Urban-rural variations in health in The Netherlands: does selective migration play a part?
Urban-rural health differences are observed in many countries, even when socioeconomic and demographic characteristics are controlled for. People living in urban areas are often found to be less healthy. One of the possible causes for these differences is selective migration with respect to health or health risk factors. This hypothesis is hardly ever empirically tested. This paper tries to assess the existence of selective urban-rural migration. Health indicators and health risk factors were measured in a 1991 population sample. Moves were registered between 1991 and 1995. Using logistic regression analyses, comparisons were made between, firstly, urban to rural movers and rural to urban movers and secondly, between movers and stayers. Region surrounding the city of Eindhoven in south eastern part of the Netherlands. Data were used of 15,895 respondents aged 20-74 in 1991. By 1995 613 subjects had moved from urban to rural and 191 subjects from rural to urban. Bivariate nor multivariate analyses show hardly and differences between movers into urban and movers into rural areas. Bivariate analyses on movers and stayers show that movers are healthier than stayers. However, when socioeconomic and demographic variables are controlled for, movers appear to be less healthy, with the exception of the younger age groups. Areas that attract many migrants from and lose few migrants to other degrees of urbanicity will in the long run obtain healthier populations, because of demographic and socioeconomic characteristics. However, if these characteristics are accounted for, the opposite is true, with the exception of younger age groups. In extreme cases this may cause spurious findings in cross sectional research into the relation between urbanicity and health. Absolute numbers of migrants need to be very high, however, to make this noticeable at the aggregate level.


Effectiveness of internet-based self-management interventions on pulmonary function in patients with chronic obstructive pulmonary disease: A systematic review and meta-analysis.
To investigate the effectiveness of internet-based self-management interventions on pulmonary function in patients with chronic obstructive pulmonary disease (COPD). Systematic review and meta-analysis. Eight electronic databases including PubMed, Web of Science, Cochrane library, Embase, CINAHL, China National Knowledge Infrastructure, Wangfang and Weipu databases were systematically searched from inception of the database to January 10, 2022. Statistical analysis was performed using Review Manager 5.4 and results were reported as mean difference (MD) or standard mean difference (SMD) with 95% confidence intervals (CI). Outcomes were the forced expiratory volume in 1 second (FEV1), forced volume capacity (FVC) and percent of FEV1/FVC. The Cochrane Risk of Bias Tool was used to assess the risk of bias of included studies. The study protocol was not registered. Eight randomized controlled trials (RCTs) including 476 participants met the inclusion criteria and were included in meta-analysis. It was found that internet-based self-management interventions showed a significant improvement in FVC(L), while FEV1 (%), FEV1 (L), FEV1/FVC (%) and FVC (%) did not significantly improve. Internet-based self-management interventions were effective in improving pulmonary function in patients with COPD, caution should be exercised in interpreting the results. RCTs of higher quality are needed in the future to further demonstrate the effectiveness of the intervention. It provides evidence for internet-based self-management interventions in improving pulmonary function in patients with COPD. The results suggested that internet-based self-management interventions could improve the pulmonary function in people with COPD. This study provides a promising alternative method for patients with COPD who have difficulty seeking face-to-face self-management interventions, and the intervention can be applied in clinical settings. No Patient or Public Contribution.


Preclinical studies on suicide gene therapy for head/neck cancer: a novel method for evaluation of treatment efficacy.
Malignancies of the oral cavity and oropharynx account for 31% of all diagnosed cancers in India. In most cases, patients present with tumours that are clinically stage III/IV where surgery, radiotherapy and chemotherapy have not been very effective. Hence, there is an urgent need for alternate treatment modalities. Gene therapy is a recent development shown to be effective in various malignancies. In this study we have attempted to cause bulk reduction in tumour volume using the HSVtk/ganciclovir strategy, solely on the basis of the 'bystander' effect. Nude mouse xenograft tumours of human head/neck cancer were engrafted with cells expressing viral thymidine kinase. After treatment with 8 mM ganciclovir for 14 days, the treatment efficacy was monitored. A novel method has been devised to evaluate cell kill microscopically in the whole tumour. Of the 11 mice included in the study, 9 showed a significant reduction in total tumour volume of treated versus control tumours (p = 0.015). Bulk reduction in tumour load can be brought about without use of viral vectors for gene transfer solely by the bystander effect.


Catalytic Synthesis of Potassium Acyltrifluoroborates (KATs) from Boronic Acids and the Thioimidate KAT Transfer Reagent.
We report the synthesis of potassium acyltrifluoroborates (KATs) by a palladium-catalyzed cross-coupling of boronic acids and the thioimidate KAT transfer reagent. The combination of widely available aryl- and vinylboronic acids with commercially available thioimidate 1 using catalytic PdII and a CuII additive enables the preparation of KATs in high yields and with good functional group tolerance. This formal insertion of CO into organoboronic acids can also be applied to boronic acid pinacol esters and potassium organotrifluoroborates using a slightly modified procedure. The cross-coupling can be telescoped into the one-pot synthesis of amides and α-aminotrifluoroborates by exploiting the unique chemistry of KATs and their trifluoroborate iminium (TIM) derivatives.


Increased Susceptibility of the CD57- NK Cells Expressing KIR2DL2/3 and NKG2C to iCasp9 Gene Retroviral Transduction and the Relationships with Proliferative Potential, Activation Degree, and Death Induction Response.
Nowadays, the use of genetically modified NK cells is a promising strategy for cancer immunotherapy. The additional insertion of genes capable of inducing cell suicide allows for the timely elimination of the modified NK cells. Different subsets of the heterogenic NK cell population may differ in proliferative potential, in susceptibility to genetic viral transduction, and to the subsequent induction of cell death. The CD57-NKG2C+ NK cells are of special interest as potential candidates for therapeutic usage due to their high proliferative potential and certain features of adaptive NK cells. In this study, CD57- NK cell subsets differing in KIR2DL2/3 and NKG2C expression were transduced with the iCasp9 suicide gene. The highest transduction efficacy was observed in the KIR2DL2/3+NKG2C+ NK cell subset, which demonstrated an increased proliferative potential with prolonged cultivation. The increased transduction efficiency of the cell cultures was associated with the higher expression level of the HLA-DR activation marker. Among the iCasp9-transduced subsets, KIR2DL2/3+ cells had the weakest response to the apoptosis induction by the chemical inductor of dimerization (CID). Thus, KIR2DL2/3+NKG2C+ NK cells showed an increased susceptibility to the iCasp9 retroviral transduction, which was associated with higher proliferative potential and activation status. However, the complete elimination of these cells with CID is impeded.


[Application of sensitivity analysis method in mode analysis of hypergravitation training facility].
To increase the natural frequencies of hypergravitation training facility. The natural frequencies of the hypergravitation training facility were modified by using sensitivity analysis method. The natural frequencies of the hypergravitation training facility were improved by modification of physical and geometrical parameters of sensitive elements. The computational results indicates that sensitivity analysis method is feasible.


Adding teeth to wave action: the destructive effects of wave-borne rocks on intertidal organisms.
Observations in rocky intertidal areas demonstrate that breaking waves 'throw' rocks and cobbles and that these missiles can damage and kill organisms. Targets in the intertidal were dented by impacts from wave-borne rocks. New dents/day in these targets was positively correlated with the daily maximum significant wave height and with new patches/day in aggregations of the barnacle Chthamalus fissus. Impact frequency was highest in the upper intertidal and varied dramatically between microhabitats on individual boulders (edges, tops and faces). These patterns were reflected in the microhabitat abundances of 'old' and 'young' barnacles. Comparisons were made of the survivorship and the frequency of shell damage in two populations of the limpet Lottia gigantea living in habitats which differed primarily in the number of moveable rocks (i.e. potential projectiles). The mortality rate and frequency of shell damage were significantly higher in the projectilerich habitat. In addition only in this habitat did the frequency of shell damage covary significantly with seasonal periods of high surf. Investigation of the response of limpet shells to impacts suggests that shell strength varies between species and increases with shell size. Species-specific patterns of non-fatal shell breakage may have evolved to absorb the energy of impacts. In two of the intertidal habitats studied, wave-borne rock damage was chronic and, at least in part, may have governed the faunal makeup of the community by contributing to the physical 'boundaries" of the environment within which the inhabitants must survive.


Fetal and maternal factors associated with neonatal adiposity as measured by air displacement plethysmography: a large cross-sectional study.
There is evidence that the fetal and early postnatal environments play a role in determining the risk of lifetime obesity, diabetes and cardiovascular disease. Neonatal body composition, as a surrogate marker of the in-utero environment, can be reliably and accurately measured by air displacement plethysmography (ADP). Our primary objective was to identify preconception, fetal and maternal factors affecting neonatal body composition. This cross-sectional study included 599 term babies born between September and October 2010 at Royal Prince Alfred Hospital, Sydney, Australia. Neonatal body fat percentage (BF%) was measured within 48 h of birth using ADP. Maternal demographic, anthropometric and medical data as well as neonatal gestational age and sex were used to develop a regression model that predicted body composition and birthweight. The mean (SD) neonatal BF% in our whole population was 9.2(4.4)%. Significant variables in the model for neonatal BF% were neonatal sex, gestational age, maternal ethnicity, gestational weight gain (GWG), pre-pregnancy BMI, parity and maternal hypertension (p<0.05); together, these explained 19% of the variation in BF%. GDM status was not a significant variable. Neonatal female sex, maternal Caucasian ethnicity and increased gestational weight gain explained the most variation and were most strongly associated with increased BF%. This study highlights maternal obesity and increased gestational weight gain as two factors that are amenable to intervention as risk factors for newborn adiposity, which is important in the future study of the "developmental origins of health and disease" hypothesis.


Progesterone-induced meiosis in Xenopus laevis oocytes: a role for cAMP at the "maturation-promoting factor" level.
Cholera toxin inhibition of progesterone-induced meiosis of Xenopus laevis oocytes in vitro has been correlated with increased cAMP levels. Inhibition of germinal vesicle breakdown (Gvbd) and cAMP increase occurred after a lag period of 2 hr, when cholera toxin was injected, or 4--5 hr, when applied externally. The ability of the maturation-promoting factor (Mpf) to provoke Gvbd when injected into recipient oocytes was found to be dependent upon whether the oocytes had been exposed to cholera toxin alone or to toxin and progesterone. With the former, cAMP levels were elevated and Mpf activity was abolished, whereas with the latter, the increase in cAMP was less pronounced and Mpf activity was observed. Injection of cAMP or its 8-thio derivatives shortly before the appearance of progesterone-induced Mpf abolished Gvbd. If injected earlier or later, no inhibition was observed. In contrast, cholera toxin inhibited maturation even when added several hours before progesterone, suggesting a sustained accumulation of cAMP. No Gvbd occurred when 8-thio-methyl-cAMP was injected together with Mpf. These data suggest that cAMP is involved in the control of the formation/amplification and/or activity of Mpf-a result which may be of general significance in cell division mechanisms.


