Deprenyl induces the tyrosine hydroxylase enzyme in the rat dopaminergic nigrostriatal system.
Chronic treatment of aged rats with deprenyl prevents age-induced protein oxidation in substantia nigra and protects tyrosine hydroxylase (TH) enzyme against inactivation [11]. With these precedents, we treated adult rats with deprenyl for 3 weeks in order to get further insight in the mechanism by which deprenyl exerts such actions. After completing the treatment, dopamine (DA) levels markedly increased in both striatum and substantia nigra while levels of the acid DA metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), decreased in the two brain areas, thus proving MAO-inhibiting properties of the treatment. We then studied the cellular expression of TH mRNA by in situ hybridization. Following treatment with deprenyl, levels of TH mRNA were significantly higher in individual dopaminergic nigral cell bodies than in those of control rats (+74%). Western blotting analysis of TH enzyme amount revealed a positive effect of the treatment in both the terminal field (+44%) and the cell body region (+31%). This correlation between TH mRNA and amount was also extended to TH enzyme activity in the two brain areas studied, which significantly increased in striatum (+57%) and substantia nigra (+35%) following deprenyl treatment. Taken together, our results clearly suggest a TH-inducing effect of deprenyl in the dopaminergic nigrostriatal system, which seems to be independent of its protective action against oxidative stress described previously. These results expand our knowledge about the beneficial effect of deprenyl in the therapy of Parkinson's disease.


Phosphate metabolism in erythrocytes of critically ill patients.
Orthophosphate (Pi), adenosine 5'-diphosphate (ADP), adenosine 5'-triphosphate (ATP) and 2,3-diphosphoglycerate (2,3-DPG) were measured in the erythrocytes of patients in an intensive care unit. The patients' plasma concentration of Pi varied from 0.1 to 4.2 mmol/l, and the corresponding concentration in erythrocytes varied from 0.1 to 2.0 mmol/litre of cells. Marked ATP depletion (less than 1 mmol/litre of cells) was only observed when erythrocyte Pi was less than 0.3 mmol/litre of cells and plasma Pi was less than 0.35 mmol/l. No dependence of 2,3-DPG concentration on the cellular concentration of Pi was detected. The phosphorylation potential [ATP]/([ADP] X [Pi]) varied inversely with the erythrocyte concentration of Pi. Hence the calculated free energy of hydrolysis of ATP in the cell increased from -58 kJ/mol in the most hypophosphataemic samples to -51 kJ/mol in the most hyperphosphataemic. Such changes may adversely affect cell function by altering the steady state mass-action ratios of ATPase reactions. When erythrocytes from normal donors were incubated in solutions containing 1 or 5 mmol/l Pi, the cellular concentrations of Pi stabilized at 1.09 and 2.85 mmol/litre of cells respectively. The corresponding rates of lactate production were 2.09 and 3.11 mmol h-1 litre-1 of cells. In spite of this stimulation of glycolysis (and hence of the flux through ATP synthesizing steps of the Embden-Meyerhof pathway), no significant change in ATP concentration was observed. As in the patients' cells, this indicates that, when extracellular Pi concentrations are perturbed, the concentrations, in erythrocytes, of organic phosphates are more closely regulated than the concentration of Pi.


Nutritional supplement use among Slovenian adolescents.
Little is known about the prevalence of nutritional supplement use in European adolescents. We conducted the present study to analyse the prevalence of nutritional supplement use and factors associated with this use among Slovenian adolescents. The nutritional supplementation practices of 818 adolescents were studied using an anonymous questionnaire. Information was sought on the type of supplements used, frequency of use and sources of information. The region of north-west Slovenia. Schoolchildren from twenty primary schools and twelve secondary schools. Some 19·3% of all adolescents reported using at least one nutritional supplement and the prevalence of use was significantly higher in adolescents who were members of sports clubs. Multivitamins were the most common nutritional supplement. Older adolescents were significantly more likely to be supplementing with iron, protein and minerals. Less than 16% of supplement users in our study sought information from health-care professionals. Nearly 62% obtained information from parents and coaches, and many adolescents appear to decide on nutritional supplementation themselves, without advice. Older adolescents were significantly more likely to combine supplements than younger adolescents. One-fifth of Slovenian adolescents use nutritional supplements. There are clear differences in supplement use between younger (age 12 years) and older (age 17 years) adolescents. Multiple use of supplements, coupled with self-managed supplementation in older adolescents, is concerning. Hence, there is an urgent need to provide accurate information regarding nutritional supplements, which will help adolescents, their parents and coaches to make informed choices about their use.


Urticaria due to polyethylene glycol-3350 and electrolytes for oral solution in a patient with jejunal nodular lymphoid hyperplasia.
Both jejunal nodular lymphoid hyperplasia (NLH) and polyethylene glycol (PEG)-3350 hypersensitivity are extremely rare. We describe a 30-year-old female who had previously taken a PEG-3350 bowel preparation without adverse effects, and presented for evaluation of chronic diarrhea. An upper and lower gastrointestinal endoscopy, and small bowel series were scheduled. PEG-3350 and electrolytes for oral solution was prescribed for bowel cleansing. During consumption of the bowel preparation she developed urticarial hypersensitivity. An alternative bowel preparation was used. Colonoscopy and upper endoscopy were normal, but small bowel series revealed innumerable sand-like lucencies in the jejunum. NLH was confirmed on biopsy from antegrade enteroscopy. This is the first case report on the pathological jejunal NLH in association with the PEG-3350 urticarial hypersensitivity. The potential pathophysiological etiology of this association is discussed.


The comparative effects of bariatric surgery on weight and type 2 diabetes.
Epidemiological evidence confirms that risk of developing type 2 diabetes is related to weight gain. Weight reduction is beneficial as relative risk is reduced to 0.13 for weight loss >20 kg. This raises the question of effectiveness of bariatric surgery on 1) weight loss and 2) diabetes-related outcomes in morbidly obese patients. We reviewed the literature using Medline. Only 2 meta-analyses reporting on both outcomes were included, as well as 50 systematic reviews or primary studies. Meta-analyses mainly based on case series data as well as controlled studies confirm that bariatric surgery is highly effective in obtaining weight reduction in morbidly obese patients up to 60% of the excess weight, along with resolution of preoperative diabetes in more than 75% of cases. Among bariatric surgery techniques, malabsorptive procedures (biliopancreatic diversion and gastric bypass) appear to be more effective on both outcomes than restrictive procedures (gastroplasty and gastric banding). Even if more studies are needed to confirm current evidence, bariatric surgery is effective for controlling diabetes. It appears as an efficient strategy from economic modeling due to savings from reduction in diabetes-related costs.


Fine binocular control in dyslexic children.
Dyslexic children often complain that letters seem to move around. The hypothesis advanced here is that this is a symptom of immature vergence control which leads to an unstable sense of visual direction. Evidence is presented that (1) sixty-seven per cent of dyslexic children exhibit poor dynamic control of vergence movements in response to a small fusion stimulus, (2) most good readers have good vergence control, (3) children with poor vergence control have reduced stereoacuity, (4) six months monocular occlusion for reading and close work assisted 51 per cent of dyslexics with unstable vergence control to improve; thereafter their reading improved rapidly also. It is concluded that defective vergence control is an important, though not the only, cause of dyslexics' problems.


How substance use differs among American secondary schools.
The purpose of this study was to examine (1) the extent to which student drug use and related measures vary among American secondary schools, and (2) how substance use varies among schools by certain school characteristics. Data come from the Monitoring the Future project's annual surveys of nationally representative samples of 8th-, 10th-, and 12th-grade students from 1991 to 2002. The results show that the preponderance of variance in drug use and related variables lies within schools; only a relatively small amount of variance is between schools. Although the variance lies primarily within schools, there remain important school-to-school differences in the extent to which students are exposed to drug use. The analyses of school characteristics show that schools do indeed differ in drug use by their students, particularly by school type, socioeconomic status, and race/ethnicity. Eighth and 10th grade (but not 12th grade) students in public schools are more likely to be cigarette smokers than students in private schools. Students in public middle schools are at higher risk for use of alcohol and marijuana; however, among 12th graders, students in Catholic schools are at higher risk. School size is generally unrelated to substance use, with few exceptions. For the most part, there is a negative association between school socioeconomic status and student substance use among 8th graders; but by 12th grade, the association tends to be positive or not significant. Racial/ethnic composition is significantly associated with student substance use, with majority African American schools typically showing the lowest rates of use at all grades.


Changes in catalase activity during follicular growth, atresia and luteinization in rat ovary.
Quantitative changes have been observed in the catalase activity during follicular growth, induced atresia and in corpora lutea of cycle and pregnancy. Large growing and preovulatory follicles showed higher enzyme activity as compared to the smaller follicles; the activity was mainly present in the thecal layer of the preovulatory follicle. After the blockade of ovulation with barbiturate, the activity increases significantly in the whole follicle and also in the thecal layers till third day of ovulation and afterward it declines on 5th day, suggesting that rise in catalase activity may exert a protective function against lytic actions of peroxide which is known to be produced in the ovary during several metabolic and steroidogenic events. The corpora lutea of the cycle showed significantly less enzyme activity than the corpora lutea of pregnancy. The significance of catalase activity during follicular and corpus luteum degeneration is discussed.


Oxidative stress induces persistent telomeric DNA damage responsible for nuclear morphology change in mammalian cells.
One main function of telomeres is to maintain chromosome and genome stability. The rate of telomere shortening can be accelerated significantly by chemical and physical environmental agents. Reactive oxygen species are a source of oxidative stress and can produce modified bases (mainly 8-oxoG) and single strand breaks anywhere in the genome. The high incidence of guanine residues in telomeric DNA sequences makes the telomere a preferred target for oxidative damage. Our aim in this work is to evaluate whether chromosome instability induced by oxidative stress is related specifically to telomeric damage. We treated human primary fibroblasts (MRC-5) in vitro with hydrogen peroxide (100 and 200 µM) for 1 hr and collected data at several time points. To evaluate the persistence of oxidative stress-induced DNA damage up to 24 hrs after treatment, we analysed telomeric and genomic oxidative damage by qPCR and a modified comet assay, respectively. The results demonstrate that the genomic damage is completely repaired, while the telomeric oxidative damage persists. The analysis of telomere length reveals a significant telomere shortening 48 hrs after treatment, leading us to hypothesise that residual telomere damage could be responsible for the telomere shortening observed. Considering the influence of telomere length modulation on genomic stability, we quantified abnormal nuclear morphologies (Nucleoplasmic Bridges, Nuclear Buds and Micronuclei) and observed an increase of chromosome instability in the same time frame as telomere shortening. At subsequent times (72 and 96 hrs), we observed a restoration of telomere length and a reduction of chromosome instability, leaving us to conjecture a correlation between telomere shortening/dysfunction and chromosome instability. We can conclude that oxidative base damage leads to abnormal nuclear morphologies and that telomere dysfunction is an important contributor to this effect.


