[Interest of an iterative specialized rehabilitation after an anterior cruciate ligament reconstruction in high level sport athletes].
The aim of this work was to assess the usefulness of specialized rehabilitation sessions after anterior cruciate ligament reconstruction in high-level athletes participating in regional-, national-, or international-level sports. We conducted a retrospective comparison between two populations: in the first, rehabilitation was limited to the early postoperative period (PO); in the second, rehabilitation sessions were repeated, once in the early postoperative period and again 90 days later (POR). The second rehabilitation period lasted two or three weeks and included an open and closed-chain muscle training program controlled by physical therapists using isokinetic devices. The sessions also included proprioceptive exercises and cardiovascular exercise reconditioning with a therapeutic project developed by the Physical Medicine and Rehabilitation physician in collaboration with other health professionals and taking into consideration the surgical recommendations and the patient's clinical status. A questionnaire was addressed to all patients one year after the operation. The response rate was 55 %. Two groups were created at random: 74 patients were in the PO group and 75 in the POR group. The two populations were comparable in terms of gender (64 men, 10 women in PO versus 57 men and 18 women in POR), sports level (regional, national, international), type of surgery (41 hamsting, 33 bone-patellar tendon-bone in PO and 43 hamstring and 32 bone-patellar tendon-bone in POR) and sports (generally rugby, soccer, handball or ski). Our results were statistically in favor of the group POR in terms of resumption of sports activities: time to return to training (7.6 versus 8.7 months, p=0.03) and time to return to competition (9.06 versus 10.84 months, p=0.007). They were also in favor of the group POR for resumption of sports activities at the former level (52.05 % versus 19.44 %, p=0.001), pain (numerical scale: 1.52 versus 2.03, p=0.021) and subjective impression (IKDC subjective score: 87.58 % versus 81.64 %, p=0.003). There was no significant difference for resumption of training (90.50 % versus 81.69 %, p=0.2) or competition (71.80 % versus 56.76 %, p=0.1) at one year, but the results were close to the level of significance. Adapted preparation before returning to sports activities using a scheme elaborated by specialists (physicians, physical therapists, trainers) provided a statistically significant improvement in time and quality of resumed activity (return to prior level, pain, subjective IKDC score) in this specific population of high-level competition athletes. A larger series would be interesting to check the statistical significance of return to training and competition at one year. Another follow-up beyond one year (1.5 or two years for example) would also provide information on the percentage of definitive return to sports in these two populations.


Clinical and psychological outcomes of receiving a variant of uncertain significance from multigene panel testing or genomic sequencing: a systematic review and meta-analysis.
This study systematically reviewed and synthesized the literature on psychological and clinical outcomes of receiving a variant of uncertain significance (VUS) from multigene panel testing or genomic sequencing. MEDLINE and EMBASE were searched. Two reviewers screened studies and extracted data. Data were synthesized through meta-analysis and meta-aggregation. The search identified 4539 unique studies and 15 were included in the review. Patients with VUS reported higher genetic test-specific concerns on the Multidimensional Impact of Cancer Risk Assessment (MICRA) scale than patients with negative results (mean difference 3.73 [95% CI 0.80 to 6.66] P = 0.0126), and lower than patients with positive results (mean difference -7.01 [95% CI -11.31 to -2.71], P = 0.0014). Patients with VUS and patients with negative results were similarly likely to have a change in their clinical management (OR 1.41 [95% CI 0.90 to 2.21], P = 0.182), and less likely to have a change in management than patients with positive results (OR 0.09 [95% CI 0.05 to 0.19], P < 0.0001). Factors that contributed to how patients responded to their VUS included their interpretation of the result and their health-care provider's counseling and recommendations. Review findings suggest there may be a need for practice guidelines or clinical decision support tools for VUS disclosure and management.


Role of the vastus medialis obliquus in repositioning the patella: a dynamic computed tomography study.
It has been assumed that patellofemoral pain syndrome results from patellar malalignment. The precise role the vastus medialis obliquus plays in mediating the underlying pathologic abnormality is unclear. The morphologic characteristics of the vastus medialis obliquus correlate to patellar malalignment in patients with patellofemoral pain syndrome. Cross-sectional study; Level of evidence, 3. One hundred twelve patients with patellofemoral pain syndrome were studied. Six sets of computed tomography axial images were assessed in which knee flexion was 0 degrees, 15 degrees, or 30 degrees and the quadriceps muscle either relaxed or contracted. Measurements of serial cross-sectional areas of the vastus medialis obliquus and patellar malalignment were made. Correlation and stepwise regression models between the vastus medialis obliquus variables and patellar malalignment (lateral shift and patellar tilt) were calculated. Statistics were calculated on 4 subgroups depending on patellofemoral malalignment type. Significant correlations were found between measures of cross-sectional areas of vastus medialis obliquus and patellar tilt at 0 degrees and 30 degrees of knee flexion. Using a regression model, it was determined that vastus medialis obliquus is predictive of patellar tilt (R(2) = 0.078-0.130). This explanation was most apparent in the subgroup of patients with extreme patellar tilt and lateral shift malalignments (R(2) up to 0.824). There are significant correlations between vastus medialis obliquus variables and patellar malalignments in extended knees of patients with patellofemoral pain syndrome. Vastus medialis obliquus muscle function is important to consider in the rehabilitation of patients with patellofemoral pain syndrome, especially those with extreme patellar tilt and lateral shift malalignments.


[Targeting epidermal growth factor receptor in non-small cell lung cancer: current advances and perspectives].
EGFR tyrosine kinase inhibitors are currently included in the therapeutic armamentarium against advanced NSCLC. However, many questions on the use of anti-EGFR treatment in NSCLC still remain to be answered. Although several biological factors that may help identify those who are likely to respond to EGFR-targeted therapies have been reported, their clinical utility in routine practice remains to be determined. Moreover, the better way to combine EGFR targeted therapies with chemotherapy, new biological agents or loco-regional therapies at earlier stages of the disease is still under investigation. Clearly, the results of ongoing and future trials are required for an appropriate use of this new class of agents in NSCLC patients.


VHL loss of function and its impact on oncogenic signaling networks in clear cell renal cell carcinoma.
Loss of von Hippel-Lindau tumor suppressor gene function occurs in familial and most sporadic clear cell renal cell carcinoma, resulting in the aberrant expression of genes that control cell proliferation, metabolism, invasion and angiogenesis. The molecular mechanisms by which loss of function leads to tumorigenesis are not yet fully defined. The von Hippel-Lindau gene product is part of an ubiquitin ligase complex that targets hypoxia inducible factors for polyubiquitination and proteasomal degradation, linking hypoxia response genes to renal cell carcinoma oncogenesis. Loss von Hippel-Lindau gene function also promotes cell invasiveness in response to hepatocyte growth factor, an important regulator of kidney development and renal homeostasis. Increased cell invasiveness is mediated by another ubiquitin ligase target with relevance to the molecular pathogenesis of renal cell carcinoma: beta-catenin. This discovery and other recent insights into kidney cancer oncogenesis implicate convergent developmental and homeostatic signaling pathways in tumorigenesis, tumor invasiveness and metastasis.


Leishmaniasis recidiva cutis in New World cutaneous leishmaniasis.
Leishmaniasis recidiva cutis (LRC) is rare in New World leishmaniasis. Only seven cases have been reported so far. Four cases are reported here. Parasite diagnosis was performed by classical methods of touch preparations, histopathologic sections, and cultures. In addition, the detection of parasite DNA by the polymerase chain reaction (PCR) was performed in all cases. Parasites were detected by at least one of the classical methods in all primary lesions; however, only the PCR was positive in the recidivant lesions. LRC cases most likely represent a reactivation of an initial infection, probably due to the persistence of parasites in scarred tissue. Although lupoid leishmaniasis (LL) has been used as a synonym of LRC, a clear difference between LRC and LL can be defined as LL is the initial clinical presentation while LRC is a recurrent lesion. The results indicate that it is not appropriate to use these two denominations as synonyms. The designation of LRC should be maintained in order to define recidives occurring at the border of an old scar of cutaneous leishmaniasis, avoiding the confusion with the lupoid form of the disease.


Genetic fine-mapping from summary data using a nonlocal prior improves the detection of multiple causal variants.
Genome-wide association studies (GWAS) have been successful in identifying genomic loci associated with complex traits. Genetic fine-mapping aims to detect independent causal variants from the GWAS-identified loci, adjusting for linkage disequilibrium patterns. We present "FiniMOM" (fine-mapping using a product inverse-moment prior), a novel Bayesian fine-mapping method for summarized genetic associations. For causal effects, the method uses a nonlocal inverse-moment prior, which is a natural prior distribution to model non-null effects in finite samples. A beta-binomial prior is set for the number of causal variants, with a parameterization that can be used to control for potential misspecifications in the linkage disequilibrium reference. The results of simulations studies aimed to mimic a typical GWAS on circulating protein levels show improved credible set coverage and power of the proposed method over current state-of-the-art fine-mapping method SuSiE, especially in the case of multiple causal variants within a locus. https://vkarhune.github.io/finimom/.


[Measuring blood flow and catheterization technic in the acute and chronic dog model].
Metabolic studies under in vivo conditions may require a simultaneous catheterization of various organs. Because of phylogenetic relationships, pigs or dogs are best suitable for metabolic investigations. Organ-specific flow rates and substrate balances can be determined by means of dye dilution techniques (indocyanine green - ICG, para-aminohippuric acid - PAH, bromsulphthalein - BSP). An easy method for catheter insertion under anesthesiological and operative conditions is described.


Preoperative Considerations in Inflammatory Bowel Disease.
Patients with ulcerative colitis and Crohn's disease often present to surgery malnourished and on combination immunosuppression. These factors affect operation selection and postoperative outcomes. Corticosteroids have a well-established detrimental effect on postoperative outcomes, whereas the impact of biologic agents is more controversial. In a patient exposed to these medications, and in the presence of other risk factors, temporary intestinal diversion is likely the best choice. Enteral nutrition may help optimize malnourished patients at high risk of adverse postoperative outcomes.


Inferior vena cava filter presenting as chronic low back pain.
Our purpose is to report a rare complication of an inferior vena cava (IVC) filter with vertebral bone penetration, interval fracture, subsequent endovascular management and outcome. We report a case of an IVC filter embedded within the second lumbar vertebral body and in which one of the primary struts fractured, which presented as chronic low back pain. The filter was retrieved percutaneously approximately 2 years after placement. A fractured small strut remained within the vertebral bone; patient's pain resolved. Symptomatic filter in situ should be retrieved even when fractured.


