Effects of systolic blood pressure on white-matter integrity in young adults in the Framingham Heart Study: a cross-sectional study.
Previous studies have identified effects of age and vascular risk factors on brain injury in elderly individuals. We aimed to establish whether the effects of high blood pressure in the brain are evident as early as the fifth decade of life. In an investigation of the third generation of the Framingham Heart Study, we approached all participants in 2009 to ask whether they would be willing to undergo MRI. Consenting patients underwent clinical assessment and cerebral MRI that included T1-weighted and diffusion tensor imaging to obtain estimates of fractional anisotropy, mean diffusivity, and grey-matter volumes. All images were coregistered to a common minimum deformation template for voxel-based linear regressions relating fractional anisotropy, mean diffusivity, and grey-matter volumes to age and systolic blood pressure, with adjustment for potential confounders. 579 (14·1%) of 4095 participants in the third-generation cohort (mean age 39·2 years, SD 8·4) underwent brain MRI between June, 2009 and June, 2010. Age was associated with decreased fractional anisotropy and increased mean diffusivity in almost all cerebral white-matter voxels. Age was also independently associated with reduced grey-matter volumes. Increased systolic blood pressure was linearly associated with decreased regional fractional anisotropy and increased mean diffusivity, especially in the anterior corpus callosum, the inferior fronto-occipital fasciculi, and the fibres that project from the thalamus to the superior frontal gyrus. It was also strongly associated with reduced grey-matter volumes, particularly in Brodmann's area 48 on the medial surface of the temporal lobe and Brodmann's area 21 of the middle temporal gyrus. Our results suggest that subtle vascular brain injury develops insidiously during life, with discernible effects even in young adults. These findings emphasise the need for early and optimum control of blood pressure. National Institutes of Health and National Heart, Lung, and Blood Institute; National Institute on Aging; and National Institute of Neurological Disorders and Stroke.


Transport cyclists and road rules: what influences the decisions they make?
To determine the level of adherence by transport cyclists to road rules in traffic situations and their reasons for non-adherence. The Safer Cycling Study was a prospective cohort study of transport and recreational cyclists. Over 2000 cyclists were recruited between March and November 2011. 770 Transport cyclists aged 18 years and older, who lived in New South Wales, Australia. Participants completed a baseline questionnaire plus provided data during a further six survey weeks over 12 months. In one of their survey weeks, cyclists were asked how often they infringed road rules and what contributory factors led to their road rule infringement. Data were collected via web-based online questionnaires. Quantitative data were analysed descriptively. Qualitative data were analysed to identify themes derived from the text. Riding on the footpath and red light infringement were the most commonly reported road rule breaches. Poor infrastructure design was the most frequently identified contributing factor to road rule breaches, followed by the speed of motorised traffic and the behaviour of other road users. A transport network needs to facilitate cyclists of all capabilities to reach their required destination in a safe and timely manner, and encourage compliance with the road rules.


Stigmatization of overweight Mexican children.
The present study was designed to determine the weight-based stigmatization of Mexican overweight (OW) and non-OW children by their mothers and peers, who rated both boys and girls with varying physical characteristics. Four hundred and thirty-two fifth and sixth graders and 342 mothers participated in the study. Children were administered a questionnaire displaying six drawings. Participants' responses were numbered in order of preference from 1 to 6 (most to least well liked). Participants were divided into categories based on socioeconomic status, ethnicity, and current body mass index. The majority of children chose the child in a wheelchair as the preferred friend. Boys and girls, Indian and non-Indian, with and without risk of OW chose the obese peer as the least-preferred friend. Non-OW girls and their mothers liked the obese child less than non-OW boys and their mothers. Agreement correlations between mothers and children were rho = 0.19 (P = 0.0001), rho = 0.17 (P = 0.001), and rho = 0.13 (P = 0.02) for the healthy child, child with missing arm, and obese child, respectively. There was a strong correlation between Indian mothers and non-OW daughters (rho = 0.54, P = 0.009) on choosing the drawing of the obese child as the least preferred friend. These data suggest an influential effect of the negative attitude of mothers toward the obese child, which are projected to their children.


Why Clinicians Should Care About the Cardiac Interstitium.
Interstitial heart disease, whether primarily from myocardial fibrosis or cardiac amyloidosis, indicates excess protein accumulation in the interstitium and constitutes a major source of heart failure with excess cardiac morbidity and mortality. Myocardial fibrosis (defined as excess myocardial collagen concentration that distorts myocardial architecture) is prevalent and causes cardiac symptoms and ultimately adverse cardiac events, such as heart failure, arrhythmia, and death. Conversely, cardiac amyloidosis is far less prevalent than myocardial fibrosis but represents a more extreme form of interstitial heart disease with marked interstitial expansion, profound architectural distortion, and then rapid clinical decline. Myocardial extracellular volume measures fundamentally advance the understanding of myocardium and specifically highlights the role of the interstitium. Rather than conceptualizing myocardium as a homogenous tissue, dichotomizing the myocardium into its interstitial (including the microvasculature) and cardiomyocyte phenotypes promotes additional understanding of heart failure pathophysiology that may spur the development of more effective therapies.


Multimorbidity in Children and Youth Across the Life-course (MY LIFE): protocol of a Canadian prospective study.
Multimorbidity, the co-occurrence of a chronic physical condition and mental disorder, affects a substantial number of children and youth and can lead to compromised quality of life, hardship for families, and an increased burden on the healthcare system. We are conducting a study to document the course of mental disorder in children and youth diagnosed with a chronic physical condition; identify predictors of child and youth multimorbidity; examine whether the effects of these predictors are moderated by relevant psychosocial and biological factors; explore potential inflammatory and stress biomarkers that mediate the onset of child and youth multimorbidity; and, assess whether multimorbidity in children and youth alters patterns of mental health service use. Multimorbidity in Children and Youth Across the Life-course (MY LIFE) is a prospective study. Two hundred and fifty children and youth aged 2-16 years diagnosed with a chronic physical condition along with one parent will be recruited from the outpatient clinics at a paediatric tertiary care centre. Data will be collected using a multi-informant, multimethod design at four time-points (at recruitment, and at 6, 12 and 24 months postrecruitment). Parents will provide reports for all children/youth. In addition, youth ≥10 years will self-report. Mental disorder will be assessed using structured interviews. On completion of data collection, participant-reported data will be linked to provincial health records to identify mental health services use. Multilevel analyses (survival, proportional hazard, structural equation modelling) will be used to address MY LIFE objectives. This study has been approved by the University of Waterloo Human Research Ethics Board and the Hamilton Integrated Research Ethics Board. Findings will be disseminated to key stakeholders using a number of outlets (peer-reviewed publications and conferences, lay informational pamphlets, social media).


CHFR, a potential tumor suppressor, downregulates interleukin-8 through the inhibition of NF-kappaB.
The mitotic checkpoint gene CHFR (checkpoint with forkhead and ring finger domains) is silenced in various human cancers by promoter hypermethylation, suggesting that CHFR is a tumor suppressor. Here, we show that CHFR functions as a negative regulator of the nuclear factor-kappaB (NF-kappaB) pathway. Expression of CHFR inhibited NF-kappaB reporter activity, whereas knockdown of CHFR activated reporter activity. These activities are independent of its RING finger domain. Furthermore, we found that CHFR physically interacts with p65 in cells. Electrophoretic mobility shift assays (EMSAs) and ELISA-based NF-kappaB-binding assays showed that CHFR negatively regulated transcriptional activity of p65. In addition, our data show that interleukin (IL)-8 is significantly downregulated by CHFR, and that the migration of human endothelial cells is suppressed in culture medium conditioned from CHFR-expressing cancer cells. Using a xenograft model, we show that neovascularization is suppressed by adenovirus-mediated transfer of CHFR. These results indicate that expression of CHFR markedly reduces the expression of IL-8 through the inhibition of NF-kappaB. As the NF-kappaB signaling pathway plays a critical role in the development and progression of cancer, our findings show the functional relationship between epigenetic alteration and inflammation/angiogenesis in human cancer cells, thereby showing several potential targets for therapeutic intervention.


Shared Genetic Control of Brain Activity During Sleep and Insulin Secretion: A Laboratory-Based Family Study.
Over the past 20 years, a large body of experimental and epidemiologic evidence has linked sleep duration and quality to glucose homeostasis, although the mechanistic pathways remain unclear. The aim of the current study was to determine whether genetic variation influencing both sleep and glucose regulation could underlie their functional relationship. We hypothesized that the genetic regulation of electroencephalographic (EEG) activity during non-rapid eye movement sleep, a highly heritable trait with fingerprint reproducibility, is correlated with the genetic control of metabolic traits including insulin sensitivity and β-cell function. We tested our hypotheses through univariate and bivariate heritability analyses in a three-generation pedigree with in-depth phenotyping of both sleep EEG and metabolic traits in 48 family members. Our analyses accounted for age, sex, adiposity, and the use of psychoactive medications. In univariate analyses, we found significant heritability for measures of fasting insulin sensitivity and β-cell function, for time spent in slow-wave sleep, and for EEG spectral power in the delta, theta, and sigma ranges. Bivariate heritability analyses provided the first evidence for a shared genetic control of brain activity during deep sleep and fasting insulin secretion rate.


Bilateral multielectrode neurophysiological recordings coupled to local pharmacology in awake songbirds.
Here we describe a protocol for bilateral multielectrode neurophysiological recordings during intracerebral pharmacological manipulations in awake songbirds. This protocol encompasses fitting adult animals with head-posts and recording chambers, and acclimating them to periods of restraint. The adaptation period is followed by bilateral penetrations of multiple electrodes to obtain acute, sensory-driven neurophysiological responses before versus during the application of pharmacological agents of interest. These local manipulations are achieved by simultaneous and restricted drug infusions carried out independently for each hemisphere. We have used this protocol to elucidate how neurotransmitter and neuroendocrine systems shape the auditory and perceptual processing of natural, learned communication signals. However, this protocol can be used to explore the neurochemical basis of sensory processing in other small vertebrates. Representative results and troubleshooting of key steps of this protocol are presented. Following the animal's recovery from head-post and recording chamber implantation surgery, the length of the procedure is 2 d.