Ability to adapt: different generations of PAMAM dendrimers show different behaviors in binding siRNA.
This paper reports a molecular dynamic study to explore the diverse behavior of different generations of poly(amidoamine) (PAMAM) dendrimers in binding siRNA. Our models show good accordance with experimental measurements. Simulations demonstrate that the molecular flexibility of PAMAMs plays a crucial role in the binding event, which is controlled by the modulation between enthalpy and entropy of binding. Importantly, the ability of dendrimers to adapt to siRNA is strongly dependent on the generation and on the pH due to backfolding. While G4 demonstrates good adaptability to siRNA, G6 behaves like a rigid sphere with a consistent loss in the binding affinity. G5 shows a hybrid behavior, maintaining rigid and flexible aspects, with a strong dependence of its properties on the pH. To define the "best binder", the mere energetic definition of binding affinity appears to be no longer effective and a novel concept of "efficiency" should be considered, being the balance between enthalpy and entropy of binding indivisible from the structural flexibility. With this aim, we propose an original criterion to define and rank the ability of these molecules to adapt their structure to bind a charged target.


Adolescent adaptation before, during and in the aftermath of the Great Recession in the USA.
This study examines the impact of the "Great Recession" (from December 2007 to June 2009) on 8th and 10th graders in the USA, using annual nationally representative data from the Monitoring the Future study. Historical changes in youth adjustment (self-esteem, depressed mood, risk taking, aggression and property crime), school achievement (grade point average [GPA], time spent on homework and educational expectations) and structured and unstructured activities (volunteering, employment, sports and evenings out for fun) were examined between 1991 and 2014. Overall, there were only slight changes in mean levels of adjustment, achievement and most youth activities. However, the percentage of youth working during the school year did decline during the Great Recession. Several longer-term trends were also evident, though not directly tied to the Great Recession. These include an increase in GPA, a decrease in time spent on homework, rising educational expectations and more time spent volunteering. Future work should assess how the shift to unpaid work activities (e.g. volunteering and internships) among youth is impacting the transition from school to work in the contemporary economy, and whether the Great Recession had deleterious impacts for younger children or among youth whose parents lost work or had their homes foreclosed.


Increasing hospital charges for adolescent idiopathic scoliosis in the United States.
Retrospective cohort study. To determine the trends and causes for increases in hospital charges in adolescent idiopathic scoliosis (AIS) fusions. Trends in utilization rates, surgical procedure types, and hospital charges for AIS fusions have not been well investigated. We used International Classification of Diseases, Ninth Revision, billing codes to identify 29,594 AIS fusion cases from the National Inpatient Service (NIS) database between 2001 and 2011. Data were trended over time, and contrasted against other common procedures. To identify specific drivers of charges, we queried our own hospital's billing system, and averaged charges from 40 cases (10 cases for each of 4 yr studied). Dollar amounts were adjusted for inflation to 2011 dollars. Utilization rates for AIS fusions have remained constant, whereas utilization of adult spinal fusions increased by 64% (P = 0.0004). Utilization of anterior thoracic fusions decreased by 80% (P < 0.0001). Mean hospital charges for AIS spinal fusions increased from $72,780 in 2001 to $155,278 in 2011 (113% increase), averaging 11.3% annually (P < 0.0001), with charges for adult spinal procedures increasing at a similar rate (13.4% annually, P < 0.0001). Charges for the other nonspine conditions increased to a lesser degree (range of 4.5%-6% annually, P < 0.001 for each). At our institution, spinal implant charges increased 27.6% annually, whereas surgeon charges decreased 0.5% annually, and all other charges increased only 5.2% annually. Over time, our surgeon used greater numbers of pedicle screws, and greater numbers of implants per surgery and per level fused (P < 0.05 for each). Implant charges were 28% of the total hospital bill in 2003, rising to 53% in 2012. Although utilization rates for AIS fusions have remained constant over time, hospital charges have increased substantively, and there has been a shift toward performing posterior only surgical procedures. This corresponds to the widespread adoption of pedicle screw-based constructs. Spinal implants may be the primary driver of increased charges. Strategies directed toward implant cost savings may thus have the largest impact. 4.


[Differences in prenatal care between health services under the Family Health Strategy and traditional primary care clinics in Rio Grande, Rio Grande do Sul State, Brazil].
This study aimed to evaluate differences in prenatal care between services under the Family Health Strategy (FHS) and traditional public primary care clinics in Rio Grande, Rio Grande do Sul State, Brazil. A cross-sectional study was performed with all women who gave birth from January 1st to December 31st, 2007, and who received prenatal care in the municipal health system. The procedures recommended by the Ministry of Health were compared according to model of care. Among the 961 pregnant women, those treated under the FHS received a higher percentage of some forms of care (use of ferrous sulfate, tetanus vaccination, and HIV and syphilis tests). Other procedures were also more frequent under the FHS, but failed to reach the recommended levels (breast examination and Pap smear). Measurement of blood pressure, uterine height, and weight were quite frequent in both groups. Identification of pregnant women in the first trimester failed to reach 70%. Women under the FHS received better care, but some procedures still fell short of expected levels, and efforts are thus needed to improve the quality of prenatal care.


Calcium channel blockade reduces mechanical strain-induced extracellular matrix gene response in lamina cribrosa cells.
This study examines the effect of the L-type calcium channel blocker verapamil on mechanical strain-induced extracellular matrix genes in optic nerve head lamina cribrosa (LC) cells. Changes in LC cell intracellular calcium [Ca(2+)]i following hypotonic cell membrane stretch were measured with the fluorescent probe fura-2/AM. Fluorescence intensity was measured, after labelling, by calcium (Ca2+) imaging confocal microscopy. Confluent human LC cell cultures were serum starved for 24 h prior to exposure to cyclical mechanical strain (1 Hz, 15%) for 24 h in the presence or absence of verapamil (10 mm). Transforming growth factor-β 1 (TGF-β1), collagen 6A3 (COL6A3) and chondroitin sulfate proteoglycan 2 (CSPG2) mRNA expression levels were assessed by quantitative RT-PCR. Hypotonic cell membrane stretch of LC cells from normal donors significantly increased [Ca2+]i (p<0.05). Exposure to cyclical mechanical strain (15% strain) produced a statistically significant increase in the three matrix genes that were examined (TGF-β1, COL6A3 and CSPG2). This response in both cyclical and mechanical stretch was significantly reduced by pretreating LC cells with the L-type calcium channel blocker verapamil (p<0.05). This study provides evidence of a novel mechanotransduction pathway linking mechanical strain, cation channel function and the induction of LC cell matrix gene transcription. This highlights the potential involvement of calcium influx in the activation of matrix remodelling responses in the optic nerve head and supports the rationale that calcium channel blockers may attenuate disease progression in glaucoma.


Combined effects of CO2 and light on the N2-fixing cyanobacterium Trichodesmium IMS101: a mechanistic view.
The marine diazotrophic cyanobacterium Trichodesmium responds to elevated atmospheric CO(2) partial pressure (pCO(2)) with higher N(2) fixation and growth rates. To unveil the underlying mechanisms, we examined the combined influence of pCO(2) (150 and 900 microatm) and light (50 and 200 micromol photons m(-2) s(-1)) on Trichodesmium IMS101. We expand on a complementary study that demonstrated that while elevated pCO(2) enhanced N(2) fixation and growth, oxygen evolution and carbon fixation increased mainly as a response to high light. Here, we investigated changes in the photosynthetic fluorescence parameters of photosystem II, in ratios of the photosynthetic units (photosystem I:photosystem II), and in the pool sizes of key proteins involved in the fixation of carbon and nitrogen as well as their subsequent assimilation. We show that the combined elevation in pCO(2) and light controlled the operation of the CO(2)-concentrating mechanism and enhanced protein activity without increasing their pool size. Moreover, elevated pCO(2) and high light decreased the amounts of several key proteins (NifH, PsbA, and PsaC), while amounts of AtpB and RbcL did not significantly change. Reduced investment in protein biosynthesis, without notably changing photosynthetic fluxes, could free up energy that can be reallocated to increase N(2) fixation and growth at elevated pCO(2) and light. We suggest that changes in the redox state of the photosynthetic electron transport chain and posttranslational regulation of key proteins mediate the high flexibility in resources and energy allocation in Trichodesmium. This strategy should enable Trichodesmium to flourish in future surface oceans characterized by elevated pCO(2), higher temperatures, and high light.


Three-dimensional crystal structure of the transcription factor PhoB receiver domain.
PhoB is the response regulator of the two-component signal transduction system activated under phosphate starvation conditions. This protein is a transcription factor that activates more than 30 genes of the pho regulon and consists of two domains: a DNA binding domain and a dimerization domain, the latter being homologous to the receiver domain described for two-component response regulators. Activation by phosphorylation induces dimerization of the protein and the consequent binding to the DNA direct repeat pho box, where it promotes the binding of RNA polymerase. In the absence of phosphorylation, the activating dimerization process can be mimicked by deletion of the DNA binding domain. The three-dimensional crystal structure of the receiver domain of PhoB from Escherichia coli has been solved by multiple anomalous diffraction using a gold derivative obtained by co-crystallization, and refined using data to 1.9 A resolution. The crystal structure reveals an alpha/beta doubly wound fold, similar to other known receivers, the most conspicuous difference being the displacement of helix alpha4 towards its N terminus. The active site includes the acidic triad Asp53 (the site of phosphorylation), Asp10 and Glu9. Lys105, from loop beta5alpha5, and Glu88, from helix alpha4, interact with Asp53 via an H-bond and a water bridge, respectively. In the asymmetric unit of the crystal there are two molecules linked by a complementary hydrophobic surface, which involves helix alpha1, loop beta5alpha5 and the N terminus of helix alpha5, and is connected to the active site through the fully conserved residue Lys105 from loop beta5alpha5. The possibility that this surface is the functional surface used for the activating dimerization is discussed.