Evaluation of natural dyes Curcuma longa and Nyctanthes arbor-tristis with different mordants on plant tissues under fluorescence microscopy.
The study reveals the effect of natural dyes Curcuma longa (rhizome) and Nyctanthes arbor-tristis (corolla tube) on various plant tissues under fluorescence microscopy. The results indicated that the auto-fluorescence was seen in some of the tissues of unstained monocot and dicot stem sections. The use of Curcuma longa dye along with different chemical mordants leads to various colors and intensity of fluorescence under different excitation filters (violet: 400-450; blue: 450-500; green: 500-570; yellow: 570-610 and red: 610-750 nm) examined. The extract of Nyctanthes arbor-tristis along with the mordants lead to bluish-orange fluorescence of vascular tissues under violet excitation filter. Among the dyes evaluated, Nyctanthes arbor-tristis showed better fluorescence than the Curcuma longa dye. Hence, the dye extracted from the corolla tube of Nyctanthes arbor-tristis is a potential natural dye and could be used as biological stain for staining plant tissues.


Fungal-bacterial biofilm mediated heavy metal rhizo-remediation.
Heavy metal pollution due to excessive use of chemical fertilizers (CF) causes major damage to the environment. Microbial biofilms, closely associated with the rhizosphere can remediate heavy metal-contaminated soil by reducing plant toxicity. Thus, this study was undertaken to examine the remedial effects of microbial biofilms against contaminated heavy metals. Fungi and bacteria isolated from soil were screened for their tolerance against Cd2+, Pb2+, and Zn2+. Three bacterial and two fungal isolates were selected upon the tolerance index (TI) percentage. Fungal-bacterial biofilms (FBBs) were developed with the most tolerant isolates and were further screened for their bioremediation capabilities against heavy metals. The best biofilm was evaluated for its rhizoremediation capability with different CF combinations using a pot experiment conducted under greenhouse conditions with potatoes. Significantly (P < 0.05), the highest metal removal percentage was observed in Trichoderma harzianum and Bacillus subtilis biofilm under in situ conditions. When compared to the 100% recommended CF, the biofilm with 50% of the recommended CF (50CB) significantly (P < 0.05) reduced soil available Pb2+ by 77%, Cd2+ by 78% and Zn2+ by 62%. In comparison to initial soil, it was 73%, 76%, and 57% lower of Pb2+, Cd2+, and Zn2+, respectively. In addition, 50CB treatment significantly (P < 0.05) reduced the metal penetration into the tuber tissues in comparison with 100 C. Thus, the function of the developed FBB with T. harzianum-B. subtilis can be used as a potential solution to remediate soil polluted with Pb2+ Cd2+ and Zn2+ metal contaminants.


Variations and Classification of Bony Septations of the Jugular Foramen: An Anatomic and Histologic Study With Application to Imaging and Surgery of the Skull Base.
Approaches to the jugular foramen can be challenging. Adding to this difficulty is the potential for a bony septation to occur in the foramen thus subdividing its contents. Although such bony septations in the jugular foramen are known, the anatomic details of these structures have not been studied well. Therefore, the present anatomic study was performed. One hundred adult human skulls (200 sides) underwent evaluation for the presence or absence of a bony septation within the jugular foramen. The source, morphology, and size were all documented. A classification scheme was developed to better describe the varied types of morphology of the jugular foramen bony septa. Select bony septations were submitted to histologic analysis using hematoxylin and eosin and Masson's trichrome. Bony bridges were found on 8.5% of sides. These were bilateral in 3% of skulls. Eight (47%) were incomplete (type I). Nine sides (53%) were found to have completely articulated bony bridges (type II) and these had articulation between the bony processes as either touching (type IIa), joint-like (type IIb), or completely fused (type IIc) morphologies. Multiple septa were observed on 2.5% of sides and these were classified as type III septa. Histologically, both incomplete and complete septa were found to be composed of normal bone tissue. Our study found significant variations regarding the bony septa of the jugular foramen. Knowledge of this anatomy can be useful for preoperative planning and intraoperative navigation with approaches to the skull base that target pathology of the jugular foramen.


The use of ultrasound in the expectant management of abruptio placentae.
The use of real-time ultrasound and antepartum nonstress testing in the management of abruptio placentae is discussed. In one patient, fetal distress developed when the retroplacental clot volume reached 480 ml. Two cases in which retroplacental clot was less than 480 ml were managed expectantly with the use of ultrasound and antepartum fetal testing, with excellent results.


Protocol: an improved method to quantify activation of systemic acquired resistance (SAR).
Plant responses triggered upon detection of an invading pathogen include the generation of a number of mobile signals that travel to distant tissues and determine an increased resistance in distal, uninfected tissues, a defense response known as systemic acquired resistance (SAR). The more direct means of measuring activation of SAR by a primary local infection is the quantification of pathogen multiplication in distal, systemic sites of secondary infection. However, while such assay provides a biologically relevant quantification of SAR, it is hampered by experimental variation, requiring many repetitions for reliable results. We propose a modification of the SAR assay based on the Arabidopsis-Pseudomonas syringae pathosystem exploiting the knowledge of source-sink relationships (orthostichies), known to centralize SAR-competency to upper leaves in the orthostichy of a lower primary infected leaf. Although many sources of variation such as genotypes of plant and pathogen, inoculation procedure, or environmental conditions are already taken into account to improve the performance of SAR assays, a strict leaf selection based on source-sink relationships is not usually implemented. We show how enacting this latter factor considerably improves data reliability, reducing the number of experimental repetitions for results. Direct selection of leaves for both primary and secondary inoculation exclusively within the orthostichy of the primary infected leaf is a key element on reducing the number of experimental repetitions required for statistically relevant SAR activation results.


Funding health and social services for older people - a qualitative study of care recipients in the last year of life.
This study explores the views of older adults who are receiving health and social care at the end of their lives, on how services should be funded, and describes their health-related expenditure. Qualitative interview study. North West England. 30 people aged 69-93 years, diagnosed with lung cancer, heart failure or stroke and judged by health professionals to be in their last year of life. Sixteen participants lived in disadvantaged areas. Views of older adults on funding of services. Participants expressed a belief in an earned entitlement to services funded from taxation, based on a broad sense of being a good citizen. Irrespective of social background, older people felt that those who could afford to pay for social care, should do so. Sale of assets and use of children's inheritance to fund care was widely perceived as an injustice. The costs of living with illness are a burden, and families are filling many of the gaps left by welfare provision. People who had worked in low-wage occupations were most concerned to justify their current acceptance of services, and distance themselves from what they described as welfare 'spongers' or 'layabouts.' There is a gap between the health and social care system that older adults expect and what may be provided by a reformed welfare state at a time of financial stringencies. The values that underpinned the views expressed--mutuality, care for the most needy, and the importance of working to contribute to society--are an important contribution to the debate on welfare funding.


Development of Antifouling and Bactericidal Coatings for Platelet Storage Bags Using Dopamine Chemistry.
Platelets have a limited shelf life, due to the risk of bacterial contamination and platelet quality loss. Most platelet storage bags are made of a mixture of polyvinyl chloride with a plasticizer, denoted as pPVC. To improve biocompatibility of pPVC with platelets and to inhibit bacterial biofilm formation, an antifouling polymer coating is developed using mussel-inspired chemistry. A copolymer of N,N-dimethylacrylamide and N-(3-aminopropyl)methacrylamide hydrochloride is synthesized and coupled with catechol groups, named DA51-cat. Under mild aqueous conditions, pPVC is first equilibrated with an anchoring polydopamine layer, followed by a DA51-cat layer. Measurements show this coating decreases fibrinogen adsorption to 5% of the control surfaces. One-step coating with DA51-cat does not coat pPVC efficiently although it is sufficient for coating silicon wafers and gold substrates. The dual layer coating on platelet bags resists bacterial biofilm formation and considerably decreases platelet adhesion. A cationic antimicrobial peptide, E6, is conjugated to DA51-cat then coated on silicon wafers and introduces bactericidal activity to these surfaces. Time-of-flight second ion-mass spectroscopy is successfully applied to characterize these surfaces. pPVC is widely used in medical devices; this method provides an approach to controlling biofouling and bacterial growth on it without elaborate surface modification procedures.


Thymidine phosphorylase expression in gastric carcinoma as a marker for metastasis.
Thymidine phosphorylase (dThdPase) is identical to platelet-derived endothelial cell growth factor (PD-ECCF) and has a function of angiogenesis in vitro and in several types of human carcinoma tissues. We have reported that expression of dThdPase was an independent prognostic factor in 116 gastric carcinomas by immunohistochemical analysis. In the present study, we updated the analysis of recurrence in 116 patients with gastric carcinomas to find how dThdPase plays an important role in progression of gastric carcinoma. Expression of dThdPase was significantly involved in the progression and metastasis of gastric carcinoma. Further, the proportion of recurrence of the patients with dThdPase-positive gastric carcinoma (23 out of 50, 46.0%) was significantly higher than that with -negative gastric carcinoma (5 out of 66, 7.6%) (p < 0.05). Interestingly, the proportion of hematogenous metastasis (liver, lung) of the patients with dThdPase-positive gastric carcinoma (8 out of 8, 100%) was significantly higher than that with -negative gastric carcinoma (0 out of 8, 0%)) (p < 0.05). The proportion of peritoneal metastasis of the patients with dThdPase-positive gastric carcinoma (10/13, 76.9%) was also significantly higher than that with -negative gastric carcinoma (3 out of 13, 23.1%)) (p < 0.05). These findings suggested that dThdPase promotes hematogenous and peritoneal metastases in gastric carcinoma. Inhibition of dThdPase may suppress hematogenous and peritoneal metastases in gastric carcinoma and improve prognosis of patients with gastric carcinoma.


Double-blind study to assess the efficacy of chlorproguanil given alone or in combination with chloroquine for malaria chemoprophylaxis in an area with Plasmodium falciparum resistance to chloroquine, pyrimethamine and cycloguanil.
In this study the efficacy of chlorproguanil (20 mg base weekly) was compared in schoolchildren with that of chloroquine (200 mg base weekly) and that of both drugs combined (20 mg base + 200 mg base weekly). The double blind trial was performed in the rice field area of the Ruzizi valley in Burundi, where Plasmodium falciparum is widely resistant to chloroquine, and where pyrimethamine resistance with cycloguanil cross-resistance had been demonstrated. After 17 weeks, when the trial was ended, 60% breakthroughs had been observed among the children taking chloroquine, 72% among those under chlorproguanil and 61% among those under chlorproguanil and chloroquine. In children weighing between 15 and 24 kg, the failure rate was significantly higher in those treated with chlorproguanil than in the group treated with chloroquine. No difference in efficacy was observed in children weighing 25 to 39 kg. There was no significant increase of efficacy when chlorproguanil was given in association with chloroquine. The mean titre of fluorescent antibodies was the same in each treated group on week 5 and week 15. The comparison of these data with the infection rates in non-protected children suggests that malaria could not be prevented with any of the drug regimens utilized in the study.