A Fragment of Collagen Type VI alpha-3 chain is Elevated in Serum from Patients with Gastrointestinal Disorders.
Extracellular matrix (ECM) remodeling is a hallmark of the pathology of gastrointestinal disorders. Collagen type VI (COL6) is produced by fibroblasts, and the COL6 α3-chain has shown to be elevated in patients with ulcerative colitis (UC), Crohn's disease (CD) and colorectal cancer (CRC). Measuring COL6α3 in serum may therefore have potential as a biomarker for gastrointestinal disorders. The aims of this study were to develop and validate a competitive ELISA targeting a specific neo-epitope of COL6α3 and evaluate its associations with the gastrointestinal disorders UC, CD and CRC, in comparison to healthy controls. A monoclonal antibody was raised against a matrix metalloproteinase-2 and -9 specific cleavage site of COL6α3 (C6Mα3) and employed in a competitive enzyme-linked immunosorbent assay (ELISA). The assay was developed and technically validated. Levels of C6Mα3 were measured in serum from patients with UC (n = 58), CD (n = 44) and CRC (n = 39) and compared to healthy controls (n = 32). The levels of C6Mα3 were elevated in patients with UC, CD and CRC patients compared to healthy controls (all p < 0.0001). The area under the receiver operating characteristics (AUROC) curve for separation of patients with UC from healthy controls was 0.972 (95% CI: 0.925-1.020, p < 0.0001), with CD from healthy controls was 0.947 (95% CI: 0.885-1.009, p < 0.0001) and with CRC from healthy controls was 0.890 (95% CI: 0.809-0.972, p < 0.0001). We developed a technically robust assay targeting a fragment of COL6, which was elevated in serum from patients with UC, CD and CRC.


Posthemorrhagic ventricular dilatation-impact on early neurodevelopmental outcome.
This study evaluates the impact of ventricular dilatation following severe (grades III or IV) intraventricular hemorrhage (IVH) in preterm neonates and the current practice of neurosurgical interventions in infants with posthemorrhagic ventricular dilatation (PHVD) and early neurodevelopmental outcome. Premature neonates born at ≤34 weeks' gestational ages with severe IVH were identified retrospectively over a 5-year period (2005 to 2009). Standard measures of ventricular dilatation on head ultrasound (HUS) were recorded. The treatment of PHVD, timing of surgery including the type of temporizing neurosurgical procedure (TNP)-either a ventricular reservoir or a subgaleal shunt-and the subsequent need for ventriculoperitoneal (VP) shunt were evaluated. Patients were retrospectively stratified to an "early" versus "late" intervention group based on HUS measures. Early intervention was defined as TNP performed when the ventricular index (VI) was >97th percentile but <97th percentile + 4 mm. Late intervention was defined as TNP performed when VI was ≥97th percentile + 4 mm. Neurodevelopmental outcomes were evaluated at 18 to 24 months. Infants followed up for neurodevelopmental testing were stratified as group A (progressive PHVD with TNP), group B (PHVD without TNP), and group C (severe IVH without PHVD). One hundred seventy-three preterm neonates with severe IVH were identified during the study period, of whom 139/173 (80%) developed PHVD. Of these, 54 (54/139, 39%) received TNP either early (4/54, 7%) or late (50/54, 93%). Of those who received TNP, 32/54 (59%) required subsequent VP shunt placement. Neurodevelopmental testing was available in 39/109 (36%) infants who survived to discharge. The mean ± standard deviation cognitive, motor, and language composite scores were 77 ± 14.8, 67 ± 15.2, 70 ± 13.8 for group A (n = 16/39), 90 ± 7.8, 84 ± 9.6, 82 ± 18.2 for group B (n = 12/39), and 95 ± 14.3, 86 ± 10.7, 94 ± 15.8 for group C (n = 11/39), respectively (p < 0.006 for group A versus group B and p < 0.004 for group A versus group C across all domains). Increasing ventricular dilatation was associated with adverse motor, cognitive, and language outcomes (p = 0.002) and neonates with progressive PHVD requiring a TNP were most adversely affected (p = 0.0006). There were no differences in any outcome measures between the two types of TNPs. Clinical and demographic characteristics of infants lost to follow-up were not significantly different than those available for follow-up. Increasing ventricular size adversely affects neurodevelopmental outcome in infants with PHVD.


Non-animal Replacements for Acute Toxicity Testing.
Current approaches to predicting adverse effects in humans from acute toxic exposure to cosmetic ingredients still heavily necessitate the use of animals under EU legislation, particularly in the context of the REACH system, when cosmetic ingredients are also destined for use in other industries. These include the LD50 test, the Up-and-Down Procedure and the Fixed Dose Procedure, which are regarded as having notable scientific deficiencies and low transferability to humans. By expanding on previous in vitro tests, such as the animal cell-based 3T3 Neutral Red Uptake (NRU) assay, this project aims to develop a truly animal-free predictive test for the acute toxicity of cosmetic ingredients in humans, by using human-derived cells and a prediction model that does not rely on animal data. The project, funded by Innovate UK, will incorporate the NRU assay with human dermal fibroblasts in animal product-free culture, to generate an in vitro protocol that can be validated as an accepted replacement for the currently available in vivo tests. To date, the project has successfully completed an assessment of the robustness and reproducibility of the method, by using sodium lauryl sulphate (SLS) as a positive control, and displaying analogous results to those of the original studies with mouse 3T3 cells. Currently, the testing of five known ingredients from key groups (a surfactant, a preservative, a fragrance, a colour and an emulsifier) is under way. The testing consists of initial range-finding runs followed by three valid runs of a main experiment with the appropriate concentration ranges, to generate IC50 values. Expanded blind trials of 20 ingredients will follow. Early results indicate that this human cell-based test holds the potential to replace aspects of in vivo animal acute toxicity testing, particularly with reference to cosmetic ingredients.


Downregulation of organic cation transporters OCT1 (SLC22A1) and OCT3 (SLC22A3) in human hepatocellular carcinoma and their prognostic significance.
Organic cation transporters (OCT) are responsible for the uptake and intracellular inactivation of a broad spectrum of endogenous substrates and detoxification of xenobiotics and chemotherapeutics. The transporters became pharmaceutically interesting, because OCTs are determinants of the cytotoxicity of platin derivates and the transport activity has been shown to correlate with the sensitivity of tumors towards tyrosine kinase inhibitors. No data exist about the relevance of OCTs in hepatocellular carcinoma (HCC). OCT1 (SLC22A1) and OCT3 (SLC22A3) mRNA expression was measured in primary human HCC and corresponding non neoplastic tumor surrounding tissue (TST) by real time PCR (n = 53). Protein expression was determined by western blot analysis and immunofluorescence. Data were correlated with the clinicopathological parameters of HCCs. Real time PCR showed a downregulation of SLC22A1 and SLC22A3 in HCC compared to TST (p ≤ 0.001). A low SLC22A1 expression was associated with a worse patient survival (p < 0.05). Downregulation was significantly associated with advanced HCC stages, indicated by a higher number of T3 tumors (p = 0.025) with a larger tumor diameter (p = 0.035), a worse differentiation (p = 0.001) and higher AFP-levels (p = 0.019). In accordance, SLC22A1 was less frequently downregulated in tumors with lower stages who underwent transarterial chemoembolization (p < 0.001) and liver transplantation (p = 0.001). Tumors with a low SLC22A1 expression (< median) showed a higher SLC22A3 expression compared to HCC with high SLC22A1 expression (p < 0.001). However, there was no significant difference in tumor characteristics according to the level of the SLC22A3 expression.In the western blot analysis we found a different protein expression pattern in tumor samples with a more diffuse staining in the immunofluorescence suggesting that especially OCT1 is not functional in advanced HCC. The downregulation of OCT1 is associated with tumor progression and a worse patient survival.


Bottom-up effects of drought on the growth and development of potato, Leptinotarsa decemlineata Say and Arma chinensis Fallou.
Global climate change will result in increasingly arid weather that will have a significant impact on agriculture. The occurrence dynamics of plants, phytophagous insects and their natural enemies under drought conditions have attracted much attention. The consequences could be useful for controlling insect herbivores. Leptinotarsa decemlineata (Say) is one of the most important pests of potato, and causes serious damage to potato production. Arma chinensis (Fallou) is a parasitoid of L. decemlineata. However, how drought will affect tritrophic interactions between potato and these insects remains unknown. In this experiment, L. decemlineata and A. chinensis were released onto potato plants under water stress. Thereafter, plant height, stem diameter and yield of potato, growth and reproduction of L. decemlineata, and the longevity of A. chinensis adults were periodically recorded. The results showed that drought had crucial effects on height, stem diameter and yield of potato (p < 0.05); it also had a significant impact on pre-oviposition period, oviposition days, fecundity and life table parameters in L. decemlineata (p < 0.05). Moreover, drought significantly reduced the longevity (p < 0.05) and survival rate of A. chinensis adults. The longevity of adult A. chinensis was only 29.00 ± 3.00 days and the harvest rate of L. decemlineata adults was only 1.42% ± 0.07% under drought treatment. In this experiment, we evaluate the bottom-up effects of drought on tritrophic interactions involving potato, L. decemlineata and A. chinensis, and discuss the implications of the findings for integrated pest management programs involving the pest. Promising future research directions are proposed. © 2022 Society of Chemical Industry.


Preserving the superficial branch of the radial nerve during carpometacarpal and metacarpophalangeal joint arthroscopy: an anatomical study.
The superficial branch of the radial nerve (SBRN) is potentially at risk during thumb carpometacarpal (TCM) or thumb metacarpophalangeal (TMP) joint arthroscopy. The aim of this anatomical study was to describe the different branching patterns of the SBRN and to optimize positioning of portals during TCM and TMP arthroscopy. The SBRN was dissected in 30 forearms. Three branches of the nerve (SR1, SR2, and SR3) were recorded and distances between SBRN branches and portals used for carpometacarpal (TCM) and metacarpophalangeal (TMP) joints of the thumb arthroscopy were measured. Three main portals were used for TCM joint arthroscopy. These portals were an ulnar portal (1-U), a radial portal (1-R), and an accessory portal (D-2). A radial metacarpophalangeal (MCP-rad) and an ulnar metacarpophalangeal (MCP-uln) portal were used for TMP joint arthroscopy. In 24 cases (80%), the 1-R portal was inserted radially (volar) to SR3 at a mean distance of 4.8 mm (0-8). In the remaining six cases (20%) when 1-R portal was inserted ulnar (dorsal) to SR3, the distance was less than 2 mm in all cases. SR3 was always far from the 1-U portal at a mean 13 mm (7-22). The D-2 portal was always close to SR2-D1 at a mean distance of 1.7 mm (0-6). The distance from SR2-D2 and D-2 portal was also inferior by 5 mm. At the level of the metacarphalangeal joint of the thumb, the MCP-rad portal was always situated dorsally and very close to SR3, at a mean distance of 1 mm (0-5). The MCP-uln portal was also situated dorsal to SR2-D1 at a mean distance of 3.7 mm (1.5-6.5). The results of this anatomical study confirm actual reported findings about the SR2 and SR3 branches. These two branches of the SBRN are the most at risk of injury during TCM and TMP joint arthroscopy. According to our measurements, the 1-U portal is a safer portal than 1-R and D-2 portal for TCM arthroscopy and should be preferred for surgery necessitating only one portal. Concerning TMP arthroscopy, the SBRN appears less at risk of injury when using a MCP-uln portal and safer than MCP-rad which is at risk at less than 5 mm from the extensor pollicis longus tendon.