MRI Assessment of Swallow Muscle Activation with the Swallow Exercise Aid and with Conventional Exercises in Healthy Volunteers: An Explorative Biomechanical Study.
Swallowing muscle strength exercises are effective in restoring swallowing function. In order to perform the exercises with progressive load, the swallow exercise aid (SEA) was developed. Precise knowledge on which muscles are activated with swallowing exercises, especially with the SEA, is lacking. This knowledge would aid in optimizing the training program to target the relevant swallowing muscles, if necessary. Three healthy volunteers performed the three SEA exercises (chin tuck against resistance, jaw opening against resistance and effortful swallow) and three conventional exercises [conventional effortful swallow (cES), Shaker and Masako] in supine position inside an MRI scanner. Fast muscle functional MRI scans (generating quantitative T2-maps) were made immediately before and after the exercises. Median T2 values at rest and after exercise were compared to identify activated muscles. After the three SEA exercises, the suprahyoid, infrahyoid, sternocleidomastoid, and lateral pterygoid muscles showed significant T2 value increase. After the Shaker, the lateral pterygoid muscles did not show such an increase, but the three other muscle groups did. The cES and Masako caused no significant increase in any of these muscle groups. During conventional (Shaker) exercises, the suprahyoid, infrahyoid, and sternocleidomastoid muscles are activated. During the SEA exercises, the suprahyoid, infrahyoid, sternocleidomastoid, and lateral pterygoid muscles are activated. The findings of this explorative study further support the potential of the SEA to improve swallowing rehabilitation.


ATM expression in rectal cancers with or without preoperative radiotherapy.
Patients with ATM (Ataxia-Telangiectasia mutated) mutation show increased sensitivity to radiation and have a higher risk of developing malignancies. The present study aimed to investigate whether ATM expression was related to radiotherapy, and clinicopathological and biological variables in rectal cancers. ATM expression was immunohistochemically examined in 78 rectal cancers from patients who participated in a Swedish rectal cancer trial of preoperative radiotherapy. Of 78 patients, 44 underwent surgery alone, and 34 underwent both preoperative radiotherapy and surgery. Fifty-eight cases had normal rectal mucosa adjacent to the tumour. The results showed that, compared to normal mucosa, tumours had less nuclear (p=0.03) but more cytoplasmic expression of ATM (p=0.004). In tumours, less expression of ATM, either in the nucleus (p=0.07) or in the cytoplasm (p=0.02 for staining intensity, and p=0.07 for staining percentage), tended to be correlated with male patients. Also, ATM expression was not related to radiotherapy or other clinicopathological and biological variables (p>0.05). In conclusion, the pattern of ATM expression was changed from normal mucosa to tumour. Less expression of ATM may be related to males.


Psychometric Properties of the Lesbian, Gay, and Bisexual Identity Scale-Turkish (LGBIS-TR).
The aim of the current study was to examine the psychometric properties of the Lesbian, Gay, and Bisexual Identity Scale (LGBIS; Mohr & Kendra, 2011) in a Turkish sample. Three hundred and ten LGB individuals participated and completed the Turkish version of the LGBIS (LGBIS-TR) along with the Satisfaction with Life, Positive and Negative Affect, and Self-Compassion Scales. Confirmatory factor analysis results yielded a good-fit for eight subscales of the LGBIS-TR. We also obtained satisfactory criterion validity and internal consistency reliability. Based on this initial study, the LGBIS-TR appears to be a psychometrically sound instrument to gauge LGB individuals' identity experiences in Turkey. We discuss the results along with previous findings and limitations of the study, and we provide implications for further research and practice.


Schizophrenia and cancer: an epidemiological study.
For decades there has been interest in the possibility that people with schizophrenia might have some protection against cancer, and that, if this were so, it might hold clues about aetiological mechanisms in schizophrenia. To study cancer incidence in schizophrenia. Cohort analysis of linked hospital and death records was used to compare cancer rates in people with schizophrenia with a reference cohort. We did not find a reduced risk for cancer overall (rate ratio 0.99,95% CI 0.90-1.08) or for most individual cancers. There was, however, a significantly low rate ratio for skin cancer (0.56,95% CI 0.36-0.83). We found no evidence that schizophrenia confers protection against cancer in general. Low rates of cancer are consistent with the hypothesis that sun exposure may influence the development of schizophrenia, although other explanations are also possible.


Parents' Personality-Disorder Symptoms Predict Children's Symptoms of Anxiety and Depressive Disorders - a Prospective Cohort Study.
Personality disorder (PD) symptomatology is characterized by interpersonal problems and emotional dysregulation, which may affect offspring of parents with PD symptoms. Notably though, studies are needed to discern (i) whether parental PDs forecast symptoms of psychiatric disorders in offspring during their childhood years and (ii) whether such prospective relations obtain after accounting for common causes (e.g., genetics, common methods). To address these issues, we followed up a community sample of Norwegian children biennially from ages 4 to 8 (n = 594), using a semi-structured psychiatric interview (PAPA/CAPA) to capture DSM-IV defined symptoms of emotional disorders. Parental symptoms of personality disorders were captured by the DSM-IV and ICD-10 Personality Questionnaire (DIP-Q), whereas depression and anxiety in caregivers were measured using the Beck Depression Inventory -II and Beck Anxiety Inventory, respectively. Upon applying a hybrid fixed and random effects method that takes into account all unmeasured time-invariant confounders, we found that: (i) Parental symptoms of DSM-IV defined Cluster A and C were related to symptoms of anxiety disorders in offspring two years later, even after accounting for children's initial levels of anxiety and parental anxiety, whereas (ii) Parental DSM-IV Cluster B predicted symptoms of depressive disorders in children, adjusted for children's initial levels of depression and parental depression. Clinical implications of the results are discussed.


An early marker for semantic memory impairment in patients with schizophrenia.
Semantic memory impairment is now a well-documented phenomenon in patients with schizophrenia. Nevertheless, the characteristics of this deficit and any early markers remain contentious. In this preliminary study, 12 schizophrenic patients underwent longitudinal assessment using a battery of semantic memory tests. Patient performance was compared to 12 matched controls. Using set criteria (derived from Warrington & Shallice, 1979), we examined whether the patients had a disorder affecting access to intact representations, or a degradation/loss of the representations themselves. The criteria were: consistency across time and modality, level of attribute information, and responsiveness to cueing. Finally, we compared patient naming for the same items across two naming tests (naming-to-description and picture naming) to determine cross-modality consistency. As expected, normal controls outperformed the patients on all tests. Naming-to-description was the most significant differentiator between patients and controls. Patients were inconsistent across both time and modality, showed minimal attributional knowledge impairment, and improved significantly with cueing on two naming tests. The profile of results indicates an access-type semantic deficit in this cohort of patients with schizophrenic. Finally, on a naming-to-description task, the patients failed to name up to 20% of items that they could name to picture. This suggests that naming-to-definition may act as an early marker of semantic memory impairment.


Peptides as Potential Biomarkers for Authentication of Mountain-Cultivated Ginseng and Cultivated Ginseng of Different Ages Using UPLC-HRMS.
The growth conditions and age of Panax ginseng are vital for determining the quality of the ginseng plant. However, the considerable difference in price according to the cultivation method and period of P. ginseng leads to its adulteration in the trade market. We herein focused on ginseng peptides and the possibility of these peptides to be used as biomarker(s) for discrimination of P. ginseng. We applied an ultraperformance liquid chromatography-high resolution mass spectrometry-based peptidomics approach to characterize ginseng peptides and discover novel peptide biomarkers for authentication of mountain-cultivated ginseng (MCG). We identified 52 high-confidence peptides and screened 20 characteristic peptides differentially expressed between MCG and cultivated ginseng (CG). Intriguingly, 6 differential peptides were expressed significantly in MCG and originated from dehydrins that accumulated during cold or drought conditions. In addition, 14 other differential peptides that were significantly expressed in CG derived from ginseng major protein, an essential protein for nitrogen storage. These biological associations confirmed the reliability and credibility of the differential peptides. Additionally, we determined several robust peptide biomarkers for discrimination of MCG through a precise selection process. These findings demonstrate the potential of peptide biomarkers for identification and quality control of P. ginseng in addition to ginsenoside analysis.


Efficacy of infliximab in intestinal Behçet's disease: a Korean multicenter retrospective study.
Although infliximab is widely accepted as a therapeutic option for inflammatory bowel disease, its therapeutic efficacy for the treatment of intestinal Behçet's disease (BD) is unknown. We investigated the short-term and long-term response rates to infliximab in intestinal BD and predictive factors of sustained treatment response following infliximab treatment. This study was conducted using a retrospective noncontrolled review of medical records from 8 tertiary hospitals in Korea. We collected clinical, demographic, and laboratory data for patients with 28 patients with intestinal BD who received at least 1 dose of infliximab. Response rates of infliximab at 2, 4, 30, and 54 weeks for each patient and factors predictive of sustained response were investigated. Adverse events were also identified. The median duration of follow-up after initial infliximab infusion was of 29.5 months. The clinical response rates at 2, 4, 30, and 54 weeks were 75%, 64.3%, 50%, and 39.1%, respectively, with clinical remission rates of 32.1%, 28.6%, 46.2%, and 39.1%, respectively. After multivariate analysis, older age at diagnosis (≥40 yr), female sex, a longer disease duration (≥5 yr), concomitant immunomodulator use, and achievement of remission at week 4 were found to be predictive factors of sustained response. There was 1 serious infection but no malignancies or deaths in this study. Infliximab was a well-tolerated and effective therapy for patients with moderate-to-severe intestinal BD. Moreover, we found 5 predictive factors associated with sustained response, which might assist in optimal patient selection for infliximab treatment.