Reliability of the telephone interview in diagnosing anxiety disorders.
The reliability of psychiatric diagnosis using the Schedule of Affective Disorders and Schizophrenia-Lifetime Version in personal and telephone interviews with 39 subjects was assessed using a 12- to 19-month test-retest design. Interrater reliability was high (kappa, .69 to .84) for the diagnosis of panic disorder, agoraphobia with panic attacks, probable panic disorder, major depression, and alcohol abuse. We conclude that it is possible to reliably make these lifetime diagnoses in a family study using the telephone interview.


Activation of the aryl hydrocarbon receptor by berberine in HepG2 and H4IIE cells: Biphasic effect on CYP1A1.
Berberine has long been considered a candidate for an antimalarial drug. It exerts a plethora of biological activities and has been used in the treatment of diarrhea and gastro-enteritis for centuries. Here we provide evidence that berberine activates the aryl hydrocarbon receptor (AhR) in human hepatoma (HepG2) and rat hepatoma cells stably transfected with a dioxin responsive element fused to the luciferase gene (H4IIE.luc). AhR was activated by high doses of berberine (10-50 microM) after 6 and 24 h of incubation as revealed by CYP1A1 mRNA expression (HepG2) and AhR-dependent luciferase activity (H4IIE.luc). Berberine induced nuclear translocation of AhR-GFP chimera transiently transfected to Hepa1c1c7 cells. In contrast, low doses of berberine (<1 microM) and prolonged times of the treatments (48 h) failed to produce any activation of AhR in H4IIE.luc cell line. HPLC analysis ruled out the hypothesis that the loss of berberine capacity to activate AhR in H4IIE.luc cells is due to metabolic inactivation of the alkaloid. We demonstrate that berberine is a potent inhibitor (IC50=2.5 microM) of CYP1A1 catalytic activity (EROD) in HepG2 cell culture and in recombinant CYP1A1 protein. Collectively, our results imply that while berberine activates the Ah receptor, it is accompanied by inactivation of the catalytic activity of CYP1A1 and occurs at concentrations that exceed those predicted to occur in vivo. Given these data, it appears that activation of the AhR pathway by berberine has a low toxicological potential.


Hormone anchored metal complexes. 1. Synthesis, structure, spectroscopy and in vitro antitumor activity of testosterone acetate thiosemicarbazone and its metal complexes.
Testosterone acetate thiosemicarbazone (TATSC, 17-beta-hydroxyandrost-4-one acetate thiosemicarbazone) was synthesized and characterized by single crystal X-ray structure determination. The copper and platinum complexes of this steroid derivative were synthesized and characterized by spectroscopy and electrochemiatry. The in vitro activity of these compounds against human breast cancer cell line MCF-7 was tested. The highest activity was found for the [Pt(TATSC)Cl(1)] followed by [Cu(TATSC)Cl(2)] and the ligand in compariosn with cisplatin.


Distribution of Onchocerca spp. microfilariae in the dermis of cattle.
A grid was drawn on a lateral half of 10 hides, from cattle infected with both Onchocerca gutturosa and Onchocerca lienalis, which were obtained from an abattoir in central Florida. Paired 7-mm diameter skin cores were taken from 24 grid sites on each hide and microfilariae (mff) extracted to determine their distribution. The only consistent pattern distribution was that mff were recovered from all 10 hides at four sample sites along the ventral midline near the umbilicus. Microfilariae were also frequently found in large numbers along the dorsal cervical midline and in the region of the tarsal and carpal-metacarpal joints.


Localization of magnetic interictal discharges in temporal lobe epilepsy.
Three young adults with intractable complex partial seizures were studied by electroencephalography, magnetoencephalography, and electrocorticography. Interictal electroencephalographic (EEG) spikes for each patient were grouped according to their morphological characteristics and distribution across channels. Mapping of simultaneously recorded magnetoencephalographic signals produced dipolar patterns from which the three-dimensional locations of equivalent current dipoles were calculated, whereas the mapping of EEG spikes showed single regions of electronegativity. The magnetic spikes were localized to the anterotemporal lobe, and the EEG spikes were localized somewhat anterior or posterior to the magnetic spikes. The magnetoencephalographic findings corresponded well with intraoperative electrocorticographic and depth-electrode findings of discharging areas located over the lateral temporal lobe and on the basal and mesial surfaces of the temporal cortex.


[Clinical safety plan in a university hospital complex. Initial diagnosis: study of adverse events].
To establish the incidence of adverse events (AEs) and incidence of patients with AEs in the University Hospital Complex of Albacete (CHUA); to identify and define the AEs which are linked to health care; to analyse avoidable AE and determine their impact; to plan improvement actions. . Retrospective cohort study. Patients registered from 5 November to 19 November, 2007. Any accident or incident reported in the medical record which injured or may have injured the patient. Adverse Events Screening Guide, adapted from the Harvard study. Spanish version of the Modular Review Form (MRF2) for retrospective case record review. Univariate and bivariate analysis and logistic regression model. The incidence of patients with AEs linked to hospital care was 6.8%. The incidence was significantly different depending on: age, presence of intrinsic or extrinsic risk factors (excluding peripheral venous catheter); 8.2% of AE was linked to care; 14.3% to medication; 26.5% to nosocomial infections; 35.7% to technical problems in procedures; 11.2% to diagnosis, and the remaining 4.1% to other types of AEs. In these incidences, 12.2% were considered mild, 78.6% moderate and 8.2% serious. Half (50%) of AEs caused an increase in hospital stay, and in 34.7% cases determined hospitalisation. A total of 63.3% of AEs were considered avoidable. The study of AEs in the CHUA represents an improvement within the hospital quality program. Incidences of patients with AEs and those related to health care fall within the range of those found in the studies where the objective was quality improvement.


Evoked potentials recorded from scalp and spinous processes during spinal column surgery.
Peroneal nerve evoked potentials were simultaneously recorded from scalp and from wire electrodes inserted into lumbar and thoracic spinous processes at multiple levels during surgery for correction of spinal column curvature in 43 patients. Spinal potentials progressively increased in latency rostrally. Over cauda equina and rostral spinal cord initially positive triphasic potentials were recorded. Over caudal spinal cord the response consisted of initial positive-negative diphasic potentials that merged with broad large negative and positive potentials. At rapid rates of stimulation, the initial diphasic component was stable but the subsequent potentials significantly diminished in amplitude. This suggests that the diphasic component reflects presynaptic activity arising in the intramedullary continuations of dorsal root fibers and that the subsequent components reflect largely postsynaptic activity. Scalp recordings at restricted bandpass (30-3000 c/sec) revealed well defined positive and negative potentials with mean peak latencies of 25.9 and 29.9 msec (PV-N1). The amplitudes and latencies of PV-N1 remained relatively stable throughout general anesthesia with halogenated agents which suggests that this component may be a reliable monitor of conduction within spinal cord afferent pathways during spinal surgery. Data are presented which suggest that selective filtering may help to distinguish faster frequency, synchronous axonal events from slower frequency, asynchronous axonal or synaptic events.


Effect of drug metabolism inducer and inhibitor on O,O,S-trimethyl phosphorothioate-induced delayed toxicity in rats.
Oral administration of O,O,S-trimethyl phosphorothioate (OOS), an impurity present in widely used organophosphorus insecticides, causes delayed toxicity in rats, i.e., death occurring as late as 28 days after the treatment. The signs of toxicity include body weight loss (maximum on day 3), red staining around the nose, mouth and eyes, and an increased level of lactate dehydrogenase (LDH) in bronchopulmonary lavage fluid accompanied by morphological alteration of non-ciliated bronchiolar epithelial Clara cells. Pretreatment with phenobarbital, piperonyl butoxide (2 h), SKF 525-A, or small multiple doses of OOS protected against the OOS-induced elevated level of bronchopulmonary lavage LDH, and the other signs of delayed toxicity including morphological alteration of Clara cells. These studies support the view that OOS-induced delayed toxicity is mediated by the cytochrome P-450 dependent metabolism of OOS, and the lung may be the major target organ of delayed toxicity produced by OOS.


The diagnosis and management of cardiovascular disease in cancer patients.
Cardiovascular disease is commonly found in cancer patients. The co-existence of heart disease and cancer in a patient often complicates treatment, because therapy for one disease may negatively affect the outcome of the other disease. In addition, guidelines for the treatment of cardiovascular disease are often based on studies, which exclude patients who have cancer. In this review we will discuss the diagnosis and management of cardiovascular disease in cancer patients. We will focus on cancer-related causes of cardiovascular disease and special treatment options for cardiovascular disease in cancer patients. The cardiac complications of cancer therapy will be discussed according to common syndromes: left ventricular dysfunction, myocardial ischemia, blood pressure changes, thromboembolism, bradyarrhythmias, and prolonged QT interval.


Maternally inherited non-syndromic hearing loss is linked with a novel mitochondrial ND6 gene mutation.
Maternally inherited non-syndromic hearing loss is linked with mitochondrial DNA mutations. This investigation demonstrates the features of a Chinese pedigree suffering from maternally inherited non-syndromic hearing loss. Biochemical characterizations included the measurements ofprotein synthesis levels, membrane potential, and the synthesis of reactive oxygen species (ROS) and adenosine triphosphate (ATP) using cybrid cell lines derived from an affected matrilineal subject and control subject. Non-congenital early or late-onset/development hearing impairment has been observed in 4 of 9 in a family (matrilineal), with different degrees of hearing impairment, ranging from normal to severe. A pedigree's whole mitochondrial genome sequence analysis revealed the homoplasmic m.14502 T > C (I58V) mutation at ND6's isoleucine location-58, and specific mitocchondrial DNA polymorphisms set haplogroups M10 were highly conserved. In vitro models indicated that m.14502 T > C mutation-derived respiratory deficiency decreases ND6 protein synthesis, mitochondrial membrane potential, and ATP synthesis. These mitochondrial dysregulations enhance the generation of ROS in the mutant cells. Identifying nuclear modifiers is essential for elucidating hearing loss's pathogenesis and furnishing novel therapeutic interventions. The m.14502 T > C mutation should be considered an inherited risk factor that can help diagnose. The data of this investigation help counsel families of individuals with hearing loss.