Enhanced light absorption of amorphous silicon thin film by substrate control and ion irradiation.
Large-area periodically aligned silicon nanopillar (PASiNP) arrays were fabricated by magnetic sputtering with glancing angle deposition (GLAD) on substrates coated by a monolayer of close-packed polystyrene (PS) nanospheres. The structure of PASiNP arrays could be manipulated by changing the diameter of PS nanospheres. Enhanced light absorptance within a wavelength range from 300 to 1,000 nm was observed as the diameter of nanopillars and porosity of PASiNP arrays increased. Meanwhile, Xe ion irradiation with dose from 1 × 10(14) to 50 × 10(14) ions/cm(2) was employed to modify the surface morphology and top structure of thin films, and the effect of the irradiation on the optical bandgap was discussed. 81.15.Cd; 78.66.Jg; 61.80.Jh.


Inherited antithrombin deficiency: a review.
Antithrombin (AT) is a potent inactivator of thrombin and factor Xa and the major inhibitor of blood coagulation. Inherited AT deficiencies are uncommon, with prevalences in the general population between 1 in 500 and 1 in 5000. They are either quantitative (type I) or qualitative (type II). Type II is subdivided into the more common, but less thrombogenic, type IIb deficiency caused by a defect in the heparin-binding region of AT and the less common, but more thrombophilic, type IIa variant caused by mutations in the thrombin-binding site. A pleiotropic type IIc deficiency also exists. In the evaluation of a thrombophilic individual, a functional AT assay (AT activity) should be used and the diagnosis of AT deficiency only established after acquired causes have been ruled out and repeat AT testing on an additional sample has been performed. A subsequent antigenic AT assay result leads to differentiation between type I and type II deficiency. Further specialized tests help subclassify the type II deficiencies, but this is typically not carried out for clinical purposes, even though it might be helpful to assess thrombosis risk. AT deficiency is associated with an increased risk for venous thromboembolism (VTE) and pregnancy loss. The association with arterial thrombosis is only weak. VTE prophylaxis and treatment management will be discussed in this article and existing treatment guidelines presented. The lack of data surrounding the use of AT concentrates and the resulting ambiguity as to when to use such concentrates will be discussed.


Identification of Eutypa lata by PCR-RFLP.
Eutypa lata is a vascular canker pathogen of woody plants commonly diagnosed by isolating the pathogen from infected tissue. Related fungi from the same family, the Diatrypaceae, also have been found in association with grapevine in Californian vineyards. An in situ polymerase chain reaction (PCR) method has been developed for detection of E. lata in infected wood tissue. However, our results indicate that this method also would amplify other Diatrypaceous fungi, which could potentially lead to an incorrect diagnosis. Therefore, we developed a PCR-restriction fragment length polymorphism (PCR-RFLP) assay. The internal transcribed spacer (ITS)1/5.8S/ITS2 ribosomal DNA region was amplified by PCR using universal primers, and RFLP patterns were determined after digestion with AluI. The restriction profiles obtained served to distinguish E. lata from wood trunk pathogens of grapevine (Phomopsis viticola, Botryodiplodia sp., Phaeoacremonium aleophilum, and Phaeomoniella chlamydospora), Diatrypaceous fungi (Diatrype sp., Diatrypella sp., Eutypella vitis, and Eutypa leptoplaca), and Cryptovalsa sp. found on dead wood of grapevine, and other Eutypa spp. (E.petrakii var. hederae, E. astroidea, E. crustata, and E. lejoplaca), with the exception of E. armeniacae, which we regard as a synonym for E. lata, and E. laevata, which has not been found on grapevine.


Sepsis-Associated Acute Kidney Disease.
About one-third of critically ill patients with acute kidney injury (AKI) develop persistently decreased kidney function, known as acute kidney disease (AKD), which may progress to chronic kidney disease (CKD). Although sepsis is the most common cause of AKI, little is known about sepsis-associated AKD. Using data from a large randomized trial including 1341 patients with septic shock, we studied patients with stage 2 or 3 AKI on day 1 of hospitalization. We defined AKD as a persistently reduced glomerular filtration rate for >7 days. In addition to clinical data, we measured several urinary biomarkers (tissue inhibitor of metalloproteinases-2 and insulin-like growth factor-binding protein 7 [TIMP-2∗IGFBP7], neutrophil gelatinase-associated lipocalin [NGAL], kidney injury molecule-1 [KIM-1], liver-type fatty acid binding protein, and type 4 collagen) at 0, 6, and 24 hours, to predict AKD. Of 598 patients, 119 (19.9%) died within 7 days, 318 (53.2%) had early reversal of AKI within the first 7 days, whereas 161 (26.9%) developed AKD. In patients with early reversal, 45 (14.2%) had relapsed AKI after early reversal, and only about one-third of these recovered. Among patients developing AKD, only 15 (9.3%) recovered renal function prior to discharge. Male sex, African American race, and underlying CKD were more predominant in patients developing AKD. None of the biomarkers tested performed well for prediction of AKD, although NGAL modestly increased the performance of a clinical model. AKD is common in patients with septic shock, especially among African American males and those with underlying CKD. Existing AKI biomarkers have limited utility for predicting AKD but might be useful together with clinical variables. Novel predictive biomarkers for renal recovery are needed.


Human metapneumovirus in patients with respiratory tract infection in Kuwait.
Human metapneumovirus (hMPV) has been recognized as an important cause of respiratory tract infections in all age groups and in all geographical area. The role of hMPV in causing respiratory tract infections in Kuwait was not yet investigated. The aim of this study was to determine the prevalence of hMPV infection in Kuwait among patients with respiratory tract infection with respect to other respiratory viruses. During January-December 2009, 460 respiratory samples from 388 patients with respiratory tract infection were collected from different hospitals. They were tested for hMPV RNA by real-time PCR, and for other respiratory viruses by conventional PCR. Out of 388 patients, 110 (28%) were positive for viral respiratory infections; 21 (5.4%) were positive for hMPV, 29 (7.5%) were positive for rhinovirus, 13 (4%) were positive for respiratory syncytial virus, and 10 (3%) were positive for adenovirus. Most (n = 19, 90.5%) of hMPV-positive patients were admitted to the intensive care unit, 76% of them were of age 2 years and below, and 24% of age 59 years and above. All hMPV-positive elderly patients had pneumonia while 50% of hMPV-positive infants had bronchopneumonia. Children with hMPV/rhinovirus co-infection (n = 3, 1%) had recurrent chest infection and frequent intensive care unit admission. The hMPV infection was mostly detected between December and May, and genotype B was more prevalent than genotype A. This is the first study demonstrating the prevalence of hMPV infection in Kuwait, and suggests that hMPV infection is prevalent in infants and elderly patients with lower respiratory tract infection.


Efficacy of common disinfectants and terbinafine in inactivating the growth of Batrachochytrium dendrobatidis in culture.
Use of disinfectants by biologists, veterinarians, and zoological facilities is a standard biosecurity procedure to prevent contamination and the spread of pathogens. We tested the efficacy of 5 disinfectants and 1 anti-fungal treatment, at 1 and 5 min contact durations, in inactivating Batrachochytrium dendrobatidis (Bd) grown on tryptone media. Our study focused on concentrations of disinfectants known to inactivate ranaviruses, which can be found at the same sites as Bd and can concurrently infect amphibians. Disinfectants tested were chlorhexidine gluconate (0.25, 0.75, and 2%), Pro-San (0.19, 0.35, and 0.47%), Virkon S (1%), household bleach (0.2, 1, and 3%), and Xtreme Mic (5%). The anti-fungal was terbinafine HCl at 0.005, 0.05, 0.1, and 1 mg ml-1. Inactivation of Bd was determined by microscopic evaluation of zoospore motility and growth of colony mass after 14 d. All disinfectants were effective at inactivating zoospore motility and colony growth of Bd at all concentrations and both contact times; however, terbinafine HCl inactivated Bd at only the highest concentration tested (1 mg ml-1) and 5 min duration. Thus, a minimum of 0.25% chlorhexidine gluconate, 0.19% Pro-San, 1% Virkon, 0.2% bleach, and 5% Xtreme Mic with 1 min contact was sufficient to inactivate Bd. Also, terbinafine HCl (1 mg ml-1) with a 5 min contact time might be effective in treating amphibians infected with Bd. Based on this study and previously published findings, 0.75% Nolvasan, 1% Virkon S, and 3% bleach with 1 min contact are sufficient to inactivate both Bd and ranaviruses.


Human skeletal muscle structure and function preserved by vibration muscle exercise following 55 days of bed rest.
Prolonged immobilization of the human body results in functional impairments and musculoskeletal system deconditioning that may be attenuated by adequate muscle exercise. In a 56-day horizontal bed rest campaign involving voluntary males we investigated the effects of vibration muscle exercise (RVE, 2x6 min daily) on the lower limb skeletal muscles using a newly designed foot plantar trainer (Galileo Space) for use at supine position during bed rest. The maximally voluntary isometric plantar flexion force was maintained following regular RVE bouts during bed rest (controls -18.6 %, P<0.05). At the start (BR2) and end of bed rest (BR55) muscle biopsies were taken from both mixed fast/slow-type vastus lateralis (VL) and mainly slow-type soleus muscle (SOL), each having n=10. RVE group: the size of myofiber types I and II was largely unchanged in VL, and increased in SOL. Ctrl group: the SOL depicted a disrupted pattern of myofibers I/II profiles (i.e., type II>140 % vs. preBR) suggesting a slow-to-fast muscle phenotype shift. In RVE-trained SOL, however, an overall conserved myofiber I/II pattern was documented. RVE training increased the activity-dependent expression of nitric oxide synthase type 1 immunofluorescence at SOL and VL myofiber membranes. These data provide evidence for the beneficial effects of RVE training on the deconditioned structure and function of the lower limb skeletal muscle. Daily short RVE should be employed as an effective atrophy countermeasure co-protocol preferentially addressing postural calf muscles during prolonged clinical immobilization or long-term human space missions.


