Cortical hyperexcitability may precede the onset of familial amyotrophic lateral sclerosis.
Familial amyotrophic lateral sclerosis (FALS) is an inherited neurodegenerative disorder of the motor neurons. While 10-15% of cases are caused by mutations in the copper/zinc superoxide-dismutase-1 (SOD-1) gene, the dying-forward hypothesis, in which corticomotoneurons induce anterograde excitotoxic motoneuron degeneration, has been proposed as a potential mechanism. The present study applied novel threshold tracking transcranial magnetic stimulation techniques to investigate the mechanisms underlying neurodegeneration in FALS. Studies were undertaken in 14 asymptomatic and 3 pre-symptomatic SOD-1 mutation carriers, followed longitudinally for up to 3-years. The pre-symptomatic subjects were asymptomatic at the time of their initial study but developed symptoms during the follow-up period. Results were compared to 7 SOD-1 FALS patients, 50 sporadic ALS patients and 55 normal controls. Short-interval intracortical inhibition (SICI) was significantly reduced in SOD-1 FALS (-1.2 +/- 0.6%) and sporadic ALS patients (-0.7 +/- 0.3%) compared to asymptomatic SOD-1 mutation carriers (9.8 +/- 1.5%, P<0.00001) and normal controls (8.5 +/- 1.0%, P<0.00001). SICI reduction was accompanied by increases in intracortical facilitation, motor evoked potential amplitudes and the slope of the magnetic stimulus-response curve. In two pre-symptomatic SOD-1 mutation carriers SICI was completely absent (SICI patient 1, -3.2%; patients 2, -1.3%), while in one subject there was a 32% reduction in SICI prior to symptom onset. These three individuals subsequently developed clinical features of ALS. Simultaneous investigation of central and peripheral excitability has established that cortical hyperexcitability develops in clinically affected SOD-1 FALS patients, similar to that seen in sporadic ALS patients, thereby suggesting that a similar pathophysiological process in evident in both familial and sporadic ALS patients. In addition, the present study has established that cortical hyperexcitability precedes the development of clinical symptoms in pre-symptomatic carriers of the SOD1 mutation, thereby suggesting that cortical hyperexcitability underlies neurodegeneration in FALS.


Induction of inhibitory factor kappaBalpha mRNA in the central nervous system after peripheral lipopolysaccharide administration: an in situ hybridization histochemistry study in the rat.
In this study we investigate the mRNA expression of inhibitory factor kappaBalpha (IkappaBalpha) in cells of the rat brain induced by an intraperitoneal (i.p.) injection of lipopolysaccharide (LPS). IkappaB controls the activity of nuclear factor kappaB, which regulates the transcription of many immune signal molecules. The detection of IkappaB induction, therefore, would reveal the extent and the cellular location of brain-derived immune molecules in response to peripheral immune challenges. Low levels of IkappaBalpha mRNA were found in the large blood vessels and in circumventricular organs (CVOs) of saline-injected control animals. After an i.p. LPS injection (2.5 mg/kg), dramatic induction of IkappaBalpha mRNA occurred in four spatio-temporal patterns. Induced signals were first detected at 0.5 hr in the lumen of large blood vessels and in blood vessels of the choroid plexus and CVOs. Second, at 1-2 hr, labeling dramatically increased in the CVOs and choroid plexus and spread to small vascular and glial cells throughout the entire brain; these responses peaked at 2 hr and declined thereafter. Third, cells of the meninges became activated at 2 hr and persisted until 12 hr after the LPS injection. Finally, only at 12 hr, induced signals were present in ventricular ependyma. Thus, IkappaBalpha mRNA is induced in brain after peripheral LPS injection, beginning in cells lining the blood side of the blood-brain barrier and progressing to cells inside brain. The spatiotemporal patterns suggest that cells of the blood-brain barrier synthesize immune signal molecules to activate cells inside the central nervous system in response to peripheral LPS. The cerebrospinal fluid appears to be a conduit for these signal molecules.


The Association Between Emotion Recognition and Internalizing Problems in Children and Adolescents: A Three-Level Meta-Analysis.
Numerous studies have explored the link between how well youth recognize emotions and their internalizing problems, but a consensus remains elusive. This study used a three-level meta-analysis model to quantitatively synthesize the findings of existing studies to assess the relationship. A moderation analysis was also conducted to explore the sources of research heterogeneity. Through a systematic literature search, a total of 42 studies with 201 effect sizes were retrieved for the current meta-analysis, and 7579 participants were included. Emotion recognition was negatively correlated with internalizing problems. Children and adolescents with weaker emotion recognition skills were more likely to have internalizing problems. In addition, this meta-analysis found that publication year had a significant moderating effect. The correlation between emotion recognition and internalizing problems decreased over time. The degree of internalizing problems was also found to be a significant moderator. The correlation between emotion recognition and internalizing disorders was higher than the correlation between emotion recognition and internalizing symptoms. Deficits in emotion recognition might be relevant for the development and/or maintenance of internalizing problems in children and adolescents. The overall effect was small and future research should explore the clinical relevance of the association.


A New Proposal for the Pathogenic Mechanism of Non-Coeliac/Non-Allergic Gluten/Wheat Sensitivity: Piecing Together the Puzzle of Recent Scientific Evidence.
Non-coeliac/non-allergic gluten/wheat sensitivity (NCG/WS) is a gluten-related disorder, the pathogenesis of which remains unclear. Recently, the involvement of an increased intestinal permeability has been recognized in the onset of this clinical condition. However, mechanisms through which it takes place are still unclear. In this review, we attempt to uncover these mechanisms by providing, for the first time, an integrated vision of recent scientific literature, resulting in a new hypothesis about the pathogenic mechanisms involved in NCG/WS. According to this, the root cause of NCG/WS is a particular dysbiotic profile characterized by decreased butyrate-producing-Firmicutes and/or Bifidobacteria, leading to low levels of intestinal butyrate. Beyond a critical threshold of the latter, a chain reaction of events and vicious circles occurs, involving other protagonists such as microbial lipopolysaccharide (LPS), intestinal alkaline phosphatase (IAP) and wheat α-amylase trypsin inhibitors (ATIs). NCG/WS is likely to be a multi-factor-onset disorder, probably transient and preventable, related to quality and balance of the diet, and not to the presence of gluten in itself. If future studies confirm our proposal, this would have important implications both for the definition of the disease, as well as for the prevention and therapeutic-nutritional management of individuals with NCG/WS.


18F-FDG-PET/CT imaging of drug-induced metabolic changes in genetically engineered mouse lung cancer models.
The most commonly used radiotracer for cancer imaging in humans and mice is 2-deoxy-2-((18)F)fluoro-d-glucose ((18)F-FDG). We have used FDG coupled with positron-emission tomography (PET) to assess the pharmacodynamic efficacy of a number of therapeutics in genetically engineered mouse lung cancer models. In this protocol, we present our approach for FDG-PET imaging of early tumor metabolic changes induced by drug treatment. Special consideration is given to animal preparation, anesthesia, and PET/computed tomography (CT) imaging of mice with lung tumors. Specifically, we recommend fasting the mice overnight to reduce background, using sevoflurane anesthesia and a "conscious" uptake period to minimize cardiac FDG uptake, adopting a relatively short duration of CT and PET scanning to facilitate serial imaging, and quantifying the comparison between the maximum standardized uptake values (SUVs) of lung tumors before and after treatment to determine treatment effects. Used in this manner, FDG-PET can rapidly assess tumor metabolism before and after treatment with an experimental therapeutic. In many cases, metabolic changes are apparent after just a single dose of treatment, helping to show target engagement and modulation by the drug (pharmacodynamic efficacy) within days of starting therapy.


Prevalence of thyroid dysfunction among Iranian older adults: a cross-sectional study.
There is limited data on the prevalence of thyroid dysfunction in the older population. This study aimed to determine the prevalence of thyroid dysfunction among a sample of Iranian older adults. A cross-sectional analysis of older adults who aged 60 years and over was conducted. A total of 363 subjects were randomly selected from Birjand longitudinal aging study (BLAS) cohort study. Serum thyroid-stimulating hormone (TSH) level, total thyroxine (T4) and total triiodothyronine (T3) were measured by the enzyme-linked immunosorbent assay (ELISA). Based on thyroid function tests and history of taking medicines used to treat thyroid disorders, participants were classified into the following groups: euthyroid, overt/subclinical hypothyroidism, and overt/subclinical hyperthyroidism. Subsequently, the crude and World Health Organization (WHO) age-standardized prevalence were estimated for different thyroid function categories. A total of 171 men and 192 women, aged 60-94 years, were randomly selected. The crude prevalence of total hypothyroidism was 22.31% (subclinical [18.46%], overt [3.86%]), and that of hyperthyroidism was 1.66% (subclinical [1.38%], overt [0.28%]). The crude prevalence of total thyroid dysfunction was, therefore, 23.97%. A female preponderance was noticed in both total (P-value = 0.035) and overt (P-value = 0.035) hypothyroidism. An increasing trend with age was noticed in the prevalence of total hypothyroidism (P-value = 0.049). Age-standardized prevalence of total hypothyroidism and hyperthyroidism was 26.63% (95% confidence interval [CI] 20.58-33.69%) and 1.11% (95% CI 0.49-2.51%), respectively. A considerable proportion of our study population demonstrated evidence of thyroid dysfunction, particularly subclinical hypothyroidism. Our findings highlight the importance of further investigation of thyroid disorders among older Iranian adults.


Eccentric movements of temporomandibular joint and upper airway volume: Three-dimensional segmentation using cone beam computed tomography.
Objective: The purpose of the present investigation was to assess whether possible changes in the dynamic movements of the TMJ might cause a greater variation between the volumes of the upper airways in open- and closed-mouth positions.Methods: CBCT scans of 92 subjects were used to assess the TMJ bilaterally. All scans were acquired in closed (CM) and maximum mouth opening (MMO) positions. The difference in the volume of the oropharyngeal cavity obtained by subtracting the CM volume from the MMO volume (delta volume or volume variation) was calculated. The resulting volume was analyzed by Mann-Whitney test for variation in rotation.Results: A significant difference was found (p-value = 0.0188) on the right side regarding changes in the rotational movement of the condyle (Mann-Whitney test).Conclusion: This study showed a relationship between degree of abnormal or limited rotation and variation in the upper airway volume on one side.