Alzheimer's disease brain extract stimulates the survival of cerebral cortical neurons from neonatal rats.
Cell cultures of neonatal rat cerebral cortex in a serum-free medium were used to investigate a lack of neuronotrophic factors in Alzheimer's disease (AD) brain. A few neurons survived in the absence of brain extract. The addition of normal brain extract resulted in a 2.5-fold increase in neuronal survival. AD brain extract contained 4-fold neuronotrophic activity of normal brain extract. These findings are in contrary to the previous hypothesis of a lacking neuronotrophic factors in AD brain. These new results may change the concept of mechanism of neuronal death in AD.


Colorimetric quantitation of filarial viability.
A simple three-step colorimetric assay based on the tetrazolium salt MTT (3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) has been developed for quantifying filarial viability. Living (but not dead) filariae take up MTT and rapidly reduce it to formazan, so staining themselves dark blue. This colour change which is easily seen provides a rapid qualitative test for filarial viability. Quantitative data can be obtained by solubilizing formazan out of the worm with DMSO and measuring the absorbance of the resulting solution at 510 nm. To date the technique has been demonstrated in several species of filariae including Onchocerca volvulus. MTT reduction is thought to be selective for NADH-dependent dehydrogenase activity in viable worms. The reaction occurs readily in all developmental stages of Dipetalonema viteae including fragments of filarial tissue. Enzyme activity in viable intact D. viteae appears to be primarily associated with the hypodermis/muscle cells, with minimal formazan formation in the gut and reproductive tracts. The application of this MTT assay as a parameter for quantifying in vitro drugs effects is described. Assay procedures have been developed and optimized with D. viteae and Brugia pahangi for the assessment of effects of macrofilariae and microfilarial release, and the activity of a range of antifilarial standards reported. Several potential applications of the technique to studies on filarial biology are discussed.


A sensitive and selective on-line amperometric sulfite biosensor using sulfite oxidase immobilized on a magnetite-gold-folate nanocomposite modified carbon-paste electrode.
We describe a novel amperometric sulfite biosensor, comprising a carbon-paste electrode (Fe3O4@Au-Cys-FA/CPE) modified with immobilized sulfite oxidase (SOx) on a gold-coated magnetite nanoparticle core, encased within a conjugated folic acid (FA) cysteine (Cys) shell. The biosensor electrode was fabricated using a polydimethylsiloxane (PDMS) and mineral oil mixture as binder, which also enhances the physical stability and sensitivity of the electrode. The developed biosensor displays good electrocatalytic activity toward oxidation of H2O2, which occurs by an enzymatic reaction between SOx and sulfite. The Fe3O4@Au-Cys-FA electrode exhibits good electrocatalytic activity, and has good retention of chemisorbed SOx on the electrode because of its large surface area. Sulfite was quantified using amperometric measurements from the Fe3O4@Au-Cys-FA/CPE biosensor, and using an in-house assembled flow cell at +0.35V (vs. Ag/AgCl), with a phosphate buffer carrier (0.10M, pH 7.0) at a flow rate of 0.8mLmin(-1). The system detects sulfite over the range 0.1-200mgL(-1) (r(2)=0.998), with a detection limit of 10µgL(-1) (3σ of blank). The system exhibits acceptable precision (%R.S.D.=3.1%), rapid sample throughput (109samplesh(-1)), and good stability (2w). The developed biosensor shows satisfactory tolerance to potential interferences, such as sugars, anions, ascorbic acid, and ethanol. We applied the developed method to the determination of sulfite content in wines and pickled food extracts, and our results are in good agreement with those obtained by the standard iodometric method.


Effects of Plyometric Jump Training on Jump and Sprint Performance in Young Male Soccer Players: A Systematic Review and Meta-analysis.
Even from a young age, modern soccer requires high levels of physical fitness development, particularly jumping and sprinting. Plyometric jump training (PJT), combined with young athletes' regular soccer sessions, has the potential to improve jumping and sprinting. However, studies exploring the effects of PJT are generally limited by small sample sizes. This problem of underpowered studies may, thus, be resolved by pooling study results in a meta-analysis. The objective of this systematic review with meta-analysis (SRMA) was to assess the effects of plyometric jump training (PJT) on jumping and sprinting among young male soccer players. The SRMA included peer-reviewed articles that incorporated PJT in healthy players (i.e., < 23 years of age), a control group, and a measure of jumping or sprinting. Means and standard deviations of outcomes were converted to Hedges' g effect sizes (ES), using the inverse variance random-effects model. Moderator analyses were conducted for PJT duration, frequency, total number of sessions, participants' chronological age, and FIFA age categories (i.e., U-17 vs. U-20 vs. U-23). A multivariate random-effects meta-regression was also conducted. Thirty-three studies were included, comprising 1499 participants. PJT improved vertical jump tests (ES = 0.60-0.98; all p < 0.01) and linear sprint performance (ES = 0.60-0.98; p < 0.03). Interventions of > 7 weeks and > 14 PJT sessions induced greater effects compared to PJT with ≤ 7 weeks and ≤ 14 total sessions on 10-m sprint performance (between group p = 0.038). PJT is effective in improving jumping and sprinting performance among young male soccer players. Greater 10-m linear sprinting improvements were noted after interventions > 7-week duration and > 14 sessions, suggesting a greater return from exposure to longer PJT interventions, partially in support for the adoption of a long-term approach to athletic development in young athletes. However, with reference to the findings of the meta-regression, and those from the remaining subgroup and single factors analysis, a robust confirmation regarding the moderator role of participant's age or PJT configuration effects on young soccer player's fitness qualities needed.


Exploring the role of metacognition in obsessive--compulsive and anxiety symptoms.
This study tests three hypotheses, predicting first that metacognition is highly correlated with anxiety and obsessive-compulsive (O-C) symptoms, second that it mediates the relationship between O-C symptoms and anxiety, and third that the meta-cognitive predictors of anxiety are different from the meta-cognitive predictors of O-C symptoms. The sample of the present study was 850 students selected from various universities in Turkey. Significant correlations between metacognition, O-C symptoms and anxiety were observed. Also, mediation analysis confirmed that metacognition fully mediated the relationship between O-C symptoms and anxiety. Consistent with our hypothesis, trait anxiety and O-C symptoms had different meta-cognitive predictors. Although, we expected that meta-cognitive beliefs would vary based on the sub-type of O-C symptoms, meta-cognitive beliefs did not differ according to the O-C symptom subtypes. We discussed results with reference to the literature of meta-cognition, anxiety and O-C symptoms.


Attachment, skin deep? Relationships between adult attachment and skin barrier recovery.
This study examined the relationship between individual differences in adult attachment and skin barrier recovery. Dating couples (N = 34) completed a self-report measure of attachment anxiety and avoidance, and during two separate laboratory visits, normal skin barrier function was disrupted using a tape-stripping procedure, followed by a 20 min discussion of personal concerns in one visit and relationship problems in the other, counterbalanced randomly across visits. Skin barrier recovery was assessed by measuring transepidermal water loss up to 2 h after skin disruption. Multilevel modeling showed that skin barrier recovery did not differ between the personal concern or relationship problem discussions. Among women, greater attachment anxiety predicted faster skin barrier recovery across the two visits, while greater attachment avoidance predicted slower skin barrier recovery. Among men, greater attachment anxiety predicted slower skin barrier recovery during the personal concern discussion only. The observed effects remained significant after controlling for transepidermal water loss in undisturbed skin, suggesting that the relationship between attachment security and skin barrier recovery was not due to other skin-related factors like sweating. Cortisol changes, self-reported emotions, stress appraisals, and supportiveness ratings were tested as potential mediators, and none explained the relationships between attachment and skin barrier recovery. These findings are the first to demonstrate associations between individual differences in attachment style and restorative biological processes in the skin, even in a sample of young dating couples in satisfied relationships.


Adhesion characteristics of human melanoma cell lines of varying metastatic potential.
The adhesive behaviour of a series of human melanoma cell lines, of varying metastatic potential, to basement membrane and stromal components was investigated in vitro. Experimental metastatic propensity was assessed from the number of pulmonary nodules formed after i.v. injection of cells into BALB/c nude mice. All cell lines showed similar kinetics of attachment when tested on plastic, type-I collagen films, type-I collagen hydrated gels, fibronectin, laminin type-IV collagen substrates and bovine aortic endothelial monolayers. Fibronectin-coated plastic compared to plastic alone produced increased cell attachment and spreading to the same extent in all the cell lines. The melanoma lines attached preferentially to cryostat sections of lung compared to other organs reflecting the pattern of organ involvement of metastasis in vivo. However, no significant quantitative differences in attachment to lung sections were seen between melanoma variants of differing metastatic capacities. Cells labelled with [125I]iododeoxyuridine to determine their initial organ distribution following i.v. injection showed that tumour-cell arrest was not significantly changed enough to explain the differing metastatic capacities. Thus it appears that adhesive properties of these melanoma cells are not correlated with their capacity to form metastases in vivo.


Acceptance of a homestay program and attitude toward community medicine among medical students.
In community-based medical education, opportunities for medical students to interact with local residents are important. To facilitate such interaction, we aimed to evaluate acceptance of a homestay program and attitude toward community medicine among medical students. The participants (n = 39) were allowed to stay in the local homes of residents for one night in August 2016, 2017, and 2018. Before and after the homestays, the students responded to a self-reported questionnaire using the visual analog scale (VAS; 0-100 mm). The questionnaire included four questions on homestay/community medical training and community medicine and four questions about attitude toward community medicine in the local areas of medical students. Then, we compared the VAS scores before and after training. The VAS scores for all questions about homestay/community medical training and community medicine significantly increased: "Is it worthwhile for you to have experience in the field of community medicine," "Did you find the homestay enjoyable," "Does the homestay add educational significance to the program," and "Is direct interaction with residents meaningful?" For the two questions about attitude toward community medicine, the VAS scores significantly increased: "Is there a challenge to practicing community medicine" and "In the future, do you want to work in Tamba area where you stayed?" The medical students were extremely enthusiastic about the educational program for community medicine involving residential homestays, which improved their attitudes toward practicing community medicine. Moreover, the students appreciated that their training sites could become their future workplaces.