Virus-expressed, recombinant single-chain antibody blocks sporozoite infection of salivary glands in Plasmodium gallinaceum-infected Aedes aegypti.
Transgenic mosquitoes resistant to malaria parasites are being developed to test the hypothesis that they may be used to control disease transmission. We have developed an effector portion of an antiparasite gene that can be used to test malaria resistance in transgenic mosquitoes. Mouse monoclonal antibodies that recognize the circumsporozoite protein of Plasmodium gallinaceum can block sporozoite invasion of Aedes aegypti salivary glands. An anti-circumsporozoite monoclonal antibody, N2H6D5, whose corresponding heavy- and light-chain gene variable regions were engineered as a single-chain antibody construct, binds to P. gallinaceum sporozoites and prevents infection of Ae. aegypti salivary glands when expressed from a Sindbis virus. Mean intensities of sporozoite infections of salivary glands in mosquitoes expressing N2scFv were reduced as much as 99.9% when compared to controls.


Resistance of the breast-fed infant to gastroenteritis.
From in-vitro studies of breast and cow's milk preparations, and of the faeces from breast-fed and bottle-fed infants, a number of factors seemed likely to influence the production and maintenance of a lactobacillary flora and low pH in the faeces of newborn infants. These were mainly attributable to the nature of the feed. It is suggested that responsible factors in breast milk include its high lactose, low protein, low phosphate content, together with its poor buffering capacity. Importance is also attached to the fact that breast milk seems to provide a fluid feed of small bulk and low residue, and that its use is unlikely to include periods of starvation. Cow's milk, on the other hand, which has a low lactose, high protein, high phosphate content, and a high buffering capacity, is a relatively bulky, high-residue feed. Feeding regimens which employ it are likely to include periods of starvation.


Management and extended outcome of patients with synchronous bilateral solid renal neoplasms in the absence of von Hippel-Lindau disease.
To gain information regarding long-term follow-up in patients with synchronous bilateral solid renal neoplasms in whom renal-preserving surgery is imperative. We examined our surgical experience and the survival outcome, as evaluated by Kaplan-Meier and log-rank analysis, of 94 patients (64 men and 30 women) who presented to the Mayo Clinic in Rochester, Minn, from 1973 to 1998 with bilateral synchronous solid renal neoplasms in the absence of von Hippel-Lindau disease. Follow-up of these patients ranged from 1 to 25 years, with a mean of 5.86 years and a median of 4.18 years. Tumors were staged according to the TNM classification. Pathologic staging and grading were usually performed on the kidney with the most extensive cancer. The Cox proportional hazards model was used to assess the relationship of grade (1-4), tumor size, and enucleation as opposed to extended (1 cm) partial nephrectomy on overall, cancer-specific, local recurrence-free, and metastasis-free survival. Seventy-one patients (76%) had bilateral synchronous renal cell carcinoma, and 14 patients (15%) had a unilateral renal cell carcinoma with a contralateral benign solid neoplasm. Nine patients (10%) had bilateral benign solid lesions. Sixty-six patients (70%) underwent a single procedure, whereas 28 (30%) underwent staged surgical procedures. Fifty-one patients (54%) are alive, and 43 (46%) have died. Twenty patients (21%) died of metastatic disease, and 5 (5%) had a local recurrence. Cancer-specific survival of the 85 patients with at least 1 renal cell carcinoma still under observation was 81% (+/- 4.9% SE) and 59% (+/- 8.1% SE) at 5 and 10 years, respectively, and survival to local recurrence was 96% (+/- 2.6% SE) at 5 years and 93% (+/- 3.7% SE) at 10 years with 14 patients still under observation. Grade 3 was a statistically significant factor for metastasis (P < .001). A significant difference in metastasis-free survival and cancer-specific survival was noted dependent on pathologic T stage (P < .001 and P = .02, respectively), with patients with local pT3 disease having a higher rate of metastasis and cancer-specific death. Multivariate analysis revealed that tumor grade was associated with metastasis-free survival (P = .002) and tumor size with cancer-specific survival (P = .04). There was no statistical significance on survival outcome end points according to procedure performed, i.e., enucleation vs extended partial nephrectomy. Long-term results of renal-preserving procedures for a series of patients with bilateral solid renal neoplasms indicate that grade, stage, and tumor size are significant predictors of outcome. Mean follow-up of over 5 years supports nephron-sparing techniques in selected patients because local recurrence was infrequent compared with distant metastasis.


Longitudinal Evaluation of Fatty Acid Metabolism in Normal and Spontaneously Hypertensive Rat Hearts with Dynamic MicroSPECT Imaging.
The goal of this project is to develop radionuclide molecular imaging technologies using a clinical pinhole SPECT/CT scanner to quantify changes in cardiac metabolism using the spontaneously hypertensive rat (SHR) as a model of hypertensive-related pathophysiology. This paper quantitatively compares fatty acid metabolism in hearts of SHR and Wistar-Kyoto normal rats as a function of age and thereby tracks physiological changes associated with the onset and progression of heart failure in the SHR model. The fatty acid analog, (123)I-labeled BMIPP, was used in longitudinal metabolic pinhole SPECT imaging studies performed every seven months for 21 months. The uniqueness of this project is the development of techniques for estimating the blood input function from projection data acquired by a slowly rotating camera that is imaging fast circulation and the quantification of the kinetics of (123)I-BMIPP by fitting compartmental models to the blood and tissue time-activity curves.


Congener-specific analysis of polychlorinated biphenyl in human blood from Japanese.
Polychlorinated biphenyl (PCB) congeners were analyzed by high resolution gas chromatography/high resolution mass spectrometry (HRGC/HRMS) of whole blood samples taken from 24 healthy adult Japanese volunteers (12 males and 12 females; age range 25-46 years). On average, 95 PCB congeners were detected in whole blood samples. The mean of total PCB concentration in whole blood was 771.9 pg g(-1) whole blood (139.6 ng per g-lipid). Congener-specific analysis identified the predominant PCB congeners as #153 (22.2%), #180 (11.6%), #138 (8.4%), #182/187 (6.6%), #118 (5.6%), #163/164 (5.0%), #99 (3.9%), #74 (3.6%), #146 (3.3%), #170 (3.0%) and #156 (2.2%), representing 75.6% of all PCBs detected in the human blood samples. Among the predominant PCB congeners, #153, #180, #138, #187 #118, #99 and #74 had chlorine as the substituent at the 2-, 4- and 5- positions of the phenyl-ring. In human blood in Japanese individuals, it is assumed that these congeners would be characteristic of the entire population, based on the relation between PCB ingestion and metabolism. Measuring 209 PCB congeners has the advantage of providing detailed information regarding the congener distribution within the blood samples, which can be compared to congener patterns in other matrices. Congener-specific analysis of 209 PCB congeners is especially useful in evaluating human exposure to PCBs.


Versatility of nasolabial flaps for the management of severe trismus in oral submucous fibrosis.
Oral submucous fibrosis (OSMF) is a chronic insidious disease affecting any part of the oral cavity and sometimes the pharynx. It is a collagen-related disorder predominantly associated with tobacco/areca nut chewing habit and characterized by progressive hyalinization of the submucosa. Prevalence of OSMF is 2.01%, and malignant transformation rate of 2.3%-7.6% has been reported in the literature. Measures such as forcing the mouth open and cutting the fibrotic bands have resulted in more fibrosis and disability. Various surgical treatment modalities have been advocated in the surgical management of OSMF with variable results. This retrospective study evaluates the efficacy of nasolabial flap in the surgical treatment of OSMF. Retrospective analysis of 42 patients who underwent surgical management of OSMF with mouth opening <20 mm by nasolabial flap at authors center from 2000 to 2015. Only the cases diagnosed as advanced OSMF based on long-standing positive history of habits (chewing tobacco, betel nut, etc.), clinical and histopathological examination. OSMF due to other causes such as nutritional deficiency, immunological diseases, and systemic illness with medically compromised patients were excluded from the study. Inferiorly based nasolabial flaps were raised in the supramuscular plane and transferred intraorally through a transbuccal tunnel. The study groups consist of 42 cases of clinical and histopathologically proven cases of OSMF treated by nasolabial flap. Out of 42 cases, 39 (92.85%) were males and 3 (7.15%) were females which showed a male predominance and the ratio was 13:1. The mean (standard deviation [SD]) preoperative mouth opening was 14.60 mm (3.06). After release of fibrotic bands, a mean forced intraoperative mouth opening of 36.27 (2.11) mm was achieved. The mean (SD) postoperative mouth opening was 33.05 mm (2.40) at the end of 2-year follow-up. The mean (SD) increase in mouth opening after surgical management at the end of 2-year follow-up is 18.46 mm (1.89). Sixteen out of 42 patients' histopathological report turned out to be dysplastic. The mean (SD) follow-up was 2.79 years (1.08). There was no incidence of infection in the transferred flap and the recipient site in all cases except one case with malignant transformation. All flaps healed without evidence of infection, dehiscence, or necrosis. Results were assessed by comparing the pre- and post-operative maximum mouth opening. The nasolabial flap is a versatile flap, which can be successfully used in the reconstruction of defects created after the release of fibrotic bands in OSMF. The versatility of the nasolabial flap has been attributed to its reliable vascularity derived from numerous vessels in the vicinity. Major advantage is the ease of elevation, proximity to the defect, suitable size for coverage of defect, minimal swallowing and speech difficulties, and a relatively cosmetic result as scar is in natural crease. All the cases treated for OSMF using bilateral nasolabial flaps showed adequate mouth opening at 2-year follow-up postoperatively, recommending its use.


Fishmeal extract bile salt lactose agar--a differential medium for enteric bacteria.
Fishmeal extract bile salt lactose agar (FEBLA), a new differential medium for enteric bacteria was developed and evaluated for its ability to grow and differentiate lactose fermenters (LF) from non-lactose fermenters (NLF) in comparison with MacConkeys agar. Performance of FEBLA was at par with the latter. On FEBLA medium, the contrast between LF and NLF colonies was pronounced and Klebsiella pneumoniae produced more mucoid colonies than on MacConkeys agar (Hi Media). Unlike MacConkeys agar, a 24 h culture of K. pneumoniae cells on FEBLA were longer and thicker with abundant capsular material around the bacilli. Escherichia coli produced long and thick cells but only after 48h. No change in cell morphology was evident with regard to Salmonella typhi, S. paratyphi A, Shigella flexneri, Pseudomonas aeruginosa, Proteus mirabilis, Proteus vulgaris, Citrobacter koseri and Acinetobacter baumannii. Performance of the medium was controlled using E. coli and S. flexneri. FEBLA is simple, cost effective and may be a suitable alternative in the preliminary identification of enteric bacteria.