Measuring accounts receivable performance: a comprehensive method.
Nonperforming assets, such as accounts receivable, are frequently cited as sources of financial difficulty for hospitals. Yet, many hospitals, relying on the traditional measure of accounts receivable--days revenue outstanding--may not have a true grasp of the real cost of their accounts receivable. The author discusses the costs imposed on a hospital by accounts receivable and describes three cost components that must be calculated if the true cost of accounts receivable is to be determined and controlled.


The dangers to children from coconut tree trauma, in KiraKira, Solomon Islands: a retrospective clinical audit.
Kirakira is small community of 3,000 people and is the capital of Makira-Ulawa province in Solomon Islands. Kirakira is an impoverished community with a small 30 bed hospital with limited resources. This audit was conducted by final year students from Bond University as part of a selective clinical placement. The audit included admissions to the hospital from 2011 to 2014. Trauma-related admissions were identified and classified according to the patient's age, sex, description of injury, mechanism of injury and whether they were transferred to the National Referral Hospital (NRH) in Honiara for further treatment. Injuries due to Coconut tree trauma were classified as being due to falls from the tree, or trauma from either falling branches or falling coconut fruit. There were 3455 admissions and 23(0.7 %) non-neonatal deaths over the 3 year period. 126(3.6 %) admissions were referred on to the NRH for further treatment. 277 (8.02 %) admissions were trauma-related with 57(21 %) of these referred on to the NRH. 142 (55 %) of the trauma admissions involved children. Coconut Tree trauma was the commonest cause of a traumatic admission to hospital. There were 49 Coconut Tree trauma admissions including 35 from falls, 12 from falling branches and two from falling coconuts. 80 % of Coconut tree trauma involved Males and the median age of those injured was 13. Primary School age children aged 6-14 years were most at risk for Coconut Tree Trauma. 15(31 %) of the Coconut tree trauma admissions were referred to NRH for further treatment. Coconut Tree Trauma is common in Kirakira and is an important preventable cause of serious injury that particularly affects primary school aged boys in Kirakira, Solomon Islands. A public education campaign that focuses on this at risk age group warning of the dangers of climbing Coconut trees should be considered.


Modulation of Symbiotic Compatibility by Rhizobial Zinc Starvation Machinery.
Pathogenic bacteria need high-affinity zinc uptake systems to counteract the nutritional immunity exerted by infected hosts. However, our understanding of zinc homeostasis in mutualistic systems such as the rhizobium-legume symbiosis is limited. Here, we show that the conserved high-affinity zinc transporter ZnuABC and accessory transporter proteins (Zip1, Zip2, and c06450) made cumulative contributions to nodulation of the broad-host-range strain Sinorhizobium fredii CCBAU45436. Zur acted as a zinc-dependent repressor for the znuC-znuB-zur operon, znuA, and c06450 by binding to the associated Zur box, but did not regulate zip1 and zip2 ZnuABC was the major zinc transporter. Combined mutants lacking znuA and one of the three accessory genes had more severe defects in nodulation and growth under zinc starvation conditions than the znuA mutant, though rhizoplane colonization by these mutants was not impaired. In contrast to the elite strain CCBAU45436, more drastic symbiotic defects were observed for the znuA mutants of other Sinorhizobium strains, which lack at least one of the three accessory genes in their genomes and are characterized by their limited host range and geographical distribution. The znu-derived mutants showed a higher expression level of nod genes involved in Nod factor biosynthesis and a reduced expression of genes encoding a type three secretion system and its effector NopP, which can interfere with the host immune system. Application of exogenous zinc restored the nodulation ability of these znu-derived mutants. Therefore, the conserved ZnuABC and accessory components in the zinc starvation machinery play an important role in modulating symbiotic compatibility.IMPORTANCE The rhizobium-legume symbiosis contributes around 65% of biological nitrogen fixation in agriculture systems and is critical for sustainable agriculture by reducing the amount of chemical nitrogen fertilizer being used. Rhizobial inocula have been commercialized for more than 100 years, but the efficiency of inoculation can vary among legume cultivars, field sites, and years. These long-lasting challenging problems impede the establishment of a sustainable agriculture, particularly in developing countries. Here, we report that rhizobial zinc starvation machinery containing a conserved high-affinity zinc transporter and accessory components makes cumulative contributions to modulating rhizobial symbiotic compatibility. This work highlights a critical role of largely unexplored nutritional immunity in the rhizobium-legume symbiosis, which makes zinc starvation machinery an attractive target for improving rhizobial symbiotic compatibility.


How does Music Affect Your Brain? A Pilot Study on EEG and Music Features for Automatic Analysis.
Music can effectively induce specific emotion and usually be used in clinical treatment or intervention. The electroencephalogram can help reflect the impact of music. Previous studies showed that the existing methods achieved relatively good performance in predicting emotion response to music. However, these methods tend to be time consuming and expensive due to their complexity. To this end, this study proposes a grey wolf optimiser-based method to predict the induced emotion through fusing electroencephalogram features and music features. Experimental results show that, the proposed method can reach a promising performance for predicting emotional response to music and outperform the alternative method. In addition, we analyse the relationship between the music features and electroencephalogram features and the results demonstrate that, musical timbre features are significantly related to the electroencephalogram features.Clinical relevance- This study targets the automatic prediction of the human response to music. It further explores the correlation between EEG features and music features aiming to provide the basis for the extension to the application of music. The grey wolf optimiser-based method proposed in this study could supply a promising avenue for the emotion prediction as induced by music.


Octopamine and tyramine respectively regulate attractive and repulsive behavior in locust phase changes.
Aggregative and solitary behaviors are universal phenomena in animals. Interestingly, locusts (Locusta migratoria) can reversibly transit their behavior between gregarious and solitary phase through conspecific attraction and repulsion. However, the regulatory mechanism of neurotransmitters underlying attraction and repulsion among locusts remains unknown. In this study, we found gregarious and solitary locusts were attracted or repulsed respectively by gregarious volatiles. Solitary locusts can transform their preference for gregarious volatiles during crowding, whereas gregarious locusts avoided their volatiles during isolation. During crowding and isolation, the activities of octopamine and tyramine signalings were respectively correlated with attraction- and repulsion-response to gregarious volatiles. RNA interference verified that octopamine receptor α (OARα) signaling in gregarious locusts controlled attraction-response, whereas in solitary ones, tyramine receptor (TAR) signaling mediated repulsion-response. Moreover, the activation of OARα signaling in solitary locusts caused the behavioral shift from repulsion to attraction. Enhancement of TAR signaling in gregarious locusts resulted in the behavioral shift from attraction to repulsion. The olfactory preference of gregarious and solitary locusts co-injected by these two monoamines displayed the same tendency as the olfactory perception in crowding and isolation, respectively. Thus, the invertebrate-specific octopamine-OARα and tyramine-TAR signalings respectively mediate attractive and repulsive behavior in behavioral plasticity in locusts.


Pulsed Doppler imaging for carotid artery disease.
Ultrasonic imaging using a six-channel pulsed Doppler system combined with Doppler spectral analysis of 65 carotid bifurcations has been studied in a prospective clinical trial. The results were compared with X-ray contrast angiography. An overall sensitivity in excess of 90 per cent was achieved using the ultrasound technique, with a specificity of 89 per cent in the detection of significant stenosis or occlusion of the internal carotid artery. The ability to recognise significant arterial stenosis with a non-invasive system suggests that it has a major part to play in screening patients with suspected carotid artery disease.


Age-associated mosaic respiratory chain deficiency causes trans-neuronal degeneration.
Heteroplasmic mitochondrial DNA (mtDNA) mutations (mutations present only in a subset of cellular mtDNA copies) arise de novo during the normal ageing process or may be maternally inherited in pedigrees with mitochondrial disease syndromes. A pathogenic mtDNA mutation causes respiratory chain deficiency only if the fraction of mutated mtDNA exceeds a certain threshold level. These mutations often undergo apparently random mitotic segregation and the levels of normal and mutated mtDNA can vary considerably between cells of the same tissue. In human ageing, segregation of somatic mtDNA mutations leads to mosaic respiratory chain deficiency in a variety of tissues, such as brain, heart and skeletal muscle. A similar pattern of mutation segregation with mosaic respiratory chain deficiency is seen in patients with mitochondrial disease syndromes caused by inherited pathogenic mtDNA mutations. We have experimentally addressed the role of mosaic respiratory chain deficiency in ageing and mitochondrial disease by creating mouse chimeras with a mixture of normal and respiratory chain-deficient neurons in cerebral cortex. We report here that a low proportion (>20%) of respiratory chain-deficient neurons in the forebrain are sufficient to cause symptoms, whereas premature death of the animal occurs only if the proportion is high (>60-80%). The presence of neurons with normal respiratory chain function does not only prevent mortality but also delays the age at which onset of disease symptoms occur. Unexpectedly, respiratory chain-deficient neurons have adverse effect on normal adjacent neurons and induce trans-neuronal degeneration. In summary, our study defines the minimal threshold level of respiratory chain-deficient neurons needed to cause symptoms and also demonstrate that neurons with normal respiratory chain function ameliorate disease progression. Finally, we show that respiratory chain-deficient neurons induce death of normal neurons by a trans-neuronal degeneration mechanism. These findings provide novel insights into the pathogenesis of mosaic respiratory chain deficiency in ageing and mitochondrial disease.


Cultural context in the effort to improve oral health among Alaska Native people: the dental health aide therapist model.
The Alaska Native people in rural Alaska face serious challenges in obtaining dental care. Itinerant care models have failed to meet their needs for more than 50 years. The dental health aide therapist (DHAT) model, which entails training midlevel care providers to perform limited restorative, surgical, and preventive procedures, was adopted to address some of the limitations of the itinerant model. We used quantitative and qualitative methods to assess residents' satisfaction with the model and the role of DHATs in the cultural context in which they operate. Our findings suggest that the DHAT model can provide much-needed access to urgent care and is beneficial from a comprehensive cultural perspective.


