diphenol g⁻¹ protein reduced 24 h proteolysis 68-87% (P < 0.001) and as little as 0.25 mmol g⁻¹ protein still decreased 24 h proteolysis 43-60% (P < 0.001). At high concentrations, clovamide inhibited 24 h proteolysis 50% (P < 0.001) in the absence of PPO, likely due to non-PPO oxidation. Monophenol p-coumaric acid did not inhibit 24 h proteolyis, although high levels of its malate ester did exhibit PPO- and oxygen-independent inhibition (37%, P < 0.001). For PPO-mediated proteolytic inhibition, pathways for both phaselic acid and chlorogenic acid may be good targets for engineering into alfalfa. Clovamide may be useful for inhibiting proteolysis without PPO.


Crosslinked cellulose developed by CuAAC, a route to new materials.
This work deals with a novel and simple approach of cellulose reticulation using the Huisgen 1,3-dipolar cycloaddition, also known as a 'click chemistry' reaction, catalysed by copper and developed by Sharpless. This reaction is carried out by the addition of a true alkyne and an azide to form a triazole ring connecting the two polysaccharide chains. The addition of two different functions will allow us to control the crosslinking reaction, to avoid intra-chain reactions and thus to promote the creation of an enhanced three-dimensional network. Azidodeoxycellulose was obtained with a DS of 1.5 from tosyl cellulose. The propargylation reaction in aqueous media leading to propargylcellulose with a DS of 1.3. CuAAC reaction was performed between azidodeoxycellulose and propargylcellulose in a DMSO/H(2)O system using CuSO(4), 5H(2)O/sodium ascorbate as catalytic system. The modified cellulose products were analysed by infrared, NMR and X-ray photoelectron spectroscopies and resulting material was analysed using scanning electron microscopy (SEM).


[Complex-formation of heparin with the plasma diabetogenic factor].
Development of complexes between diabetogenic factor and heparin was shown to be responsible for effective neutralization of the factor activity. The complexes of heparin and the diabetogenic factor were obtained when various rations of the reagents were used; properties of the complexes were studied. The complexes produced, in the ratios of heparin/diabetogenic factor 1:1, 1:3, 1:6, 1:12, did not exhibit the nonenzymatic fibrinolytic activity.


Volatile anticancer drug determination by thermal desorption technique with polydimethylsiloxane-coated macroporous silica adsorbent in gas chromatography-mass spectrometry.
An analytical method for quantifying the volatile anticancer drugs ifosfamide (IF) and cyclophosphamide (CP) in air was developed on the basis of thermal desorption (TD)-gas chromatography-mass spectrometry. Polydimethylsiloxane-coated macroporous silica was used as the adsorbent. The extraction tube was prepared by packing 0.2 g of adsorbent particles into a glass tube. The extraction and desorption efficiencies of the proposed method were quantitatively investigated in this study. The limits of detection of the proposed method for IF and CP were 3.3 ng L-1 at an air sampling volume of 3.0 L (30 min). The sensitivity of the proposed method was compared with using a Tenax TA packed tube that is widely used as the extraction medium in TD analysis. Finally, detection of IF and CP that evaporated from aqueous standard solution was investigated.


HIV Response Interventions that Integrate HIV Molecular Cluster and Social Network Analysis: A Systematic Review.
Due to improved efficiency and reduced cost of viral sequencing, molecular cluster analysis can be feasibly utilized alongside existing human immunodeficiency virus (HIV) prevention strategies. The goal of this paper is to elucidate how HIV molecular cluster and social network analyses are being integrated to implement HIV response interventions. We searched PubMed, Scopus, PsycINFO, and Cochrane Library databases for studies incorporating both HIV molecular cluster and social network data. We identified 32 articles that combined analyses of HIV molecular sequences and social or sexual networks. All studies were descriptive. Six studies described network interventions informed by molecular and social data but did not fully evaluate their efficacy. There is no current standard for incorporating molecular and social network analyses to inform interventions or data demonstrating its utility. More research must be conducted to delineate benefits and best practices for leveraging molecular data for network-based interventions.


[The influence of antimetabolites on Trichomonas vaginalis as an experimental model].
The present study was concerned with the relationship between antimetabolites and Trichomonas vaginalis. In all of the strains (with p-nitrobenzylether of N-acetyldiiodtryrosine) tested, the growth of Trichomonas vaginalis was identical to that of the control series at concentrations up to 2 mg/ml. At higher concentrations a decrease in multiplication was noted. In the experimental series with antitrypsin, from 1 mg/ml produced an inhibiting effect upon the Trichomonas population. Further investigations on the combined inhibition test are envisaged.


Exploiting directed self-assembly and disassembly for off-to-on fluorescence responsive live cell imaging.
A bio-responsive nanoparticle was formed by the directed self-assembly (DSA) of a hydrophobic NIR-fluorophore with poloxamer P188. Fluorophore emission was switched off when part of the nanoparticle, however upon stimulus induced nanoparticle dis-assembly the emission switched on. The emission quenching was shown to be due to fluorophore hydration and aggregation within the nanoparticle and the turn on response attributable to nanoparticle disassembly with embedding of the fluorophore within lipophilic environments. This was exploited for temporal and spatial live cell imaging with a measurable fluorescence response seen upon intracellular delivery of the fluorophore. The first dynamic response, seen within minutes, was from lipid droplets with other lipophilic regions such as the endoplasmic reticulum, nuclear membranes and secretory vacuoles imageable after hours. The high degree of fluorophore photostability facilitated continuous imaging for extended periods and the off to on switching facilitated the real-time observation of lipid droplet biogenesis as they emerged from the endoplasmic reticulum. With an in-depth understanding of the principles involved, further assembly controlling functional responses could be anticipated.