An enzyme-based system for extraction of small extracellular vesicles from plants.
Plant-derived nanovesicles (NVs) and extracellular vesicles (EVs) are the next generation of nanocarrier platforms for biotherapeutics and drug delivery. EVs exist not only in the extracellular space, but also within the cell wall. Due to the limitations of existing isolation methods, the EVs extraction efficiency is low, and a large amount of plant material is wasted, which is of concern for rare and expensive medicinal plants. We proposed and validated a novel method for isolation of plant EVs by enzyme degradation of the plant cell wall to release the EVs. The released EVs can easily be collected. The new method was used for extraction of EVs from the roots of Morinda officinalis (MOEVs). For comparison, nanoparticles from the roots (MONVs) were extracted using the grinding method. The new method yielded a greater amount of MOEVs, and the vesicles had a smaller diameter compared to MONVs. Both MOEVs and MONVs were readily absorbed by endothelial cells without cytotoxic effect and promoted the expression of miR-155. The promotion of miR-155 by MOEVs was dose-dependent. More importantly, we found that MOEVs and MONVs were enriched toward bone tissue. These results support our hypothesis that EVs in plants could be efficiently extracted by enzymatic cell wall digestion and confirm the potential of MOEVs as therapeutic agents and drug carriers.


The sleep of 'morning' and 'evening' types.
A questionnaire developed by Ostberg to differentiate 'morning' types from 'evening' types was administered to 100 college students. The actual sleep behavior of the 11 extreme 'morning' types (larks) and the 10 extreme 'evening' types (owls) was monitored for two weeks with a sleep log and the Post-sleep Inventory. Data was collected from the owls for a further two-week period in which the owls had been instructed to attempt to arise at the lark arousal time. In addition to going to bed earlier and getting up earlier than the owls, the larks had a less variable sleep length and awakening time and took shorter naps than the owls. Larks further reported fewer physical problems and less mental activity across the night as well as more adequate sleep than owls, who differed little from the normal college population even after having their awakening time shifted.


Control of adaptive immune responses by Toll-like receptors.
Recently, there has been considerable interest in how adaptive immune responses are controlled by the innate immune system. In particular, researchers have focused on how the differentiation of CD4 T cells is directed upon priming by dendritic cells. The identification of the Toll-like receptors as a family of pattern-recognition receptors involved in controlling dendritic cell activation has focused attention on these receptors as possible regulators of adaptive immune responses. However, recent studies have suggested that Toll-like receptors may only control the induction of Th1 responses and that a separate system of recognition regulates Th2 responses.


Transformed but not normal hepatocytes express UCP2.
Uncoupling protein 2 (UCP2) expression in liver is restricted to non-parenchymal cells. By means of differential display screening between normal rat liver and H4IIE hepatoma cells we have isolated a cDNA clone encompassing part of UCP2 cDNA. Northern blot analysis revealed that UCP2 is expressed in some hepatocarcinoma cell lines, while it is absent in adult hepatocytes. UCP2 mRNA in H4IIE cells was downregulated when cells were cultured for 36 h in 0.1% serum and its expression was restored upon addition of 10% serum or phorbol esters. Hypomethylation of UCP2 was observed in transformed UCP2 expressing cells. Our results indicate that UCP2 is expressed in some hepatocarcinoma cell lines and that serum components may participate in maintaining elevated UCP2 levels.


Potential ecological risk of heavy metals in sediments from the Mediterranean coast, Egypt.
Mediterranean Sea, Egypt is an economically important marine environment. During the last decades there has been extensive increase in the levels of urbanization and industrialization along its coastal area. Therefore, the present work attempts to determine the status of heavy metals distribution in sediment samples, and their ecological risk assessment in the studied area. Twenty surfacial sediment samples were collected from different selected stations along the Egyptian Mediterranean Sea. The samples were homogenized and placed into sealed polyethylene bags, carried to the laboratory in an ice box and stored at -20 °C in the dark until analysis. The results revealed that Fe had the highest mean value (243-38045 μgg(-1)) followed by Mn (17-1086 μgg(-1)), and a lower concentrations were found for Co (0.43-26.39 μgg(-1)) and Cd (0.04-0.47 μgg(-1)). Risk assessment showed that Cd had the highest ecological risk (Er = 21.52), followed by Pb (Er = 3.01), while Zn had the lowest risk (Er = 0.23). Both the ecotoxicological index method and the potential ecological risk index (RI) suggested that the combined ecological risk of the studied metals may be low. Multivariate statistical analysis (Cluster and Factor analysis) suggested that the lithogenic factor dominants the distribution of most part of the considered metals in the study area. Multivariate analysis has been proved to be an effective tool for providing suggestive information regarding heavy metal sources and pathways. The results of this study provide valuable information about metal contamination in sediments along the Mediterranean Sea for over than 1200 km.


Brain computation. Selective information routing by ventral hippocampal CA1 projection neurons.
The hippocampus computes diverse information involving spatial memory, anxiety, or reward and directly projects to several brain areas. Are different computations transmitted to all downstream targets uniformly, or does the hippocampus selectively route information according to content and target region? By recording from ventral hippocampal CA1 neurons in rats during different behavioral tasks and determining axonal projections with optogenetics, we observed subsets of neurons changing firing at places of elevated anxiety or changing activity during goal approach. Anxiety-related firing was selectively increased in neurons projecting to the prefrontal cortex. Goal-directed firing was most prominent in neurons targeting the nucleus accumbens; and triple-projecting neurons, targeting the prefrontal cortex, amygdala, and nucleus accumbens, were most active during tasks and sharp wave/ripples. Thus, hippocampal neurons route distinct behavior-contingent information selectively to different target areas.


Behavioral measures to reduce non-adherence in renal transplant recipients: a prospective randomized controlled trial.
Solid-organ transplant recipients present a high rate of non-adherence to drug treatment. Few interventional studies have included approaches aimed at increasing adherence. The objective of this study was to evaluate the impact of an educational and behavioral strategy on treatment adherence of kidney transplant recipients. In a randomized prospective study, incident renal transplant patients (n = 111) were divided into two groups: control group (received usual transplant patient education) and treatment group (usual transplant patient education plus ten additional weekly 30-min education/counseling sessions about immunosuppressive drugs and behavioral changes). Treatment adherence was assessed using ITAS adherence questionnaire after 3 months. Renal function at 3, 6, and 12 months, and the incidence of transplant rejection were evaluated. The non-adherence rates were 46.4 and 14.5 % in the control and treatment groups (p = 0.001), respectively. The relative risk for non-adherence was 2.59 times (CI 1.38-4.88) higher in the control group. Multivariate analysis demonstrated a 5.84 times (CI 1.8-18.8, p = 0.003) higher risk of non-adherence in the control group. There were no differences in renal function and rejection rates between groups. A behavioral and educational strategy addressing the patient's perceptions and knowledge about the anti-rejection drugs significantly improved the short-term adherence to immunosuppressive therapy.


Sodium borohydrate (NaBH4) pretreatment for efficient enzymatic saccharification of wheat straw.
In this study, the aim was to examine bioethanol production of wheat straw residues using an alternative chemical, sodium borohydrate (NaBH(4)) in chemical pretreatment step. The obtained results showed that sodium hydroxide (NaOH) and NaBH(4) treated straw resulted in 87.8% and 83.3% glucan conversion in enzymatic hydrolysis, but hydrogen peroxide (H(2)O(2)) (74.7%) and sulfuric acid (H(2)SO(4)) (71.7%) had lower glucan conversion. The highest ethanol yield from untreated straw (115 g/kg) was observed for 4% NaBH(4) pretreated sample (60 min) and the theoretical yield (86.9%) was also calculated to be highest for the sample.


Effects of gatekeeper trainings from the Austrian national suicide prevention program.
The development and implementation of gatekeeper trainings were first goals in the national suicide prevention strategy "Suicide Prevention Austria" (SUPRA). The current study aims to assess the short- and longer-term effects of the SUPRA gatekeeper trainings in comparison with established gatekeeper trainings. We evaluated 28 gatekeeper trainings including 427 participants by assessing improvement of knowledge (facts about suicide and suicide prevention), gatekeeper self-efficacy and attitudes, and gatekeeper behavior (e.g., asking depressed people about suicide). Assessments were immediately before and after the gatekeeper trainings, with an additional follow-up 6 months later. Effects were compared with benchmark effects of established gatekeeper trainings. There were substantial improvements in knowledge, self-efficacy and attitudes immediately after the training, comparable or larger than known from evaluations of established gatekeeper trainings. Most of these changes were upheld in the follow-up assessment, with effects comparable to other gatekeeper trainings. There was only a small increase of self-reported gatekeeper behavior, in line with results from other gatekeeper trainings. The SUPRA gatekeeper training had some beneficial effects in the short- and longterm, with effect sizes comparable to established gatekeeper trainings.


Effect of clozapine and adjunctive high-dose glycine in treatment-resistant schizophrenia.
The focus of this study was the systematic evaluation of the clinical effects of glycine as an adjunct to the atypical antipsychotic clozapine in the treatment of schizophrenia. In a double-blind, placebo-controlled study, 19 patients with chronic, treatment-resistant schizophrenia who were maintained on optimal doses of clozapine (400-1200 mg/day) were administered either 30 g/day of glycine (N=9) or placebo (N=10) for 12 weeks. Clinical evaluations with the Brief Psychiatric Rating Scale, the Scale for the Assessment of Negative Symptoms, and the Simpson-Angus movement scale were completed biweekly. The use of glycine as an adjunct to clozapine was not effective in decreasing positive or negative symptoms. In contrast, the patients treated with clozapine without glycine had a 35% reduction in positive symptoms. These preliminary data suggest that glycine may interfere with the antipsychotic efficacy of atypical neuroleptics such as clozapine.