Utility of computed tomography or magnetic resonance imaging evaluation of ventricular morphology in suspected cerebrospinal fluid shunt malfunction.
It is common to evaluate children with suspected CSF shunt malfunctions using CT of the head or, more recently, "quick brain" MRI. However, the reliability of using ventricular behavior, as assessed on cranial imaging during previous presentations with shunt obstructions, is not well defined. The authors conducted a study to determine if CT or MRI of ventricular morphology added useful clinical information in the evaluation of shunt malfunctions. A retrospective chart review of children operated on at Texas Children's Hospital from February 20, 2011, to June 18, 2013, for shunt obstruction was conducted. Inclusion criteria involved age 3 years or older in patients who had undergone two or more shunt revisions for intraoperatively confirmed obstructions. Patients with shunt infection but without shunt obstruction and patients with fourth ventricular shunt failure were excluded from the study. Preoperative CT or MRI results were dichotomized into two distinct categories, as determined by a radiologist's report: either dilation of the ventricular system in comparison with prior scans at points the shunt was deemed functional, or no dilation of the ventricular system in comparison such scans. Determination of the presence of shunt obstruction was assessed by findings documented by the surgeon in the operative report. Each case was then analyzed to see if the patient has a reliable pattern of ventricular dilation, or no dilation, at times of shunt obstruction. Forty-two patients (25 males and 17 females) were included in the study. There were a total of 117 patient encounters analyzed and an average of 2.79 encounters per patient. The mean age at shunt failure presentation was 10.8 years (range 3-23 years). In 4 encounters, patients presented with a CSF leak or pseudomeningocele. Twenty-seven patients (64%) consistently demonstrated dilation of the ventricular system during episodes of shunt obstruction. Four patients (10%) consistently demonstrated no dilation during episodes of shunt obstruction. Eleven patients (26%) demonstrated inconsistent changes in ventricular size at times of shunt obstruction. In those first patient encounters with shunt obstruction presenting with ventricular dilation, 92% (49 of 53) of subsequent encounters demonstrated ventricular dilation with shunt obstruction presentations. Historical CT or MRI data regarding ventricular morphology patterns seen during prior examinations of shunt obstructions may inform a clinician's judgment of shunt obstruction on subsequent presentations, but they are not conclusive. In the present series, the authors found that changes in the morphology of a given patient's ventricular system when shunt obstruction occurs were often consistent and predictable, but not always. It remains imperative, however, that cranial images obtained to rule out shunt malfunction be compared with prior studies.


Sleep Duration and Hypertension: Epidemiological Evidence and Underlying Mechanisms.
While the contribution of several physiological systems to arterial blood pressure regulation has been studied extensively, the role of normal and disrupted sleep as a modifiable determinant of blood pressure control, and in the pathophysiology of hypertension, has only recently emerged. Several sleep disorders, including sleep apnea and insomnia, are thought to contribute to the development of hypertension, although less attention is paid to the relationship between sleep duration and blood pressure independent of sleep disorders per se. Accordingly, this review focuses principally on the physiology of sleep and the consequences of abnormal sleep duration both experimentally and at the population level. Clinical implications for patients with insomnia who may or may not have abbreviated sleep duration are explored. As a corollary, we further review studies of the effects of sleep extension on blood pressure regulation. We also discuss epidemiological evidence suggesting that long sleep may also be associated with hypertension and describe the parabolic relationship between total sleep time and blood pressure. We conclude by highlighting gaps in the literature regarding the potential role of gut microbial health in the cross-communication of lifestyle patterns (exercise, diet, and sleep) with blood pressure regulation. Additionally, we discuss populations at increased risk of short sleep, and specifically the need to understand mechanisms and therapeutic opportunities in women, pregnancy, the elderly, and in African Americans.


Modelling nitrous oxide emissions from mown-grass and grain-cropping systems: Testing and sensitivity analysis of DailyDayCent using high frequency measurements.
The DailyDayCent biogeochemical model was used to simulate nitrous oxide (N2O) emissions from two contrasting agro-ecosystems viz. a mown-grassland and a grain-cropping system in France. Model performance was tested using high frequency measurements over three years; additionally a local sensitivity analysis was performed. Annual N2O emissions of 1.97 and 1.24kgNha-1year-1 were simulated from mown-grassland and grain-cropland, respectively. Measured and simulated water filled pore space (r=0.86, ME=-2.5%) and soil temperature (r=0.96, ME=-0.63°C) at 10cm soil depth matched well in mown-grassland. The model predicted cumulative hay and crop production effectively. The model simulated soil mineral nitrogen (N) concentrations, particularly ammonium (NH4+), reasonably, but the model significantly underestimated soil nitrate (NO3-) concentration under both systems. In general, the model effectively simulated the dynamics and the magnitude of daily N2O flux over the whole experimental period in grain-cropland (r=0.16, ME=-0.81gNha-1day-1), with reasonable agreement between measured and modelled N2O fluxes for the mown-grassland (r=0.63, ME=-0.65gNha-1day-1). Our results indicate that DailyDayCent has potential for use as a tool for predicting overall N2O emissions in the study region. However, in-depth analysis shows some systematic discrepancies between measured and simulated N2O fluxes on a daily basis. The current exercise suggests that the DailyDayCent may need improvement, particularly the sub-module responsible for N transformations, for better simulating soil mineral N, especially soil NO3- concentration, and N2O flux on a daily basis. The sensitivity analysis shows that many factors such as climate change, N-fertilizer use, input uncertainty and parameter value could influence the simulation of N2O emissions. Sensitivity estimation also helped to identify critical parameters, which need careful estimation or site-specific calibration for successful modelling of N2O emissions in the study region.


Antifungal features and properties of chitosan/sandalwood oil Pickering emulsion coating stabilized by appropriate cellulose nanofiber dosage for fresh fruit application.
A novel composite edible coating film was developed from 0.8% chitosan (CS) and 0.5% sandalwood oil (SEO). Cellulose nanofibers (CNFs) were used as a stabilizer agent of oil-in-water Pickering emulsion. We found four typical groups of CNF level-dependent emulsion stabilization, including (1) unstable emulsion in the absence of CNFs; (2) unstable emulsion (0.006-0.21% CNFs); (3) stable emulsion (0.24-0.31% CNFs); and (4) regular emulsion with the addition of surfactant. Confocal laser scanning microscopy was performed to reveal the characteristics of droplet diameter and morphology. Antifungal tests against Botrytis cinerea and Penicillium digitatum, between emulsion coating stabilized with CNFs (CS-SEOpick) and CS or CS-SEO was tested. The effective concentration of CNFs (0.24%) may improve the performance of CS coating and maintain CS-SEO antifungal activity synergistically confirmed with a series of assays (in vitro, in vivo, and membrane integrity changes). The incorporation of CNFs contributed to improve the functional properties of CS and SEO-loaded CS including light transmission at UV and visible light wavelengths and tensile strength. Atomic force microscopy and scanning electron microscopy were employed to characterize the biocompatibility of each coating film formulation. Emulsion-CNF stabilized coating may have potential applications for active coating for fresh fruit commodities.


[Genotypic peculiarities of morphogenesis in barley anther culture].
Evaluation of haploid production indicator variability caused by growth conditions of donor plants, regime and mode of spike pretreatment and nutrient medium composition has been carried out. Maintained ranks of the genotypes involved into experiment show the importance of genetic component in the whole variability and actuality of profound investigation on the mechanism of genetic control ofculture ability.


Potential Causes of Elevated REE after High-Intensity Exercise.
Resting energy expenditure (REE) increases after an intense exercise; however, little is known concerning mechanisms. The purpose of this study was to determine effects of a single bout of moderate-intensity continuous (MIC) aerobic exercise, or high-intensity interval (HII) exercise on REE under energy balance conditions. Thirty-three untrained premenopausal women were evaluated at baseline, after 8-16 wk of training, 22 h after either MIC (50% peak V˙O2) or HII (84% peak V˙O2). Participants were in a room calorimeter during and after the exercise challenge. Food intake was adjusted to obtain energy balance across 23 h. REE was measured after 22 h after all conditions. Twenty-three-hour urine norepinephrine concentration and serum creatine kinase activity (CrKact) were obtained. Muscle biopsies were obtained in a subset of 15 participants to examine muscle mitochondrial state 2, 3, and 4 fat oxidation. REE was increased 22 h after MIC (64 ± 119 kcal) and HII (103 ± 137 kcal). Markers of muscle damage (CrKact) increased after HII (9.6 ± 25.5 U·L) and MIC (22.2 ± 22.8 U·L), whereas sympathetic tone (urine norepinephrine) increased after HII (1.1 ± 10.6 ng·mg). Uncoupled phosphorylation (states 2 and 4) fat oxidation were related to REE (r = 0.65 and r = 0.55, respectively); however, neither state 2 nor state 4 fat oxidation increased after MIC or HII. REE was not increased after 8 wk of aerobic training when exercise was restrained for 60 h. Under energy balance conditions, REE increased 22 h after both moderate-intensity and high-intensity exercise. Exercise-induced muscle damage/repair and increased sympathetic tone may contribute to increased REE, whereas uncoupled phosphorylation does not. These results suggest that moderate- to high-intensity exercise may be valuable for increasing energy expenditure for at least 22 h after the exercise.


The role of the heme oxygenase system in the metabolic syndrome.
Molecular chaperones and the heat shock response play a major role in the maintenance of cellular homeostasis under various pathological conditions. In particular, their role is to regulate protein conformation, protect proteins from misfolding and aggregation, and maintain signalling and organellarnetworks. Among variousheat shock proteins, Hsp32 also known as heme oxygenase-1 (HO-1), has demonstrated an important role in metabolic syndrome. In particular, the HO system seems to play a major role in the complex pathophysiological cascade involved in insulin resistance mechanisms, and adipocyte functions as measured by the release of important adipokynes. The aim of the present review is to point out the role of HO-1 in metabolic syndrome, and how to exploit its beneficial effects as a therapeutic strategy to prevent complicationsof andto improve insulin sensitivity.