Excitatory and inhibitory lateral interactions effects on contrast detection are modulated by tRNS.
Contrast sensitivity for a Gabor signal is affected by collinear high-contrast Gabor flankers. The flankers reduce (inhibitory effect) or increase (facilitatory effect) sensitivity, at short (2λ) and intermediate (6λ) target-to-flanker separation respectively. We investigated whether these inhibitory/facilitatory sensitivity effects are modulated by transcranial random noise stimulation (tRNS) applied to the occipital and frontal cortex of human observers during task performance. Signal detection theory was used to measure sensitivity (d') and the Criterion (C) in a contrast detection task, performed with sham or tRNS applied over the occipital or the frontal cortex. After occipital stimulation results show a tRNS-dependent increased sensitivity for the single Gabor signal of low but not high contrast. Moreover, results suggest a dissociation of the tRNS effect when the Gabor signal is presented with the flankers, consisting in a general increased sensitivity at 2λ where the flankers had an inhibitory effect (reduction of inhibition) and a decreased sensitivity at 6λ where the flankers had a facilitatory effect on the Gabor signal (reduction of facilitation). After a frontal stimulation, no specific effect of the tRNS was found. We account for these complex interactions between tRNS and flankers by assuming that tRNS not only enhances feedforward input from the Gabor signal to the cortex, but also enhances the excitatory or inhibitory lateral intracortical input from the flankers. The boosted lateral input depends on the excitation-inhibition (E/I) ratio, namely when the lateral input is weak, it is boosted by tRNS with consequent modification of the contrast-dependent E/I ratio.


Antitumor Effects and Mechanisms of AZD4547 on FGFR2-Deregulated Endometrial Cancer Cells.
Uncontrolled activation of FGFRs induces the progression of various cancers. It was recently reported that FGFR2-activating mutants are implicated in about 12% of endometrial carcinomas. AZD4547, a potent pan-FGFR inhibitor, is currently being evaluated in clinical trials for several FGFR-driven cancers. However, AZD4547 has not been examined yet against FGFR2 mutant-driven endometrial cancers. Thus, we evaluated the activity of AZD4547 against four different endometrial cancer cells, including AN3-CA, MFE296, MFE280, and HEC1A, where all but HEC1A cells express distinctive FGFR2 mutations. We found that AZD4547 exhibits potent antiproliferative activity (EC50 = 31 nmol/L) against AN3-CA cells harboring FGFR2-K310R/N550K mutant. Analysis using a phospho-kinase array revealed that AZD4547 blocks FGFR2 downstream signaling, such as p38, ERK1/2, JNK, p70S6K, and PLCγ. Moreover, oral administration of AZD4547 (30 mg/kg, every day) remarkably delayed tumor growth in a mouse xenograft model of AN3-CA cells. Unbiased reporter gene assay showed that AZD4547 antagonizes the aFGF-induced activation of several transcription factors, including EGR1, ELK-1/SRF, AP-1, and NFκB. Genome-wide transcriptome analysis revealed that AZD4547 perturbs a number of transcriptions, and EGR1 was identified as one of the major targets of AZD4547. The significance of the FGFR2-EGR1 axis in endometrial cancer progression has not been reported. In addition, using kinome-wide inhibition profiling analysis, we first identified potential new target kinases of AZD4547, including MAP4K3, MAP4K5, IRR, RET, and FLT3. Our study demonstrated that AZD4547 exhibits its therapeutic activity against endometrial cancer cells by perturbing various regulatory mechanisms related to FGFR signaling.


Tests for genetic interactions in type 1 diabetes: linkage and stratification analyses of 4,422 affected sib-pairs.
Interactions between genetic and environmental factors lead to immune dysregulation causing type 1 diabetes and other autoimmune disorders. Recently, many common genetic variants have been associated with type 1 diabetes risk, but each has modest individual effects. Familial clustering of type 1 diabetes has not been explained fully and could arise from many factors, including undetected genetic variation and gene interactions. To address this issue, the Type 1 Diabetes Genetics Consortium recruited 3,892 families, including 4,422 affected sib-pairs. After genotyping 6,090 markers, linkage analyses of these families were performed, using a novel method and taking into account factors such as genotype at known susceptibility loci. Evidence for linkage was robust at the HLA and INS loci, with logarithm of odds (LOD) scores of 398.6 and 5.5, respectively. There was suggestive support for five other loci. Stratification by other risk factors (including HLA and age at diagnosis) identified one convincing region on chromosome 6q14 showing linkage in male subjects (corrected LOD = 4.49; replication P = 0.0002), a locus on chromosome 19q in HLA identical siblings (replication P = 0.006), and four other suggestive loci. This is the largest linkage study reported for any disease. Our data indicate there are no major type 1 diabetes subtypes definable by linkage analyses; susceptibility is caused by actions of HLA and an apparently random selection from a large number of modest-effect loci; and apart from HLA and INS, there is no important susceptibility factor discoverable by linkage methods.


Effect of using an interactive booklet about childhood respiratory tract infections in primary care consultations on reconsulting and antibiotic prescribing: a cluster randomised controlled trial.
To establish whether an interactive booklet on respiratory tract infections in children reduces reconsultation for the same illness episode, reduces antibiotic use, and affects future consulting intentions, while maintaining parental satisfaction with care. Pragmatic cluster randomised controlled trial. 61 general practices in Wales and England. 558 children (6 months to 14 years) presenting to primary care with an acute respiratory tract infection (7 days or less). Children with suspected pneumonia, asthma or a serious concomitant illness, or needing immediate hospital admission were excluded. Three withdrew and 27 were lost to follow-up, leaving 528 (94.6%) with main outcome data. Clinicians in the intervention group were trained in the use of an interactive booklet on respiratory tract infections and asked to use the booklet during consultations with recruited patients (and provide it as a take home resource). Clinicians in the control group conducted their consultations as usual. The proportion of children who attended a face-to-face consultation about the same illness during the two week follow-up period. Secondary outcomes included antibiotic prescribing, antibiotic consumption, future consulting intentions, and parental satisfaction, reassurance, and enablement. Reconsultation occurred in 12.9% of children in the intervention group and 16.2% in the control group (absolute risk reduction 3.3%, 95% confidence interval -2.7% to 9.3%, P=0.29). Using multilevel modelling (at the practice and individual level) to account for clustering, no significant difference in reconsulting was noted (odds ratio 0.75; 0.41 to 1.38). Antibiotics were prescribed at the index consultation to 19.5% of children in the intervention group and 40.8% of children in the control group (absolute risk reduction 21.3%, 95% confidence interval 13.7 to 28.9), P<0.001). A significant difference was still present after adjusting for clustering (odds ratio 0.29; 0.14 to 0.60). There was also a significant difference in the proportion of parents who said they would consult in the future if their child developed a similar illness (odds ratio 0.34; 0.20 to 0.57). Satisfaction, reassurance, and parental enablement scores were not significantly different between the two groups. Use of a booklet on respiratory tract infections in children within primary care consultations led to important reductions in antibiotic prescribing and reduced intention to consult without reducing satisfaction with care. Current Controlled Trials ISRCTN46104365.


Tumour-derived PGD2 and NKp30-B7H6 engagement drives an immunosuppressive ILC2-MDSC axis.
Group 2 innate lymphoid cells (ILC2s) are involved in human diseases, such as allergy, atopic dermatitis and nasal polyposis, but their function in human cancer remains unclear. Here we show that, in acute promyelocytic leukaemia (APL), ILC2s are increased and hyper-activated through the interaction of CRTH2 and NKp30 with elevated tumour-derived PGD2 and B7H6, respectively. ILC2s, in turn, activate monocytic myeloid-derived suppressor cells (M-MDSCs) via IL-13 secretion. Upon treating APL with all-trans retinoic acid and achieving complete remission, the levels of PGD2, NKp30, ILC2s, IL-13 and M-MDSCs are restored. Similarly, disruption of this tumour immunosuppressive axis by specifically blocking PGD2, IL-13 and NKp30 partially restores ILC2 and M-MDSC levels and results in increased survival. Thus, using APL as a model, we uncover a tolerogenic pathway that may represent a relevant immunosuppressive, therapeutic targetable, mechanism operating in various human tumour types, as supported by our observations in prostate cancer.Group 2 innate lymphoid cells (ILC2s) modulate inflammatory and allergic responses, but their function in cancer immunity is still unclear. Here the authors show that, in acute promyelocytic leukaemia, tumour-activated ILC2s secrete IL-13 to induce myeloid-derived suppressor cells and support tumour growth.


A cluster randomised controlled effectiveness trial evaluating perinatal home visiting among South African mothers/infants.
Interventions are needed to reduce poor perinatal health. We trained community health workers (CHWs) as home visitors to address maternal/infant risks. In a cluster randomised controlled trial in Cape Town townships, neighbourhoods were randomised within matched pairs to 1) the control, healthcare at clinics (n = 12 neighbourhoods; n = 594 women), or 2) a home visiting intervention by CBW trained in cognitive-behavioural strategies to address health risks (by the Philani Maternal, Child Health and Nutrition Programme), in addition to clinic care (n = 12 neighbourhoods; n = 644 women). Participants were assessed during pregnancy (2% refusal) and 92% were reassessed at two weeks post-birth, 88% at six months and 84% at 18 months later. We analysed 32 measures of maternal/infant well-being over the 18 month follow-up period using longitudinal random effects regressions. A binomial test for correlated outcomes evaluated overall effectiveness over time. The 18 month post-birth assessment outcomes also were examined alone and as a function of the number of home visits received. Benefits were found on 7 of 32 measures of outcomes, resulting in significant overall benefits for the intervention compared to the control when using the binomial test (p = 0.008); nevertheless, no effects were observed when only the 18 month outcomes were analyzed. Benefits on individual outcomes were related to the number of home visits received. Among women living with HIV, intervention mothers were more likely to implement the PMTCT regimens, use condoms during all sexual episodes (OR = 1.25; p = 0.014), have infants with healthy weight-for-age measurements (OR = 1.42; p = 0.045), height-for-age measurements (OR = 1.13, p<0.001), breastfeed exclusively for six months (OR = 3.59; p<0.001), and breastfeed longer (OR = 3.08; p<0.001). Number of visits was positively associated with infant birth weight ≥2500 grams (OR = 1.07; p = 0.012), healthy head-circumference-for-age measurements at 6 months (OR = 1.09, p = 0.017), and improved cognitive development at 18 months (OR = 1.02, p = 0.048). Home visits to neighbourhood mothers by CHWs may be a feasible strategy for enhancing maternal/child outcomes. However, visits likely must extend over several years for persistent benefits. ClinicalTrials.gov NCT00996528.