Relationship between astringency and phenolic composition of commercial Uruguayan Tannat wines: Application of boosted regression trees.
Phenolic compounds play a major role in the intensity and characteristics of wine astringency. However, studies involving commercial wine samples are still scarce. The aim of the present work was to study the relationship between astringency and phenolic composition of commercial Uruguayan Tannat wines using boosted regression trees (BRT), a novel predictive method. Forty commercial Tannat wines were evaluated by a trained sensory panel (9 members), who assessed their total astringency intensity using time-intensity (TI) and described their astringency sub-qualities using a check-all-that-apply (CATA) question composed of sixteen terms. The polyphenolic profiles of the wines were determined by HPLC-MS and conventional oenological parameters were also obtained. Fifty BRT models with different partitions of the data in training and test sets were built for astringency maximum intensity (Imax) and for the frequency of use of the 16 astringency sub-qualities considered in the CATA question. As predictor variables, 84 phenolic compounds and oenological parameters were considered for all BRT models. Both strong and weak predictive models were obtained for each response variable. Predictive accuracy was much higher for astringency intensity than for the frequency of mention of astringency sub-qualities. Still, the BRT models allowed to point out to some compositional variables most likely involved in wine astringency perception. Total tannin concentration (chemically determined) was the most relevant explanatory variable for sensory astringency, while flavan-3-ols were the individual phenolic compounds with the highest contribution to astringency, particularly some dimers, trimers and the sum of non-galloylated tetramers. However, the effect of these predictors differed according to the astringency sub-quality considered as response. As expected, non-linear relationships between phenolic compounds and astringency were found. These results contribute to the understanding of the influence of phenolic composition on wine astringency and stress the potential of BRT models for identifying the compounds responsible for this complex sensory characteristic.


Radiation therapy in endemic (African) Kaposi's sarcoma.
Evaluating the role of radiation therapy in the treatment of the endemic, African variant of Kaposi's sarcoma. A retrospective analysis. Between 1978 and 1990, 28 symptomatic African patients with the African Human Immunodeficiency Virus negative type of Kaposi's sarcoma were referred to the Johannesburg General Hospital. Following staging, all patients were treated with radiation therapy. Doses ranged between 8-10 Gy (single fraction) or 14-24 Gy fractionated over 1-3 weeks. Complete and partial regression of cutaneous lesions was achieved in 9 (32%) and 15 (54%) patients, retrospectively. A complete/near-complete alleviation of symptoms was achieved in all patients. Response rate and duration of response was not influenced by age, radiation modality or schedule. Side effects were minimal. Our study emphasizes the high radiosensitivity of the endemic, African type of Kaposi's sarcoma, indicating its usefulness as the treatment of choice for this disease.


Impact of phenylketonuria type meal on appetite, thermic effect of feeding and postprandial fat oxidation.
Dietary management of phenylketonuria (PKU) requires the replacement of natural protein-containing foods with special low protein foods. The effect of a PKU type diet on factors contributing to energy balance requires investigation. To investigate the impact of a PKU type meal on appetite ratings, gut appetite hormones, thermic effect of feeding (TEF) and fat oxidation. Twenty-three healthy adults (mean ± SD age: 24.3 ± 5.1 years; BMI: 22.4 ± 2.5 kg/m2) participated in a randomized, crossover design study. Each participant conducted two (PKU and Control) experimental trials which involved consumption of a PKU type meal and protein substitute drink or an isocaloric and weight matched ordinary meal and protein-enriched milk. Appetite, metabolic rate, fat oxidation measurements and blood collections were conducted for the duration of 300 min. On the completion of the measurements ad libitum buffet dinner was served. Responses of appetite ratings, plasma concentrations of GLP-1 and PYY (P > 0.05, trial effect, two-way ANOVA) and energy intake during ad libitum buffet dinner (P > 0.05, paired t-test) were not significantly different between the two trials. The TEF (PKU, 10.2 ± 1.5%; Control, 13.2 ± 1.0%) and the total amount of fat oxidized (PKU, 18.90 ± 1.10 g; Control, 22.10 ± 1.10 g) were significantly (P < 0.05, paired t-tests) lower in the PKU than in the Control trial. The differences in TEF and fat oxidation were significant (P < 0.05, paired t-tests) for the post-meal period. Consumption of a meal composed of special low protein foods has no detrimental impact on appetite and appetite hormones but produces a lower TEF and postprandial fat oxidation than an ordinary meal. These metabolic alterations may contribute to the increased prevalence of obesity reported in patients with PKU on contemporary dietary management. The trial has been registered in ClinicalTrials as NCT02440932.


A catechol bioadhesive for rapid hemostasis and healing of traumatic internal organs and major arteries.
Uncontrolled hemorrhage caused by trauma to internal organs or major arteries poses critical threats to lives. However, rapid hemostasis followed by tissue repair remains an intractable challenge in surgery owing to the lack of ideal internal-use adhesives that can achieve fast and robust wet adhesion and accelerate wound healing. Herein, we develop a robust hemostatic bioadhesive (CAGA) from novel highly-branched aminoethyl gelatin with end-grafted abundant catechol (Gel-AE-Ca). The unique chemical structure of Gel-AE-Ca makes CAGA capable of gelling on wet tissues via synergetic cross-linking of catechol-Fe3+ chelation and horseradish peroxidase (HRP)/H2O2-triggered covalent bonds using a dual-channel needle, meeting the key demands of internal medical applications (e.g., instant and strong wet adhesion, injectability, biocompatibility, self-healing, stretching flexibility, infection resistance, and proper biodegradability). It exhibits rapid gelation within 10 s and robust wet tissue adhesion up to 115.0 ± 13.1 kPa of shear strength and 245.0 ± 33.8 mm Hg of sealing strength. In vivo trials demonstrate that CAGA can not only effectively seal anastomosis of the carotid artery, but achieve rapid hemostasis on the sites of liver incisions and penetrating cardiac wounds within 10 s. The wound closure by CAGA and its timely biodegradation promote wound healing of the vital organs.


"Bath salts" intoxication: a case report.
We present a case of a potentially lethal ingestion of "Bath Salts." After presentation, we briefly review the epidemiology and pathology of "bath salts" ingestion.


[Breech Presentation: CNGOF Guidelines for Clinical Practice - Epidemiology, Risk Factors and Complications].
To study the frequency, the risk factors and the mode of delivery of breech presentation. To analyze the perinatal morbidity and mortality associated with breech presentation in comparison to cephalic presentation from all mode of delivery. MedLine and Cochrane Library databases search in French and English and review of the main foreign guidelines between 1980 and 2019. Three modes of breech presentation exist according to fetal lower limbs position: frank in 2/3 of cases, complete in 1/3 of cases or, more rarely, incomplete (LE3). About 5% of women gave birth in breech presentation in France (LE3). As the frequency of breech presentation decreases with increasing gestational age, this incidence is lower after 37 WG and represents only 3% of term deliveries (LE3). Congenital uterine malformation (LE3) and fibroma (LE3), prematurity (LE3), oligoamnios (LE3), some fetal congenital malformations (LE3) and low birthweight for gestational age (LE3) are the main risk factors with breech presentation. In France, one-third of women with a term fetus in breech presentation attempt a vaginal delivery (LE3), which is successful in 70% of cases (LE3). Neonatal outcome is not associated with type of breech presentation (frank or complete) in case of vaginal delivery attempt after 37 WG (LE3). Overall, perinatal morbidity and mortality after 37 WG of breech presentation appear to be greater than in cephalic presentation from all mode of delivery (LE3). The risk of traumatic injury in breech delivery is estimated under 1% (LE3). The most common injuries are collarbone fractures, hematomas or contusions, and brachial plexus injury (LE3). Breech presentation is associated with an increased risk of hip dysplasia (LE3) and cesarean delivery does not seem to be a protective factor (LE3). Breech presentation does not appear to be associated with an increased risk of cerebral palsy compared to cephalic presentation after exclusion of fetuses with congenital malformations (LE3). Worldwide, mode of delivery of breech presentation has undergone profound changes since the publication of the TBT (Term Breech Trial). There are intrinsic factors associated with breech presentation, which should not be overlooked when interpreting the increased perinatal morbidity and mortality observed in case of breech presentation.


Bioaccumulation behaviour of transplants of the lichen Flavoparmelia caperata in relation to total deposition at a polluted location in Portugal.
This experiment compares the short and long time element accumulation behaviour of transplants of Flavoparmelia caperata lichen thalli and total deposition in an atmospheric polluted area. It was found that lichens exposed for a short time behaved differently from lichens in cumulative exposition suggesting the presence of acclimatization behaviour. The lichen transplant elemental content does not unequivocally represent the average or cumulative environmental availability of the exposure period. Reflection characteristics depend on the element and the lichen physiological conditions. Good correlations between lichen elemental contents and total deposition were obtained when a physiological lichen parameter was introduced in a mathematical model, suggesting that metabolically mediated accumulation is important.


[Orthopedic rheumatology].
Rheumatic diseases with their progressive inflammatory systematic nature are important diseases any clinical practising orthopaedic doctor is frequently confronted with. In case of mono- or polyarticular joint swelling, stiffness or inflammatory arthralgia, rheumatoid arthritis has to be deliberated particularly in differential diagnostic considerations. When diagnosed early, a joint treatment by an internal specialist as well as the initiation of a basic medicamentous therapy are highly recommended. Therefore, corticosteroids and disease modifying anti-rheumatic drugs (DMARDs) such as methotrexate can be used, in case of failure a treatment with biologicals should follow. The operative therapy depends on the stadium of joint destruction. In early stadiums (LDE 0-3) and in case of therapy resistant inflammation a synovectomy should be performed as a preventive intervention. Given an already advanced destruction, alloarthroplasty or arthrodesis are indicated as reconstructive procedures.


The effect of bioturbation by Lumbriculus variegatus on transport and distribution of lead in a freshwater microcosm.
The present study investigated the effect of bioturbation by the oligochaete worm Lumbriculus variegatus on the transport and environmental distribution of lead (Pb). Experiments used L. variegatus at densities of 0 ind./m(2), 2093 ind./m(2), and 8372 ind./m(2), in freshwater microcosms with Pb-spiked sediment. At the end of the 14-d experiment, Pb levels in the water column, tissues of L. variegatus, and sediment were determined, and bioturbation was quantified using luminophores. The bioturbation by L. variegatus increased Pb transport from the sediment to the water column. However, it did not significantly affect Pb bioaccumulation by L. variegatus or Pb levels in the sediment. The biodiffusion coefficient (Db) was positively related to worm density, but did not differ between Pb-spiked sediment and uncontaminated sediment. The latter finding suggests that Pb at the 100 μg/g concentration used in the present study did not affect L. variegatus bioturbation. The present study shows that bioturbation can enhance Pb transfer across the sediment-water interface and thus enhance Pb availability to organisms in the water column.


An unusual case of abdominal pain in a female child.
Non-traumatic abdominal pain is a common presenting complaint in emergency department (ED) patients, quoted in some contemporary literature as being the third most frequent reason for ED visits. We present the ED and hospital course of an unusual case of an 11 year old female with right lower quadrant abdominal pain. The admission assessment of this patient was "possible appendicitis versus gastroenteritis"; however, laparatomy revealed a right adnexal torsion. The need for emergency medicine physicians to always include gynecologic and other less common causes in the differential diagnosis and workup of abdominal pain in children is emphasized.