Evolution of the multifaceted eukaryotic akirin gene family.
Akirins are nuclear proteins that form part of an innate immune response pathway conserved in Drosophila and mice. This studies aim was to characterise the evolution of akirin gene structure and protein function in the eukaryotes. akirin genes are present throughout the metazoa and arose before the separation of animal, plant and fungi lineages. Using comprehensive phylogenetic analysis, coupled with comparisons of conserved synteny and genomic organisation, we show that the intron-exon structure of metazoan akirin genes was established prior to the bilateria and that a single proto-orthologue duplicated in the vertebrates, before the gnathostome-agnathan separation, producing akirin1 and akirin2. Phylogenetic analyses of seven vertebrate gene families with members in chromosomal proximity to both akirin1 and akirin2 were compatible with a common duplication event affecting the genomic neighbourhood of the akirin proto-orthologue. A further duplication of akirins occurred in the teleost lineage and was followed by lineage-specific patterns of paralogue loss. Remarkably, akirins have been independently characterised by five research groups under different aliases and a comparison of the available literature revealed diverse functions, generally in regulating gene expression. For example, akirin was characterised in arthropods as subolesin, an important growth factor and in Drosophila as bhringi, which has an essential myogenic role. In vertebrates, akirin1 was named mighty in mice and was shown to regulate myogenesis, whereas akirin2 was characterised as FBI1 in rats and promoted carcinogenesis, acting as a transcriptional repressor when bound to a 14-3-3 protein. Both vertebrate Akirins have evolved under comparably strict constraints of purifying selection, although a likelihood ratio test predicted that functional divergence has occurred between paralogues. Bayesian and maximum likelihood tests identified amino-acid positions where the rate of evolution had shifted significantly between paralogues. Interestingly, the highest scoring position was within a conserved, validated binding-site for 14-3-3 proteins. This work offers an evolutionary framework to facilitate future studies of eukaryotic akirins and provides insight into their multifaceted and conserved biochemical functions.


Sexual behavior and oral contraception: a pilot study.
Oral contraceptives (OCs) induce mood and libido changes. The aim of this study was to evaluate in young, eumenorrheic, healthy women the sexual behavior and the genital vascular effects of an OC containing 30 µg ethinylestradiol (EE) and 3 mg drospirenone (DRSP). The main outcome measures are McCoy Female Sexuality Questionnaire (MFSQ), the labia minora thickness and vaginal introitus area, the pulsatility index (PI) of clitoral and labia minora arteries, and hormonal and biochemical assays. Twenty-two adult, eumenorrheic, healthy women were administered the two-factor Italian MFSQ. The labia minora thickness was studied by two-dimensional ultrasonographic, and the clitoral and labia minora arteries were evaluated by color Doppler; three-dimensional static volumes of the vulvar area were calculated. Hormonal (estradiol, androstenedione, and testosterone) and biohumoral (sex hormone binding globulin) parameters were assayed. Subjects were studied in baseline conditions and after 3 months of therapy with an OC (Yasmin®, Bayer-Schering Italia, Milan, Italy; -30 µg EE + 3 mg DRSP). After 3-month treatment, the labia minora thickness and the vaginal introitus area significantly decreased in comparison with the baseline values, whereas the PI of the dorsal clitoral artery and the posterior labial artery significantly increased. The OC use induced a significant decrease of the two-factor Italian MFSQ score, a reduction of the number of intercourse/week, and a reduction of the frequency of orgasm during intercourse. The item 18 (pain during intercourse) worsened after OC. The treatment with Yasmin® (Bayer-Schering Italia) is associated with increased pain during intercourse, with decreased libido and spontaneous arousability, and with diminished frequency of sexual intercourse and orgasm.


[Characteristics of the spontaneously transformed human endothelial cell line ECV304. II. Functional responses of the ECV304 cells].
Functional responses of the spontaneously transformed human endothelial cell line ECV304 were studied in order to asses its applicability as an endothelial cell model for studying angiogenesis and signal transduction. The dependence of proliferation activity of this line on the presence of growth factor was shown. The absent serum in culture medium resulted in blocking of cells in G1-phase of a cell cycle which is not typical for tumor cell lines. Low doses of beta particles emitted during [3H]thymidine decay resulted in blocking the proliferation of these cells in G2M-phase in a dose-dependent manner. Incubation of the cells with another source of beta particles, 3H2O, under condition of equal specific activities of tritium resulted in preferable accumulation of the cells in S-phase. The different efficiency of beta particles of tritium as a part of 3H2O molecule or thymidine demonstrates that various mechanisms are responsible for various check points. The check point of G1/S is absent and that complies with the presence of deletion of chromosome 9 in locus p21. The level of NO produced by constitutive form of NO-synthase in ECV304 cells was relatively low and not modified by inducible NO-synthase inhibitors. The data obtained suggest that ECV304 line cells retained the properties of the initial spontaneously transformed cell line obtained from human umbilical vein (HUVEC) as well as they can be used as a model system for further studies of the properties of vascular endothelial.


Risk factors for obstructive lung disease.
To assess the role of various risk factors in the pathogenesis of chronic obstructive lung disease (COLD), 163 men and women were followed for approximately 6 yr. Subjects were either community volunteers or relatives of patients with antitrypsin deficiency (PiZ or MZ phenotype). At the onset of the study no subject was receiving medical care for COLD. Covariance analysis revealed that expiratory airflow rates declined excessively in male subjects who had the PiMZ phenotype and reported a family history of lung disease. In subjects with the combination of characteristics, loss of lung function approximated that reported in subjects who have established COLD. In several such subjects, abnormalities have progressed so that they now require treatment. Changes in lung function were less striking in the presence of only 1 or 2 of the 3 risk factors studied. These findings demonstrated that the characteristics of the population being studied can influence the outcome of an investigation. This effect may help account fo the conflicting results of previous investigations designed to assess the role of the PiMZ phenotype in the pathogenesis of COLD.


Reassessing racial and socioeconomic disparities in environmental justice research.
The number of studies examining racial and socioeconomic disparities in the geographic distribution of environmental hazards and locally unwanted land uses has grown considerably over the past decade. Most studies have found statistically significant racial and socioeconomic disparities associated with hazardous sites. However there is considerable variation in the magnitude of racial and socioeconomic disparities found; indeed, some studies have found none. Uncertainties also exist about the underlying causes of the disparities. Many of these uncertainties can be attributed to the failure of the most widely used method for assessing environmental disparities to adequately account for proximity between the hazard under investigation and nearby residential populations. In this article, we identify the reasons for and consequences of this failure and demonstrate ways of overcoming these shortcomings by using alternate, distance-based methods. Through the application of such methods, we show how assessments about the magnitude and causes of racial and socioeconomic disparities in the distribution of hazardous sites are changed. In addition to research on environmental inequality, we discuss how distance-based methods can be usefully applied to other areas of demographic research that explore the effects of neighborhood context on a range of social outcomes.


Sarcocystis spp. in domestic sheep in Kunming City, China: prevalence, morphology, and molecular characteristics.
Sheep (Ovis aries) are intermediate hosts for at least six named species of Sarcocystis: S. tenella, S. arieticanis, S. gigantea, S. medusiformis, S. mihoensis, and S. microps. Here, only two species, S. tenella and S. arieticanis, were found in 79 of 86 sheep (91.9%) in Kunming, China, based on their morphological characteristics. Four genetic markers, i.e., 18S rRNA gene, 28S rRNA gene, mitochondrial cox1 gene, and ITS-1 region, were sequenced and characterized for the two species of Sarcocystis. Sequences of the three former markers for S. tenella shared high identities with those of S. capracanis in goats, i.e., 99.0%, 98.3%, and 93.6%, respectively; the same three marker sequences of S. arieticanis shared high identities with those of S. hircicanis in goats, i.e., 98.5%, 96.5%, and 92.5%, respectively. No sequences in GenBank were found to significantly resemble the ITS-1 regions of S. tenella and S. arieticanis. Identities of the four genetic markers for S. tenella and S. arieticanis were 96.3%, 95.4%, 82.5%, and 66.2%, respectively.


Women's anxiety in old age and long-term care provision for the elderly.
The purpose of this study was to verify the differences in women's anxiety in old age, the expected long-term care provision, and the expected final location for terminal care for the women themselves and for their parents. In addition, we examined factors that related to their anxiety and needs. The subjects were 1,000 women of the Seikatsu Club customer cooperative association in Chiba; 539 responded to our survey. The subjects were more anxious for their parents than for themselves. They more strongly expected long-term care for their parents to be provided by their family than they expected the same for themselves. Although no differences were observed in the expected location for terminal care, most subjects expected their home to be the terminal location. Analysis by the multiple logistic regression model indicated that the following factors were significantly related to the anxiety in old age: age odds ratio [OR = 1.81], employment [OR = 2.25] for women, and planning to live with parents [OR = 2.42], housing conditions [OR = 0.56] for parents. The following factors were significantly related to the expected long-term care provision: age [OR = 2.22] for women, and age [OR = 2.15], living with parents [OR = 3.58], and employment [OR = 2.33] for parents. Age [OR = 2.14] for women, and planning to live with parents [OR = 2.09] for parents were significantly related to the expected final location of terminal care. This survey showed that women expected long-term care for their parents to be provided by their family, while many expected public long-term care services for themselves. This is the biggest difference in women's outlook on long-term care for their parents and for themselves. Multivariate analysis suggested that women aged 40 years or over, who will need long-term care in the future, tended to expect public home care services for themselves. It is virtually certain that the demand for public home care services will increase in the future.


Albumin usage in clinical medicine: tradition or therapeutic?
Plasma protein therapies have been sheltered historically from the scrutiny of evidence-based medicine. Thus, a number of albumin solutions became part of the established therapeutic armamentarium with a very modest evidence base. As evidence-based medicine has turned its focus on plasma protein therapies, albumin's appropriate use has become increasingly questioned. Concurrently, interest in other colloid plasma expanders has increased as efforts to address their side-effects have resulted in new products. The decade-old meta-analysis from the Cochrane collaboration linking albumin with increased mortality, although currently disproven, has resulted in ongoing scrutiny of albumin's safety and has led to a large randomized clinical trial which, while demonstrating equivalent safety with saline, has also shown equivalent mortality in the patient population assessed. Albumin's manufacture yields products which vary between different brands, as well as occasionally between batches from the same brand. These changes affect albumin's physiologic properties and may contribute to the different therapeutic effects observed in clinical practice. More clinical investigations of albumin's therapeutic role are needed before its unique biological features can be shown to result in therapeutically useful drugs.