Health benefit costs and absenteeism due to insomnia from the employer's perspective: a retrospective, case-control, database study.
To objectively assess the economic impact of insomnia on direct medical and prescription costs and indirect absence-related salary replacement costs and on absences and to compare the prevalence and costs of comorbidities in employees with and without insomnia. A retrospective analysis was performed on employee data from the Human Capital Management Services Research Reference Database (January 2001-September 2007). Employees were identified as having insomnia (ICD-9 criteria) based on history of receiving medications used to treat insomnia or physician's diagnosis of insomnia. Control employees had no history of medications used to treat insomnia and no insomnia diagnosis. Annual costs and number of absences were compared using 2-part regression models, controlling for demographics, job information, geographic region, comorbid disorders, and the Charlson Comorbidity Index score. Comorbidity prevalence, costs, and services were compared. Data were collected for 299,188 employees (17,230 employees with insomnia and 281,958 control employees). Annual mean incremental costs were $2,053 greater (in total) for employees with insomnia compared with controls (specific increments: medical $751, drug $735, sick leave $208, short-term disability $179, long-term disability $10, and workers' compensation $170). Employees with insomnia missed a mean of 3.10 more workdays annually than those without insomnia. Nearly all comorbid conditions were more prevalent, were more costly, and resulted in a greater utilization of services in employees with insomnia compared to those without. All of the above comparisons were significant (P < .05). Insomnia was associated with increased costs, greater absenteeism, and an increased number of comorbid conditions in an employed population. Consistent with other analyses based on these data, the study estimated the annual cost of insomnia in the US civilian labor force to be approximately $15.0-17.7 billion (US dollars).


Level of clinical evidence presented at the open and closed American Shoulder and Elbow Surgeons annual meeting over 10 years (2005-2014).
The American Shoulder and Elbow Surgeons (ASES) annual scientific meetings are premier forums whereby orthopaedic surgeons are informed of the latest research advances in shoulder and elbow surgery. The purpose of the present study was to assess the Level of evidence (LOE) in the clinical papers presented at both the open and closed ASES annual scientific meetings from 2005 to 2014. Secondarily, the study evaluated whether there were any changes in the distribution of LOE over this period of time. Two reviewers independently evaluated the abstracts of 532 paper presentations at either the open or closed ASES annual meetings. The independent reviewers first screened the abstracts for clinical evidence and excluded cadaveric, biomechanical, technique, and review studies. The included abstracts were then independently graded for methodological quality using LOE from Level I (highest quality) to IV (lowest quality) based on the classification system created by The American Academy of Orthopaedic Surgeons (AAOS). Overall, 421 presentations were included and graded for LOE. In general, 17% of the presentations were graded level I; 15% level II; 25% level III; and 43% assigned a LOE of IV. Chi-square analysis demonstrated a statistically significant improvement in the LOE of presentations at the open and closed ASES meetings combined (p = 0.028) between the years 2005 and 2014. In particular, the proportion of presentations graded as level IV significantly decreased over this period (p = <0.001). While most presentations at the ASES annual scientific meetings were of lower LOEs the percentage of level I evidence is greater than that reported at other Orthopaedic meetings. There has been a significant improvement in the LOE of clinical research at open and closed ASES meetings from 2005 to 2014. Specifically, the proportion of level IV studies have dramatically decreased over time.


Pomegranate peel extract reduced colonic damage and bacterial translocation in a mouse model of infectious colitis induced by Citrobacter rodentium.
The pomegranate fruit peel is a rich source of polyphenols including punicalins, punicalagins, and ellagic acids, but is considered an agricultural waste product. Pomegranate derived products have been reported to have a wide variety of health promoting benefits including antibacterial properties in vitro but there is limited evidence of their antibacterial properties in vivo. The purpose of this study was to test the in vivo antibacterial properties of a pomegranate peel extract (PPX) containing punicalin, punicalagin, and ellagic acid. C3H/He mice were orally pre-treated with water or PPX prior to infection with the mouse bacterial pathogen, Citrobacter rodentium (Cr) that mimics many aspects of human enteropathogenic Escherichia coli infections. Fecal excretion of Cr was monitored and mice were euthanized on day 12 post-infection to assess Cr colonization of the colon and spleen, histological changes, and gene expression. PPX-treatment reduced Cr infection induced weight loss and mortality that was observed in water-treated infected mice. However, Cr colonization of the colon and clearance was unaffected by PPX-treatment. Consistent with this, PPX treatment did not alter the potent Th1/Th17 pro-inflammatory response elicited by Cr infection. Significant colonization of the spleen was only seen in water-treated infected mice and was inversely correlated with the dose of PPX administered. PPX treatment decreased the extent of Cr-induced colon damage that correlated with decreased mortality and reduced colonization of the spleen. Thus, a pomegranate peel extract contains bioactive compounds that mitigate the deleterious effects of an in vivo infection with the model enteropathogenic bacteria, Cr.


Luteibacter rhizovicinus gen. nov., sp. nov., a yellow-pigmented gammaproteobacterium isolated from the rhizosphere of barley (Hordeum vulgare L.).
Three strains of Gram-negative, aerobic, yellow-pigmented, chemo-organotrophic bacteria, motile by a polar flagellum, were isolated from the rhizosphere of spring barley (Hordeum vulgare L.) at a research field near Copenhagen, Denmark. The three strains, LJ79, LJ96T and LJ99, formed visible colonies on one-tenth-strength tryptic soy broth supplemented with agar (1/10 TSBA) after incubation for 6 days at 15 degrees C. The strains hydrolysed starch, casein (skimmed milk), gelatin and various pentoses and hexoses and grew on MacConkey agar and full-strength TSBA. Growth on 1/10 TSBA occurred at 4-30 degrees C, pH 6-9 and 0-3 % (w/v) NaCl. The strains had identical 16S rRNA gene sequences and ERIC (enterobacterial repetitive intergenic consensus sequence) fingerprint profiles, but could be differentiated by their RAPD (random amplified polymorphic DNA) fingerprint patterns. Strain LJ96(T) had a DNA G+C content of 64.3 mol% and the major fatty acids were 15 : 0 iso (23.4 %), 17 : 1 iso omega9c (25.5 %) and 17 : 0 iso (18.1 %). Phylogenetic analysis of the 16S rRNA gene sequences of the three strains showed 96 % sequence similarity to Rhodanobacter lindaniclasticus LMG 18385T, 95 % to Frateuria aurantia DSM 6220T and 96 % to Fulvimonas soli LMG 19981T. Using LJ96T DNA as probe, DNA-DNA hybridizations documented the relationship of the three strains to a single species (87.4-98.7 % relatedness) and showed less than 30 % relatedness to Frateuria aurantia DSM 6220T and Fulvimonas soli DSM 14263T. Rhodanobacter lindaniclasticus LMG 18385T is not extant and the strain not available from any public strain collections, thus DNA-DNA hybridization could not include this strain. On the basis of genotypic and phenotypic characteristics, the three yellow-pigmented strains could also be differentiated from Frateuria aurantia, Fulvimonas soli and Rhodanobacter lindaniclasticus. The name Luteibacter rhizovicinus gen. nov., sp. nov. is proposed, with the type strain LJ96T (=DSM 16549T=ATCC BAA-1015T).


A Systematic Review of the Effects of Single-Event Multilevel Surgery on Gait Parameters in Children with Spastic Cerebral Palsy.
Three-dimensional gait analysis (3DGA) is commonly used to assess the effect of orthopedic single-event multilevel surgery (SEMLS) in children with spastic cerebral palsy (CP). The purpose of this systematic review is to provide an overview of different orthopedic SEMLS interventions and their effects on 3DGA parameters in children with spastic CP. A comprehensive literature search within six databases revealed 648 records, from which 89 articles were selected for the full-text review and 24 articles (50 studies) included for systematic review. The Oxford Centre for Evidence-Based Medicine Scale and the Methodological Index for Non-Randomized Studies (MINORS) were used to appraise and determine the quality of the studies. Except for one level II study, all studies were graded as level III according to the Oxford Centre for Evidence-Based Medicine Scale. The MINORS score for comparative studies (n = 6) was on average 15.7/24, while non-comparative studies (n = 18) scored on average 9.8/16. Nineteen kinematic and temporal-distance gait parameters were selected, and a majority of studies reported improvements after SEMLS interventions. The largest improvements were seen in knee range of motion, knee flexion at initial contact and minimal knee flexion in stance phase, ankle dorsiflexion at initial contact, maximum dorsiflexion in stance and in swing phase, hip rotation and foot progression angles. However, changes in 3DGA parameters varied based on the focus of the SEMLS intervention. The current article provides a novel overview of a variety of SEMLS interventions within different SEMLS focus areas and the post-operative changes in 3DGA parameters. This overview will assist clinicians and researchers as a potential theoretical framework to further improve SEMLS techniques within different SEMLS focus groups. In addition, it can also be used as a tool to enhance communication with parents, although the results of the studies can't be generalised and a holistic approach is needed when considering SEMLS in a child with spastic CP.


[Effect of vaccination against GnRH (Bopriva®) in the male pubertal calf].
The objective of this experiment was to investigate the effectiveness of a newly developed bovine anti-GnRH vaccine (Bopriva®, Pfizer Animal Health, Australia). A total of 12 peripubertal bull calves aged between 6 and 8 months were used, 2 randomly selected animals served as controls. Animals were vaccinated twice at an interval of 4 weeks with 1ml of Bopriva® (400 μg GnRH-protein-conjugate) subcutaneously in the neck and observed for a total of 36 weeks. Scrotal circumference was measured every week and blood samples were also taken weekly for the determination of testosterone and GnRH antibodies. Three months after the second injection (booster), 5 animals were slaughtered and their testes histologically examined. GnRH antibody titers rapidly began to rise after the second vaccination and reached peak values 3 weeks later. Testosterone concentrations decreased to values below 0.5 ng/ml serum 1 week after the booster and remained at this low level for at least 10 weeks. The following increase of testosterone occurred individually within 11 and 23 weeks after the booster injection. Histological examination of testes in vaccinated animals showed an incomplete spermatogenesis with impaired or no production of spermatids and a reduced diameter of seminiferous tubules. From our results we conclude that in the peripubertal bull two injections with the new bovine anti-GnRH vaccine 4 weeks apart is effective in suppressing testicular growth and testosterone secretion during at least 10 weeks after the booster injection.