Inhibition of IL-1R1/MyD88 signalling promotes mesenchymal stem cell-driven tissue regeneration.
Tissue injury and the healing response lead to the release of endogenous danger signals including Toll-like receptor (TLR) and interleukin-1 receptor, type 1 (IL-1R1) ligands, which modulate the immune microenvironment. Because TLRs and IL-1R1 have been shown to influence the repair process of various tissues, we explored their role during bone regeneration, seeking to design regenerative strategies integrating a control of their signalling. Here we show that IL-1R1/MyD88 signalling negatively regulates bone regeneration, in the mouse. Furthermore, IL-1β which is released at the bone injury site, inhibits the regenerative capacities of mesenchymal stem cells (MSCs). Mechanistically, IL-1R1/MyD88 signalling impairs MSC proliferation, migration and differentiation by inhibiting the Akt/GSK-3β/β-catenin pathway. Lastly, as a proof of concept, we engineer a MSC delivery system integrating inhibitors of IL-1R1/MyD88 signalling. Using this strategy, we considerably improve MSC-based bone regeneration in the mouse, demonstrating that this approach may be useful in regenerative medicine applications.


TSG-6: a multifunctional protein associated with inflammation.
TSG-6 expression is upregulated in many cell types in response to a variety of proinflammatory mediators and growth factors. This protein is detected in several inflammatory disease states (e.g. rheumatoid arthritis) and in the context of inflammation-like processes, such as ovulation, and is often associated with extracellular matrix remodelling. TSG-6 has anti-inflammatory and chondroprotective effects in various models of inflammation and arthritis, which suggest that it is a component of a negative feedback loop capable of downregulating the inflammatory response. Growing evidence also indicates that TSG-6 acts as a crucial factor in ovulation by influencing the expansion of the hyaluronan-rich cumulus extracellular matrix in the preovulatory follicle. TSG-6 is a member of the Link module superfamily and binds to hyaluronan (a vital component of extracellular matrix), as well as other glycosaminoglycans, via its Link module. In addition, TSG-6 forms both covalent and non-covalent complexes with inter-alpha-inhibitor (a serine protease inhibitor present at high levels in serum) and potentiates its anti-plasmin activity.


Muscular endurance and surface electromyogram in isometric and dynamic exercise.
In nine male volunteers, the endurance time for sustained isometric exercise (right-angle elbow flexion) and dynamic exercise (continuous concentric and eccentric elbow flexions) was measured at different contraction levels. Intermittent isometric exercises were also performed by four of the subjects in whom surface electromyographic elbow flexor recordings were obtained during the three types of exercise. A rapid decrease of the endurance time was seen at contraction levels above 15-20% of the maximum voluntary contraction for both the sustained isometric and dynamic exercise. There were no significant difference between the regression of the endurance time vs. the contraction level for the sustained isometric exercise and that of the dynamic exercise. However, the endurance time was enhanced in the intermittent isometric exercise compared with the sustained isometric exercise. The development of muscle fatigue was well correlated to change of the myoelectric rootmean-square amplitude and the mean power frequency. Differences in exercise did not significantly affect the relation between the time constant of the mean power frequency decrease and the endurance time.


Rationale and design of a randomized trial evaluating an external support device for saphenous vein coronary grafts.
Coronary artery bypass grafting (CABG) is the most common revascularization approach for the treatment of multi-vessel coronary artery disease. While the internal mammary artery is nearly universally used to bypass the left anterior descending coronary artery, autologous saphenous vein grafts (SVGs) are still the most frequently used conduits to grafts the remaining coronary artery targets. Long-term failure of these grafts, however, continues to limit the benefits of surgery. The Cardiothoracic Surgical Trials Network trial of the safety and effectiveness of a Venous External Support (VEST) device is a randomized, multicenter, within-patient trial comparing VEST-supported versus unsupported saphenous vein grafts in patients undergoing CABG. Key inclusion criteria are the need for CABG with a planned internal mammary artery to the left anterior descending and two or more saphenous vein grafts to other coronary arteries. The primary efficacy endpoint of the trial is SVG intimal hyperplasia (plaque + media) area assessed by intravascular ultrasound at 12 months post randomization. Occluded grafts are accounted for in the analysis of the primary endpoint. Secondary confirmatory endpoints are lumen diameter uniformity and graft failure (>50% stenosis) assessed by coronary angiography at 12 months. The safety endpoints are the occurrence of major adverse cardiac and cerebrovascular events and hospitalization within 5 years from randomization. The results of the VEST trial will determine whether the VEST device can safely limit SVG intimal hyperplasia in patients undergoing CABG as treatment for coronary atherosclerotic disease.