Evaluation of the characteristics of primary iridociliary cysts using ultrasound biomicroscopy at a tertiary care centre.
To evaluate the ultrasound biomicroscopic characteristics of primary iridociliary cysts presenting to a Canadian tertiary care centre. Retrospective study. A total of 189 patients (212 eyes) referred to the Sinai Health System (Toronto) for suspected iris abnormalities. Clinical records of patients referred between March 2016 and October 2019 were reviewed. All patients were evaluated and received a diagnosis of an iridociliary cyst using ultrasound biomicroscopy (UBM). Data were collected for age, sex, involvement (iris vs ciliary body), laterality, size, and location on initial examination and subsequent follow-up. Of the 189 patients (212 eyes) with iridociliary cysts, more were female (65.1%) versus male (34.9%). The highest incidence occurred in females aged 21-30 years (13.2%). The iris pigment epithelium was involved in 84.4%, and only the ciliary body was involved in 3.8%. Both the iris pigment epithelium and the ciliary body were involved in 10.8%. The size of the cysts ranged between 0.5 and 4.41 mm in diameter. Cysts greater than 1 mm in diameter occurred in 78.7%, and 86.8% of cysts occurred unilaterally. Twelve percent were multicystic, and 8.5% were multiloculated, with 1% exhibiting both features. Twenty-three eyes (12.2%) were reviewed at 1 year of follow-up with UBM. Stable iridociliary cysts with no appreciable change in size were seen in 73.9% (n = 17). Iridociliary cyst growth was noted at 4 months in 1 patient. Information regarding iridociliary cysts is not easily available in the literature. UBM is a helpful clinical tool in the evaluation of iris abnormalities. Iridociliary cysts tend to be stable and compatible with a low rate of complications.


Adaptive bias correction for improved subseasonal forecasting.
Subseasonal forecasting-predicting temperature and precipitation 2 to 6 weeks ahead-is critical for effective water allocation, wildfire management, and drought and flood mitigation. Recent international research efforts have advanced the subseasonal capabilities of operational dynamical models, yet temperature and precipitation prediction skills remain poor, partly due to stubborn errors in representing atmospheric dynamics and physics inside dynamical models. Here, to counter these errors, we introduce an adaptive bias correction (ABC) method that combines state-of-the-art dynamical forecasts with observations using machine learning. We show that, when applied to the leading subseasonal model from the European Centre for Medium-Range Weather Forecasts (ECMWF), ABC improves temperature forecasting skill by 60-90% (over baseline skills of 0.18-0.25) and precipitation forecasting skill by 40-69% (over baseline skills of 0.11-0.15) in the contiguous U.S. We couple these performance improvements with a practical workflow to explain ABC skill gains and identify higher-skill windows of opportunity based on specific climate conditions.


Adhesion of cultured human endothelial cells onto methacrylate polymers with varying surface wettability and charge.
The adhesion of human endothelial cells (HEC) onto a series of well-characterized methacrylate polymer surfaces with varying wettabilities and surface charges was studied either in serum-containing (CMS) or in serum-free (CM) culture medium. HEC adhesion in CMS onto (co)polymers of hydroxyethyl methacrylate (HEMA) and methyl methacrylate (MMA) was found to be optimal on the moderately wettable copolymer (mol ratio 25 HEMA/75 MMA). Positively-charged copolymers of HEMA or MMA with trimethylaminoethyl methacrylate-HCl salt (TMAEMA-Cl), both with mol ratios of 85/15 and a negatively-charged copolymer of MMA with methacrylic acid (MAA), mol ratio 85/15, showed high numbers of adhering HEC. In CM, HEC adhered onto the three charged copolymers mentioned above, but neither onto the copolymer of HEMA and MAA (mol ratio 85/15) nor onto the HEMA/MMA co- and homopolymers. Complete cell spreading in CM was only observed on the positively-charged copolymers.


Increased progesterone production during the luteal phase of menstruation may decrease anesthetic requirement.
Besides having important hormonal effects, progesterone has depressant and hypnotic effects on the brain. In this study, we compared women in the follicular phase with low progesterone levels and in the luteal phase with high progesterone levels regarding their anesthetic requirements. Twenty patients with menstrual cycle days from 1 to 10 (follicular group) and 20 patients with menstrual cycle days from 18 to 24 (luteal group) were included in the study. Anesthesia was induced with fentanyl and thiopental; relaxation was secured with rocuronium, and anesthesia was maintained with a mixture of nitrous oxide 2 L/min and oxygen 2 L/min plus sevoflurane. The delivered sevoflurane concentration was adjusted to sustain a constant bispectral index value that averaged 46 in both groups. To determine the progesterone levels, blood samples were taken from all patients before surgery. We found that progesterone levels were 0.86 +/- 0.30 ng/mL in the follicular group and 7.48 +/- 3.86 ng/mL in the luteal group. The minimum alveolar anesthetic concentration (MAC)-hour (MAC-h) value of sevoflurane in the follicular group (1.55 +/- 0.18 MAC-h) was significantly larger than in the luteal group (1.3 +/- 0.13 MAC-h) (P < 0.0001). The sevoflurane requirements were larger in the follicular group during the maintenance phase of anesthesia. In conclusion, high progesterone levels during the luteal phase might be the cause of decreased anesthetic requirement. The aim of this study was to determine the effect of high progesterone levels on anesthetic requirement. We measured progesterone levels before surgery and calculated the sevoflurane dose (MAC-h) required to maintain a constant bispectral index value. The dose of sevoflurane correlated inversely with serum progesterone concentrations.


Neuropsychological effects of ethylene dichloride exposure.
Production of 1,2-dichloroethane (EDC) has increased and exposure to it has been reported to produce adverse effects in animals and CNS effects in humans. A group of 221 EDC exposed hazardous clean-up workers incurred chronic exposure to EDC without protective equipment. A clinical history and the following tests were administered: the WHO Adult Environmental Neurobehavioral Test Battery (AENTB), Wechsler Adult Intelligence Scale (WAIS-III), Wechsler Memory Scale (WMS-III); WRAT 3 Reading, Cancellation H, Trail Making, Stroop, Rey Osterreith, Animal Naming, COWAT, TOMM, Rey 15, Lanthony d-15 Color Vision, and Vistech Contrast Sensitivity. Mood and symptoms were assessed with the SCL90-R, BDI, BAI and IES. The clinical neuropsychological evaluation of these workers indicates lower neuropsychological functioning in the domains of processing speed; attention; cognitive flexibility; motor coordination and speed; verbal memory; verbal fluency; and visuo-spatial abilities. These workers also showed disturbed mood and impaired vision. Dose/response relationships between exposure to EDC and test scores are shown.


Predictors of health-related quality of life and participation after brain injury rehabilitation: The role of neuropsychological factors.
The aims of this longitudinal study were: (1) to assess associations between neuropsychological factors and health-related quality of life (HRQoL) and participation three months after discharge from inpatient acquired brain injury (ABI) rehabilitation; and (2) to determine the best neuropsychological predictor of HRQoL and participation after controlling for demographic and injury-related factors. Patients with ABI (n = 100) were assessed within approximately two weeks of enrolment in inpatient rehabilitation. Predictor variables included demographic and injury-related characteristics and the following neuropsychological factors: active and passive coping, attention, executive functioning, verbal memory, learning potential, depressive symptoms, motivation, extraversion, neuroticism and self-awareness. Bivariate analyses revealed that passive coping, executive functioning, depressive symptoms, extraversion, and neuroticism were significantly associated with HRQoL and/or participation. Neuropsychological factors significantly explained additional variance in HRQoL (18.1-21.6%) and participation (6.9-20.3%) after controlling for demographic and injury-related factors. However, a higher tendency towards passive coping was the only significant neuropsychological predictor (β = -0.305 to -0.464) of lower HRQoL and participation. This study shows that neuropsychological functioning, and in particular passive coping, plays a role in predicting HRQoL and participation after inpatient ABI rehabilitation and emphasises the importance of addressing patients' coping styles in an early phase of ABI rehabilitation.


Mycotoxins in potato tubers infected byFusarium sambucinum.
Potato tubers artificially infected withF. sambucinum were contaminated with diacetoxyscirpenol in concentrations up to 200 μ/tuber. The toxin could also be found in tubers without any disease symptoms. The duration of storage and an increased temperature raised toxin production in infected tubers. Susceptibility of potato cultivars towardsF. sambucinum was well correlated with toxin levels. The concentration of diacetoxyscirpenol in the susceptible cultivar was five times higher compared to the more resistant one. The toxin could not only be found in rotten tuber tissue but also in distant healthy looking parts. There is a gradient in toxin concentrations showing a strong decline with an increasing distance from the infection point. Tissue being 10-15 mm far from the diseased area contained up to 110 μg/kg. Consumers should pay attention to the fact that cutting out the diseased tissue may be not sufficient enough to prevent the intake of mycotoxins.


Comparison of populations of mould species in homes in the UK and USA using mould-specific quantitative PCR.
To compare the populations of 81 mould species in homes in the USA and UK using mould-specific quantitative polymerase chain reaction (MSQPCR) technology. Dust samples were obtained from randomly selected homes in the UK (n=11). The mould populations in British homes were compared with those found in typical homes (no visible mould) in the USA (in the state of Ohio, n=45). Only 13 of 81 species screened showed significantly different concentrations in these two sets of home. Although only a small survey, the results suggest that typical mould profiles in the USA (Ohio) and British homes are very similar. Analysis of 26 mould indicator species revealed that the British homes fell into two clusters, tentatively identified as 'atypical' and 'typical' mould conditions. MSQPCR analysis of dust samples can provide an objective measure of indoor moulds which could lead to better management of their health effects.


Multiplex RNA-based detection of clinically relevant MET alterations in advanced non-small cell lung cancer.
MET inhibitors have shown activity in non-small-cell lung cancer patients (NSCLC) with MET amplification and exon 14 skipping (METΔex14). However, patient stratification is imperfect, and thus, response rates have varied widely. Here, we studied MET alterations in 474 advanced NSCLC patients by nCounter, an RNA-based technique, together with next-generation sequencing (NGS), fluorescence in situ hybridization (FISH), immunohistochemistry (IHC), and reverse transcriptase polymerase chain reaction (RT-PCR), exploring correlation with clinical benefit. Of the 474 samples analyzed, 422 (89%) yielded valid results by nCounter, which identified 13 patients (3%) with METΔex14 and 15 patients (3.5%) with very-high MET mRNA expression. These two subgroups were mutually exclusive, displayed distinct phenotypes and did not generally coexist with other drivers. For METΔex14, 3/8 (37.5%) samples positive by nCounter tested negative by NGS. Regarding patients with very-high MET mRNA, 92% had MET amplification by FISH and/or NGS. However, FISH failed to identify three patients (30%) with very-high MET RNA expression, among which one received MET tyrosine kinase inhibitor treatment deriving clinical benefit. Our results indicate that quantitative mRNA-based techniques can improve the selection of patients for MET-targeted therapies.