[Effect of the intraventricular administration of vasopressin and oxytocin on hypothalamic self stimulation].
The influence of 500 microunits oxytocin as well as 50 micrunits lysine-vasopressin on hypothalamic self-stimulation rate after intraventricular application was studied. Oxytocin caused an increase and vasopressin a decrease in the self-stimulation rate.


A prospective randomized trial of HLA-matched versus mismatched single-donor platelet transfusions in cancer patients.
The use of histocompatability antigen (HLA)-matched platelets has been advocated for the support of thrombocytopenic cancer patients. We randomized 78 newly diagnosed cancer patients prospectively (before thrombocytopenia) to receive either HLA-matched or mismatched single-donor platelet transfusions. Three hundred forty-one platelet transfusions were given for 80 separate episodes of therapy-induced thrombocytopenia in 33 patients. Forty-five patients receiving intensive chemotherapy did not develop significant (less than 20,000 platelets/mm3) thrombocytopenia and did not receive a platelet transfusion. No marked difference was observed between the matched and mismatched groups in regard to number of total platelet transfusions per patient (median, 3 vs. 5, respectively; P = 0.076), number of platelet transfusions per episode (median, 3.0 vs. 3.5, respectively; P = 0.28), or days between transfusions (median, 2 vs. 2, respectively, P greater than 0.4). Bleeding episodes, although rare, tended to be of increased severity in the mismatched group. Febrile patients receiving mismatched platelets tended to have a lower posttransfusion increment increase than their nonfebrile counterparts (P = 0.068), although a similar trend could not be demonstrated between febrile and nonfebrile patients who received matched platelets (P = 0.22). Patients treated as outpatients had significantly higher posttransfusion increments than when transfused as inpatients when they were given mismatched platelets (P less than 0.0005). Development of antiplatelet antibody did not appear to affect response to platelet transfusions. Only one patient developed sustained high-level antibody titers. In patients where thrombocytopenia was significant, the transfusion of HLA-matched platelets did not appear to offer a significant advantage. However, HLA-matched platelet transfusions tended to be associated with higher posttransfusion increments in febrile patients and a trend toward fewer severe bleeding episodes. A multi-institution trial containing a large number of patients is needed to evaluate trends observed in this study.


Effects of moisture content and porosity on the thermal conductivity and volumetric specific heat capacity of pharmaceutical powders.
Thermal conductivity and specific heat capacity are two important parameters for the drying process of pharmaceutical materials during methods such as wet granulation that can be observed in the overall tablet manufacturing process. In this study, a transient line heat source method was used for the first time to determine the thermal conductivity and volumetric specific heat capacity of common pharmaceutical components and binary mixtures, with moisture content ranging from 0 % to 30 % w.b and active ingredient loading between 0 % and 50 % by weight. A three-parameter least squares regression model relating the thermal properties to moisture content and porosity was evaluated at a 95 % confidence interval, with R2 values ranging from 0.832 to 0.997. Relationships were established between thermal conductivity, volumetric specific heat capacity, porosity, and moisture content for pharmaceutical ingredients including acetaminophen, microcrystalline cellulose, and lactose monohydrate.


The effect of severe dietary restriction on intramuscular glutamine concentrations and protein synthetic rate.
An investigation was carried out to examine the relationship between fractional muscle protein synthetic rate (FSR) and intramuscular glutamine concentration ({GLN}(i)) in rats that had a dietary intake which was deficient in both protein and energy. Young male rats (38 days old) were fed for 48 h on either 1) 25% of the ad lib intake of a 20% protein diet, or 2) glucose alone, sufficient to provide the same energy intake as in 1). In a separate study, 33 day old rats were starved completely for 48 h. Appropriate controls were included in both studies. Muscle FSR, which was reduced by 40% in both groups of energy restricted rats (P<0.001), was associated with a small increase in {GLN}(i) (P<0.05). Starvation produced a 60% reduction in FSR (P<0.01) and a 45% (P<0.05) reduction in {GLN}(i). It is concluded that reductions in muscle protein synthesis can occur by mechanisms independent of intramuscular glutamine concentration.


The chemistry and conformational and biological analysis of vitamin D3, its metabolites and analogues.
The chemical properties, stereochemical relationships and solution conformation, as assessed in part by proton NMR spectroscopy, for vitamin D3, its major metabolites [including 1alpha,25-(OH)2D3, its hormonally active form] and a number of A-ring and side chain analogues are evaluated and discussed in relation to their biological activity. In particular the relative ability of many of these seco-steroids to compete both with 25-OHD3 for its chick serum binding protein and 1alpha,25-(OH)2-D3 for its chick intestinal cytosol-chromatin receptor system was quantitated, in vitro. Further, the relative effectiveness of all these metabolites and analogues to mediate in vivo intestinal calcium absorption and bone calcium mobilization was determined. Collectively these chemical and biological studies constitute a "systems analysis" of the various steroid structural parameters both required and tolerated by the multi-stepped endocrine system associated with the biological actions of vitamin D.


Object-based Encoding in Visual Working Memory: Evidence from Memory-driven Attentional Capture.
Visual working memory (VWM) adopts a specific manner of object-based encoding (OBE) to extract perceptual information: Whenever one feature-dimension is selected for entry into VWM, the others are also extracted. Currently most studies revealing OBE probed an 'irrelevant-change distracting effect', where changes of irrelevant-features dramatically affected the performance of the target feature. However, the existence of irrelevant-feature change may affect participants' processing manner, leading to a false-positive result. The current study conducted a strict examination of OBE in VWM, by probing whether irrelevant-features guided the deployment of attention in visual search. The participants memorized an object's colour yet ignored shape and concurrently performed a visual-search task. They searched for a target line among distractor lines, each embedded within a different object. One object in the search display could match the shape, colour, or both dimensions of the memory item, but this object never contained the target line. Relative to a neutral baseline, where there was no match between the memory and search displays, search time was significantly prolonged in all match conditions, regardless of whether the memory item was displayed for 100 or 1000 ms. These results suggest that task-irrelevant shape was extracted into VWM, supporting OBE in VWM.


Marker-assisted introgression of genes into rye translocation leads to the improvement in bread making quality of wheat (Triticum aestivum L.).
Introgression of genes from related species can be a powerful way to genetically improve crop yields, but selection for one trait can come at the cost to others. Wheat varieties with translocation of the short arm of chromosome 1 from the B genome of wheat (1BS) with the short arm of chromosome 1 from rye (1RS) are popular globally for their positive effect on yield and stress resistance. Unfortunately, this translocation (1BL.1RS) is also associated with poor bread making quality, mainly due to the presence of Sec-1 on its proximal end, encoding secalin proteins, and the absence of Glu-B3/Gli-B1-linked loci on its distal end, encoding low molecular weight glutenin subunits (LMW-GS). The present study aims to replace these two important loci on the 1RS arm with the wheat 1BS loci, in two popular Indian wheat varieties, PBW550 and DBW17, to improve their bread-making quality. Two donor lines in the cultivar Pavon background with absence of the Sec-1 locus and presence of the Glu-B3/Gli-B1 locus, respectively, were crossed and backcrossed with these two selected wheat varieties. In the advancing generations, marker assisted foreground selection was done for Sec-1- and Glu-B3/Gli-B1+ loci while recurrent parent recovery was done with the help of SSR markers. BC2F5 and BC2F6 near isosgenic lines (NILs) with absence of Sec-1 and presence of Glu-B3/Gli-B1 loci were evaluated for two years in replicated yield trials. As a result of this selection, thirty promising lines were generated that demonstrated improved bread making quality but also balanced with improved yield-related traits compared to the parental strains. The study demonstrates the benefits of using marker-assisted selection to replace a few loci with negative effects within larger alien translocations for crop improvement.


Epidemiological Characteristics of Major Joints Fracture-Dislocations.
To describe the epidemiological features of major joints fracture-dislocations between 2015 and 2019. This retrospective study enrolled patients with majorintra-articular fracture-dislocations who were treated in the third hospital of Hebei Medical University from January 2015 to December 2019. A total of 582 patients (389 [66.84%] males and 193 [33.16%] females) were identified. The distribution characteristics of intra-articular fracture-dislocations involving shoulder, elbow, wrist, hip, knee, and ankle joints were included. The potential associations between fractures with concomitant dislocations and related factors, such as age, gender and sites were explored. There were 92 cases (15.81%) of shoulder joints, 67 cases (11.51%) of elbow joints, 45 cases (7.73%) of wrist joints, 181 cases (31.10%) of hip joints, 42 cases (7.22%) of knee joints, and 155 cases (26.63%) of ankle joints. The overall male-to-female ratio was 2.02:1.The highest proportion age group of the six types intra-articular fracture-dislocations included the ages 25-34 years. For males, the highest proportion age group was 25-34 years, for females, it was 45-54 years. For male patients, hip was the most common, accounted for 35.48%, but ankle fracture-dislocation was the most common for females, accounted for 30.57%. The highest proportion age group of shoulder fracture-dislocation included the ages 55-64 years(22.83%), with a male to female ratio of 1.24:1. While the age group with the highest risk of elbow, wrist, hip, knee and ankle fracture- dislocation was 25-34 years (28.36%) with a male to female ratio of 2.19:1, 25-34 years (31.11%) with a male to female ratio of 8:1, 45-54 years (27.07%) with a male to female ratio of 3.21:1, 15-24 years (45.24%) with a male to female ratio of 0.75:1, 25-44 years (43.87%) with a male to female ratio of 1.63:1, respectively. The most common site of joint fracture-dislocation in different age groups was corresponding as follows, 0-14 years(elbow), 15-24 years(knee), 25-34 years(hip), 35-44 years(hip), 45-54 years(hip), 55-64 years(ankle), 65-74 years(shoulder), ≥75 years(shoulder). Major joints fracture-dislocations were most common in the hip and the least common in the knee, and there were more men than women. Hip was the most common affected joint in men while ankle in women. Age and sex factors can significantly affect the location of intra articular fracture and dislocation. The current study could aid orthopaedic surgeons in a better understanding of this injury and help to implement targeted preventive measures.