Dissociative effects of age on neural differentiation at the category and item level.
Increasing age is associated with age-related neural dedifferentiation, a reduction in the selectivity of neural representations which has been proposed to contribute to cognitive decline in older age. Recent findings indicate that when operationalized in terms of selectivity for different perceptual categories, age-related neural dedifferentiation, and the apparent age-invariant association of neural selectivity with cognitive performance, are largely restricted to the cortical regions typically recruited during scene processing. It is currently unknown whether this category-level dissociation extends to metrics of neural selectivity defined at the level of individual stimulus items. Here, we examined neural selectivity at the category and item levels using multivoxel pattern similarity analysis (PSA) of fMRI data. Healthy young and older male and female adults viewed images of objects and scenes. Some items were presented singly, while others were either repeated or followed by a 'similar lure'. Consistent with recent findings, category-level PSA revealed robustly lower differentiation in older than younger adults in scene-selective, but not object-selective, cortical regions. By contrast, at the item level, robust age-related declines in neural differentiation were evident for both stimulus categories. Moreover, we identified an age-invariant association between category-level scene-selectivity in the parahippocampal place area and subsequent memory performance, but no such association was evident for item-level metrics. Lastly, category and item-level neural metrics were uncorrelated. Thus, the present findings suggest that age-related category- and item-level dedifferentiation depend on distinct neural mechanisms.


Adenovirus E4orf6 oncoprotein modulates the function of the p53-related protein, p73.
Recently, several proteins have been identified that are related in their sequence to the p53 tumor-suppressor protein. One of these proteins, which is termed p73, exhibits sequence homology to the p53 transcriptional activation, DNA binding, and oligomerization domains. The adenovirus E1B 55-kDa protein, the adenovirus E4orf6 protein, and SV40 T antigen each can bind to p53 and inhibit p53 function. Here we demonstrate that the adenovirus E4orf6 protein, but not the E1B 55-kDa protein or T antigen, interacts with p73. The E4orf6 protein inhibits p73-mediated transcriptional activation and cell killing in a manner similar to its effect on p53. Thus, only a subset of viral oncoproteins that antagonize p53 function also interacts with the related p73 protein.


Diet-Related and Gut-Derived Metabolites and Health Outcomes: A Scoping Review.
We conducted a scoping review to map available evidence about the health impact of gut microbiota-derived metabolites. We searched PubMed and Embase for studies that assessed the health impact of ten metabolites on any health condition: deoxycholate or deoxycholic acid (DCA), lithocholate or lithocholic acid (LCA), glycolithocholate or glycolithocholic acid, glycodeoxycholate or glycodeoxycholic acid, tryptamine, putrescine, d-alanine, urolithins, N-acetylmannosamine, and phenylacetylglutamine. We identified 352 eligible studies with 168,072 participants. Most (326, 92.6%) were case-control studies, followed by cohort studies (14, 4.0%), clinical trials (8, 2.3%), and cross-sectional studies (6, 1.7%). Most studies assessed the following associations: DCA on hepatobiliary disorders (64 studies, 7976 participants), colorectal cancer (19 studies, 7461 participants), and other digestive disorders (27 studies, 2463 participants); LCA on hepatobiliary disorders (34 studies, 4297 participants), colorectal cancers (14 studies, 4955 participants), and other digestive disorders (26 studies, 2117 participants); putrescine on colorectal cancers (16 studies, 94,399 participants) and cancers excluding colorectal and hepatobiliary cancers (42 studies, 4250 participants). There is a need to conduct more prospective studies, including clinical trials. Moreover, we identified metabolites and conditions for which systemic reviews are warranted to characterize the direction and magnitude of metabolite-disease associations.


Endovascular versus neurosurgical aneurysm treatment: study protocol for the development and validation of a clinical prediction tool for individualised decision making.
Treatment decisions for aneurysmal subarachnoid haemorrhage patients should be supported by individualised predictions of the effects of aneurysm treatment. We present a study protocol and analysis plan for the development and external validation of models to predict benefit of neurosurgical versus endovascular aneurysm treatment on functional outcome and durability of treatment. We will use data from the International Subarachnoid Aneurysm Trial for model development. The outcomes are functional outcome, measured with modified Rankin Scale at 12 months, and any retreatment or rebleed of the target aneurysm during follow-up. We will develop an ordinal logistic regression model and Cox regression model, considering age, World Federation of Neurological Surgeons grade, Fisher grade, vasospasm at presentation, aneurysm lumen size, aneurysm neck size, aneurysm location and time-to-aneurysm-treatment as predictors. We will test for interactions with treatment and with baseline risk and derive individualised predicted probabilities of treatment benefit. A benefit of ≥5% will be considered clinically relevant. Discriminative performance of the outcome predictions will be assessed with the c-statistic. Calibration will be assessed with calibration plots. Discriminative performance of the benefit predictions will be assessed with the c-for benefit. We will assess internal validity with bootstrapping and external validity with leave-one-out internal-external cross-validation. The medical ethical research committee of the Erasmus MC University Medical Center Rotterdam approved the study protocol under the exemption category and waived the need for written informed consent (MEC-2020-0810). We will disseminate our results through an open-access peer-reviewed scientific publication and with a web-based clinical prediction tool.


Toxoplasma gondii and Neospora caninum antibodies in dogs from Grenada, West Indies.
Toxoplasma gondii and Neospora caninum are structurally similar parasites with many common hosts. The prevalence of antibodies to T. gondii and N. caninum was determined in sera from dogs in Grenada, West Indies. Using a modified agglutination test, antibodies to T. gondii were found in 52 (48.5%) of the 107 dogs, with titers of 1:25 in 17, 1:50 in 19, 1:100 in 7, 1:1,600 in 5, and 1:3,200 or higher in 4. Seroprevalence increased with age from 2.2% in dogs <6 mo old to 18.9% in dogs older than 2 yr, indicating postnatal transmission of T. gondii in this population of canines. There was no correlation between the health of the dogs and the seroprevalence or magnitude of the T. gondii titer. Antibodies to N. caninum were determined by the indirect immunofluorescent antibody test (IFAT). Two of the 107 dogs had N. caninum antibodies (IFAT titers 1:100 and 1:400); these dogs had T. gondii titers of 1:1,600 and 1:50, respectively. Results indicate that these 2 structurally similar protozoa are antigenically different.


p38 and c-Jun N-terminal kinase mitogen-activated protein kinase signaling pathways play distinct roles in the response of organogenesis-stage embryos to a teratogen.
Mitogen-activated protein kinase (MAPK) signaling plays an important role during embryo development. We hypothesize that MAPK activation is a determinant of the fate of organogenesis-stage embryos exposed to insult. To test this hypothesis, CD1 mice were exposed to a model teratogen, hydroxyurea, on gestational day 9. Hydroxyurea exposure triggered a dramatic, transient increase in the activation of p38 MAPKs and c-Jun N-terminal kinases (JNKs) in embryos, without activating extracellular signal-regulated kinases 1 and 2. Selectively blocking p38 MAPKs with 4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)1H-imidazole (SB203580) enhanced hydroxyurea-induced fetal mortality without affecting growth retardation or the incidence of deformities among surviving fetuses. In contrast, selectively blocking JNKs with JNK peptide inhibitor 1, L-stereoisomer did not affect hydroxyurea-induced fetal death but increased the incidence of the hindlimb defects observed. Thus, p38 MAPKs and JNKs play distinct roles in protecting the conceptus against insult. Pharmacological inhibition of teratogen exposure induced MAPK activation has adverse consequences on the embryo.


A lectin with mycelia differentiation and antiphytovirus activities from the edible mushroom Agrocybe aegerita.
A lectin named AAL has been purified from the fruiting bodies of the edible mushroom Agrocybe aegerita. AAL consisted of two identical subunits of 15.8 kDa, its pI was about 3.8 determined by isoelectric focusing, and no carbohydrate was discerned. Being treated by pyrogultamate aminopeptidase, the blocked N-terminus of AAL was sequenced as QGVNIYNI. AAL agglutinated human and animal erythrocytes regardless of blood type or animal species. Its hemagglutinating activity was unaffected by acid or alkali treatment and demetalization or addition of divalent metals Mg(2+), Ca(2+) and Zn(2+). AAL was toxic to mice: its LD50 was 15.85 mg per kilogram body weight by intraperitoneal injection. In this study, two novel activities of AAL were proved. It showed inhibition activity to infection of tobacco mosaic virus on Nicotiana glutinosa. The result of IEF suggested that AAL attached to TMV particles. Mycelia differentiation promotion was the other interesting activity. AAL promoted the differentiation of fruit body primordia from the mycelia of Agrocybe aegerita and Auricularia polytricha. AAL antiserum was prepared and immunologically cross-reactived with several proteins from five other kinds of mushrooms. These results suggested that AAL probably was a representative of a large protein family, which plays important physiological roles in mushroom.


Squamous cell carcinoma of the oral mucosa after release of submucous fibrosis and bilateral small radial forearm flap reconstruction.
Oral submucous fibrosis is a collagen disorder that affects the submucosal layer of the upper digestive tract. The major cause is the habit of betel quid chewing, which is common in central, southern, and southeast Asia. The progressive and irreversible course of disease results with trismus, dysphagia, xerostomia, and rhinolalia. The most serious complication of this disorder is the development of oral carcinoma, and the incidence in different series varies from 1.9 to 10 percent. A sufficient mouth opening can be achieved by complete release of fibrotic tissue, and coronoidectomy and temporal muscle myotomy when needed, and reconstruction of the resultant defect can be best achieved by microsurgical free-tissue transfer because of the discouraging results with skin grafting or local flaps. From April of 1997 to May of 2001, a total of 26 patients received reconstructive surgery with small radial forearm flaps after release of submucous fibrosis with or without temporalis muscle myotomy and coronoidectomy. All patients were men, with a mean age of 40.1 years (range, 18 to 62 years) and all had a history of betel nut chewing ranging from 8 to 40 years. The interincisal distance ranged from 5 to 29 mm, with a mean of 15 mm, before operation. After the release procedure, the interincisal distance increased to 40 mm (range, 35 to 50 mm). At a follow-up period of 3 to 48 months, the interincisal distance was a mean of 35 mm (range, 18 to 57 mm), with an average increase of 20 mm compared with the preoperative distance. During follow-up, three patients developed squamous cell carcinoma of the oral cavity 24 to 36 months after submucous fibrosis release. Two of them occurred in the release site and the other one occurred at the soft palate. Oral cancer occurred in three of 13 patients who had received release of submucous fibrosis and who were followed for longer than 2 years (range, 24 to 48 months), which means that 23 percent of these patients developed squamous cell carcinoma of the intraoral mucosa. High risk of cancer occurrence strongly indicates the importance of an earlier and more aggressive surgical approach toward submucous fibrosis, and long-term follow-up on a regular basis. The purpose of an early and aggressive approach to submucous fibrosis is to provide a good quality of life to the patient by improving oral hygiene and oral intake quality and at the same time to obtain a sufficient mouth opening, which is mandatory for the inspection of the excision site and the remaining oral mucosa during follow-up.