High-speed depolymerization at actin filament ends jointly catalysed by Twinfilin and Srv2/CAP.
Purified actin filaments depolymerize slowly, and cytosolic conditions strongly favour actin assembly over disassembly, which has left our understanding of how actin filaments are rapidly turned over in vivo incomplete. One mechanism for driving filament disassembly is severing by factors such as Cofilin. However, even after severing, pointed-end depolymerization remains slow and unable to fully account for observed rates of actin filament turnover in vivo. Here we describe a mechanism by which Twinfilin and Cyclase-associated protein work in concert to accelerate depolymerization of actin filaments by 3-fold and 17-fold at their barbed and pointed ends, respectively. This mechanism occurs even under assembly conditions, allowing reconstitution and direct visualization of individual filaments undergoing tunable, accelerated treadmilling. Further, we use specific mutations to demonstrate that this activity is critical for Twinfilin function in vivo. These findings fill a major gap in our knowledge of cellular disassembly mechanisms, and suggest that depolymerization and severing may be deployed separately or together to control the dynamics and architecture of distinct actin networks.


Functional reorganization of the noradrenergic system after partial fornix section: a behavioral and autoradiographic study.
Previous experiments revealed that the cholinergic deficit in rats with a partial fornix section was accompanied by an increase in turnover of noradrenaline (NE) in the hippocampus. This noradrenergic hyperactivity contributed to the cognitive deficit in lesioned rats, probably by interaction with the cholinergic system. The present experiment examines the reorganization of the noradrenergic system after the damage induced by partial fornix section and attempts to determine if the increase in NE turnover is of locus coeruleus (LC) origin, or if it is a result of local regulation at the noradrenergic terminals. Rats were submitted to knife-cut section of the fornix, resulting in a decrease in choline acetyltransferase activity in the hippocampus, correlated with a significant behavioral deficit in a spatial memory task. Lesioned rats learned a nonspatial memory task normally. Sections of brains of these rats were submitted to quantitative autoradiography. [125I]Iodopindolol binding was assessed in the dorsal and ventral hippocampus to determine availability of beta receptors. This was found to be significantly lower in lesioned rats. [125I]Iodoclonidine was used to determine alpha 2 receptors binding in dorsal and ventral hippocampus and in LC. There was no difference in alpha 2 receptors in LC, a significant decrease in dorsal regions of the hippocampus, and a significant increase in ventral regions. Muscarinic M1 receptors in the hippocampus showed no changes after the lesion.


A novel splice site mutation in gene C2orf37 underlying Woodhouse-Sakati syndrome (WSS) in a consanguineous family of Pakistani origin.
Woodhouse-Sakati Syndrome (WSS) is a rare autosomal recessive multisystemic disorder that is marked by hypogonadism, alopecia, intellectual disability, deafness, diabetes mellitus and progressive extrapyramidal defects. Mutations in the gene C2orf37 are the cause of Woodhouse-Sakati syndrome. In the present study, a four-generation consanguineous family with clinical manifestations of WSS was ascertained from a remote region of Pakistan. Linkage in the family was tested using microsatellite markers linked to several genes involved in producing WSS related phenotypes. Linkage in the family was established to the gene C2orf37, mapped on chromosome 2q22.3-2q35. DNA sequence analysis revealed a novel splice site mutation involving a homozygous G→A transition in the splice donor site of intron 3 (c.321+1G>A) of C2orf37. This study presents a first report of Woodhouse-Sakati syndrome identified in Pakistani population.


Beyond maternal mortality--magnitude, interrelationship, and consequences of women's health, pregnancy-related complications and nutritional status on pregnancy outcomes.
The magnitude of maternal mortality in developing countries and its disparity with similar statistics from the developed world has touched a responsive chord among policy makers and health services program officials. What is not well appreciated, however, is that maternal mortality is only the tip of the iceberg--for every one maternal death, acute obstetrical complications cause suffering in nearly 100 women, 250 women contract a sexually transmitted disease, and 1000 women suffer stunting and/or anemia. All of these problems impact on the pregnancy outcome, both for the woman as well as for the newborn. Through a review of the literature, the magnitude, interrelationships and consequences of these various problems are described. The woman and the newborn are a dyad, a unit; what affects the woman typically affects the fetus and is manifest in the newborn. Safe motherhood programs need to pay attention to both, realizing that interventions aimed at the women can benefit the next generation.


Using specific cytotoxics with a targeted mind.
It is largely known that clinical activity of a given cytotoxic agent may vary between different patients. This suggests that breast cancer sub-types can be identified within the endocrine-resistant cohort, each of them with a specific degree of sensitivity to different cytotoxic drugs. Pre-clinical and early clinical data suggest that in the future some molecular markers might have practical value in predicting cytotoxics activity in the clinical setting. The most relevant evidence is summarized below according to the type of cytotoxic agent: (a) Anthracyclines Topoisomerase II alpha (topo II) gene aberrations (amplification or deletion) and/or topo II protein overexpression seem to predict response to topo II inhibitors such as anthracyclines. Of note, HER-2 amplified tumors have a concomitant topo II gene aberration in approximately 50% of cases. Moreover, the majority of hyper-proliferating tumors carry topo II protein overexpression. Early clinical data suggest the existence of a direct correlation between anthracyclines activity and the presence of topo II gene aberration or topo II protein overexpression. (b) Taxanes Microtubule-associated parameters (MTAP) such as the TAU protein, HER-2 gene amplification, and p-53 gene mutations, have been suggested as potential predictive markers for taxanes. Although early clinical data support pre-clinical experiments, the lack of large prospectively designed clinical studies makes it difficult to draw conclusions on the predictive value of these molecular markers. (c) DNA-damaging agents The BRCA 1 protein seems to play a major role in activating DNA repair mechanisms. Loss-of-function BRCA 1 mutations might lead to a substantial deficit in DNA repair mechanisms. This could ultimately translate into increased tumor sensitivity to DNA-damaging agents such as alkylating compounds and platinum-derivates. Pre-clinical and early clinical data seem to suggest that some BRCA 1 gene mutations might render the tumor more sensitive to DNA-damaging agents and clinical studies have recently been activated to investigate properly this hypothesis. A new generation of ongoing clinical studies and a "focused" use of the gene micro-array technology will hopefully clarify the complex interaction existing between molecular targets and cytotoxic drug activity. This "targeted" approach to chemotherapy might ultimately lead to a more effective strategy in breast cancer medical treatment.


A comparative study of the effect of carbamazepine and valproic acid on the pharmacokinetics and metabolic profile of topiramate at steady state in patients with epilepsy.
To compare the influence of enzyme-inducing comedication and valproic acid (VPA) on topiramate (TPM) pharmacokinetics and metabolism at steady state. Three groups were assessed: (a) patients receiving TPM mostly alone (control group, n =13); (b) patients receiving TPM with carbamazepine (CBZ; n = 13); and (c) patients receiving TPM with VPA (n = 12). TPM and its metabolites were assayed in plasma and urine by liquid chromatography-mass spectrometry (LC-MS). No significant differences were found in TPM oral (CL/F) and renal (CL(r)) clearance between the VPA group and the control group. Mean TPM CL/F and CL(r) were higher in the CBZ group than in controls (2.1 vs. 1.2 L/h and 1.1 vs. 0.6L/h, respectively; p < 0.05). In all groups, the urinary recovery of unchanged TPM was extensive and accounted for 42-52% of the dose (p > 0.05). Urinary recovery of 2,3-O-des-isopropylidene-TPM (2,3-diol-TPM) accounted for 3.5% of the dose in controls, 2.2% in the VPA group (p > 0.05), and 13% in the CBZ group (p < 0.05). The recovery of 10-hydroxy-TPM (10-OH-TPM) was twofold higher in the CBZ group than in controls, but it accounted for only <2% of the dose. The plasma concentrations of TPM metabolites were severalfold lower than those of the parent drug. Renal excretion remains a major route of TPM elimination, even in the presence of enzyme induction. The twofold increase in TPM-CL/F in patients taking CBZ can be ascribed, at least in part, to stimulation of the oxidative pathways leading to formation of 2,3-diol-TPM and 10-OH-TPM. VPA was not found to have any clinically significant influence on TPM pharmacokinetic and metabolic profiles.


10-Year oncological outcome report after second conservative treatment for ipsilateral breast tumor event.
To analyze long-term oncological outcome after 2nd conservative treatment (2ndCT) for patients with ipsilateral 2nd ipsilateral breast tumor event (2ndIBTE). In this retrospective observational study (N°F20210402152843), patients with 2ndIBTE underwent 2ndCT (lumpectomy + tumor bed re-irradiation). 3rdIBTE (3rdIBTE-FS), regional relapse- (RRFS) and metastatic disease- (MD-FS) free survivals as well as disease-free (DFS), specific (SS) and overall (OS) survival were analyzed. Late toxicity was reported. Between 09/2000 and 04/2022, 244 patients presented a 2ndIBTE and underwent a 2ndCT. Among them, 113 pts with a minimum follow-up of 60 months were analyzed. Median time interval between 1st and 2ndIBTE was 13.5 years [2-35]. Median 2ndIBTE age was 66.2 years [31-85]. 2ndIBTE were adenocarcinomas (77 %). Tumor size was < 20 mm (86.7 %). 2ndIBTE were grade 1/2 (75 %), with positive hormonal receptor (85 %) and clear surgical margins (no ink on tumor, 90.3 %). In the APBI classification, 21 pts were high-risk (18.6 %), while 77 % were Luminal A/BHer2-. With a MFU of 121.5 months [CI95% 111.7-129.6], 10-year 3rdIBTE-FS was 89 % [83-96]. Then-year RRFS, MDFS, DFS, SS and OS were 94 % [89-100], 89 % [83-96], 78 % [70-87], 95 % [91-100] and 94 % [90 -99] respectively. In multivariate analysis, APBI classification (high-risk; HR2.66 [1.01-7.1], p = 0.049) and tumor size (≥20 mm; HR2.64 [1.02-6.8], p = 0.045) were considered independent prognostic factors for DFS.Ninety-seven late complications were observed (fibrosis 64 %) with 6.2 % G ≥ 3 late toxicity. Cosmetic outcome was excellent/good in 91.2 %. With long follow-up, 2ndIBTE managed with 2ndCT allows second breast preservation without oncological outcome compromise and acceptable G ≥ 3 toxicity.