Time-Resolved Measurements of Nitric Oxide, Nitrogen Dioxide, and Nitrous Acid in an Occupied New York Home.
Indoor oxidizing capacity in occupied residences is poorly understood. We made simultaneous continuous time-resolved measurements of ozone (O3), nitric oxide (NO), nitrogen dioxide (NO2), and nitrous acid (HONO) for two months in an occupied detached home with gas appliances in Syracuse, NY. Indoor NO and HONO mixing ratios were higher than those outdoors, whereas O3 was much lower (sub-ppbv) indoors. Cooking led to peak NO, NO2, and HONO levels 20-100 times greater than background levels; HONO mixing ratios of up to 50 ppbv were measured. Our results suggest that many reported NO2 levels may have a large positive bias due to HONO interference. Nitrous acid, NO2, and NO were removed from indoor air more rapidly than CO2, indicative of reactive removal processes or surface uptake. We measured spectral irradiance from sunlight entering the residence through glass doors; hydroxyl radical (OH) production rates of (0.8-10) × 107 molecules cm-3 s-1 were calculated in sunlit areas due to HONO photolysis, in some cases exceeding rates expected from ozone-alkene reactions. Steady-state nitrate radical (NO3) mixing ratios indoors were predicted to be lower than 1.65 × 104 molecules cm-3. This work will help constrain the temporal nature of oxidant concentrations in occupied residences and will improve indoor chemistry models.


[An infant feeding update program at healthcare centers and its impact on breastfeeding and morbidity].
This study evaluated the impact of an infant feeding update program on exclusive breastfeeding and the incidence of diarrhea and respiratory illness in infants. A randomized cluster field study was conducted in the city of Porto Alegre, Rio Grande do Sul State, Brazil, with 20 healthcare centers. Health professionals received information on the Ten Steps to Healthy Feeding for Children up to Two Years of Age. We evaluated 619 infants 6-9 months of age. The results showed longer duration of exclusive breastfeeding (p = 0.02) in the intervention group but no significant differences in the incidence of diarrhea or respiratory symptoms. Complementary analyses showed that exclusive breastfeeding was longer in the group of children without the occurrence of diarrhea (p = 0.001) or respiratory symptoms (p = 0.03). The data suggest that the training was insufficient to affect incidence of illness, but that it was effective in extending exclusive breastfeeding.


Management of functional neuroendocrine tumors of the pancreas.
Pancreatic neuroendocrine tumors (pNETs) constitute a heterogenous group of malignancies with varying clinical presentation, tumor biology and prognosis. The incidence of pNETs has steadily increased during the last decades with an estimated incidence 2012 of 4.8/100,000. Recent whole genome sequencing of pNETs has demonstrated mutations in the DNA repair genes MUTYH and point mutations and gene fusions in four main pathways from chromatin remodeling, DNA damage repair, activation of mechanistic target of rapamycin (mTOR) signaling and the telomere maintenance. This new information will be the foundation for new therapies in the near future for malignant pNETs. The functioning pNETs constitute about 30-40% of all pNETs displaying nine different clinical syndromes: insulinoma, Zollinger-Ellison, Verner-Morrison, glucagonoma, somatostatinomas, ectopic adrenocorticotropic hormone (ACTH) and parathyroid hormone related peptide (PTH-rP) syndromes. Single patients might also present carcinoid syndrome. The diagnostic work-up include histopathology with the new WHO 2017 Classification, biomarkers (CgA, NSE), radiology and molecular imaging including CT-scan, magnetic resonance imaging (MRI), ultrasound and PET-scan. A cornerstone in the treatment of pNETs is surgery which is rarely curative but can reduce the clinical symptoms by debulking which also include radiofrequency ablation, embolization of liver metastases. Medical treatment includes chemotherapy and the targeted agents such as everolimus, sunitinib and peptide receptor radiotherapy (PRRT). Somatostatin analogs has for the last decades been the main stay for management for clinical symptoms related to functioning pNETs and is often combined with new targeted agents as well as chemotherapy. Long-term management of functioning pNETs need a combination of different procedures, surgery, local ablation, targeted agents and somatostatin analogs. Future therapies might be based on the recent advances in molecular genetics and tumor biology.


The effectiveness of naltrexone combined with current smoking cessation medication to attenuate post smoking cessation weight gain: a literature review.
Smoking is the number one cause of preventable morbidity and mortality globally and although many countries have invested heavily in smoking cessation programs, 21% of the global population still smoke. Post cessation weight gain has been identified as a barrier to attempting cessation and is implicated in the high rates of relapse. Naltrexone has been touted as a possible solution to address post smoking cessation weight gain. The results from seven original studies assessing the effectiveness of naltrexone in combination with existing smoking cessation medications to attenuate post smoking cessation weight gain were obtained and critically reviewed. Five returned positive results and two returned results that were statistically insignificant. The positive results were seen more often in those identified as more likely to exhibit hedonic eating behaviour for example women and participants who were categorised as overweight or obese. The evidence suggests further investigation in to a combination of naltrexone and approved smoking cessation medications is warranted and could provide a solution to attenuate post smoking cessation weight gain especially in women and those classified as overweight or obese. This may provide the tool required to remove a perceived barrier to smoking cessation and improve global statistics.


Care Coordination Program for Children With Complex Chronic Conditions Discharged From a Rural Tertiary-Care Academic Medical Center.
Hospital discharge offers an opportunity to initiate coordination of follow-up care, preventing readmissions or emergency department (ED) recidivism. We evaluated how revisits and costs of care varied in a 12-month period between children in a care coordination program at our center (enrolled after hospital discharge with a tracheostomy or on a ventilator) and children with complex chronic condition discharges who were not enrolled. Children ages 1 to 17 years were retrospectively included if they had a hospital discharge in 2017 with an International Classification of Diseases, 10th Revision code meeting complex chronic condition criteria or if they were in active follow-up with the care coordination program. Revisits and total costs of care were compared over 2018 for included patients. Seventy patients in the program were compared with 56 patients in the control group. On bivariate analysis, the median combined number of hospitalizations and ED visits in 2018 was lower among program participants (0 vs 1; P = .033), and program participation was associated with lower median total costs of care in 2018 ($700 vs $3200; P = .024). On multivariable analysis, care coordination program participation was associated with 59% fewer hospitalizations in 2018 (incidence rate ratio: 0.41; 95% confidence interval: 0.23 to 0.75; P = .004) but was not significantly associated with reduced ED visits or costs. The care coordination program is a robust service spanning the continuum of patient care. We found program participation to be associated with reduced rehospitalization, which is an important driver of costs for children with medical complexity.


Extracorporeal membrane oxygenation for refractory septic shock in children: one institution's experience.
To report our institutional experience of venoarterial extracorporeal membrane oxygenation (ECMO) in children with septic shock and circulatory collapse. Retrospective case series. Intensive care unit of a tertiary pediatric referral center. Forty-five children with refractory septic shock who received venoarterial ECMO for hemodynamic support. Venoarterial ECMO. We measured mean arterial pressure and inotropes before cannulation, ventilator settings, oxygenation, site and cause of infection, time on ECMO, complications of ECMO relating to the circuit or anticoagulation, survival to hospital discharge, and functional outcome assessment. Between July 1988 and October 2006, 441 children at our institution received extracorporeal life support for a variety of indications. Forty-five (10%) with septic shock received venoarterial ECMO specifically for hemodynamic support. Eighteen (40%) of these had suffered cardiac arrest and were receiving chest compressions immediately before cannulation. The median time spent on ECMO was 84 hrs (range, 32-135). There were mechanical problems with the ECMO circuit requiring intervention in 17 (38%) patients, such as oxygenator or pump head failure, clots in the circuit, or cannulae malposition. This caused no long-term harm in any but one of the patients, who died during a circuit change. Eleven patients (24%) had clinically apparent episodes of bleeding that required surgical intervention or blood transfusion. Twenty-one (47%) patients survived to hospital discharge. Atrioaortic cannulation through a sternotomy incision was associated with an improvement in survival to hospital discharge (73% of those with central cannulation survived vs. 44% without, p = .05). No survivors had severe disability at long-term follow-up. Extracorporeal membrane oxygenation can be safely used to resuscitate and support children with sepsis and refractory shock. Sepsis and multiorgan failure should not be considered a contraindication to ECMO. This study adds support to existing guidelines.


Pattern formation in the visual centers of the Drosophila brain: wingless acts via decapentaplegic to specify the dorsoventral axis.
A stepwise morphogenetic program of cell division and cell fate determination generates the precise neuronal architecture of the visual centers of the Drosophila brain. Here, we show that the assembly of the target structure for ingrowing retinal axons involves cell-cell interactions mediated by the secreted product of the wingless (wg) gene. wg, expressed in two symmetrical domains of the developing brain, is required to induce and maintain the expression of the secreted decapentaplegic (dpp) gene product in adjacent domains. wg and dpp function are required for target field neurons to adopt their proper fates and to send axons into the developing target structure. These observations implicate a cascade of diffusible signaling molecules in patterning the visual centers of the Drosophila brain.


Correlation maps allow neuronal electrical properties to be predicted from single-cell gene expression profiles in rat neocortex.
The computational power of the neocortex arises from interactions of multiple neurons, which display a wide range of electrical properties. The gene expression profiles underlying this phenotypic diversity are unknown. To explore this relationship, we combined whole-cell electrical recordings with single-cell multiplex RT-PCR of rat (p13-16) neocortical neurons to obtain cDNA libraries of 26 ion channels (including voltage activated potassium channels, Kv1.1/2/4/6, Kvbeta1/2, Kv2.1/2, Kv3.1/2/3/4, Kv4.2/3; sodium/potassium permeable hyperpolarization activated channels, HCN1/2/3/4; the calcium activated potassium channel, SK2; voltage activated calcium channels, Caalpha1A/B/G/I, Cabeta1/3/4), three calcium binding proteins (calbindin, parvalbumin and calretinin) and GAPDH. We found a previously unreported clustering of ion channel genes around the three calcium-binding proteins. We further determined that cells similar in their expression patterns were also similar in their electrical properties. Subsequent regression modeling with statistical resampling yielded a set of coefficients that reliably predicted electrical properties from the expression profile of individual neurons. This is the first report of a consistent relationship between the co-expression of a large profile of ion channel and calcium binding protein genes and the electrical phenotype of individual neocortical neurons.