Diagnosis and Differential Diagnosis of Parkinson Disease.
Parkinsonism is one of the most common neurologic disorders in the aging population. Although Parkinson disease (PD) is the most common cause, there is a lengthy differential diagnosis. The diagnosis of PD hinges on recognizing its typical features, including bradykinesia, rest tremor, unilateral onset, cogwheel rigidity, and beneficial and sustained response to levodopa. Equally important is to be familiar with the "red flags," which are features not expected with PD and suggest an alternative diagnosis, usually a parkinsonian syndrome. In general, it is best to have the diagnosis confirmed by a neurologist, especially one with expertise in movement disorders.


Cognitive ability and continuous measures of relative hand skill: a note.
This note re-examines a finding by Crow et al. [Crow, T. J., Crow, L. R., Done, D. J., & Leask, S. (1998). Relative hand skill predicts academic ability: Global deficits at the point of hemispheric indecision. Neuropsychologia, 36(12), 1275-1281] that equal skill of right and left hands is associated with deficits in cognitive ability. This is consistent with the idea that failure to develop dominance of one hemisphere is associated with various pathologies such as learning difficulties. Using the same data source but utilising additional data, evidence is found of a more complex relationship between cognitive ability and relative hand skill.


Atorvastatin rescues vascular endothelial injury in hypertension by WWP2-mediated ubiquitination and degradation of ATP5A.
As a widely used lipid-lowering drug in clinical practice, atorvastatin is widely recognized for its role in protecting vascular endothelium in the cardiovascular system. However, a clear mechanistic understanding of its action is lacking. Here, we found that atorvastatin counteracted angiotensin II-induced vascular endothelial injury in mice with hypertension. Mechanistically, atorvastatin up-regulated WWP2, a E6AP C-terminus (HECT)-type E3 ubiquitin ligase with an essential role in regulating protein ubiquitination and various biological processes, thereby rescuing vascular endothelial injury. By ubiquitinating ATP5A (ATP synthase mitochondrial F1 complex subunit alpha), WWP2 degraded ATP5A via the proteasome pathway, stabilizing Bcl-2/Bax in the mitochondrial pathway of apoptosis. Moreover, atorvastatin further ameliorated death of vascular endothelial cells and improved vascular endothelial functions under WWP2 overexpression, whereas WWP2 knockout abrogated these beneficial effects of atorvastatin. Furthermore, we generated endothelial cell-specific WWP2 knockout mice, and this WWP2-mediated mechanism was faithfully recapitulated in vivo. Thus, we propose that activation of a WWP2-dependent pathway that is pathologically repressed in damaged vascular endothelium under hypertension is a major mechanism of atorvastatin. Our findings are also pertinent to develop novel therapeutic strategies for vascular endothelial injury-related cardiovascular diseases.


Determination of chromosome 13 status in bone marrow cells of patients with multiple myeloma using combined morphologic and fluorescence in situ hybridization analysis.
Deletion of chromosome 13q is believed to be an adverse prognostic marker in patients with multiple myeloma (MM). Interphase fluorescence in situ hybridization (I-FISH) is the method of choice for detection of chromosome 13q deletion (del13q). However, I-FISH has high false-positive rates attributed to a low percentage of plasma cells (PC), which are responsible for MM, in bone marrow (BM) samples from MM patients. In an attempt to overcome this problem, combined morphologic and I-FISH analyses were performed by a unique system that allows rapid automatic scanning of a large number of cells with simultaneous determination of the lineage of specific cells carrying del13q. The percentage of PC with del13q in BM samples from 40 MM patients was calculated. In addition, we established a useful prognostic ratio defined as the number of PC with del13q divided by the number of non-PC with del13q (PDP/PDNP), which may help to precisely define the putative role of del13q in prediction response of MM patients to new therapeutic compounds. We suggest this technique as a novel sensitive and specific method for detection of del13q in a minor PC population of MM patients.


Expression of genes encoding laccase and manganese-dependent peroxidase in the fungus Ceriporiopsis subvermispora is mediated by an ACE1-like copper-fist transcription factor.
The effect of copper on the expression of genes encoding the ligninolytic enzymes laccase (lcs) and manganese peroxidase (mnp) in Ceriporiopsis subvermispora was evaluated. This metal increased transcript levels of lcs, mnp1 and mnp2. This finding was not unexpected in the case of lcs, since its promoter contains a putative ACE element. Originally characterized in the yeast Saccharomyces cerevisiae, ACE is the target sequence of the ACE1 copper-responsive transcription factor in this microorganism. Analysis of the promoter regions of mnp genes revealed the presence of formerly unnoticed ACE elements. Based on the ace1 gene from Phanerochaete chrysosporium, we isolated and characterized an ACE1-like transcription factor from C. subvermispora (Cs-ACE1) through complementation of a S. cerevisiae ace1Delta strain. Surprisingly, ACE1 factors from both basidiomycetes exhibit substantial differences, not only structurally but also in their ability to complement the aforementioned yeast strain. Specific binding of Cs-ACE1 to its cognate DNA sequence was confirmed by electrophoretic mobility-shift assays.


Assessment of fracture healing in orthopaedic trauma.
Fracture healing is a complex physiologic process, relying on the crucial interplay between biological and mechanical factors. It is generally assessed using imaging modalities, including conventional radiology, CT, MRI and ultrasound (US), based on the fracture and patient features. Although these techniques are routinely used in orthopaedic clinical practice, unfortunately, they do not provide any information about the biomechanical status of the fracture site. Therefore, in recent years, several non-invasive techniques have been proposed to assess bone healing using ultrasonic wave propagation, changes in electrical properties of bones and callus stiffness measurement. Moreover, different research groups are currently developing smart orthopaedic implants (plates, intramedullary nails and external fixators), able to provide information about the fracture healing process. These devices could significantly improve orthopaedic and trauma clinical practice in the future and, at the same time, reduce patients' exposure to X-rays. This study aims to define the role of traditional imaging techniques and emerging technologies in the assessment of the fracture healing process.


'Why are there so many drums playing until dawn?' Exploring the role of Gamba spirits and healers in the post-war recovery period in Gorongosa, Central Mozambique.
In the wake of a civil war, local resources can play a potential role in shaping the recovery process by providing both old and new exegeses for the disturbing effects of the past. Using the case of Gorongosa, this article aims to explore the ways in which the war has impacted upon traditional medicine by creating Gamba spirits that cause havoc but can also transform the psychosocial hurts of war survivors. Historically, traditional healing practice was under the sole responsibility of the Dzoca, an ancestral spirit that for generations was embodied in living people through lineage descent to exercise its healing powers. There is consensus among healers that the Gamba spirit and healers emerged after the war and are rapidly spreading throughout Gorongosa. I explore the emic theories to explain the Gamba's puzzling origins and the role they are currently playing in Gorongosa.


Early amidation approach to 3-[(4-amido)pyrrol-2-yl]-2-indolinones.
A new synthesis of 3-[(4-amido)pyrrol-2-yl]-2-indolinones has been developed, where the amide side chain was installed prior to pyrrole formation. This strategy precludes the need to use any coupling reagents to install the amide side chain. This process includes a zinc-free alternative to the Knorr pyrrole synthesis.


Chagasic patients with indeterminate clinical form of the disease have high frequencies of circulating CD3+CD16-CD56+ natural killer T cells and CD4+CD25High regulatory T lymphocytes.
Several studies have demonstrated that different clinical manifestations of human Chagas' disease are associated with distinct and complex host-parasite relationships directly involving the immune system. In this context, it has been proposed that tissue damage might be more severe in the absence of regulatory mechanisms that involve both innate and adaptive immune responses. Herein, we describe a descriptive phenotypic profile focusing on the frequency of major regulatory T cells [CD4+CD25high and natural killer T (NKT) lymphocytes] in different clinical forms of Chagas' disease. Ex vivo immunophenotyping of whole blood demonstrated that the indeterminate clinical form displays a higher frequency of both CD4+CD25high and NKT regulatory cells (CD3+CD16-CD56+), associated with increased levels of circulating cytotoxic NK cells (CD3-CD16+CD56+ and CD3-CD16+CD56dim NK cells). By contrast, the increased percentage of activated CD8+HLA-DR+ T-cell subset was exclusively associated with severe clinical forms of Chagas' disease. We hypothesize that regulatory T cells may be able to control the deleterious cytotoxic activity in the indeterminate clinical form by inhibiting the activation of CD8+HLA-DR+ T cells. The lack of regulated populations in cardiac and digestive clinical forms could account for impaired immune response that culminates in strong cytotoxic activity and tissue damage.


Effect of an in-situ simulation workshop on home birth practice in Australia.
Interprofessional training programs for obstetric emergencies have been introduced for up-skilling birth unit staff in hospitals but not frequently used in training midwives and paramedicine staff for home birth emergency. Practical Obstetric Multiprofessional Training (PROMPT) has previously been described in the home birth setting using in-situ simulation training of home births for midwifery and paramedicine staff. The aim of this study was to evaluate the benefit of the home birth simulation in clinical practice and to explore how the simulation program prepared the midwives for a birth-related emergency in a publicly funded home birth program. Midwives conducting home births, the midwifery educator and the simulated woman in labour (n=9) attended an interview that explored how the midwives' learning through simulation affected their home birth clinical practice. The simulated woman and the facilitator who conducted the simulation for more than six years were also interviewed to comment on the observed change in performance in simulation. The interview transcripts were thematically analysed. The themes that were identified and agreed upon, were applying learning to clinical practice, learning in teams, valuing realism, facilitating simulation based education and managing variation. In-situ nature of simulation with home birth midwives and paramedical staff facilitated learning transfer and team-based approach to practice. The careful simulation design provided a breadth of experience in emergencies. Applying learning to prepare for clinical emergency situations changed the midwives' approach in managing home births. This provided evidence for a change in behaviour (Level 3 Kirkpatrick's framework) and transfer of learning, leading to changed protocols (Level 4a Kirkpatrick's framework).