Reversible median nerve impairment after three weeks of repetitive work.
Objectives The aim of this study was to evaluate the development of impaired median nerve function in relation to hand-intensive seasonal work. We hypothesized that at end-season, median nerve conduction would be impaired and then recover within weeks. Methods Using nerve conduction studies (NCS), we examined median nerve conduction before, during, and after engaging in 22 days of mink skinning. For a subgroup, we used goniometry and surface electromyography to characterize occupational mechanical exposures. Questionnaire information on symptoms, disability, and lifestyle factors was obtained. Results The study comprised 11 male mink skinners with normal median nerve conduction at pre-season (mean age 35.7 years, mean number of seasons with skinning 8.9 years). Mink skinning was characterized by a median angle of wrist flexion/extension of 16º extension, a median velocity of wrist flexion/extension of 22 °/s, and force exertions of 11% of maximal voluntary electrical activity. At end-season, mean distal motor latency (DML) had increased 0.41 ms (P<0.001), mean sensory nerve conduction velocity (SNCV) digit 2 had decreased 6.3 m/s (P=0.004), and mean SNCV digit 3 had decreased 6.2 m/s (P=0.01); 9 mink skinners had decreases in nerve conduction, 5 fulfilled electrodiagnostic criteria and 4 fulfilled electrodiagnostic and clinical criteria (a positive Katz hand diagram) for carpal tunnel syndrome (CTS). Three to six weeks post-season, the changes had reverted to normal. Symptom and disability scores showed corresponding changes. Conclusions In this natural experiment, impaired median nerve conduction developed during 22 days of repetitive industrial work with moderate wrist postures and limited force exertion. Recovery occurred within 3-6 weeks post-season.


Acute myocardial infarction in sickle cell anemia.
Typical acute myocardial infarction in a well-documented case of sickle cell disease, to our knowledge, has not been reported. A patient with hemoglobin SS proved by electrophoresis with typical clinical manifestation and diagnostic ECG changes died suddenly. Autopsy findings were confirmatory, but no atherogenic lesions were present. Possible mechanisms for acute infarction are discussed, including sludging of sickle cells, coronary spasm, thrombus formation, and severe anemia associated with any or all of the aforementioned.


Association of plasma growth arrest-specific protein 6 (Gas6) concentrations with albuminuria in patients with type 2 diabetes.
New biomarkers are required to detect diabetic nephropathy earlier in persons with type 2 diabetes mellitus. Recent experimental studies indicate that growth arrest-specific protein 6 (Gas6) may have a role in pathogenesis of complications associated with diabetes. The objective of the current study is to examine whether plasma Gas6 concentrations are associated with albuminuria in persons with type 2 diabetes mellitus. About 32 patients with diabetes which have micro or macroalbuminuria, 37 patients with diabetes and normoalbuminuria, and 30 healthy volunteers were recruited. Plasma Gas6 levels were measured by ELISA. Hemoglobin A1c (HbA1c), serum C reactive protein, fibrinogen and 24-h urine samples for microalbuminuria were analyzed by Primus PDQ, Beckman Coulter Immage 800, STA Compact and Roche Cobas Integra 800 analyzer, respectively. Statistical analysis was performed using SPSS (Statistical Package for Social Sciences) for Windows 11.5. There was a noteworthy difference among the three groups for Gas6 according to the Kruskal-Wallis test (p < 0.01). Plasma Gas6 concentrations were higher in patients with micro or macroalbuminuria [20.9 ng/mL (16.7-27.0); median (25-75% percentile)] compared to patients with normoalbuminuria [16.5 ng/mL (13.1-22.9)], and healthy controls [15.3 ng/mL (8.3-33.6)]. In conclusion, this is the first study indicating that plasma Gas6 levels are associated with albuminuria in patients with type 2 diabetes. This study could be considered a starting point to focus on the association between Gas6 and diabetic nephropathy.


Malignancy risk of sonographically benign appearing purely solid adnexal masses in asymptomatic postmenopausal women.
To assess the natural history of benign appearing purely solid ovarian lesions in asymptomatic postmenopausal women. Retrospective observational cohort study comprising 99 women (mean age, 58.2 years, ranging from 50 to 77 years) diagnosed as having a purely solid ovarian lesion at transvaginal ultrasound between April 2001 and October 2015. Inclusion criteria were as follows: asymptomatic postmenopausal women with a well-defined purely solid ovarian lesion with International Ovarian Tumor Analysis color score 1 or 2, without ascites and/or signs of carcinomatosis. Clinical, sonographic, biochemical (CA-125), and histologic data (in case of surgery) were retrieved for analysis. Patients who were managed conservatively were assessed by transvaginal sonography every 6 months for a minimum of a year. In case of bilateral lesions we used the largest one for analysis. Five women (5.1%) had bilateral lesions. Mean size of the lesion was 2.9 cm (range, 1.0-7.8 cm). Most lesions were homogeneous (96.0%). Acoustic shadowing was present in 59.6% of cases. International Ovarian Tumor Analysis color score was 1 in 77.8% and 2 in 22.2% of the cases, respectively. Median CA-125 was 10.8 IU/mL (range, 3.0-403.0 IU/mL). Forty-two women underwent surgery after diagnosis (histologic diagnoses were as follows: fibroma (n = 26), fibrothecoma (n = 5), dermoid (n = 3), Brenner tumor (n = 3), endometrioma (n = 2), thecoma (n = 1), primary invasive cancer (n = 2). One case of invasive cancer CA-125 was 403.0 IU/mL and in the other case CA-125 was 6.0 IU/mL. They both were stage 1. Fifty-seven women were managed with serial follow-up. With a median follow-up time of 36 months (range, 12-142 months) all these lesions had no change and women remain asymptomatic. Considering all 99 cases the risk of malignancy is 2% (95% CI, 0.1-7.5). The risk of malignancy of benign appearing purely solid adnexal masses in asymptomatic postmenopausal women is low. Conservative management of these lesions might be an option.


Isolated right segmental hepatic duct injury: a diagnostic and therapeutic challenge.
Biliary leaks and injuries are not an uncommon occurrence following laparoscopic cholecystectomy. Bile leaks associated with the biliary anatomic variant of a low-inserting right segmental hepatic duct can be particularly difficult to diagnose in that results of endoscopic retrograde cholangiography (ERC) are usually interpreted as "normal" with no leaks demonstrated. The aim of this study was to describe a single institution's experience with nine patients with biliary leaks associated with this anatomic variant and to discuss their management. A retrospective analysis of the hospital records of all patients with bile duct injuries managed at a single institution between 1980 and July 1998, inclusive, was performed. Nine patients were identified as having an isolated right segmental hepatic duct injury associated with a biliary leak. Seven (78%) of the nine patients had undergone a laparoscopic cholecystectomy, whereas the remaining two patients (22%) had undergone an open cholecystectomy. All of the patients had undergone endoscopic retrograde cholangiography at outside institutions, the results of which had been interpreted as normal with no apparent leaks. The median interval from the time of cholecystectomy to referral was 1.4 months. All patients were managed with initial percutaneous access of the involved right segmental biliary system, with placement of a percutaneous transhepatic stent. After the biliary leak was controlled, all patients underwent Roux-en-Y hepaticojejunostomy to the isolated biliary segment. All patients had an uncomplicated postoperative course. There were no postoperative anastomotic leaks. Postoperative stenting was maintained for a mean of 8 months. Six (67%) of the nine patients had a long-term successful outcome with minimal or no symptoms. In three patients, recurrent symptoms with pain and/or cholangitis developed at a mean of 34 months. All three patients underwent percutaneous cholangiography, which demonstrated an anastomotic stricture, and all were managed with percutaneous balloon dilatation with a successful outcome. Currently eight (89%) of the nine patients are asymptomatic, with a mean follow-up of 70.4 months (range 12 to 226 months). One patient had intermittent right upper quadrant pain with normal liver function tests but has not required intervention. Isolated right segmental hepatic ductal injury with biliary leakage is an uncommon complication following laparoscopic cholecystectomy. A diagnostic dilemma is created by the presence of a bile leak with a normal endoscopic retrograde cholangiogram. Management begins with percutaneous access of the transected isolated ductal system followed by reconstruction as a Roux-en-Y hepaticojejunostomy.


The genetic control of the immune response to staphylococcal nuclease VI. Recombination between genes determining the A/J anti-nuclease idiotypes and the heavy chain allotype locus.
Rat antisera detecting binding site-specific idiotypic determinants on anti-nuclease antibodies from A/J mice have been used to define the A/J anti-nuclease idiotype and to investigate its genetic linkage as a variable region marker. Analysis of the segregation of the A/J idiotype in progeny of the backcross (B10.A X A/J) X B10.A showed linkage of the idiotype to the Ig-1e heavy chain allotype locus. There was, however, a very high apparent frequency of recombination, with 7 of 101 backcross animals having a recombinant phenotype. All of these putative recombinants were accounted for by Ig-1b/Ig-1b homozygotes which bore the A/J idiotype, and none by Ig-1b/Ig-1e heterozygotes lacking the idiotype. On progeny testing of these animals in another backcross to B10.A the recombinant trait bred true. If this idiotype is indeed a marker for variable region structural genes, then the germ line gene pool must be very large or there must be special genetic mechanism to account for the increased recombinational frequency observed.


ACHESS--The Australian study of child health in same-sex families: background research, design and methodology.
There are an increasing number of children in Australia growing up with same-sex attracted parents. Although children from same-sex parent families do in general perform well on many psychosocial measures recent research is beginning to consider some small but significant differences when these children are compared with children from other family backgrounds. In particular studies suggest that there is an association between the stigma that same-sex parent families experience and child wellbeing. Research to date lacks a holistic view with the complete physical, mental and social wellbeing of children not yet addressed. In addition, most studies have focused only on families with lesbian parents and have studied only small numbers of children. The Australian Study of Child Health in Same-Sex Families (ACHESS) is a national study that aims to determine the complete physical, mental and social wellbeing of Australian children under the age 18 years with at least one parent who self identifies as being same-sex attracted. There will be a particular focus on the impact that stigma and discrimination has on these families. Parent and child surveys will be used to collect data and will be available both online and in paper form. Measures have been chosen whenever possible that have sound conceptual underpinnings, robust psychometric properties and Australian normative data, and include the Child Health Questionnaire (CHQ), the Strengths and Difficulties Questionnaire (SDQ) and the Kessler Psychological Distress Scale (K10). ACHESS aims to be the largest study of its kind and will for the first time produce a detailed quantitative analysis of Australian children with same-sex attracted parents. By inviting participants to take part in further research it will also establish a valuable cohort of children, and their families, to launch future waves of research that will help us better understand the health and wellbeing of children with same-sex attracted parents.