A model for human cytochrome P450 2D6 based on homology modeling and NMR studies of substrate binding.
The cytochrome P450 responsible for the debrisoquine/sparteine polymorphism (P450 2D6) has been produced in large quantities by expression of a modified cDNA in baculovirus. A polyhistidine extension was incorporated at the C-terminus of the expressed protein, which, after purification of the protein on a nickel-agarose column, could be removed proteolytically by treatment with thrombin. Purified yields of P450 2D6 were 2.4 mg from 700 mL of cell culture. The protein had a greater than 90% heme content and was fully active, having no residual absorbance at 420 nm in the reduced CO complex. The quantities produced allowed direct study of the interaction of the substrate codeine with the enzyme by paramagnetic relaxation effects on the NMR spectrum of the substrate. Distances between the heme iron atom and substrate protons were calculated from these experiments, and the orientation of the substrate in the binding pocket was determined. This showed that codeine was bound with the methoxy group of the molecule closest to the heme iron (iron-methyl proton distance of 3.1 +/- 0.1 A), consistent with the observed O-demethylation to morphine. A model of the complex Of P450 2D6 with codeine was built from a multiple sequence and structure alignment of the known crystal structures for P450s, incorporating the experimental constraints derived from the NMR studies. This showed that the overall fold Of P450 2D6 is more similar to that of P450 BM3 than to either P450 cam or P450 terp. Codeine binds to P450 2D6 so that the methoxy group is directly above the A ring of the heme, while the basic nitrogen interacts with the carboxylate of aspartate 301.


Fine wine or sour grapes? A systematic review and meta-analysis of the impact of red wine polyphenols on vascular health.
Red wine polyphenols (RWP) are plant-based molecules that have been extensively studied in relation to their protective effects on vascular health in both animals and humans. The aim of this review was to quantify and compare the efficacy of RWP and pure resveratrol on outcomes measures of vascular health and function in both animals and humans. Comprehensive database searches were carried out through PubMed, Web of Science and OVID for randomised, placebo-controlled studies in both animals and humans. Meta-analyses were carried out on acute and chronic studies of RWP in humans, alongside sub-group analysis where possible. Risk-of-bias assessment was carried out for all included studies based on randomisation, allocation, blinding, outcome data reporting, and other biases. 48 animal and 37 human studies were included in data extraction following screening. Significant improvements in measures of blood pressure and vascular function following RWP were seen in 84% and 100% of animal studies, respectively. Human studies indicated significant improvements in systolic blood pressure overall (- 2.6 mmHg, 95% CI: [- 4.8, - 0.4]), with a greater improvement in pure-resveratrol studies alone (- 3.7 mmHg, 95% CI: [- 7.3, - 0.0]). No significant effects of RWP were seen in diastolic blood pressure or flow-mediated dilation (FMD) of the brachial artery. RWP have the potential to improve vascular health in at risk human populations, particularly in regard to lowering systolic blood pressure; however, such benefits are not as prevalent as those observed in animal models.


Target site recognition by a diversity-generating retroelement.
Diversity-generating retroelements (DGRs) are in vivo sequence diversification machines that are widely distributed in bacterial, phage, and plasmid genomes. They function to introduce vast amounts of targeted diversity into protein-encoding DNA sequences via mutagenic homing. Adenine residues are converted to random nucleotides in a retrotransposition process from a donor template repeat (TR) to a recipient variable repeat (VR). Using the Bordetella bacteriophage BPP-1 element as a prototype, we have characterized requirements for DGR target site function. Although sequences upstream of VR are dispensable, a 24 bp sequence immediately downstream of VR, which contains short inverted repeats, is required for efficient retrohoming. The inverted repeats form a hairpin or cruciform structure and mutational analysis demonstrated that, while the structure of the stem is important, its sequence can vary. In contrast, the loop has a sequence-dependent function. Structure-specific nuclease digestion confirmed the existence of a DNA hairpin/cruciform, and marker coconversion assays demonstrated that it influences the efficiency, but not the site of cDNA integration. Comparisons with other phage DGRs suggested that similar structures are a conserved feature of target sequences. Using a kanamycin resistance determinant as a reporter, we found that transplantation of the IMH and hairpin/cruciform-forming region was sufficient to target the DGR diversification machinery to a heterologous gene. In addition to furthering our understanding of DGR retrohoming, our results suggest that DGRs may provide unique tools for directed protein evolution via in vivo DNA diversification.


The rises and falls of disconnection syndromes.
In a brain composed of localized but connected specialized areas, disconnection leads to dysfunction. This simple formulation underlay a range of 19th century neurological disorders, referred to collectively as disconnection syndromes. Although disconnectionism fell out of favour with the move against localized brain theories in the early 20th century, in 1965, an American neurologist brought disconnection to the fore once more in a paper entitled, 'Disconnexion syndromes in animals and man'. In what was to become the manifesto of behavioural neurology, Norman Geschwind outlined a pure disconnectionist framework which revolutionized both clinical neurology and the neurosciences in general. For him, disconnection syndromes were higher function deficits that resulted from white matter lesions or lesions of the association cortices, the latter acting as relay stations between primary motor, sensory and limbic areas. From a clinical perspective, the work reawakened interest in single case studies by providing a useful framework for correlating lesion locations with clinical deficits. In the neurosciences, it helped develop contemporary distributed network and connectionist theories of brain function. Geschwind's general disconnectionist paradigm ruled clinical neurology for 20 years but in the late 1980s, with the re-emergence of specialized functional roles for association cortex, the orbit of its remit began to diminish and it became incorporated into more general models of higher dysfunction. By the 1990s, textbooks of neurology were devoting only a few pages to classical disconnection theory. Today, new techniques to study connections in the living human brain allow us, for the first time, to test the classical formulation directly and broaden it beyond disconnections to include disorders of hyperconnectivity. In this review, on the 40th anniversary of Geschwind's publication, we describe the changing fortunes of disconnection theory and adapt the general framework that evolved from it to encompass the entire spectrum of higher function disorders in neurology and psychiatry.


Characteristics and VA health care utilization of U.S. Veterans who completed suicide in Oregon between 2000 and 2005.
Oregon Violent Death Reporting System data were linked with Veterans Affairs (VA) administrative data to identify and describe veterans who completed suicide in Oregon from 2000 to 2005 (n = 968), and to describe their VA health care utilization in the year prior to death. Twenty-two percent had received health care in the VA system. Of these, 57% did not have mental health diagnoses and 58% had not seen mental health professionals. A larger proportion of those who accessed care were VA-enrolled and received service-connected disability benefits. Fifty-five veterans were hospitalized during the year prior to death. Of these, 33% completed suicide within 30 days of a hospitalization. Further development of suicide prevention strategies for veterans in the community, including general medical treatment settings, is indicated.


Gene polymorphism and prediction of toxicity to platinum-based chemotherapy in patients with gynecologic cancer.
The relationship between single nucleotide polymorphisms (SNPs) at various loci and adverse drug reactions (ADRs) in patients with gynecologic cancer receiving platinum-based chemotherapy (PPCT) remains unexplored. This research aimed to investigate the correlation between SNPs at several loci (e.g., GSTP1 rs1695, MTHFR rs1801133, XPC rs2228001, TP53 rs1042522, and ERCC1 rs3212986) and ADRs in patients with gynecologic cancer receiving PPCT. A total of 244 patients with gynecologic cancer who received first-line PPCT were included in this retrospective study. Blood fluorescence quantitative polymerase chain reaction was used to detect genotypes. Logistic regression, Pearson's Chi-square test, and Fisher's exact test were used to explore the correlations between these SNPs and the occurrence of ADRs. The logistic regression results showed that different genotypes of the five genes had no statistical significance in the overall grade greater than or equal to 3 ADRs. The results of Pearson's Chi-square test showed the same results. On specific adverse reactions, we found that the rs1042522 GG genotype significantly increased the risk of grade greater than or equal to 3 leucopenia compared with the CG and the CC genotypes (p = 0.002). The rs1695 AG genotype showed higher correlation for grade greater than or equal to 3 neutropenia (p = 0.020). The rs2228001 CC genotype also had a higher risk for grade greater than or equal to 3 neutropenia (p = 0.003). This study found that whereas the overall grade greater than or equal to 3 adverse reactions in patients with gynecologic cancer receiving PPCT were not associated with SNPs, specific SNPs (rs1042522 GG, rs1695 AG, and rs2228001 CC) were linked to higher risks of leucopenia and neutropenia, indicating their potential as predictors of hematotoxicity in PPCT-treated patients with gynecologic cancer.


Interrogating health-related public databases from a food toxicology perspective: computational analysis of scoring data.
Over the last 15 years, an expanding number of databases with information on noxious effects of substances on mammalian organisms and the environment have been made available on the Internet. This set of databases is a key source of information for risk assessment within several areas of toxicology. Here we present features and relationships across a relatively wide set of publicly accessible databases broadly within toxicology, in part by clustering multi-score representations of such repositories, to support risk assessment within food toxicology. For this purpose 36 databases were each scrutinized, using 18 test substances from six different categories as probes. Results have been analyzed by means of various uni- and multi-variate statistical operations. The former included a special index devised to afford context-specific rating of databases across a highly heterogeneous data matrix, whereas the latter involved cluster analysis, enabling the identification of database assemblies with overall shared characteristics. One database - HSDB - was outstanding due to rich and qualified information for most test substances, but an appreciable fraction of the interrogated repositories showed good to decent scoring. Among the six chosen substance groups, Food contact materials had the most comprehensive toxicological information, followed by the Pesticides category.