[Aortoiliac reconstruction after kidney transplantation. Strategies to avoid ischemic damage of the transplant].
The rising life expectancy of patients undergoing kidney transplantation and the improvement in the function rate of the allografts have led to an increasing number of patients suffering from arteriosclerosis-related diseases of the aortoiliac arteries. In these particular cases, an interruption of the blood supply of the allograft is always necessary for operative repair of the aortic and iliac arteries. This means a high risk of ischemic damage to the transplanted kidney. Between 1987 and 2000, 1,076 kidney transplantations were performed in our department. During this time, 14 reconstructive operations of the aortoiliac arteries were performed in 12 patients (6 women, 6 men, average age 55.2 (45-71) years). Operations were indicated in patients suffering from occlusive disease with imminent extremity or allograft loss, and symptomatic or asymptomatic aneurysms with a maximum diameter of more than 4 cm. In patients presenting with thoracoabdominal (1) and abdominal aortic aneurysms (3), protection of the transplanted kidney was performed by axilloiliac or axillofemoral bypass. Hypothermic flush-perfusion of the allograft containing PGE1 and heparin was performed in seven of nine operations for occlusive disease. None of the patients presented with a permanent decrease in kidney function, six patients showed temporary creatinine elevation, and in nine patients creatinine levels at discharge were lower than they were preoperatively. None of the patients died. Reviewing all reported methods of allograft protection, we recommend a three-step strategy including sequential clamp technique (ischemia < 30 min.), hypothermic flush-perfusion (ischemia < or = 60 min.), and temporary axilloiliac/femoral shunt (ischemia > 60 min), depending on the expected renal ischemia time.


Current trends in analytical strategies for the chromatographic determination of nitrofuran metabolites in food samples. An update since 2012.
Nitrofurans (NFs) are synthetic broad-spectrum antibacterial and antiparasitic drugs, which recently were extensively used in veterinary practice. In the body of animals, NFs are converted into carcinogenic and mutagenic metabolites that can be accumulated in foods of animal origin having an adverse effect on human health. Therefore, NFs are currently banned in animal husbandry and aquaculture of many countries. However, the data from monitoring the quality of food products indicate that, despite the prohibitions established by the law, they still are used not only in the developing countries but also in the European Union, due to their high antibacterial activity, low cost, and accessibility. Thus, it is of great importance for human health to develop reliable and sensitive analytical methods for monitoring NF metabolites in animal-derived foods. The objective of this review is to summarize the pretreatment strategies and chromatographic methods that have been reported during the last decade for the determination of NF metabolites in food samples, and to outline the future trends with an emphasis on the novel solutions in this area.


Assessment of scheduling for patients referred for an abnormal red reflex.
Scheduling lag time is the time between the date of an appointment and the date an appointment was created in the scheduling system. We sought to determine the scheduling lag time in a pediatric ophthalmology clinic for children <8 years of age, referred by a primary care provider for an abnormal red reflex (ARR), cataract, leukocoria, or retinoblastoma. The median scheduling lag time was 1.8 days (IQR, 0.8-5.0). Of the 106 total appointments, 89 (84%) were completed as scheduled, 12 (11%) were canceled, and 5 (5%) were no-shows. Ten patients (12%) were never seen. There was a shorter scheduling lag time for completed visits (median, 1.1 days; IQR, 0.2-4.0) than canceled visits (median, 12.0 days; IQR, 3.1-48.5; P < 0.001). Monitoring of the scheduling lag time for urgent referrals may be a metric for quality improvement in pediatric ophthalmology.


Adjuvants influence the maturation of VRC01-like antibodies during immunization.
Once naive B cells expressing germline VRC01-class B cell receptors become activated by germline-targeting immunogens, they enter germinal centers and undergo affinity maturation. Booster immunizations with heterologous Envs are required for the full maturation of VRC01-class antibodies. Here, we examined whether and how three adjuvants, Poly(I:C), GLA-LSQ, or Rehydragel, that activate different pathways of the innate immune system, influence the rate and type of somatic mutations accumulated by VRC01-class BCRs that become activated by the germline-targeting 426c.Mod.Core immunogen and the heterologous HxB2.WT.Core booster immunogen. We report that although the adjuvant used had no influence on the durability of plasma antibody responses after the prime, it influenced the plasma VRC01 antibody titers after the boost and the accumulation of somatic mutations on the elicited VRC01 antibodies.


Development of 5-fluorouracil-dichloroacetate mutual prodrugs as anticancer agents.
5-Fluorouracil (5-FU) is one of the most widely applied chemotherapeutic agents with a broad spectrum of activity. However, despite this versatile activity, its use poses many limitations. Herein, novel derivatives of 5-FU and dichloroacetic acid have been designed and synthesized as a new type of codrugs, also known as mutual prodrugs, to overcome the drawbacks of 5-FU and enhance its therapeutic efficiency. The stability of the obtained compounds has been tested at various pH values using different analytical techniques, namely HPLC and potentiometry. The antiproliferative activity of the new 5-FU derivatives was assessed in vitro on SK-MEL-28 and WM793 human melanoma cell lines in 2D culture as well as on A549 human lung carcinoma, MDA-MB-231 breast adenocarcinoma, LL24 normal lung tissue, and HMF normal breast tissue as a multicellular 3D spheroid model cultured in standard (static) conditions and with the use of microfluidic systems, which to a great extent resembles the in vivo environment. In all cases, new mutual prodrugs showed a higher cytotoxic activity toward cancer models and lower to normal cell models than the parent 5-FU itself.


One-year follow-up of direct myocardial gene transfer of vascular endothelial growth factor-2 using naked plasmid deoxyribonucleic acid by way of thoracotomy in no-option patients.
This phase I open label, dose-escalating study shows that gene transfer of vascular endothelial growth factor-2 naked deoxyribonucleic acid by direct myocardial injection by way of thoracotomy in patients with Canadian Cardiovascular Society class 3 or 4 angina is feasible and safe. The procedure is well tolerated, with few major adverse cardiac events at 1 year, and without complications directly related to gene expression. In this prospective, nonblinded study, the procedure is associated with clinical improvement; however, there was no angiographic evidence of angiogenesis and there is a great potential for a sham or placebo effect in the study patients. A randomized phase III trial is underway that will help determine the efficacy of vascular endothelial growth factor-2 gene transfer in "no-option" patients.


Multiple sclerosis and allied white matter diseases.
Advanced magnetic resonance imaging (MRI) approaches are extensively used for the assessment of central nervous system (CNS) damage in patients with multiple sclerosis (MS) and allied white matter diseases. Through their ability to obtain simultaneous measures of abnormalities of structure and function at a global and regional level, these techniques, which include magnetization transfer MRI, diffusion tensor MRI and proton MR spectroscopy, are contributing to filling the voids between clinical and MRI measures. As a consequence, they are dramatically improving our understanding of the mechanisms related to the accumulation of irreversible disability in these conditions. Future improvements, including the development of new sequences and post-processing methods as well as the use of high-field MRI, despite being a major technical challenge, hold new and exciting promise.


Neural network and spline-based regression for the prediction of salivary hypofunction in patients undergoing radiation therapy.
This study leverages a large retrospective cohort of head and neck cancer patients in order to develop machine learning models to predict radiation induced hyposalivation from dose-volume histograms of the parotid glands. The pre and post-radiotherapy salivary flow rates of 510 head and neck cancer patients were used to fit three predictive models of salivary hypofunction, (1) the Lyman-Kutcher-Burman (LKB) model, (2) a spline-based model, (3) a neural network. A fourth LKB-type model using literature reported parameter values was included for reference. Predictive performance was evaluated using a cut-off dependent AUC analysis. The neural network model dominated the LKB models demonstrating better predictive performance at every cutoff with AUCs ranging from 0.75 to 0.83 depending on the cutoff selected. The spline-based model nearly dominated the LKB models with the fitted LKB model only performing better at the 0.55 cutoff. The AUCs for the spline model ranged from 0.75 to 0.84 depending on the cutoff chosen. The LKB models had the lowest predictive ability with AUCs ranging from 0.70 to 0.80 (fitted) and 0.67 to 0.77 (literature reported). Our neural network model showed improved performance over the LKB and alternative machine learning approaches and provided clinically useful predictions of salivary hypofunction without relying on summary measures.


A Cu(111)@metal-organic framework as a tandem catalyst for highly selective CO2 electroreduction to C2H4.
Here, we report an improved tandem catalytic mechanism for electroreduction of CO2 to C2H4. Cu(111) nanoparticles with an average size of 5.5 ± 0.9 nm were anchored on a conductive Cu-based metal-organic framework (Cu-THQ) by in situ electrochemical synthesis. Compared to Cu(111) nanoparticles, the C2H4 faradaic efficiency of the tandem catalyst Cu(111)@Cu-THQ was increased doubly.


Failure pressures after repairs of 2-cm × 2.5-cm rhinologic dural defects in a porcine ex vivo model.
The objective of this study was to determine failure pressures of 6 rhinologic repair techniques of large skull base/dural defects in a controlled, ex vivo model. Failure pressures of 6 dural repairs in a porcine model were studied using a closed testing apparatus; 24-mm × 19-mm dural defects were created; 40-mm × 34-mm grafts composed of porcine Duragen (Integra), fascia lata, and Biodesign (Cook) were used either with or without Tisseel (Baxter International Inc.) to create 6 repairs: Duragen/no glue (D/NG), Duragen/Tisseel (D/T), fascia lata/no glue (FL/NG), fascia lata/Tisseel (FL/T), Biodesign/no glue (B/NG), and Biodesign/Tisseel (B/T). Saline was infused at 30 mL/hour, applying even force to the underside of the graft until repair failure. Five trials were performed per repair type for a total of 30 repairs. Mean failure pressures were as follows: D/NG 1.361 ± 0.169 cmH2 O; D/T 9.127 ± 1.805 cmH2 O; FL/NG 0.200 ± 0.109 cmH2 O; FL/T 7.833 ± 2.657 cmH2 O; B/NG 0.299 ± 0.109 cmH2 O; and B/T 2.67 ± 0.619 cmH2 O. There were statistically significant differences between glued (Tisseel) and non-glued repairs for each repair category (p < 0.05). All glued repairs performed better than non-glued repairs. Both D/T and FL/T repairs performed better than B/T repairs. No repair tolerated pressures throughout the full range of adult supine intracranial pressure.


Magnetic Fe3O4/bamboo-based activated carbon/UiO-66 composite as an environmentally friendly and effective adsorbent for removal of Bisphenol A.
The magnetic Fe3O4/bamboo-based activated carbon/Zr-based metal-organic frameworks composite (Fe3O4/BAC/UiO-66) was prepared by hydrothermal method. The as-prepared material was analyzed via TEM, XRD, FT-IR, BET-BJH, VSM and XPS techniques, the results showed that it had good dispersion and magnetic separation capacity (Ms = 44.06 emu∙g-1). Then, the adsorption properties of materials for bisphenol A (BPA) were studied. The results revealed that the removal efficiency of 50 mg·L-1 BPA by 0.1 g of adsorbent can reach 87.18-95% in a wide pH range. Langmuir isotherm model and pseudo-second-order kinetic well fitted the adsorption data. The thermodynamic data indicated that the adsorption process was spontaneous and endothermic. Moreover, BAC as a supporter and UiO-66 as the functional part in the ternary composite may have a synergistic effect, which was beneficial for the removal of contaminants. The Fe3O4/BAC/UiO-66 can be simply separated from the water using its strong magnetism after finish adsorption process, which effectively avoids secondary contamination.