Rapid assay to identify the two genetic forms of Culex (Culex) pipiens L. (Diptera: Culicidae) and hybrid populations.
A previously developed method to identify members of the Culex pipiens complex exploiting polymorphisms in a nuclear intron (acetylcholinesterase [ACE] based-assay) cannot differentiate the two forms of Cx. pipiens: form pipiens and form molestus. Notably, the two forms seem to differ extensively in behavior and physiology and likely have very different epidemiologic importance. Because they are morphologically indistinguishable, molecular methods are critical for the evaluation of their relative importance. Although the two forms of Cx. pipiens have been distinguished using a panel of microsatellite loci, such a protocol is laborious and expensive. We developed a rapid assay based on polymorphisms in the flanking region of a microsatellite locus. Used in conjunction with the ACE-assay, this new assay allows the identification of pure and hybrid populations of the two Cx. pipiens forms as well as those including Cx. quinquefasciatus. We discuss the usefulness of the method as well as limitations to its application.


Electrically induced transmissivity modulation in polymeric thin film Fabry-Perot etalons.
We report the observation of electrically induced changes in transmissivity in Fabry-Perot devices consisting of spin-cast azo-dye/polymer films deposited between gold mirrors. In poled samples the observed modulation shows a linear dependence on the applied modulating voltage. The ratio of the transmissivity modulation observed using incident transverse magnetic polarization to that observed using transverse electric polarization is used to demonstrate that the electrooptic effect dominates the modulation. This is, to our knowledge, the first reported use of a polymeric thin film linear electrooptic material in a Fabry-Perot structure and demonstrates the use of etalons to enhance electrooptic effects in very thin films.


Human-impacted areas of France are environmental reservoirs of the Pseudallescheria boydii/Scedosporium apiospermum species complex.
Species of the Pseudallescheria boydii/Scedosporium apiospermum complex (PSC) are emerging fungal pathogens able to chronically colonize the airways of patients with cystic fibrosis (CF). As P. boydii was found more frequently colonizing the lungs of CF patients in France than in other European countries in a previous report, the present study was conducted in order to clarify distribution of PSC species in France and to characterize their natural habitat. The highest densities of PSC isolates were found in human-impacted areas, i.e. agricultural areas, fluids obtained from wastewater treatment plants, playgrounds and industrial areas. PSC was not detected from soil samples collected in forests. Most PSC culture-positive soil samples exhibited a pH range of 6-8. Scedosporium dehoogii, the most abundant species, was detected in all human-impacted area types except vineyards, whereas Scedosporium aurantiacum was mostly found in agricultural areas. Pseudallescheria boydii and S. apiospermum were predominantly isolated from seashores and playgrounds respectively. Pseudallescheria minutispora was found only once from a playground. This study highlights potential sources of contamination of the patients, especially in the CF context.


Characterization of vasculogenic potential of human adipose-derived endothelial cells in a three-dimensional vascularized skin substitute.
The need for clinically applicable skin substitutes continues to be a matter of fact. Hypothetically, a laboratory grown autologous skin analog with near normal architecture might be a suitable approach to yield both satisfactory functional and cosmetic long-term results. In this study, we explored the use of human endothelial cells derived from freshly isolated adipose stromal vascular fraction (SVF) in a three-dimensional (3D) co-culture model of vascularized bio-engineered skin substitute. The SVF was isolated from human white adipose tissue samples and keratinocytes from human skin biopsies. The SVF, in particular endothelial cells, were characterized using flow cytometry and immuofluorescence analysis. Endothelial and mesenchymal progenitors from the SVF formed blood capillaries after seeding into a 3D collagen type I hydrogel in vitro. Subsequently, human keratinocytes were seeded on the top of those hydrogels to develop a vascularized dermo-epidermal skin substitute. Flow cytometric analysis of surface markers of the freshly isolated SVF showed the expression of endothelial markers (CD31, CD34, CD146), mesenchymal/stromal cell-associated markers (CD44, CD73, CD90, CD105), stem cell markers (CD49f, CD117, CD133), and additionally hematopoietic markers (CD14, CD15, CD45). Further analysis of white adipose-derived endothelial cells (watECs) revealed the co-expression of CD31, CD34, CD90, CD105, and partially CD146 on these cells. WatECs were separated from adipose-stromal cells (watASCs) using FACS sorting. WatASCs and watECs cultured separately in a 3D hydrogel for 3 weeks did not form any vascular structures. Only if co-cultured, both cell types aligned to develop a ramified vascular network in vitro with continuous endothelial lumen formation. Transplantation of those 3D-hydrogels onto immuno-incompetent rats resulted in a rapid connection of human capillaries with the host vessels and formation of functional, blood-perfused mosaic human-rat vessels within only 3-4 days. Adipose tissue represents an attractive cell source due to the ease of isolation and abundance of endothelial as well as mesenchymal cell lineages. Adipose-derived SVF cells exhibit the ability to form microvascular structures in vitro and support the accelerated blood perfusion in skin substitutes in vivo when transplanted.


[Evaluation of cerebral perfusion during aortic clamping and cross-clamping in patients undergoing resection for abdominal aortic aneurysm. A study with transcranial doppler].
To evaluate the cerebral blood flow parameters assessed by transcranial Doppler during aortic cross-clamping and unclamping in patients undergoing abdominal aortic aneurysmectomy. Invasive intraoperative monitoring of mean arterial pressure (MAP) and PaCO2, and right middle cerebral artery (RMCA) monitoring of blood flow parameters (mean velocity "Vm" and pulsatility index "PI") by transcranial Doppler were performed as well as evaluation of the four parameters during these subsequent periods: pre-cross-clamping, pre-unclamping, unclamping and 1-5-10-20 minutes after abdominal aortic unclamping. No significative changes of MAP, PaCO2, Vm and PI were noticed during the aortic cross-clamping period (77.5 +/- 18.5 SD minutes). During aortic unclamping Vm and MAP decreased (64 +/- 20 vs 52 +/- 20 cm/sec, p < 0.05, and 101 +/- 8 vs 80 +/- 15 mmHg, p < 0.01, respectively). At the 1th post-unclamping minute there was an increase from pre-unclamping values of Vm (75 +/- 20 cm/sec, p < 0.05) and PaCO2 (42 +/- 1.5 vs 36 +/- 2 mmHg, p < 0.05), with persistent reduction of MAP (92 +/- mmHg, p < 0.05), even more evident at the 5th post-unclamping minute (Vm = 93 +/- 25 cm/sec; PaCO2 = 46 +/- 1.2 mmHg, p < 0.001, and MAP returned to pre-unclamping value), in which there was also a decrease of PI (0.65 +/- 0.16 vs 0.78 +/- 0.2, p < 0.05). At the 10th minute Vm (83 +/- 24 cm/sec, p < 0.02) and PaCO2 (41 +/- 1.5 mmHg, p < 0.05) increments were present together with persistent reduction of PI (0.69 +/- 0.17, p < 0.05), while at the 20th post-unclamping minute also Vm, PaCO2 and PI returned to their pre-unclamping values. The Vm decrease at aortic unclamping might correlate with the acute changes in MAP (blood steal hypovolemia) and is likely due to an inadequate cerebral autoregulatory response to abrupt MAP changes. The arterial CO2 increase after aortic unclamping could lead to a dilation of cerebral arterioles and a rise of CBF (increase of Vm and decrease of PI). Transcranial Doppler is a simple and reliable technique for the monitoring of cerebral blood flow parameters and seems to be quite suitable for the recognition and the quantification of changes in these parameters induced by surgical manoeuvres able to produce hemodynamic instability.


How dieting makes the lean fatter: from a perspective of body composition autoregulation through adipostats and proteinstats awaiting discovery.
Whether dieting makes people fatter has been a subject of considerable controversy over the past 30 years. More recent analysis of several prospective studies suggest, however, that it is dieting to lose weight in people who are in the healthy normal range of body weight, rather than in those who are overweight or obese, that most strongly and consistently predict future weight gain. This paper analyses the ongoing arguments in the debate about whether repeated dieting to lose weight in normal-weight people represents unsuccessful attempts to counter genetic and familial predispositions to obesity, a psychosocial reaction to the fear of fatness or that dieting per se confers risks for fatness and hence a contributing factor to the obesity epidemic. In addressing the biological plausibility that dieting predisposes the lean (rather than the overweight or obese) to regaining more body fat than what had been lost (i.e. fat overshooting), it integrates the results derived from the re-analysis of body composition data on fat mass and fat-free mass (FFM) losses and recoveries from human studies of experimental energy restriction and refeeding. These suggest that feedback signals from the depletion of both fat mass (i.e. adipostats) and FFM (i.e. proteinstats) contribute to weight regain through the modulation of energy intake and adaptive thermogenesis, and that a faster rate of fat recovery relative to FFM recovery (i.e. preferential catch-up fat) is a central outcome of body composition autoregulation in lean individuals. Such a temporal desynchronization in the restoration of the body's fat vs. FFM results in a state of hyperphagia that persists beyond complete recovery of fat mass and interestingly until FFM is fully recovered. However, as this completion of FFM recovery is also accompanied by fat deposition, excess fat accumulates. In other words, fat overshooting is a prerequisite to allow complete recovery of FFM. This confers biological plausibility for post-dieting fat overshooting - which through repeated dieting and weight cycling would increase the risks for trajectories from leanness to fatness. Given the increasing prevalence of dieting in normal-weight female and male among young adults, adolescents and even children who perceive themselves as too fat (due to media, family and societal pressures), together with the high prevalence of dieting for optimizing performance among athletes in weight-sensitive sports, the notion that dieting and weight cycling may be predisposing a substantial proportion of the population to weight gain and obesity deserves greater scientific scrutiny.


Socioeconomic and racial/ethnic oral health disparities among US older adults: oral health quality of life and dentition.
This study aims to examine if older adults living in poverty and from minority racial/ethnic groups experienced disproportionately high rates of poor oral health outcomes measured by oral health quality of life (OHQOL) and number of permanent teeth. Cross-sectional analysis of 2,745 community-dwelling adults aged ≥65 years from the National Health and Nutrition Examination Survey (NHANES) 2005-2008. Oral health outcomes were assessed by questionnaire using the NHANES-Oral Health Impact Profile for OHQOL and standardized examination for dentition. Logistic and linear regression analyses were used to determine the association between oral health outcomes and predictors of interest. All analyses were weighted to account for complex survey sampling methods. Both poverty and minority race/ethnicity were significantly associated with poor oral health outcomes in OHQOL and number of permanent teeth. Distribution of scores for each OHQOL domain varied by minority racial/ethnic group. Oral health disparities persist in older adults living in poverty and among those from minority racial/ethnic groups. The racial/ethnic variation in OHQOL domains should be further examined to develop interventions to improve the oral health of these groups.