High magnetoresistance at low magnetic fields in self-assembled ZnO-Co nanocomposite films.
The solid phase growth of self-assembled nanocrystals embedded in a crystalline host matrix opens up wide perspectives for the coupling of different physical properties, such as magnetic and semiconducting. In this work, we report the pulsed laser growth at room temperature of thin films composed of a dispersed array of ferromagnetic Co (0001) nanoclusters with an in-plane mono-size width of 1.3 nm, embedded in a ZnO (0001) crystalline matrix. The as-grown films lead to very high values of magnetoresistance, ranging at 9 T from -11% at 300 K to -19% at 50 K, with a steep decrease of the magnetoresistance at low magnetic fields. We establish the relationship between the magnetoresistance behavior and the magnetic response of the Co nanocluster assembly. A spin-dependent tunneling of the electrons between the Co nanoclusters through and by the semi-insulating ZnO host is achieved in our films, promising with regard to magnetic field sensors or Si-integrated spintronic devices. The effects of thermal annealing are also discussed.


Role of cell surface contact in the kinetics of superoxide production by granulocytes.
The complement-derived anaphylatoxin C5a and a putative analogue of bacterial chemotactic factor (N-formyl-methionyl-leucyl-phenylalanyl [fMLP]), as well as bacterial lipid A, all stimulate human granulocyte (PMN) adhesiveness and superoxide (O-2) production in a concentration-dependent manner. Since attachment of particulate matter to the PMN membrane is an early event in the triggering of respiratory burst of these cells, we further examined how adherence might modulate the release of O-2 induced by soluble mediators of inflammation. We found that both the quantity and kinetics of O-2 production depend on prior attachment of the cells to a surface. In stirred suspensions of PMN, fMLP induces only a short burst (2.5 min) of O-2 release associated with reversible PMN aggregation. The magnitude, but not the time course, of both these responses depend on the fMLP concentration. Unlike the short respiratory response of cells in suspension, PMN allowed to settle onto stationary petri dishes, then overlaid with fMLP, rapidly spread and attach to the surface where they remain and release O-2 throughout the 60-min test period. Prolonged O-2 release also follows fMLP stimulation in suspensions of PMN pretreated with cytochalasin B, in which case aggregation becomes irreversible during the 20-min burst. If fMLP is slowly infused into a suspension of cells at 37 degrees C or if PMN are challenged at 0 degrees C, and then warmed to 37 degrees C, O-2 release greatly decreases or becomes undetectable. Suspended PMN do not respond to a second challenge by the same stimulus regardless of the rate or temperature at which the first stimulus was added, a phenomenon formerly described as desensitization. However, if PMN challenged with fMLP in suspension undergo the short respiratory response and then are later placed in petri dishes, they adhere and resume production of O-2 without further stimulation. Chemotactic factor-induced adherence and O-2 release of PMN on a surface is entirely independent of either the mode of activation or prior O-2 release during preincubation in suspension. Human C5a also promotes PMN adherence and prolonged O-2 release in petri dishes. Furthermore, lipid A increases O-2 release and adherence of settled PMN, but fails to elicit either response from suspended PMN. These results indicate that cell surface contact plays an essential role in triggering the respiratory burst of PMN activated by soluble stimuli. This long-lasting O-2 release by chemotactic factor-stimulated PMN may play a significant role in inflammatory reactions when PMN become adherent in vivo.


Role of angiotensin II and oxidative stress in renal inflammation by hypernatremia: benefits of atrial natriuretic peptide, losartan, and tempol.
The body regulates plasma sodium levels within a small physiologic range, despite large variations in daily sodium and water intake. It is known that sodium transport in the kidneys plays an important role in hypoxia, being the major determinant of renal oxygen consumption. Tubular epithelial cell hypoxia is an important contributor to the development of renal inflammation, and the damage may progress to structural injury, ending in acute renal failure. In this review, we will summarize the renal inflammatory effects of high acute plasma sodium (acute hypernatremia), and the molecular mechanisms involved. We will also discuss recent findings related to the role of oxidative stress and angiotensin II (Ang II) in the pathogenesis of renal injury. We will comment on the effects of agents used to prevent or attenuate the inflammatory response, such as the atrial natriuretic peptide, the superoxide dismutase mimetic - tempol, and losartan.


Solution-processed highly bright and durable cesium lead halide perovskite light-emitting diodes.
Recently, CsPbBr3 perovskites have been emerging as very promising green emission materials for light-emitting diodes (LEDs) due to their high color purity, low cost and high photoluminescence quantum yield (PLQY). However, the corresponding LED performance is still low and far behind CH3NH3PbBr3; it is due to the lack of proper perovskite film preparation methods and interfacial engineering. Herein, we report highly bright and durable CsPbBr3-based LEDs fabricated using a one-step solution method. The precursor solution is prepared by simply dissolving CsPbBr3 powder and a CsBr additive in dimethyl sulfoxide (DMSO). We find that the CsBr additive not only significantly enhances the PLQY but also induces directional crystal growth into micro-plates, forming a smooth perovskite film for LEDs. LEDs employing such high quality films show a high luminance of 7276 cd m-2 and high color purity with a full width at half maximum of 18 nm. Furthermore, the as-fabricated LEDs reveal an outstanding ambient stability with a decent luminance output (>100 cd m-2, steady increase without any degradation trend) for at least 15 h under a constant driving current density (66.7 mA cm-2). And we propose two reasons for this unique luminance increasing behavior: (1) the CsPbBr3 perovskite is thermally stable and can survive from joule heat; and (2) on the other hand, the joule heating will induce interface or crystalline film annealing, reduce device resistance and then enhance the luminance output.


Occupation and survival: a 25-year follow-up study of an aging population.
In this retrospective study of an elderly population cohort living in a defined Swedish rural area, the relationship between occupation and survival as a measure of objective health was investigated. The cohort has been followed for 25 years. On the basis of the baseline socioeconomic interview from assessments performed when the participants were 67 years of age, an index of active participation in daily occupation was devised. The index was used to investigate the covariation between generic everyday occupation and long-time survival. For the female participants, Kaplan-Meier curves demonstrated differences in survival between the "less active" and "more active," and Cox regression survival analyses resulted in a significant covariance between occupation and survival. For the male participants, no such differences were found. The significant results for the women implied support for the core assumption of occupational therapy that a relationship exists between occupation and health. The lack of differences in survival among more active and less active men demonstrates the complexity of studying occupation.


Hematohidrosis: A rare clinical entity.
Hematohidrosis is a rare clinical condition of sweating blood. A 13-year-old boy was presented to the department of dermatology with a history of spontaneous bleeding from skin since January 2007. During examination, it disappeared as soon as it was mopped leaving behind no sign of trauma only to reappear within a few seconds. This confirms that it was sweating of blood and not bleeding. Bleeding time, clotting time and prothrombin time was normal. Patient was diagnosed with hematohidrosis clinically by exclusion, confirmed by benzidine test, biochemical and microscopic examination of fluid. At present, no treatment is available for this condition. Etiology is unknown till date. Stress may be a precipitating factor.


Pre-clinical evaluation of a P. berghei-based whole-sporozoite malaria vaccine candidate.
Whole-sporozoite vaccination/immunization induces high levels of protective immunity in both rodent models of malaria and in humans. Recently, we generated a transgenic line of the rodent malaria parasite P. berghei (Pb) that expresses the P. falciparum (Pf) circumsporozoite protein (PfCS), and showed that this parasite line (PbVac) was capable of (1) infecting and developing in human hepatocytes but not in human erythrocytes, and (2) inducing neutralizing antibodies against the human Pf parasite. Here, we analyzed PbVac in detail and developed tools necessary for its use in clinical studies. A microbiological contaminant-free Master Cell Bank of PbVac parasites was generated through a process of cyclic propagation and clonal expansion in mice and mosquitoes and was genetically characterized. A highly sensitive qRT-PCR-based method was established that enables PbVac parasite detection and quantification at low parasite densities in vivo. This method was employed in a biodistribution study in a rabbit model, revealing that the parasite is only present at the site of administration and in the liver up to 48 h post infection and is no longer detectable at any site 10 days after administration. An extensive toxicology investigation carried out in rabbits further showed the absence of PbVac-related toxicity. In vivo drug sensitivity assays employing rodent models of infection showed that both the liver and the blood stage forms of PbVac were completely eliminated by Malarone® treatment. Collectively, our pre-clinical safety assessment demonstrates that PbVac possesses all characteristics necessary to advance into clinical evaluation.


Increased alpha (8-12 Hz) activity during slow wave sleep as a marker for the transition from implicit knowledge to explicit insight.
The number reduction task (NRT) allows us to study the transition from implicit knowledge of hidden task regularities to explicit insight into these regularities. To identify sleep-associated neurophysiological indicators of this restructuring of knowledge representations, we measured frequency-specific power of EEG while participants slept during the night between two sessions of the NRT. Alpha (8-12 Hz) EEG power during slow wave sleep (SWS) emerged as a specific marker of the transformation of presleep implicit knowledge to postsleep explicit knowledge (ExK). Beta power during SWS was increased whenever ExK was attained after sleep, irrespective of presleep knowledge. No such EEG predictors of insight were found during Sleep Stage 2 and rapid eye movement sleep. These results support the view that it is neuronal memory reprocessing during sleep, in particular during SWS, that lays the foundations for restructuring those task-related representations in the brain that are necessary for promoting the gain of ExK.


Endothelial, epithelial, and fibroblast cells exhibit specific splicing programs independently of their tissue of origin.
Alternative splicing is the main mechanism of increasing the proteome diversity coded by a limited number of genes. It is well established that different tissues or organs express different splicing variants. However, organs are composed of common major cell types, including fibroblasts, epithelial, and endothelial cells. By analyzing large-scale data sets generated by The ENCODE Project Consortium and after extensive RT-PCR validation, we demonstrate that each of the three major cell types expresses a specific splicing program independently of its organ origin. Furthermore, by analyzing splicing factor expression across samples, publicly available splicing factor binding site data sets (CLIP-seq), and exon array data sets after splicing factor depletion, we identified several splicing factors, including ESRP1 and 2, MBNL1, NOVA1, PTBP1, and RBFOX2, that contribute to establishing these cell type-specific splicing programs. All of the analyzed data sets are freely available in a user-friendly web interface named FasterDB, which describes all known splicing variants of human and mouse genes and their splicing patterns across several dozens of normal and cancer cells as well as across tissues. Information regarding splicing factors that potentially contribute to individual exon regulation is also provided via a dedicated CLIP-seq and exon array data visualization interface. To the best of our knowledge, FasterDB is the first database integrating such a variety of large-scale data sets to enable functional genomics analyses at exon-level resolution.


High-sensitivity optical pulse characterization using Sagnac electro-optic spectral shearing interferometry.
An electro-optic spectral shearing interferometer for high-sensitivity optical pulse characterization is described. Two replicas of the test pulse counterpropagate in a Sagnac interferometer with orthogonal polarization states, resulting in two relatively sheared copolarized replicas after temporal phase modulation. The polarization interferometer is intrinsically stable, and its birefringence sets the delay between interfering replicas to reduce the spectrometer resolution requirement. Experimental implementations demonstrate real-time pulse characterization at average powers as low as 1 nW with spectral shears as high as 280 GHz.