A selective and sensitive D-xylose electrochemical biosensor based on xylose dehydrogenase displayed on the surface of bacteria and multi-walled carbon nanotubes modified electrode.
A novel Nafion/bacteria-displaying xylose dehydrogenase (XDH)/multi-walled carbon nanotubes (MWNTs) composite film-modified electrode was fabricated and applied for the sensitive and selective determination of d-xylose (INS 967), where the XDH-displayed bacteria (XDH-bacteria) was prepared using a newly identified ice nucleation protein from Pseudomonas borealis DL7 as an anchoring motif. The XDH-displayed bacteria can be used directly, eliminating further enzyme-extraction and purification, thus greatly improved the stability of the enzyme. The optimal conditions for the construction of biosensor were established: homogeneous Nafion-MWNTs composite dispersion (10 μL) was cast onto the inverted glassy carbon electrode, followed by casting 10-μL of XDH-bacteria aqueous solution to stand overnight to dry, then a 5-μL of Nafion solution (0.05 wt%) is syringed to the electrode surface. The bacteria-displaying XDH could catalyze the oxidization of xylose to xylonolactone with coenzyme NAD(+) in 0.1M PBS buffer (pH7.4), where NAD(+) (nicotinamide adenine dinucleotide) is reduced to NADH (the reduced form of nicotinamide adenine dinucleotide). The resultant NADH is further electrocatalytically oxidized by MWNTs on the electrode, resulting in an obvious oxidation peak around 0.50 V (vs. Ag/AgCl). In contrast, the bacteria-XDH-only modified electrode showed oxidation peak at higher potential of 0.7 V and less sensitivity. Therefore, the electrode/MWNTs/bacteria-XDH/Nafion exhibited good analytical performance such as long-term stability, a wide dynamic range of 0.6-100 μM and a low detection limit of 0.5 μM D-xylose (S/N=3). No interference was observed in the presence of 300-fold excess of other saccharides including D-glucose, D-fructose, D-maltose, D-galactose, D-mannose, D-sucrose, and D-cellbiose as well as 60-fold excess of L-arabinose. The proposed microbial biosensor is stable, specific, sensitive, reproducible, simple, rapid and cost-effective, which holds great potential in real applications.


Nocardia sp. carboxylic acid reductase: cloning, expression, and characterization of a new aldehyde oxidoreductase family.
We have cloned, sequenced, and expressed the gene for a unique ATP- and NADPH-dependent carboxylic acid reductase (CAR) from a Nocardia species that reduces carboxylic acids to their corresponding aldehydes. Recombinant CAR containing an N-terminal histidine affinity tag had K(m) values for benzoate, ATP, and NADPH that were similar to those for natural CAR, and recombinant CAR reduced benzoic, vanillic, and ferulic acids to their corresponding aldehydes. car is the first example of a new gene family encoding oxidoreductases with remote acyl adenylation and reductase sites.


Studies on heart failure in old age (Part II). Hemodynamic effects of propranolol and isoproterenol in elderly patients with heart failure.
Hemodynamic responses to propranolol and isoproterenol were examined in elderly patients with heart failure. The results obtained are as follows: 1. Patients with mild heart failure showed greater reduction than control group in heart rate and cardiac output after intravenous propranolol. These enhanced hemodynamic responses to propranolol would be the evidence of increased adrenergic activity even in mild heart failure. 2. Intravenous propranolol in the small dosage of 0.03 mg/kg showed only a negligible hemodynamic deterioration even in patients with heart failure. 3. Hemodynamic responses to beta-adrenergic stimulator, isoproterenol, were depressed in severe heart failure.


Hereditary or Not? Understanding Serrated Polyposis Syndrome.
To present the current understanding of the diagnosis, management, and potential genetic causes of serrated polyposis syndrome. The clinical criteria for serrated polyposis syndrome was recently updated and now includes individuals with five or more serrated polyps proximal to the rectum that are 5 mm in size or greater and at least two that are 10 mm in size of greater as well as individuals with 20 or more serrated polyps throughout the colon with at least five proximal to the rectum. There is a significant risk for colon cancer in first-degree relatives of individuals with serrated polyposis syndrome. However, less than 3% of serrated polyposis syndrome cases are explained by identifiable germline mutations, with mutations in RNF43 being the only currently validated genetic cause. Serrated polyposis syndrome is rarely explained by identifiable germline mutations, but there remains an increased risk for colorectal cancer in first-degree relatives. Referral for genetic counseling and testing is recommended for individuals with serrated polyposis syndrome and a personal history of coexisting adenomatous polyposis or with a concerning family history and can be considered for all individuals with serrated polyposis syndrome. Close endoscopic surveillance of those with serrated polyposis syndrome and their first-degree relatives is recommended. Continued efforts at identifying hereditary causes of serrated polyposis are needed.


Using natural variation to investigate the function of individual amino acids in the sucrose-binding box of fructan:fructan 6G-fructosyltransferase (6G-FFT) in product formation.
Enzymes of the glycosyl hydrolase family 32 are highly similar with respect to primary sequence but catalyze divergent reactions. Previously, the importance of the conserved sucrose-binding box in determining product specificity of onion fructan:fructan 6G-fructosyltransferase (6G-FFT) was established [Ritsema et al., 2004, Plant Mol. Biol. 54: 853-863]. Onion 6G-FFT synthesizes the complex fructan neo-series inulin by transferring fructose residues to either a terminal fructose or a terminal glucose residue. In the present study we have elucidated the molecular determinants of product specificity by substitution of individual amino acids of the sucrose binding box with amino acids that are present on homologous positions in other fructosyltransferases or vacuolar invertases. Substituting the presumed nucleophile Asp85 of the beta-fructosidase motif resulted in an inactive enzyme. 6G-FFT mutants S87N and S87D did not change substrate or product specificities, whereas mutants N84Y and N84G resulted in an inactive enzyme. Most interestingly, mutants N84S, N84A, and N84Q added fructose residues preferably to a terminal fructose and hardly to the terminal glucose. This resulted in the preferential production of inulin-type fructans. Combining mutations showed that amino acid 84 determines product specificity of 6G-FFT irrespective of the amino acid at position 87.


Is It Safe to Re-Harvest the Anterior Iliac Crest to Manage Le Fort I Interpositional Defects in Young Adults With a Repaired Cleft?
Re-harvesting the anterior iliac crest to obtain autogenous bone grafts is a controversial practice. The purpose of this study was to assess the feasibility and associated disability of re-harvesting the anterior iliac crest. To address the research purpose, the authors executed a retrospective case series study. The sample consisted of young adult patients with cleft (<26 yr old) with prior harvesting of the anterior iliac crest during mixed dentition for management of an alveolar cleft(s) and then re-harvesting of the same donor site for management of interpositional defects after Le Fort I advancement. Wound-healing parameters were reviewed at the donor and recipient sites. A survey questionnaire was provided after completion of treatment to document patient perception of early and any long-term donor-site disability. Descriptive statistics were computed for the variables. The sample was composed of 27 patients with a mean age at re-harvesting of 17 years (range, 14 to 25 yr). Patients underwent on average 7.4-mm horizontal advancement, 2.4-mm lengthening, and 2.6-mm transverse expansion of the maxilla. Adequate bone graft was re-harvested to accomplish objectives in all cases. There were no perioperative complications at the donor or recipient sites. Twenty-six of the 27 patients (97%) had fewer donor-site recovery difficulties at the time of re-harvesting compared with the first time graft was taken. There were no cases of lateral femoral cutaneous nerve injury and no long-term discomfort with walking, running, or other activities. The study confirms the safety and efficacy of re-harvesting corticocancellous bone from the anterior iliac crest for management of interpositional defects associated with Le Fort I advancement in young adults with a repaired cleft.


Identification of oestrus cows based on vocalisation characteristics and machine learning technique using a dual-channel-equipped acoustic tag.
Timely and accurate detection of oestrus in cows is an essential element of the good management of dairy farms. At present, the detection of cows in oestrus by acoustic means is impeded by the problems of filtering, incomplete feature selection, and poor recognition accuracy. To overcome these difficulties, this study proposes a sound detection method for cows in oestrus based on machine learning technology using an optimal feature combination and an optimal time window. Firstly, a dual-channel sound detection tag consisting of a unidirectional microphone and an omnidirectional microphone (OM) was developed. The Least Mean Squares adaptive algorithm based on wavelet thresholds was used to filter the signals from the OM, and the dual-channel endpoint detection algorithm was used to identify the lowing of individual cows. The Friedman analysis was then used to select the sound features with significant differences before and after oestrus in terms of time, frequency, and cepstrum, and these were used to determine the most acceptable feature combination. We then analysed the effects of Back Propagation Neural Network (BPNN), Cartesian Regression Tree, Support Vector Machine, and Random Forest classification on the accuracy, precision, sensitivity, specificity, and F1 score of oestrus discrimination. Different time windows were used, and the discrimination performance of these algorithms was evaluated using the Area under Receiver Operating Characteristic Curve to find the most satisfactory match between the time window and the recognition algorithm. The dual-channel acoustic tag's accuracy, precision, sensitivity, and specificity results were 91.25, 98.83, 91.75, and 83.68%, respectively. BPNN with the 70 ms time window and the feature combination (spectral roll-off + spectral flatness + Mel-Frequency Cepstrum Coefficients) was confirmed as the most suitable oestrus recognition method. The average accuracy, precision, sensitivity, specificity, and F1 score of this method were 97.62, 98.07, 97.17, 97.19, and 97.63%, respectively. Based on these results, the approach was shown to be a feasible means of oestrus detection in dairy cows. Based on its ability to differentiate cows and its consistency, it was demonstrated that sound has the potential to replace accelerometers as an early indicator of oestrus in dairy cows.


CCL8 secreted by tumor-associated macrophages promotes invasion and stemness of glioblastoma cells via ERK1/2 signaling.
Tumor-associated macrophages (TAMs) constitute a large population of glioblastoma and facilitate tumor growth and invasion of tumor cells, but the underlying mechanism remains undefined. In this study, we demonstrate that chemokine (C-C motif) ligand 8 (CCL8) is highly expressed by TAMs and contributes to pseudopodia formation by GBM cells. The presence of CCL8 in the glioma microenvironment promotes progression of tumor cells. Moreover, CCL8 induces invasion and stem-like traits of GBM cells, and CCR1 and CCR5 are the main receptors that mediate CCL8-induced biological behavior. Finally, CCL8 dramatically activates ERK1/2 phosphorylation in GBM cells, and blocking TAM-secreted CCL8 by neutralized antibody significantly decreases invasion of glioma cells. Taken together, our data reveal that CCL8 is a TAM-associated factor to mediate invasion and stemness of GBM, and targeting CCL8 may provide an insight strategy for GBM treatment.