Weekly Fluctuations in, and Associations Between, Salivary Hormone Responses, Load, and Well-Being During the Pre-season in Professional Male Basketball Players.
Kamarauskas, P, Scanlan, A, Ferioli, D, and Conte, D. Weekly fluctuations in, and associations between, salivary hormone responses, load, and well-being during the pre-season in professional male basketball players. J Strength Cond Res 38(1): 128-135, 2024-This study aimed to (a) quantify weekly fluctuations in hormonal responses (testosterone [T], cortisol [C], and their ratio [T:C]), external (PlayerLoad [PL] and PL·minute-1) and internal (session rating of perceived exertion load [sRPE-load], summated heart rate zones [SHRZs], and percentage of maximal heart rate [%HRmax]) load measures, and well-being measured using a self-reported questionnaire and (b) determine the associations between weekly changes in hormonal responses and load measures with weekly changes in well-being during the pre-season phase in basketball players. Twenty-one professional male basketball players (age: 26.2 ± 4.9 years) were monitored during a 5-week pre-season phase. Linear mixed models were used to determine weekly differences in each variable and associations between weekly changes in hormonal and load variables with weekly changes in well-being. Findings revealed that T (p < 0.001) and T:C (p = 0.002) increased toward the end of the pre-season phase. Moreover, higher (p < 0.05) external (PL·minute-1) and internal (%HRmax) load intensities were evident during the first 3 weeks of the pre-season, with no significant fluctuations in other load variables. Weekly changes in PL and sRPE-load were negatively associated (p < 0.05) with weekly changes in well-being, albeit weak in magnitudes (R2 = 0.061-0.105). These results highlight that a periodized approach was undertaken across the pre-season predominantly predicated on altering weekly load intensities, which coincided with positive hormonal responses toward the end of the pre-season. In addition, weak relationships were evident between weekly changes in hormonal responses and load measures with well-being, emphasizing that a low commonality may be present between these constructs.


oxLDL-induced decrease in lipid order of membrane domains is inversely correlated with endothelial stiffness and network formation.
Oxidized low-density lipoprotein (oxLDL) is a major factor in development of atherosclerosis. Our earlier studies have shown that exposure of endothelial cells (EC) to oxLDL increases EC stiffness, facilitates the ability of the cells to generate force, and facilitates EC network formation in three-dimensional collagen gels. In this study, we show that oxLDL induces a decrease in lipid order of membrane domains and that this effect is inversely correlated with endothelial stiffness, contractility, and network formation. Local lipid packing of cell membrane domains was assessed by Laurdan two-photon imaging, endothelial stiffness was assessed by measuring cellular elastic modulus using atomic force microscopy, cell contractility was estimated by measuring the ability of the cells to contract collagen gels, and EC angiogenic potential was estimated by visualizing endothelial networks within the same gels. The impact of oxLDL on endothelial biomechanics and network formation is fully reversed by supplying the cells with a surplus of cholesterol. Furthermore, exposing the cells to 7-keto-cholesterol, a major oxysterol component of oxLDL, or to another cholesterol analog, androstenol, also results in disruption of lipid order of membrane domains and an increase in cell stiffness. On the basis of these observations, we suggest that disruption of lipid packing of cholesterol-rich membrane domains plays a key role in oxLDL-induced changes in endothelial biomechanics.


Going beyond the borders: pyrrolo[3,2-b]pyrroles with deep red emission.
A two-step route to strongly absorbing and efficiently orange to deep red fluorescent, doubly B/N-doped, ladder-type pyrrolo[3,2-b]pyrroles has been developed. We synthesize and study a series of derivatives of these four-coordinate boron-containing, nominally quadrupolar materials, which mostly exhibit one-photon absorption in the 500-600 nm range with the peak molar extinction coefficients reaching 150 000, and emission in the 520-670 nm range with the fluorescence quantum yields reaching 0.90. Within the family of these ultrastable dyes even small structural changes lead to significant variations of the photophysical properties, in some cases attributed to reversal of energy ordering of alternate-parity excited electronic states. Effective preservation of ground-state inversion symmetry was evidenced by very weak two-photon absorption (2PA) at excitation wavelengths corresponding to the lowest-energy, strongly one-photon allowed purely electronic transition. π-Expanded derivatives and those possessing electron-donating groups showed the most red-shifted absorption- and emission spectra, while displaying remarkably high peak 2PA cross-section (σ 2PA) values reaching ∼2400 GM at around 760 nm, corresponding to a two-photon allowed higher-energy excited state. At the same time, derivatives lacking π-expansion were found to have a relatively weak 2PA peak centered at ca. 800-900 nm with the maximum σ 2PA ∼50-250 GM. Our findings are augmented by theoretical calculations performed using TD-DFT method, which reproduce the main experimental trends, including the 2PA, in a nearly quantitative manner. Electrochemical studies revealed that the HOMO of the new dyes is located at ca. -5.35 eV making them relatively electron rich in spite of the presence of two B--N+ dative bonds. These dyes undergo a fully reversible first oxidation, located on the diphenylpyrrolo[3,2-b]pyrrole core, directly to the di(radical cation) stage.


Changes in lower limb kinematics, kinetics, and muscle activity in subjects with functional instability of the ankle joint during a single leg drop jump.
The purpose of this study was to identify differences in 3D kinematics, kinetics, and ankle joint muscle activity in subjects with functional instability (FI) of the ankle joint during a drop jump. Twenty-four subjects with the subjective complaint of FI of the ankle joint and 24 noninjured control subjects performed 10 single leg drop jumps onto a force-plate. Timing and magnitude of kinetic data, timing of kinematic data, and integrated EMG (IEMG) activity of the rectus femoris, peroneus longus, tibialis anterior, and soleus muscles during two 200-ms time periods either side of initial contact (IC) with the ground were analyzed and compared between groups. Subjects with FI demonstrated a significant decrease in pre-IC peroneus longus IEMG activity, which was accompanied by a change in frontal plane movement at the ankle joint during the same time period. Following IC, FI subjects were less efficient than control group subjects in reaching the closed packed position of the ankle joint. Significant differences were seen between the groups' time-averaged and peak vertical and sagittal components of ground reaction force. The altered pre-IC peroneus longus IEMG and increased inversion of the ankle joint observed in FI subjects could help to explain why subjects with FI may suffer from inversion injury to their ankle joint when subjected to an unanticipated ground contact. The kinematic and kinetic differences observed in subjects with FI may lead to repeated injury and damage to the supporting structures of the ankle joint.


A link between c-Myc-mediated transcriptional repression and neoplastic transformation.
Recent studies indicate that the transcription factor c-Myc contributes to oncogenesis by altering the expression of genes involved in cell proliferation, but its precise function in neoplasia remains ambiguous. The ability of c-Myc to bind the sequence CAC(G/A)TG and transactivate appears to be linked to its transforming activity; however, c-Myc also represses transcription in vitro through a pyrimidine-rich cis element termed the initiator (Inr). In transfection experiments using the adenoviral major late (adML) promoter, which contains two Myc binding sites and an Inr, we determined that c-Myc represses transcription through the initiator in vivo. This activity requires the dimerization domain and amino acids 106 to 143, which are located within the transactivation domain and are necessary for neoplastic transformation. We studied a lymphoma-derived c-Myc substitution mutation at 115-Phe, which is within the region required for transcriptional suppression, and found the mutant more effective than wild-type c-Myc in transforming rodent fibroblasts and in suppressing the adML promoter. Our studies of both loss-of-function and gain-of-function c-Myc mutations suggest a link between c-Myc-mediated neoplastic transformation and transcriptional repression through the Inr.


[A model of the regulation of involuntary movements of the eye].
Within the scope of the concepts on the look control mechanism, i. e. the system of interrelated control of head and eye movements a mathematical model is considered which described the control system over eye involuntary movements with quadratic criterion of its work quality. Assuming the optimal character of the control system under study and taking into account the experimental data on the eye movements parameters the relationship between the parameters of the criterion introduced and retinotopic relation of a locus of lateral geniculate is estimated.


Vanillin Cross-Linked Chitosan Film with Controlled Release of Green Tea Polyphenols for Active Food Packaging.
We report a novel cross-linked chitosan composite film containing vanillin, glycerol, and green tea extract. The effects of vanillin-mediated cross-linking and the incorporation of antimicrobial green tea polyphenols were investigated. The cross-linking effect, confirmed by Fourier transform infrared (FTIR) analysis, increased the tensile strength of the biopolymer film to 20.9 ± 3 MPa. The release kinetics of polyphenols from the chitosan-vanillin matrix was studied, and we reported an initial burst release (8 h) followed by controlled release (8 to 400 h). It was found that both vanillin and green tea polyphenols were successful inhibitors of foodborne bacteria, with a minimum inhibitory concentration of the tea polyphenols determined as 0.15 mg/mL (Staphylococcus aureus). These active components also displayed strong antioxidant capacities, with polyphenols quenching >80% of 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals at all concentrations tested. Degradation results revealed that there was a significant (>85%) mass loss of all samples after being buried in compost for 12 weeks. The biopolymeric films, prepared by solvent casting methods, adhere to green chemistry and waste valorization principles. The one-pot recipe reported may also be applied to other cross-linkers and active compounds with similar chemical functionalities. Based on the obtained results, the presented material provides a promising starting point for the development of a degradable active packaging material.


The meaning of postpartum sexual health for women living in Spain: a phenomenological inquiry.
Sexual health is a multidimensional phenomenon constructed by personal, social, and cultural factors but continues to be studied with a biomedical approach. During the postpartum period, a woman transitions to mother, as well as partner-to-parent and couple-to-family. There are new realities in life in the postpartum period, including household changes and new responsibilities that can impact the quality of sexual health. This phenomenon is understudied especially in the context of Spain. The purpose of this study was to describe the lived experience of postpartum sexual health among primiparous women giving birth in Catalonia (Spain). This was a phenomenological study with a purposive sample of primiparous women. Data was collected through semi-structured interviews until saturation. Analysis followed Colaizzi's seven-step process with an eighth translation step added to limit cross-cultural threats to validity. Also, the four dimensions of trustworthiness were established through strategies and techniques during data collection and analysis. Ten women were interviewed from which five themes emerged, including: Not feeling ready, inhibiting factors, new reality at home, socio-cultural factors, and the clinician within the health system. Returning to sexual health led women to engage in experiential learning through trial and error. Most participants reported reduced libido, experienced altered body image, and recounted resumption of sexual activity before feeling ready. A common finding was fatigue and feeling overloaded by the demands of the newborn. Partner support was described as essential to returning to a meaningful relationship. Discussions about postpartum sexual health with clinicians were described as taboo, and largely absent from the care model. Evidence-based practices should incorporate the best evidence from research, consider the postpartum sexual health experiences and preferences of the woman, and use clinician expertise in discussions that include the topic of postpartum sexual health to make decisions. As such, human caring practices should be incorporated into clinical guidelines to recognize the preferences of women. Clinicians need to be authentically present, engage in active communication, and individualize their care. More qualitative studies are needed to understand postpartum sexual health in different contexts, cultures, and countries and to identify similarities and differences through meta-synthesis.