Luminance and Luminous Intensity Indicatrices of lsobilateral Leaves.
The luminance and luminous intensity characteristics of the leaves of several forest species of eucalypts have been investigated and compared with freshly smoked magnesium oxide. Results indicate that different species of the same genus can have distinctive indicatrices. Inspection of the indicatrices for the leaves showed that, for practical purposes, three types of reflection are recognizable, i.e., diffuse, spread, reflex. It seems important therefore that the research worker should be aware of the type of reflection being measured, since this may influence his conclusions. The cusp in the direction of reflex reflection was found to increase rapidly about the normal (0 degrees ) to the leaf's surface and to attain a maximum at the normal. As the angle of incident light is increased from 0 degrees to 45 degrees or more, the spread reflection component becomes increasingly conspicuous. With normal incidence, the maximum luminous intensity was attained in the direction of reflex reflection, but rapidly decreased toward zero beyond about +/-60 degrees to the normal.


Clinicopathological significance of SOX4 expression in primary gallbladder carcinoma.
SOX4, as a member of the SRY-related HMG-box (SOX) transcription factor family, has been demonstrated to be involved in tumorigenesis of many human malignancies; however, its role in primary gallbladder carcinoma (PGC) is still largely unknown. The aim of this study was to investigate SOX4 expression in PGC and its prognostic significance. From 1997 to 2006, 136 patients underwent resection for PGC. The median follow-up was 12.8 months. Immunostainings for SOX4 were performed on these archival tissues. The correlation of SOX4 expression with clinicopathological features including survival was analyzed. SOX4 was expressed in 75.0% (102/136) of PGC but not in the normal epithelium of the gallbladder. In addition, the over-expression of SOX4 was significantly associated with low histologic grade (P = 0.02), low pathologic T stage (P = 0.02), and early clinical stage (P = 0.03). The levels of SOX4 immunostainings in PGC tissues with positive nodal metastasis were also significantly lower than those without (P = 0.01). Moreover, Kaplan-Meier curves showed that SOX4 over-expression was significantly related to better overall (P = 0.008) and disease-free survival (P = 0.01). Furthermore, multivariate analyses showed that SOX4 expression was an independent risk factor for both overall (P = 0.03, hazard ratio, 3.682) and disease-free survival (P = 0.04, hazard ratio, 2.215). Our data indicate for the first time that the over-expression of SOX4 in PGC was significantly correlated with favorable clinicopathologic features and was an independent prognostic factor for better overall and disease-free survival in patients. Therefore, SOX4 might be an auxiliary parameter for predicting malignant behavior for PGC. The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1534825818694957.


Lipid-soluble components in cigarette smoke induce mitochondrial production of reactive oxygen species in lung epithelial cells.
Reactive oxygen species (ROS) present in cigarette smoke (CS) are thought to contribute to the development of COPD. Although CS-ROS can hardly enter airway epithelial cells, and certainly not the circulation, systemic levels of ROS have been found to be elevated in COPD patients. We hypothesize that lipophilic components present in CS can enter airway epithelial cells and increase intracellular ROS production by disturbing mitochondrial function. Different airway epithelial cells were exposed to CS extract (CSE), hexane-treated CSE (CSE without lipophilic components), gaseous-phase CS, and water-filtered CS (gaseous-phase CS without ROS). Mitochondrial membrane potential (Deltapsi(m)) and ATP levels were assessed using the bronchial epithelial cell line Beas-2b. ROS generation measured directly by DCF fluorescence and indirectly by measuring free thiol groups (-SH) upon exposure to CS was assessed using lung alveolar epithelial cells devoid of functional mitochondria (A549-rho0), with normal A549 cells serving as controls. In Beas-2b cells, CSE (4 h) caused a dose-dependent decrease in Deltapsi(m) and ATP levels, whereas hexane-treated CSE did not. DCF fluorescence in A549 cells increased in response to CSE, whereas this was not the case in A549-rho0 cells. Exposure of A549 cells to CS resulted in a rapid decrease in free -SH, whereas exposure to ROS-depleted CS only resulted in a delayed decrease. This delayed decrease was less pronounced in A549-rho0 cells. Lipophilic components in CS disturb mitochondrial function, which contributes to increased intracellular generation of ROS. Our results are of importance in understanding the systemic effects of smoking observed in patients with COPD.


Enhanced Transitions of Care: Centralizing Discharge Phone Calls Improves Ability to Reach Patients and Reduces Hospital Readmissions.
The discharge phone call (DPC) is an important initiative aimed at improving transitions of care and reducing readmissions. It is of added importance as financial penalties will be imposed on hospitals with "excessive" Medicare readmissions. This study examines the impact of DPCs on percentages of patients reached through the DPCs and hospital readmission rates based on the centralized or noncentralized mode of DPCs. The health system centralized the Studer Group Discharge Phone Call program into one central call center with the goals of reaching more discharged patients and to ultimately reduce hospital readmissions. The study analyzed hospital visits from 74,754 patient admissions that could result in an unplanned hospital readmission. Hospital discharge data were analyzed from August 2010 to January 2014. Primary outcomes included DPCs reaching discharged patients and effects on hospital readmission rates as a result of centralizing the DPC program. Centralized DPCs are significantly associated with increases in the percentage of patients reached by the DPC, which in turn reduces readmissions rates. Patients not reached were 1.32 times more likely to be readmitted than patients reached by centralized DPCs. Centralizing the DPC program within a call center helps reach more patients and reduce readmission rates further compared with noncentralized DPCs.


Viscum album L. extracts in breast and gynaecological cancers: a systematic review of clinical and preclinical research.
Viscum album L. extracts (VAE, European mistletoe) are a widely used medicinal plant extract in gynaecological and breast-cancer treatment. Systematic review to evaluate clinical studies and preclinical research on the therapeutic effectiveness and biological effects of VAE on gynaecological and breast cancer. Search of databases, reference lists and expert consultations. Criteria-based assessment of methodological study quality. 19 randomized (RCT), 16 non-randomized (non-RCT) controlled studies, and 11 single-arm cohort studies were identified that investigated VAE treatment of breast or gynaecological cancer. They included 2420, 6399 and 1130 patients respectively. 8 RCTs and 8 non-RCTs were embedded in the same large epidemiological cohort study. 9 RCTs and 13 non-RCTs assessed survival; 12 reported a statistically significant benefit, the others either a trend or no difference. 3 RCTs and 6 non-RCTs assessed tumour behaviour (remission or time to relapse); 3 reported statistically significant benefit, the others either a trend, no difference or mixed results. Quality of life (QoL) and tolerability of chemotherapy, radiotherapy or surgery was assessed in 15 RCTs and 9 non-RCTs. 21 reported a statistically significant positive result, the others either a trend, no difference, or mixed results. Methodological quality of the studies differed substantially; some had major limitations, especially RCTs on survival and tumour behaviour had very small sample sizes. Some recent studies, however, especially on QoL were reasonably well conducted. Single-arm cohort studies investigated tumour behaviour, QoL, pharmacokinetics and safety of VAE. Tumour remission was observed after high dosage and local application. VAE application was well tolerated. 34 animal experiments investigated VAE and isolated or recombinant compounds in various breast and gynaecological cancer models in mice and rats. VAE showed increase of survival and tumour remission especially in mice, while application in rats as well as application of VAE compounds had mixed results. In vitro VAE and its compounds have strong cytotoxic effects on cancer cells. VAE shows some positive effects in breast and gynaecological cancer. More research into clinical efficacy is warranted.


Posterior (outward) migration of the lamina cribrosa and early cupping in monkey experimental glaucoma.
To quantify the lamina cribrosa insertion into the peripapillary sclera and optic nerve pia in normal (N) and early experimental glaucoma (EEG) monkey eyes. Perfusion-fixed optic nerve heads (ONHs) from 21 animals were digitally reconstructed three dimensionally and delineated. Anterior Laminar Insertion Position (ALIP), Posterior Laminar Insertion Position (PLIP), Laminar Insertion Length (LIL; distance between the anterior and posterior laminar insertions), and Scleral Thickness (at the Anterior Sub-arachnoid space) were calculated for each ONH. Animals were pooled into four groups based on the kill condition (N vs. EEG) and perfusion IOP (10, 30, or 45 mm Hg) of each eye: N10-N10 (n = 6), N30/45-N10 (n = 6), EEG10-N10 (n = 3), and EEG30/45-N10 (n = 6). Glaucomatous EEG versus N eye differences in each group and each animal were required not only to achieve statistical significance (P < 0.05) but also to exceed physiologic intereye differences within the bilaterally normal groups. ALIP was significantly posterior (outward) in the EEG compared with N10 eyes of the EEG30/45-N10 group and 5 of 9 individual EEG eyes (difference range, 12-49 μm). PLIP was significantly posterior in the EEG eyes of both EEG groups and in 6 of 9 individual EEG eyes (range, 25-83 μm). LIL ranged from 90 to 190 μm in normal eyes and was significantly increased within the EEG eyes of both EEG groups and in 7 of 9 individual EEG eyes (difference range, 30-47 μm). Posterior migration of the lamina cribrosa is a component of early cupping in monkey EEG.


Sperm competition risk drives rapid ejaculate adjustments mediated by seminal fluid.
In many species, males can make rapid adjustments to ejaculate performance in response to sperm competition risk; however, the mechanisms behind these changes are not understood. Here, we manipulate male social status in an externally fertilising fish, chinook salmon (Oncorhynchus tshawytscha), and find that in less than 48 hr, males can upregulate sperm velocity when faced with an increased risk of sperm competition. Using a series of in vitro sperm manipulation and competition experiments, we show that rapid changes in sperm velocity are mediated by seminal fluid and the effect of seminal fluid on sperm velocity directly impacts paternity share and therefore reproductive success. These combined findings, completely consistent with sperm competition theory, provide unequivocal evidence that sperm competition risk drives plastic adjustment of ejaculate quality, that seminal fluid harbours the mechanism for the rapid adjustment of sperm velocity and that fitness benefits accrue to males from such adjustment.