Social capital components and social support of persons with multiple sclerosis: a systematic review of the literature from 2000 to 2018.
Purpose: To identify experiences of persons with multiple sclerosis (MS) in terms of social capital and its components (i.e., social networks, trust, and interpersonal relationships) and social support based on the current scientific knowledge.Methods: Systematic literature review was conducted through PubMed, Scopus, Web of Science, ProQuest, and PsycINFO. Included articles were published from 2000 to 2018 and met specific selection criteria. Screening of records determined eligible studies for inclusion to data extraction and synthesis process.Results: A total of 551 abstracts were screened, of which 34 studies met all selection criteria. The themes that emerged referred to the impact of physical and cognitive impairments on social functioning, stigma, psychosocial, emotional and mental challenges, association of quality of life with social capital components and social support, and contribution of social support to improvement of social functioning and health of persons with MS. Persons with MS face a series of issues regarding social support and social capital-related components, primarily facing psychological difficulties, difficulties with making and maintaining interpersonal relationships, and limitations for participating in social and daily activities due to the symptoms of MS, particularly fatigue.Conclusion: It appears that the ability to seek and maintain social relationships and to participate in social and daily activities is important for persons with MS. This has an impact on their quality of life, as well as on their health functioning, however issues around mobility and stigmatization of their condition hinder their social functioning.


Tumors of the peripheral nervous system: analysis of prognostic factors in a series with long-term follow-up and review of the literature.
OBJECT Only a few published studies of the surgical treatment of benign peripheral nerve sheath tumors (BPNSTs), malignant peripheral nerve sheath tumors (MPNSTs), and peripheral non-neural sheath tumors (PNNSTs) have analyzed the results and possible prognostic factors using multivariate analysis. The authors report on their surgical series of cases of BPNSTs, MPNSTs, and PNNSTs with long-term follow-up and analyze the role of selected factors with respect to the prognosis and risk of recurrence of these tumors using multivariate analysis. They also review the pertinent literature and discuss their results in its context. METHODS The authors retrospectively reviewed data from cases involving patients who underwent resection of a peripheral nerve tumor between January 1983 and December 2013 at their institution. Of a total of 200 patients, 150 patients (with 173 surgically treated tumors) had adequate follow-up data available for analysis. Pain was assessed using a visual analog scale (VAS), and motor and sensory function were assessed by means of the Louisiana State University grading system. They also analyzed the relationship between tumor recurrence and patient sex, patient age, diagnosis of neurofibromatosis (NF), tumor histopathology, tumor size, tumor location, and extent of resection (subtotal vs gross-total resection), using univariate and multivariate analyses. RESULTS There was a statistically significant improvement in the mean VAS pain score (preoperative 3.96 ± 2.41 vs postoperative 0.95 ± 1.6, p = 0.0001). Motor strength and sensory function were significantly improved after resection of tumors involving the brachial plexus (p = 0.0457 and p = 0.0043, respectively), tumors involving the upper limb (p = 0.0016 and p = 0.0016, respectively), BPNSTs (p = 0.0011 and p < 0.0001, respectively), and tumors with dimensions less than 5 cm (motor strength: p = 0.0187 and p = 0.0021 for ≤ 3 cm and 3-5 cm tumors, respectively; sensory function: p = 0.0003 and p = 0.0001 for ≤ 3 cm and 3-5 cm tumors, respectively). Sensory function showed a statistically significant improvement also in patients who had undergone resection of tumors involving the lower limb (p = 0.0118). Total resection was associated with statistically significant improvement of motor strength (p = 0.0251) and sensory function (p < 0.0001). In univariate analysis, a history of NF (p = 0.0034), a diagnosis of MPNST or PNNST (p < 0.0001), and subtotal resection (p = 0.0042) were associated with higher risk of tumor recurrence. In multivariate analysis (logistic regression analysis), a history of NF (OR 9.28%, 95% CI 1.62-52.94, p = 0.0121) and a diagnosis of MPNST (OR 0.03%, 95% CI 0.002-0.429, p = 0.0098) or PNNST (OR 0.081%, 95% CI 0.013-0.509, p = 0.0077) emerged as independent prognostic factors for tumor recurrence. CONCLUSIONS A total resection should be attempted in all cases of peripheral nervous system tumors (irrespective of the supposed diagnosis and tumor dimensions) because it is associated with better prognosis in term of functional outcome and overall survival. Moreover, a total resection predicts a lower risk of tumor recurrence. Patients with a history of NF and tumors with malignant histology remain a challenge both for neurosurgeons and oncologists due to higher recurrence rates and the lack of standardized adjuvant therapies.


Sensory Integration Concerns in Children With Functional Defecation Disorders: A Scoping Review.
We examined the literature to identify reports of sensory integration concerns in children with functional defecation issues and to explore whether difficulty processing sensation may be related to their challenging bowel management behaviors. A scoping review was used to address the research question. We sourced articles from six databases in three languages, searched reference lists of all included articles, and identified additional articles through discussion with experts in the field. Twelve articles were included in the final synthesis, identifying 15 challenging behaviors potentially related to sensory integration concerns. We summarize research documenting sensory integration concerns in children with functional defecation issues, providing researchers and clinicians with an overview of the current state of understanding.


Effects of microsolvation on a SN2 reaction: indirect atomistic dynamics and weakened suppression of reactivity.
Systematic studies of microsolvation in the gas phase have enriched our knowledge of solvent effects. Here, the dynamics of a prototype SN2 reaction of a hydrated fluoride ion with methyl iodide is uncovered employing direct dynamics simulations that show strikingly distinct features from those determined for an unsolvated system. An indirect scattering is found to prevail, which occurs dominantly by forming hydrated F-(H2O)-HCH2I and F-(H2O)-CH3I pre-reaction complexes at low energies, but proceeds through their water-free counterparts at higher energies. This finding is in strong contrast to a general evolution from indirect to direct dynamics with enhancing energy for the unsolvated substitution reactions, and this discrepancy is understood by the substantial steric hindrance introduced by a water molecule. As established in experiments, solvation suppresses the reactivity, whereas we find that this depression is remarkably frustrated upon raising the energy given that collision-induced dehydration essentially diminishes the water block for reactive collisions. The present study sheds light on how solute-solvent interactions affect the underlying dynamics at a deeper atomic level, thereby promoting our understanding of the fundamental solvent effects on chemical reactions in solution.


Systemic Resistance Induced by Trichoderma hamatum 382 in Cucumber Against Phytophthora Crown Rot and Leaf Blight.
Phytophthora root rot, crown rot, leaf and stem blight, and fruit rot of cucumber can cause serious losses, and are difficult to control. Although composts can be used successfully for control of Phytophthora root rots, little is known about their effects on Phytophthora diseases of aboveground plant parts. This research shows that the severity of Phytophthora root and crown rot of cucumber caused by Phytophthora capsici was suppressed significantly in cucumber transplants produced in a composted cow manure-amended mix compared with those in a dark sphagnum peat mix. In split root bioassays, Trichoderma hamatum 382 (T382) inoculated into the compost-amended potting mix significantly reduced the severity of Phytophthora root and crown rot on paired roots in the peat mix. This effect did not differ significantly from that provided by a drench with benzothiadiazole (BTH) or mefenoxam (Subdue MAXX). Based on area under disease progress curves, T382 also significantly reduced the severity of Phytophthora leaf blight in transplants produced in the compost mix compared with controls not inoculated with T382. Efficacy of T382 did not differ significantly from that provided by a drench with BTH. T382 re-mained spatially separated from the pathogen in plants in both the split root and leaf blight bioassays, suggesting that these effects were systemic in nature.


Two mechanisms of nanoparticle generation in picosecond laser ablation in liquids: the origin of the bimodal size distribution.
The synthesis of chemically clean and environmentally friendly nanoparticles through pulsed laser ablation in liquids has shown a number of advantages over conventional chemical synthesis methods and has evolved into a thriving research field attracting laboratory and industrial applications. The fundamental understanding of processes leading to the nanoparticle generation, however, still remains elusive. In particular, the origin of bimodal nanoparticle size distributions in femto- and picosecond laser ablation in liquids, where small nanoparticles (several nanometers) with narrow size distribution are commonly observed to coexist with larger (tens to hundreds of nanometers) ones, has not been explained so far. In this paper, joint computational and experimental efforts are applied to understand the mechanisms of nanoparticle formation in picosecond laser ablation in liquids and to explain the bimodal nanoparticle size distributions. The results of a large-scale atomistic simulation reveal the critical role of the dynamic interaction between the ablation plume and the liquid environment, leading to the generation of large nanoparticles through a sequence of hydrodynamic instabilities at the plume-liquid interface and a concurrent nucleation and growth of small nanoparticles in an expanding metal-liquid mixing region. The computational predictions are supported by a series of stroboscopic videography experiments showing the emergence of small satellite bubbles surrounding the main cavitation bubble generated in single pulse experiments. Carefully timed double pulse irradiation triggers expansion of secondary cavitation bubbles indicating, in accord with the simulation results, the presence of localized sites of laser energy deposition (possibly large nanoparticles) injected into the liquid at the early stage of the bubble formation.


Preliminary results of the global audit of treatment of refractory status epilepticus.
The treatment of refractory and super refractory status epilepticus is a "terra incognita" from the point of view of evidence-based medicine. As randomized or controlled studies that are sufficiently powered are not feasible in relation to the many therapies and treatment approaches available, we carried out an online multinational audit (registry) in which neurologists or intensivists caring for patients with status epilepticus may prospectively enter patients who required general anesthesia to control the status epilepticus (SE). To date, 488 cases from 44 different countries have been collected. Most of the patients had no history of epilepsy and had a cryptogenic etiology. First-line treatment was delayed and not in line with current guidelines. The most widely used anesthetic of first choice was midazolam (59%), followed by propofol and barbiturates. Ketamine was used in most severe cases. Other therapies were administered in 35% of the cases, mainly steroids and immunotherapy. Seizure control was achieved in 74% of the patients. Twenty-two percent of patients died during treatment, and four percent had treatment actively withdrawn because of an anticipated poor outcome. The neurological outcome was good in 36% and poor in 39.3% of cases, while 25% died during hospitalization. Factors that positively influenced outcome were younger age, history of epilepsy, and low number of different anesthetics tried. This article is part of a Special Issue entitled "Status Epilepticus".