Epidemiology of drowning in Mangalore, a coastal Taluk of South India.
Drowning is a major global public health problem which is amenable to prevention. According to the Global Burden of Diseases 2000 data, the number of deaths caused due to drowning is 449,000 people worldwide (7.4 per 100,000 population). The aim of this study is to derive a profile of drowning victims, to identify the successful drowning preventive measures that may be adopted or enhanced in Mangalore, a coastal Taluk of South India. Retrospective study of deaths caused due to drowning in an 11 years period between 1994 and 2005 was done by reviewing the medical records, the findings of which have been described later. Epidemiologic profiles of populations at risk and the contributing factors are highlighted while public safety measures are recommended.


Predictors of ethylene glycol ingestion cases called into a regional poison center.
Poison center consultations for potential toxic alcohol poisonings are challenging because blood levels are typically not immediately available. The primary objective of this study was to determine whether readily obtainable laboratory values can be used to accurately and rapidly diagnose these poisonings. Over a 15-month period, patients with a history of toxic alcohol ingestion or a metabolic acidemia (pH ≤ 7.30 or serum bicarbonate ≤ 18 mEq/L) that prompted a poison center consultation were enrolled. A predictive logistic regression model was used to assess the combined ability of serum pH, calcium, osmolar gap, and anion gap levels to predict a final diagnosis of toxic alcohol poisoning. There were 102 subjects included in the analysis. A total of 44% (45/102) patients had a final diagnosis of ethylene glycol (EG) poisoning. Higher levels of calcium, osmolar gap, and anion gap were independently associated with statistically significant or marginally significant increases in the odds of a final diagnosis of EG poisoning. The c-index was estimated at 0.81, indicating that the model showed a reasonable ability to discriminate EG cases from others. The final model had a sensitivity and specificity of 78% and 89%, respectively, and positive and negative predictive values of 84% and 83% respectively. The combination of elevated calcium, osmolar gap, and anion gap is associated with a high likelihood of EG poisoning, but clinician gestalt is still essential for its diagnosis. Further refinement of the model is needed.


Can Surrogate Markers Help Define Cardiovascular Disease in Youth?
Non-invasive measurements such as arterial stiffness serve as proxy surrogates for detection of early atherosclerosis and ASCVD risk stratification. These surrogate measurements are influenced by age, gender, and ethnicity and affected by the physiological changes of puberty and somatic growth in children and adolescents. There is no consensus of the ideal method to measure surrogate markers in youth (< 18 years of age), nor standardized imaging protocols for youth. Currently, pediatric normative data are available but not generalizable. In this review, we provide rationale on how currently used surrogates can help identify subclinical atherosclerosis in youth and affirm their role in identifying youth at risk for premature CVD.


Reaching the Monophyly: Re-Evaluation of the Enigmatic Species Tenuibiotus hyperonyx (Maucci, 1983) and the Genus Tenuibiotus (Eutardigrada).
Revisions and redescriptions of taxa described in the past and that are now categorized as insufficiently diagnosed often play a crucial role in making further progress in modern taxonomy in many groups of organisms. Here we revised an enigmatic tardigrade species Tenuibiotus hyperonyx (Maucci, 1983) based on the newly discovered topotypic population from the Italian Alps. We performed an integrative analysis of morphological and genetic data in order to present an upgraded species description and elucidate its phylogenetic position. Our results enabled us to confidently place T.hyperonyx within the family Richtersiusidae, as a member of the genus Diaforobiotus. This change, together with a re-assessment of microphotographs of the Tenuibiotus willardi (Pilato, 1977) and Tenuibiotus bozhkae Pilato, Kiosya, Lisi, Inshina & Biserov, 2011 types, led to the discussion on species composition with narrative taxa amendments for the taxonomic parties involved in the proposed alteration.


Cadmium and/or copper excess induce interdependent metal accumulation, DNA methylation, induction of metal chelators and antioxidant defences in the seagrass Zostera marina.
In this investigation, we assessed the effects of Cu and/or Cd excess on physiological and metabolic processes of the widespread seagrass Zostera marina. Adult were exposed to low Cd and Cu (0.89 and 0.8 μM, respectively) and high Cd and Cu (8.9 and 2.4 μM, respectively) for 6 d at: Control conditions; low Cu; high Cu; low Cd; high Cd; low Cd and low Cu; and high Cd and high Cu. Photosynthetic performance decreased under single and combined treatments, although effects were more negative under Cu than Cd. Total Cu accumulation was higher than Cd, under single and combined treatments; however, their accumulation was generally lower when applied together, suggesting competition among them. Levels of glutathione (GSH) and phytochelatins (PCs) followed patterns similar to metal accumulation, with up to PC5, displaying adaptations in tolerance. A metallothionein (MET) gene showed upregulation only at high Cd, low Cu, and high Cu. The expression of the enzymes glutathione reductase (GR), ascorbate peroxidase (APX), and catalase (CAT) was greatest at high Cu, and at high Cd and Cu together; the highest expression was under Cu, alone and combined. Both metals induced upregulation of the DNA methyltransferases CMT3 and DRM2, with the highest expression at single Cu. The DNA demethylation ROS1 was overexpressed in treatments containing high Cu, suggesting epigenetic modifications. The results show that under copper and/or cadmium, Z. marina was still biologically viable; certainly based, at least in part, on the induction of metal chelators, antioxidant defences and methylation/demethylation pathways of gene regulation.


Control of energy spread and dark current in proton and ion beams generated in high-contrast laser solid interactions.
By using temporal pulse shaping of high-contrast, short pulse laser interactions with solid density targets at intensities of 2 × 10(21) W cm(-2) at a 45° incident angle, we show that it is possible to reproducibly generate quasimonoenergetic proton and ion energy spectra. The presence of a short pulse prepulse 33 ps prior to the main pulse produced proton spectra with an energy spread between 25% and 60% (ΔE/E) with energy of several MeV, with light ions becoming quasimonoenergetic for 50 nm targets. When the prepulse was removed, the energy spectra was broad. Numerical simulations suggest that expansion of the rear-side contaminant layer allowed for density conditions that prevented the protons from being screened from the sheath field, thus providing a low energy cutoff in the observed spectra normal to the target surface.


Cavernous hemangioma of the neck simulating thyroglossal cyst.
A rare case of cavernous hemangioma simulating a thyroglossal duct cyst was reported. It is recommended that these be treated by total excision, including hyoid bone, to prevent recurrence.


Prediction of cerebral blood flow restoration after extracranial-intracranial bypass surgery using superficial temporal artery duplex ultrasonography (STDU).
We investigated the availability of superficial temporal artery (STA) duplex ultrasonography (STDU) for evaluating the improvement of cerebral hemodynamics after extracranial-intracranial (EC-IC) bypass. This study included 56 consecutive patients who underwent EC-IC bypass for occlusive disease of their cerebral arteries. STA duplex ultrasonography (STDU) was performed to measure the flow velocity, pulsatility index, and diameter of ipsilateral STA before and 14 days after EC-IC bypass. Regional cerebral blood flow (rCBF) and acetazolamide (ACZ) reactivity of ipsilateral MCA territory were evaluated by quantitative single photon emission computed tomography. The mean flow velocities of ipsilateral STA were significantly higher (p < 0.0001) and PI value was significantly lower (p < 0.0001) 14 days after EC-IC bypass than before. The diameter of ipsilateral STA was also larger 14 days after EC-IC bypass than before (p < 0.0001). STA mean flow velocity was significantly correlated with the rCBF 14 days after EC-IC bypass (R = 0.55, p < 0.0001). The post-surgical STA mean flow velocity cut-off value over 58.2 cm/sec yielded the highest diagnostic accuracy (sensitivity, 75%; specificity, 74%) for excellent rCBF value (> or =40 ml/100 g/min) after EC-IC bypass. The ipsilateral STA mean blood flow velocity is a highly sensitive parameter for predicting rCBF in the ipsilateral MCA territory after EC-IC bypass.


Selectively high expression of the transcription factor AP1 in telencephalic structures of epileptic E1 mice.
In ddY mouse brain, the transcription factors AP1 and CREB were rich in the cerebral cortex, hippocampus and cerebellum but relatively poor in the striatum, hypothalamus and midbrain. In contrast, the transcription factor Myc was rather poorly distributed in mouse brain under the conditions employed. Among these 3 transcription factors examined, DNA binding activities of only AP1 were invariably higher in telencephalic structures, such as the cortex, hippocampus and striatum, of the epileptic El mice than in those of parent ddY mice. These results suggest that the transcription factor AP1 may be at least in part responsible for molecular mechanisms underlying pathogenesis of a variety of abnormal symptoms observed in epileptic El mice.


1998: the centenary of the discovery of the Golgi apparatus.
1998 is the year of the centenary of the discovery of the Golgi apparatus. This event is considered in its historical context: the first cell theory of 1838-1839, the first polemics in cytology and the research on the cell organelles at the turn of the century. The first approaches to clarify the physiological significance of the apparatus is traced from Golgi (1909) to Bowen (1929).


In vivo efficacy of voriconazole and posaconazole therapy in a novel invertebrate model of Aspergillus fumigatus infection.
The emergence of azole resistance in Aspergillus fumigatus is a clinically important issue in the management of invasive aspergillosis as it could limit therapeutic options. Accurate measurement of in vitro antifungal activity in terms of minimum inhibitory concentration (MIC) is considered of clinical relevance and often gives useful therapeutic information for physicians. However, the lack of in vitro-in vivo correlation is frequent and the observed in vitro phenotype does not always correlate with the in vivo response. In this regard, a wild-type strain and five A. fumigatus cyp51A mutated strains showing different azole susceptibility profiles were used to investigate whether the greater wax moth (Galleria mellonella) is an alternative model to assess the in vivo efficacy of voriconazole and posaconazole. Administration of both azoles improved the survival of larvae infected with susceptible strains. However, those larvae infected with resistant strains did not respond to treatment. The phenotype observed in vitro was found to correlate with the efficacy observed in vivo. Moreover, using this in vivo model, the pharmacodynamic target predicting therapeutic success (AUC(0-24)/MIC) was in the same range as previously described, allowing the use of the G. mellonella model to predict the azole susceptibility profile of A. fumigatus strains.