Diagnostic value of a urine test in pregnancy of unknown location.
Pregnancy of unknown location (PUL) is a term used when there is a positive pregnancy test but no sonographic evidence for an intrauterine pregnancy (IUP) or ectopic pregnancy (EP). This term is a classification and not a final diagnosis. This study aimed to evaluate the diagnostic value of the Inexscreen test on the outcome of patients with pregnancies of unknown location. In this prospective study, a total of 251 patients with a diagnosis of pregnancy of unknown location at the gynecologic emergency department of the La Conception Hospital, Marseille, France, between June 2015 and February 2019 were included. The Inexscreen (semiquantitative determination of intact human urinary chorionic gonadotropin) test was performed on patients with a diagnosis of pregnancy of unknown location. They participated in the study after information and consent collection. The main outcome measures (sensitivity, specificity, predictive values, and the Youden index) of Inexscreen were calculated for the diagnosis of abnormal pregnancy (nonprogressive pregnancy) and ectopic pregnancy. The sensitivity and specificity of Inexscreen for the diagnosis of abnormal pregnancy in patients with pregnancy of unknown location were 56.3% (95% confidence interval, 47.0%-65.1%) and 62.8% (95% confidence interval, 53.1%-71.5%), respectively. The sensitivity and specificity of Inexscreen for the diagnosis of ectopic pregnancy in patients with pregnancy of unknown location were 81.3% (95% confidence interval, 57.0%-93.4%) and 55.6% (95% confidence interval, 48.6%-62.3%), respectively. The positive predictive value and negative predictive value of Inexscreen for ectopic pregnancy were 12.9% (95% confidence interval, 7.7%-20.8%) and 97.4% (95% confidence interval, 92.5%-99.1%), respectively. Inexscreen is a rapid, non-operator-dependent, noninvasive, and inexpensive test that allows the selection of patients at high risk of ectopic pregnancy in case of pregnancy of unknown location. This test allows an adapted follow-up according to the technical platform available in a gynecologic emergency service.


Determination of acrolein in human urine by headspace gas chromatography and mass spectrometry.
A rapid and sensitive headspace gas chromatographic and mass spectrometric (GC-MS) method was developed for the determination of acrolein in human urine. A 0.5-ml urine sample in a glass vial containing propionaldehyde as an internal standard was heated at 80 degrees C for 5 min. A 0.1-ml volume of headspace vapor was injected into a GC-MS instrument. Acrolein and propionaldehyde were coeluted at 3.1 min using a DB-1 capillary column, and well separated by selective ion monitoring (SIM) mode using ions m/z 56.05 and m/z 58.05. The interassay and intraassay coefficient of variation were 0.99% and 3.3%. The calibration curve demonstrated a good linearity throughout concentrations ranging from 1 to 1000 nM. However, due to a wide variation of acrolein evaporation rates from human urine, a calibration curve must be established for each urine specimen using a standard addition method and detection limit varied from 1 to 5 nM. The total analysis time for two samples from one urine specimen required about 15 min. Therefore, this method is convenient for the urgent monitoring of urinary acrolein in patients to whom alkylating agents are administered.


Common carotid trunk and right vertebral artery originating from the right common carotid artery in a patient with carotid stenosis.
Truncus bicaroticus is a very rare vascular malformation. In this report, we present a very rare anomaly in a patient with left internal carotid artery stenosis together with truncus bicaroticus and right vertebral artery originating from the right common carotid artery.


Multifocal infantile hepatic hemangiomas--imaging strategy and response to treatment after propranolol and steroids including review of the literature.
Infantile hepatic hemangioma is the most common benign liver tumor during infancy. Prompt diagnosis and timely institution of therapy are of utmost importance. Magnetic resonance imaging (MRI) plays a key role in the correct diagnosis and monitoring of treatment. We report on a 15-week-old girl with multifocal infantile hemangiomas of the liver and high output congestive heart failure. Diagnosis was confirmed by MRI. Subsequent treatment with propranolol and steroids showed dramatic regression of the lesions within 24 weeks. We present the characteristic MRI findings and discuss treatment options together with a comprehensive review of the relevant literature. Conclusion Propranolol appears highly efficacious in the management of infantile hepatic hemangioma; dedicated MRI is essential in confirming the diagnosis and monitoring of treatment.


The critical review of methodologies and approaches to assess the inherent skin sensitization potential (skin allergies) of chemicals. Part II.
To identify specific cases, classes or specific use situations of chemicals for which 'safety thresholds' or 'safety limits' were set (in regulations, standards, in scientific research/clinical work, etc.) and critically review the scientific and methodological parameters used to set those limits.


Covalent Cross-Linking of 2H-MoS2 Nanosheets.
The combination of 2D materials opens a wide range of possibilities to create new-generation structures with multiple applications. Covalently cross-linked approaches are a ground-breaking strategy for the formation of homo or heterostructures made by design. However, the covalent assembly of transition metal dichalcogenides flakes is relatively underexplored. Here, a simple covalent cross-linking method to build 2H-MoS2 -MoS2 homostructures is described, using commercially available bismaleimides. These assemblies are mainly connected vertically, basal plane to basal plane, creating specific molecular sized spaces between MoS2 sheets. Therefore, this straightforward approach gives access to the controlled connection of sulfide-based 2D materials.


Aqueous extract of Teucrium polium ameliorates diabetes and induced-prostatic complication.
Prostatic complications are common among diabetic patients. Previous research demonstrates that Teucrium polium (T. polium) has beneficial effects in diabetic cases. This study, therefore, aimed to evaluate the impacts of T. polium aqueous extract on the prostate of diabetic rats. Diabetes was induced in male Wistar rats by intraperitoneal injection of streptozotocin (50 mg/kg). a total of 40 Rats were randomly divided into the following groups: Control, Control + TP100 (TP100), Diabetic, Diabetic + TP100 (DTP100) and Diabetic + TP200 (DTP200). The intervention was done orally once per day for 56 days (8 weeks). An oral glucose tolerance test was conducted, glucose and insulin levels were assessed. Microscopic features of the ventral prostatic lobe were evaluated pathologically. T. polium at both doses significantly reduced glucose levels in an insulin-independent pathway. T. polium at both doses significantly improved prostate weight, prostate epithelium height, and prostate secretory activity in comparison with the diabetic group. Interestingly, treatment of T. polium to healthy rats led to decreased epithelial height. It could be deduced that T. polium has useful impacts on glucose control and may prevent prostatic complications. The online version contains supplementary material available at 10.1007/s40200-022-00979-4.


Updates of underactive bladder: a review of the recent literature.
Underactive bladder (UAB) is a major component of lower urinary tract symptoms. The physiopathology mechanisms underlying UAB include detrusor underactivity, acontractile detrusor, and reduced or absent bladder sensation. UAB can influence lower and upper urinary tract function and lead to serious consequences; however, the symptom syndrome is poorly understood and incompletely researched at present. Moreover, there is no agreement among authorities regarding the terminology, definition, epidemiology, classification, risk factors, animal model, pathogenesis, diagnosis, and treatment of UAB. In this review, we discuss the current terminology, epidemiology, physiopathology, evaluation, and management of UAB.


Reconstruction of the mandibular denture bearing area and freeing of the tongue after tumor surgery.
Vestibuloplasty together with a loosening of the tongue and covering the mucosal defects either with a split thickness skin graft or an autologous mucosal graft was performed on 35 patients previously treated for squamous cell carcinoma. The interval between tumor resection and the reconstructive procedures averaged 20 months. In 34 patients the denture bearing area improved, and in 31 patients, better mobility of the tongue occurred with, therefore, better phonation.


Monoamine oxidase B inhibitors based on natural privileged scaffolds: A review of systematically structural modification.
Monoamine oxidase is a flavin enzyme that catalyzes the oxidation of monoamine neurotransmitters in the brain. Various toxic by-products, aldehydes and hydrogen peroxide produced during the catalytic process, can cause oxidative stress and neuronal cell death. Overexpression of MAO-B and insufficient dopamine concentration are recognized as pathological factors in neurodegenerative diseases (NDs) including Parkinson's disease (PD) and Alzheimer's disease (AD). Therefore, the inhibition of MAO-B is an attractive target for the treatment of NDs. Despite significant efforts, few selective and reversible MAO-B inhibitors have been clinically approved. Natural products have emerged as valuable sources of lead compounds in drug discovery. Compounds such as chromone, coumarin, chalcone, caffeine, and aurone, present in natural structures, are considered as privileged scaffolds in the synthesis of MAO-B inhibitors. In this review, we summarized the structure-activity relationship (SAR) of MAO-B inhibitors based on the naturally privileged scaffolds over the past 20 years. Additionally, we proposed a balanced discussion on the advantages and limitations of natural scaffold-based MAO-B inhibitors with providing a future perspective in drug development.


Macrophage-like tumor cells as tools to study chemoattractive activity.
Macrophage-like tumor cells can be obtained in large quantities as rather homogeneous populations, making these cells useful for chemotaxis assays. Therefore, macrophage-like cells J774A, WEHI-3, P388D1, IC-21, and NCTC 1469, all of murine origin, and U937 of human origin, were tested for chemotactic activity to a number of chemoattractive agents, such as casein, an N-formyl tetrapeptide (N-formyl-L-norleucyl-L-leucyl-L-phenylalanyl-L-tyrosine), and culture supernatants of murine SL2 lymphoma cells. J774A and WEHI-3 macrophage-like cells of murine (BALB/c) origin expressed the strongest chemotactic activity to casein and N-formyl tetrapeptide, respectively. The results show that: very standardized chemotaxis assays can be performed using these cell lines; these assays require appropriate cell line-stimulus combinations; there are substantial differences among cell lines as to sensitivity to various chemoattractive substances; macrophage cell lines and functional mutants may be helpful for the study of receptors for chemotaxins and the study of transducer signals for chemotaxis.


Effects of anesthetics on microvascular reactivity measured by vascular occlusion tests during off-pump coronary artery bypass surgery: a randomized controlled trial.
Microvascular function may be modulated by various anesthetics. Desflurane and propofol anesthesia have different effects on microvascular function. However, there are few reports on the effects of sevoflurane and desflurane on microvascular function during cardiac surgery. We compared the effects of sevoflurane and desflurane on microvascular reactivity, as measured by the vascular occlusion tests (VOTs) during off-pump coronary artery bypass (OPCAB) surgery. Patients undergoing OPCAB were eligible for study inclusion. Patients were excluded if they were unsuitable for treatment with volatile agents or the VOT, had renal failure or uncontrolled diabetes, or were pregnant. The enrolled patients were randomized to receive sevoflurane or desflurane during surgery. Tissue oxygen saturation (StO2) dynamics during the VOT were measured at baseline (pre-anesthesia), pre-anastomosis, post-anastomosis of vessel grafts, and at the end of surgery. Macrohemodynamic variables, arterial blood gas parameters, and in-hospital adverse events were also evaluated. A total of 64 patients (32 in each group) were analyzed. StO2 dynamics did not differ between the groups. Compared to baseline, StO2 and the rate of recovery following vascular occlusion decreased at the end of surgery in both groups (adjusted p-value, < 0.001), and no group difference was observed. Macrohemodynamic variables, blood gas analysis results, and the rate of postoperative in-hospital adverse events were similar between the groups. Microvascular reactivity, as measured by the VOT during OPCAB, showed no difference between the sevoflurane and desflurane groups. Also, there were no group differences in macrohemodynamics or the rate of postoperative adverse events. TRIAL REGISTRATION : Clinicaltrials.gov, identifier NCT03209193; registered on July 3, 2017.