Optimization of SPIO Injection for Sentinel Lymph Node Dissection in a Rat Model.
The magnetic technique, consisting of a magnetic tracer and a handheld magnetometer, is a promising alternative technique for sentinel lymph node dissection (SLND) and was shown to be non-inferior to the standard technique in terms of identification rates. In this study, injection characteristics (iron dose, dilution, time course and massaging) were evaluated to optimize magnetic tracer uptake in the sentinel lymph nodes (SLN) in a rat hindleg model. 202 successful SLNDs were performed. Iron uptake in the SLN is proportional (10% utilization rate) to the injection dose between 20 and 200 μg, showing a plateau uptake of 80 μg in the SLN around 1000 μg injection. Linear regression showed that time had a higher impact than dilution, on the SLN iron uptake. Massaging showed no significant change in iron uptake. The amount of residual iron at the injection site was also proportional to the injection dose without any plateau. Time was a significant factor for wash-out of residual iron. From these results, preoperative injection may be advantageous for SLN detection as well as reduction in residual iron at the injection site by potential decrease in required injection dose.


Safety and efficacy of Rotigotine in hospedalized patients with Vascular Parkinsonism aged 75 and older: effects on movement, praxis capacities, time-space orientation, quality of life and adherence to medical therapy.
In hospitals without stroke unit Department, the patients with acute ischemic stroke are stabilized in First Aid and sent to the Department of Internal Medicine. During the hospedalization period the patients undergo medical therapy for the stabilization of hemodynamic parameters and instrumental examinations for the determination of cardiovascular risk and thromboembolic evaluation. All patients are subjected to multidimensional evaluation of cognitive, praxis capacities, spatial-temporal orientation, quality of life and adherence to medical therapy. The aim of this study is evaluate the effect of Rotigotine patch on the impairment of neuro-cognitive capacity throught a continuous dopaminergic stimulation with transdermal administration. We have observed 19 patients (10 male and 9 female with range age 75-92 yrs) with Acute Ischemic Stroke stabilized in First Aid Depatment. The outcomes were the neurological changes from the baseline to 7 days in the clinical summury score on MMSE (on a scale from 0 to 30, with higher scores indicating fewer symtoms and lower physical limitations), Morinsky scale (on scale from 0 to 8, indicating adherence to therapy) and swallowing test (acts/minute). During the first week the patients were undergone to treatment with rotigotine 2 mg/24 hours. At the end of the treatment we obtained a statistically significant correlation about improvement of MMSE, Morinsky scale and swallowing test from a basal value. Rotigotine transdermal patches could be a new useful approach in the treatment of elderly hospetalized patients with acute ischaemic stroke correlated with cognitive impairment. Data shown that low dose of rotigotine patch could improves cognitive and praxis functions and therefore the quality of life of the hospitalized elderly patients. Rotigotine was effective and well-tolerated when used in routine clinical practice. Our data gave comfortable results but further evaluation are needed to have conclusive results.


Extraction of antioxidant and antiproliferative ingredients from fruits of Rubus chingii Hu by active tracking guidance.
Rubus chingii Hu, namely "Fu-pen-zi" in Chinese, has been used as a functional food in China for a long time. This study aims to identify its bioactive constituents with antioxidant and anti-tumor properties. R. chingii was extracted with 95% ethanol and then partitioned into four fractions: petroleum ether fraction, ethyl acetate fraction, n-butanol fraction, and water fraction. Results showed that the ethyl acetate fraction had the strongest antioxidant activity and cytotoxicity against human cancer cell lines (HepG-2, Bel-7402, A549 and MCF-7). Therefore, four compounds were isolated from the ethyl acetate fraction, and they were identified as ent-16α,17-dihydroxy-kauran-19-oic acid, tormentic acid, oleanolic acid and β-daucosterol, the first two of which were isolated and identified from R. chingii for the first time. In particular, tormentic acid exhibited excellent cytotoxicity activities against human tumor cell lines. The results obtained in this work might contribute to the understanding of biological activities of R. chingii and further investigation on its potential application is valued for food and drugs.


Survival, growth and reproduction of non-native Nile tilapia II: fundamental niche projections and invasion potential in the northern Gulf of Mexico.
Understanding the fundamental niche of invasive species facilitates our ability to predict both dispersal patterns and invasion success and therefore provides the basis for better-informed conservation and management policies. Here we focus on Nile tilapia (Oreochromis niloticus Linnaeus, 1758), one of the most widely cultured fish worldwide and a species that has escaped local aquaculture facilities to become established in a coastal-draining river in Mississippi (northern Gulf of Mexico). Using empirical physiological data, logistic regression models were developed to predict the probabilities of Nile tilapia survival, growth, and reproduction at different combinations of temperature (14 and 30°C) and salinity (0-60, by increments of 10). These predictive models were combined with kriged seasonal salinity data derived from multiple long-term data sets to project the species' fundamental niche in Mississippi coastal waters during normal salinity years (averaged across all years) and salinity patterns in extremely wet and dry years (which might emerge more frequently under scenarios of climate change). The derived fundamental niche projections showed that during the summer, Nile tilapia is capable of surviving throughout Mississippi's coastal waters but growth and reproduction were limited to river mouths (or upriver). Overwinter survival was also limited to river mouths. The areas where Nile tilapia could survive, grow, and reproduce increased during extremely wet years (2-368%) and decreased during extremely dry years (86-92%) in the summer with a similar pattern holding for overwinter survival. These results indicate that Nile tilapia is capable of 1) using saline waters to gain access to other watersheds throughout the region and 2) establishing populations in nearshore, low-salinity waters, particularly in the western portion of coastal Mississippi.


Large plasmidome of dairy Lactococcus lactis subsp. lactis biovar diacetylactis FM03P encodes technological functions and appears highly unstable.
Important industrial traits have been linked to plasmids in Lactococcus lactis. The dairy isolate L. lactis subsp. lactis biovar diacetylactis FM03P was sequenced revealing the biggest plasmidome of all completely sequenced and published L. lactis strains up till now. The 12 plasmids that were identified are: pLd1 (8277 bp), pLd2 (15,218 bp), pLd3 (4242 bp), pLd4 (12,005 bp), pLd5 (7521 bp), pLd6 (3363 bp), pLd7 (30,274 bp), pLd8 (47,015 bp), pLd9 (15,313 bp), pLd10 (39,563 bp), pLd11 (9833 bp) and pLd12 (3321 bp). Structural analysis of the repB promoters and the RepB proteins showed that eleven of the plasmids replicate via the theta-type mechanism, while only plasmid pLd3 replicates via a rolling-circle replication mechanism. Plasmids pLd2, pLd7 and pLd10 contain a highly similar operon involved in mobilisation of the plasmids. Examination of the twelve plasmids of L. lactis FM03P showed that 10 of the plasmids carry putative genes known to be important for growth and survival in the dairy environment. These genes encode technological functions such as lactose utilisation (lacR-lacABCDFEGX), citrate uptake (citQRP), peptide degradation (pepO and pepE) and oligopeptide uptake (oppDFBCA), uptake of magnesium and manganese (2 mntH, corA), exopolysaccharides production (eps operon), bacteriophage resistance (1 hsdM, 1 hsdR and 7 different hsdS genes of a type I restriction-modification system, an operon of three genes encoding a putative type II restriction-modification system and an abortive infection gene) and stress resistance (2 uspA, cspC and cadCA). Acquisition of these plasmids most likely facilitated the adaptation of the recipient strain to the dairy environment. Some plasmids were already lost during a single propagation step signifying their instability in the absence of a selective pressure. Lactococcus lactis FM03P carries 12 plasmids important for its adaptation to the dairy environment. Some of the plasmids were easily lost demonstrating that propagation outside the dairy environment should be minimised when studying dairy isolates of L. lactis.


Complications after gamma knife radiosurgery for benign meningiomas.
To analyse the results of gamma knife radiosurgery (GKS) for the treatment of intracranial meningiomas and to assess possible factors related to the outcome and complications of such treatment. The authors retrospectively reviewed the clinical and radiological data of 179 patients (194 lesions) treated with GKS for meningiomas between May 1992 and October 2000. The mean follow up duration was 37.3 months (range 6.4 to 86.3 months). The study determined the correlation between radiosurgical outcome including imaging changes after GKS and multiple factors such as tumour location and size, patient characteristics, venous sinus status, pre-GKS degree of oedema, other treatment modalities, and radiosurgical parameters. The radiological control rate was 97.1%. Magnetic resonance imaging (MRI) showed complications after GKS in 35 lesions (25.0%) among the 140 lesions followed up with MRI. Complications were divided into peritumorous imaging changes (33 lesions; 23.6%) and transient cranial nerve dysfunction (two lesions; 1.4%). Radiation induced imaging changes were seen mostly in convexity, parasagittal, and falx meningiomas that were deeply embedded in the cortex. About 60% of these were asymptomatic and the overall rate of symptomatic imaging changes was 9.3%. Neurological deficit related to imaging changes developed in only three patients, and all the symptoms were transient. GKS for intracranial meningiomas seems to be a safe and effective treatment. However, meningiomas of the convexity, parasagittal region, or falx cerebri have a higher incidence of peritumorous imaging changes after GKS than those of the skull base. Therefore, the use of GKS needs to be considered very cautiously in cerebral hemispheric meningiomas, taking into consideration patient age and general condition, tumour size and location, pattern of cortical embedding, relation between the tumour and venous sinuses, presenting symptoms, and patient preference.


Characterization of human spermatogonial stem cell markers in fetal, pediatric, and adult testicular tissues.
Autologous spermatogonial stem cell (SSC) transplantation is a potential therapeutic modality for patients with azoospermia following cancer treatment. For this promise to be realized, definitive membrane markers of prepubertal and adult human SSCs must be characterized in order to permit SSC isolation and subsequent expansion. This study further characterizes the markers of male gonocytes, prespermatogonia, and SSCs in humans. Human fetal, prepubertal, and adult testicular tissues were analyzed by confocal microscopy, fluorescence-activated cell sorting, and qRT-PCR for the expression of unique germ cell membrane markers. During male fetal development, THY1 and KIT (C-Kit) are transient markers of gonocytes but not in prespermatogonia and post-natal SSCs. Although KIT expression is detected in gonocytes, THY1 expression is also detected in the somatic component of the fetal testes in addition to gonocytes. In the third trimester of gestation, THY1 expression shifts exclusively to the somatic cells of the testes where it continues to be detected only in the somatic cells postnatally. In contrast, SSEA4 expression was only detected in the gonocytes, prespermatogonia, SSCs, and Sertoli cells of the fetal and prepubertal testes. After puberty, SSEA4 expression can only be detected in primitive spermatogonia. Thus, although THY1 and KIT are transient markers of gonocytes, SSEA4 is the only common membrane marker of gonocytes, prespermatogonia, and SSCs from fetal through adult human development. This finding is essential for the isolation of prepubertal and adult SSCs, which may someday permit fertility preservation and reversal of azoospermia following cancer treatment.