Binding of nitrobenzylthioinosine to high-affinity sites on the nucleoside-transport mechanism of HeLa cells.
Nitrobenzylthioinosine (NBMPR) binds reversibly, but with high affinity (Kd 0.1--1.2 nM), to inhibitory sites on nucleoside-transport elements of the plasma membrane in a variety of animal cells. The present study explored relationships in HeLa cells between NBMPR binding and inhibition of uridine transport. The Km value for inward transport of uridine by HeLa cells in both suspension and monolayer culture was about 0.1 mM. The affinity of the transport-inhibitory sites for uridine (Kd 1.7 mM), inosine (Kd 0.4 mM) and other nucleoside permeants was low relative to that for NBMPR. The pyrimidine homologue of NBMPR, nitrobenzylthiouridine, also exhibited low affinity for the NBMPR-binding sites. Pretreatment of HeLa cells with p-chloromercuribenzene sulphonate (p-CMBS) or N-ethylmaleimide (NEM) decreased binding of NBMPR to its high-affinity sites and inhibited uridine transport, indicating the presence of thiol groups essential to both processes. NEM, a more penetrable reagent than p-CMBS, inhibited binding and transport at much lower concentrations than the latter compound. Pretreatment of cells with concentrations of p-CMBS that alone had no effect on either NBMPR binding or uridine transport increased the sensitivity of transport to NBMPR inhibition and changed the shape of the NBMPR concentration-effect curve, suggesting synergistic inhibiton of uridine-transport activity by these two agents.


Protection against influenza virus infection by nasal vaccination in advance of sublethal irradiation.
The effect of sublethal gamma-ray irradiation on the protection conferred by a nasal influenza vaccine was investigated in BALB/c mice. A radiation dose of 7 Gy was selected as the sublethal dose as this caused exacerbation of the influenza but was not lethal in the mouse model. Mice were irradiated 7 days before, on the same day as, and 7 days after, administration of a nasal influenza vaccine, and were then infected with a lethal dose of the virus 4 weeks after vaccination. Almost all mice irradiated 7 days before or on the same day as vaccination died from viral pneumonia around 7 days after the challenge infection, whereas all mice irradiated 7 days after vaccination survived with no sign of infection. In mice irradiated 7 days after vaccination, both local anti-viral IgA and systemic IgG antibodies were produced in parallel with a marked reduction in lung viral titer, although no antibody production and no reduction in lung viral titer were detected in mice irradiated 7 days before, or on the same day as, vaccination. These results clearly demonstrate that vaccination with influenza virus before irradiation can protect mice from subsequent infection. This may be applicable to patients due to receive sublethal irradiation for bone marrow transplantation.


High-frequency organization and synchrony of activity in the purkinje cell layer of the cerebellum.
The cerebellum controls complex, coordinated, and rapid movements, a function requiring precise timing abilities. However, the network mechanisms that underlie the temporal organization of activity in the cerebellum are largely unexplored, because in vivo recordings have usually targeted single units. Here, we use tetrode and multisite recordings to demonstrate that Purkinje cell activity is synchronized by a high-frequency (approximately 200 Hz) population oscillation. We combine pharmacological experiments and modeling to show how the recurrent inhibitory connections between Purkinje cells are sufficient to generate these oscillations. A key feature of these oscillations is a fixed population frequency that is independent of the firing rates of the individual cells. Convergence in the deep cerebellar nuclei of Purkinje cell activity, synchronized by these oscillations, likely organizes temporally the cerebellar output.


The effect of cervical spine isometric contract-relax technique on hamstring extensibility.
Objectives: To re-investigate the effect of a cervical isometric contract-relax technique on hamstring extensibility and examine the duration of any treatment effect.Methods: Forty asymptomatic participants were randomly assigned equally to either an experimental or control group. Both groups underwent pre and post hamstring extensibility measurements using passive knee extension with the thigh maintained at 90 degrees of hip flexion, with the examiner blinded to treatment allocation of the participants. Torque was measured with a hand held dynamometer to maintain consistent force in pre and post measurements. The experimental group received an upper cervical isometric contract-relax treatment. A digital camera recorded the knee extension angles and the images were computer analysed to determine hamstring extensibility.Results: A split plot ANOVA (SPANOVA) revealed no significant hamstring extensibility differences between or within the groups, immediately or at 30 minutes.Conclusion: The cervical isometric contract-relax treatment produced no significant effect to the extensibility of the hamstring. This study does not support the use of cervical techniques to alter hamstring extensibility.


Profiling of carotenoids in tomato juice by one- and two-dimensional NMR.
Epidemiological data have shown a link between dietary intake of tomatoes and tomato products (rich in carotenoids) and a decreased risk of chronic diseases. The carotenoid profile in tomato products depends on tomato variety as well as the thermal conditions used in processing. The final carotenoid profile may affect the bioaccessibility and bioavailability of these biomolecules. Therefore, nondestructive, reliable methods are needed to characterize the structural and stereochemical variation of carotenoids. CDCl(3) rapid extraction was used to extract carotenoids from tomato juice as an alternative rapid procedure that minimizes solvents and time consumption prior to NMR analysis. The profile of these biomolecules was characterized by application of high-resolution multidimensional NMR techniques using a cryogenic probe. The combination of homonuclear and heteronuclear two-dimensional NMR techniques served to identify (all-E)-, (5Z)-, (9Z)-, and (13Z)-lycopene isomers and other carotenoids such as (all-E)-beta-carotene and (15Z)-phytoene dissolved in the extracted lipid mixture. The use of one-dimensional NMR enabled the rapid identification of lycopene isomers, thereby minimizing further isomerization of (all-E)-lycopene as compared to HPLC data. On the basis of the assignments accomplished, the carotenoid profile of typical tomato juice was successfully determined with minimal purification procedures.


Managed retreat through voluntary buyouts of flood-prone properties.
Retreat from some areas will become unavoidable under intensifying climate change. Existing deployments of managed retreat are at small scale compared to potential future needs, leaving open questions about where, when, and how retreat under climate change will occur. Here, we analyze more than 40,000 voluntary buyouts of flood-prone properties in the United States, in which homeowners sell properties to the government and the land is restored to open space. In contrast to model-based evaluation of potential future retreat, local governments in counties with higher population and income are more likely to administer buyouts. The bought-out properties themselves, however, are concentrated in areas of greater social vulnerability within these counties, pointing to the importance of assessing the equity of buyout implementation and outcomes. These patterns demonstrate the challenges associated with locally driven implementation of managed retreat and the potential benefits of experimentation with different approaches to retreat.


Potential epigenetic mechanisms in psychotherapy: a pilot study on DNA methylation and mentalization change in borderline personality disorder.
Genetic and early environmental factors are interwoven in the etiology of Borderline Personality Disorder (BPD). Epigenetic mechanisms offer the molecular machinery to adapt to environmental conditions. There are gaps in the knowledge about how epigenetic mechanisms are involved in the effects of early affective environment, development of BPD, and psychotherapy response. We reviewed the available evidence of the effects of psychotherapy on changes in DNA methylation and conducted a pilot study in a sample of 11 female adolescents diagnosed with BPD, exploring for changes in peripheral DNA methylation of FKBP5 gene, which encodes for a stress response protein, in relation to psychotherapy, on symptomatology and underlying psychological processes. For this purpose, measures of early trauma, borderline and depressive symptoms, psychotherapy outcome, mentalization, and emotional regulation were studied. A reduction in the average FKBP5 methylation levels was observed over time. Additionally, the decrease in FKBP5 methylation observed occurred only in those individuals who had early trauma and responded to psychotherapy. The results suggest an effect of psychotherapy on epigenetic mechanisms associated with the stress response. The finding that epigenetic changes were only observed in patients with early trauma suggests a specific molecular mechanism of recovery. The results should be taken with caution given the small sample size. Also, further research is needed to adjust for confounding factors and include endocrinological markers and therapeutic process variables.


[Ejaculatory duct obstruction].
Prostatic cysts are rare lesions with a reported incidence from 1 to 7.9%. They have been associated with primary infertility. The main characteristic is the benign course and positive prognosis after correct surgical management. We present three clinical cases, two with primary infertility and another with a history of primary infertility who presented with recurrent hemospermia and refractory medical treatment. All patients had hypospermia and alteration of the seminal parameters represented by moderate oligospermia (MOS), asteno- and teratozoospermia, in addition to hemospermia in two patients. Diagnosis was confirmed by transrectal ultrasound. Transurethral resection (TUR) of the cyst was performed in two cases and resection of the veru montanum in one, obtaining improvement in the seminal parameters after 1 month of follow-up and acceptable parameters for spontaneous conception at 6 months. Infertility associated with partially obstructed ejaculatory ducts may be suspected clinically by hypospermia. Transrectal ultrasound is essential to confirm the diagnosis. TUR of this lesion reestablishes the free passage of semen in almost all patients, with potential recovery of fertility 6 months after treatment.


Distributions of p-values smaller than .05 in psychology: what is going on?
Previous studies provided mixed findings on pecularities in p-value distributions in psychology. This paper examined 258,050 test results across 30,710 articles from eight high impact journals to investigate the existence of a peculiar prevalence of p-values just below .05 (i.e., a bump) in the psychological literature, and a potential increase thereof over time. We indeed found evidence for a bump just below .05 in the distribution of exactly reported p-values in the journals Developmental Psychology, Journal of Applied Psychology, and Journal of Personality and Social Psychology, but the bump did not increase over the years and disappeared when using recalculated p-values. We found clear and direct evidence for the QRP "incorrect rounding of p-value" (John, Loewenstein & Prelec, 2012) in all psychology journals. Finally, we also investigated monotonic excess of p-values, an effect of certain QRPs that has been neglected in previous research, and developed two measures to detect this by modeling the distributions of statistically significant p-values. Using simulations and applying the two measures to the retrieved test results, we argue that, although one of the measures suggests the use of QRPs in psychology, it is difficult to draw general conclusions concerning QRPs based on modeling of p-value distributions.