Reversal of voters' positions since the privatization of spirits sales in Washington State.
In 2011, Washington State voters approved Initiative 1183 (I-1183), the privatization of liquor sales. The aim here was to examine how voter support for privatization has changed since I-1183 passed. Data came from five state-representative surveys, with recruitment between 2014 and 2016 (N = 4,290). Primary outcomes were voting on I-1183 (vs. not), voting for (vs. against) I-1183, and changing vote for I-1183 to against among those who voted for it (vs. not changing). Bivariate and multivariable logistic regressions were used for analyses. Results show that voting for (vs. against) I-1183 was related to 2.59 (P < 0.001) times greater odds of wanting to change one's vote. This difference was large enough to have changed the result of the election if voters could know their later opinions. Among those who voted for I-1183, odds of retracting support were positively related to total past 12-month drink volume. Those who agreed that number of stores selling liquor should decrease were more likely to change votes from for to against, while those who considered that youth alcohol abuse has remained the same since privatization were less likely to change votes. Thus, in the years immediately following liquor privatization in Washington State, public opinion has changed enough to shift the result of the election from supporting privatization to rejecting it. Findings are especially relevant for other US states and countries considering privatization.


Current clinical trials with authentic recombinant somatropin in Japan.
A total of 25 children with hGH deficiency were treated with recombinant somatropin, 0.5 IU/kg/week i.m. for approximately 12 months in a multicentre study. Sixteen patients were previously untreated with any hGH preparation (naïve group) and 9 patients had been treated with pituitary hGH for 4-42 months (previously treated group). The height gain after 12 months with the present treatment was 7.7 +/- 1.8 cm/year in the naïve group and 5.8 +/- 1.0 cm/year in the previously treated group. Using the criteria proposed by the Foundation for Growth Science in Japan, recombinant somatropin treatment was effective in 15 of 16 patients (93.8%) of the naïve group and in all of the 9 patients (100%) in the switched group. Anti-hGH antibody was observed in none of 9 patients in the previously treated group throughout the study period. It was observed in only 2 of 16 patients after 6 months of treatment and 1 of 16 patients after 12 months of treatment in the naïve group. No side-effects or abnormalities in laboratory findings were observed.


Ball milling and acetic acid co-modified sludge biochar enhanced by electrochemistry to activate peroxymonosulfate for sustainable degradation of environmental concentration neonicotinoids.
Neonicotinoids pose potential serious risks to human health even at environmental concentration and their removal from water is considered as a great challenge. A novel ball milling and acetic acid co-modified sludge biochar (BASBC) was the first time synthesized, which performed superior physicochemical characteristics including larger surface area, more defect structures and functional groups (e.g., CO and -OH). Electrochemistry was introduced to enhance BASBC for peroxymonosulfate (PMS) activation (E/BASBC/PMS) to degrade environmental concentration neonicotinoids (e.g., imidacloprid (IMI)). The degradation efficiency of IMI was 95.2% within 60 min (C0 (PMS)= 1 mM, E= 25 V, m (BASBC)= 10 mg). Solution pH and anionic species/concentrations were critical affecting factors. The scavenging and electron paramagnetic resonance experiments suggested that •OH and 1O2 were the dominant reactive oxygen species contributing to IMI degradation. Three degradation pathways were proposed and pathway Ⅲ was the main one. 86.1% of IMI were mineralized into non-toxic CO2 and H2O, and others were converted into less toxic intermediates. Also, E/BASBC/PMS system achieved the sustainable degradation of IMI in the cycle experiments. Additionally, it exhibited excellent degradation performance for other three typical neonicotinoids (96.6% of thiacloprid (THI), 96.5% of thiamethoxam (THX) and 82.6% of clothianidin (CLO)) with high mineralization efficiencies (87.8% of THI, 90.5% of THX and 75.4% of CLO).


Undergraduate medical students' perceptions and expectations of theatre-based learning: how can we improve the student learning experience?
Much of the student experience in theatre depends on the interaction between student and surgeon, and having the opportunity to take part in procedures. Theatre-based teaching can be seen as having little inherent benefit otherwise. We wished to identify other factors contributing to the experience of theatre-based teaching. A questionnaire survey, using forced-choice and open questions, of undergraduate medical students with experience of surgical attachments. 54 final (5th) year medical students, University of Aberdeen. Responses on the closed questions are presented as percentages. The themes arising from the open questions were identified and the relationships among these themes explored. Student expectations of learning focused on knowledge acquisition. Students learning experiences varied widely, depending on how welcome they felt in theatre. Visibility and active participation influenced the experience. Students did not feel adequately prepared for getting the most out of this learning experience. The student experience may be skewed by unrealistic expectations of theatre-based learning. Clear and realistic learning objectives, preparation in terms of familiarity with the environment and staff roles, embedding the experience in the patient's journey/care pathways, faculty expectations being clearly communicated to clinical teaching staff and, perhaps above all, approachability of theatre staff are likely to improve the learning experience.


Allergic reactions to antivenom in a patient bitten twice by the same snake within a month: A rare case report and literature review.
Antivenom is the most effective method currently available for the treatment of poisonous snake bite. Allergic reactions to antivenom have been reported in the past. Here we shared a case of allergic reactions to antivenom in an old male patient who was bitten twice by the same snake (probably same one) at the same biting site within a month whereas the patient did not show any allergic disorder in the first bitten. Envenomations twice in a short period time by the same kind of snake are very rare. Physician should be alert to the occurrence of allergic reactions in treating this type of patients with antivenom. The skin allergy test has a certain value in predicting the allergic response before the second use of antivenom. Desensitization may reduce the incidence of allergic reactions, but this is insufficient. Rather than non-IgE-mediated immediate hypersensitivity, patients receiving the second treatment of antivenom may develop IgE-mediated immediate hypersensitivity. Once happened, the antivenom treatment should be stopped promptly and anti-allergy treatment should be given immediately.


Infection with hepatitis delta and human immunodeficiency viruses among hemophiliacs in Japan.
Two hundred two patients with hemophilia, dependent solely on imported coagulation factor concentrates, were tested for markers of hepatitis B virus infection, antibody to hepatitis delta virus (anti-HD), and antibody to human immunodeficiency virus (anti-HIV). Nine carriers of hepatitis B surface antigen (HBsAg) were identified. Six (66.7%) of them were positive for anti-HD, a prevalence much higher than that in HBsAg carriers without hemophilia in Japan (1/113 or 0.9%, p less than 0.001). Anti-HIV was found in 96 (47.5%), in sharp contrast to the low prevalence (0/1205) in apparently healthy blood donors (p less than 0.001). These results implicated imported plasma products in the transmission of both delta and human immunodeficiency viruses to hemophiliacs. An efficient method for the sterilization of plasma products is warranted to prevent exposure of hemophiliacs to the accompanying pathogenic viruses.


Risk of traumatic intracranial haemorrhage in children with bleeding disorders.
To assess computerised tomography (CT) use and the risk of intracranial haemorrhage (ICH) in children with bleeding disorders following a head trauma. Design: Multicentre prospective observational study. 10 paediatric emergency departments (ED) in Australia and New Zealand. Children <18 years with and without bleeding disorders assessed in ED following head trauma between April 2011 and November 2014. Data collection of patient characteristics, management and outcomes. Rate of CT use and frequency of ICH on CT. Of 20 137 patients overall, 103 (0.5%) had a congenital or acquired bleeding disorder. CT use was higher in these patients compared with children without bleeding disorders (30.1 vs. 10.4%; rate ratio 2.91 95% CI 2.16-3.91). Only one of 31 (3.2%) children who underwent CT in the ED had an ICH. This patient rapidly deteriorated in the ED on arrival and required neurosurgery. None of the patients with bleeding disorders who did not have a CT obtained in the ED or had an initial negative CT had evidence of ICH on follow up. Although children with a bleeding disorder and a head trauma more often received a CT scan in the ED, their risk of ICH seemed low and appeared associated with post-traumatic clinical findings. Selective CT use combined with observation may be cautiously considered in these children based on clinical presentation and severity of bleeding disorder.


Partial sleep deprivation impacts impulsive action but not impulsive decision-making.
Sleep deprivation may lead to increased impulsivity, however, previous literature has focused on examining effects of total sleep deprivation (TSD) rather than the more common condition, partial sleep deprivation (PSD) or 'short sleep'. Moreover, it has been unclear whether PSD impacts impulse-related cognitive processes, and specifically if it differentially affects impulsive action versus impulsive decision-making. We sought to determine if short compared to long sleep (6 vs. 9h/night) impacts impulsive action via behavioral inhibition (Go/No-Go), and/or impulsive decision-making processes of risk taking (Balloon Analogue Risk Task [BART]) and preferences for immediate over delayed rewards (Delay Discounting). In a within-subject design, 34 participants (71% female, mean age=37.0years, SD=10.54) were assigned to four consecutive nights of 6h/night (short sleep) and 9h/night (long sleep) in their own home in random counterbalanced order. Sleep was measured via wrist-worn actigraphs to confirm adherence to the sleep schedules (mean short sleep=5.9h, SD=0.3; mean long sleep=8.6h, SD=0.3, p<0.001). The Go/No-Go, BART, and Delay Discounting tasks were completed following both sleep conditions. Participants had more inhibition errors on the Go/No-Go task after short (mean false alarms=19.79%, SD=14.51) versus long sleep (mean=15.97%, SD=9.51, p=0.039). This effect was strongest in participants reporting longer habitual time in bed (p=0.04). There were no differences in performance following long- versus short-sleep for either delay discounting or the BART (p's>0.4). Overall, these results indicate that four days of PSD diminishes behavioral inhibition abilities, but may not alter impulsive decision-making. These findings contribute to the emerging understanding of how partial sleep deprivation, currently an epidemic, impacts cognitive ability. Future research should continue to explore the connection between PSD and cognitive functions, and ways to minimize the occurrence and negative consequences of short sleep.