[Can ischaemic stroke be prevented with statins?].
Statins provide a reduction in the risk for ischaemic stroke in patients with coronary artery disease, known atherosclerotic disease, and in patients with risk factors for arterial vascular disease. There is also considerable interest in whether or not statins should be used as a secondary prophylaxis for stroke. This review is based on articles included on Medline that consider the association between cholesterol and cerebrovascular disease and the use of statins in ischaemic stroke. Cholesterol is a much weaker risk factor for ischaemic stroke than for coronary heart disease. It is especially associated with thromboembolic stroke due to atherosclerosis of the larger vessels. Meta-analysis of earlier studies in patients with coronary artery disease and several more recent studies which include patients with other atherosclerotic disease and risk factors for atherosclerosis have clearly shown a relative risk reduction for ischaemic stroke of between 20 and 30%. Since these studies were of patients in age groups in which stroke rarely occurs, the relative risk reduction was moderate. Risk reduction seems similar in all age groups with atherosclerotic heart disease and for all cholesterol levels. A reduced risk for a new stroke has to date not been shown for patients with previous stroke. Given the fact that stroke is caused by several mechanisms and is often not caused by atherosclerosis of larger vessels, definite advice cannot be given on secondary prevention with statins in all stroke patients. At present there are no results from studies where only ischaemic stroke patients were included and with a sufficient number of older patients.


Risk factors of sagittal decompensation after long posterior instrumentation and fusion for degenerative lumbar scoliosis.
A retrospective study of clinical results of operative treatment for degenerative lumbar scoliosis. To determine the risk factors of sagittal decompensation after long instrumentation and fusion to L5 or S1. Little is known about the risk factors for sagittal decompensation, which was defined in this study as sagittal C7 plumb falling anterior >8 cm from the posterosuperior corner of the sacrum. Forty-five patients (mean age: 64.4 year) with adult degenerative lumbar scoliosis were reviewed retrospectively with a minimum 2 years. The mean number of levels fused was 6.1 +/- 1.6 segments. The upper instrumented vertebra ranged from T9 to L2. The lower instrumented vertebra was L5 and S1 in 24 and 21 patients, respectively. Sagittal decompensation (SD) developed in 19 patients. The most significant risk factors of SD were preoperative sagittal imbalance and high pelvic incidence. The preoperative sagittal C7 plumb was more positive (67.9 mm) in the decompensation group than in the balance group (37.0 mm) (P = 0.002). There was a significant difference in pelvic incidence between 61.7 degrees in the decompensation and 54.9 degrees in the balance group (P = 0.01). The preoperative lumbar lordosis was hypolordotic in the decompensation group, however, it was not found to be a risk factor. Pseudarthrosis was identified at the lumbosacral junction in 5 patients, and 4 of them (80%) had SD. SD developed in 55% of patients who had loosening of the distal screws and 50% of patients with hypolordotic lumbar fusion. Distal adjacent segment disease was more likely to cause SD than proximal adjacent segment disease. Sagittal decompensation is common after long posterior instrumentation and fusion for degenerative lumbar scoliosis. It is mostly associated with complications at the distal segments, including pseudarthrosis and implant failure at the lumbosacral junction. Restoration of optimal lumbar lordosis and secure lumbosacral fixation is necessary especially in patients with preoperative sagittal imbalance and high pelvic incidence in order to prevent sagittal decompensation after surgery.


Changing incidence of primary total hip arthroplasty and total knee arthroplasty for primary osteoarthritis.
This study reports on the incidence of primary total hip arthroplasty (THA) and total knee arthroplasty (TKA) for primary osteoarthritis in Australia. Age-specific and gender-specific numbers for Australia, 1994 through 1998, and South Australia, 1988 through 1998, were obtained. Incidences were calculated per 100,000 population. In Australia, primary THA increased from 50.9/10(5) (1994) to 60.9/10(5) (1998). TKA increased from 56.4/10(5) to 76.8/10(5). Stratified by age and gender, changes in incidence for South Australia with respect to time were tested using regression analysis. South Australia showed a significant increase in the overall incidence of THA (P=.012) and TKA (P<.001), although this was not uniform across all age groups. No significant gender differences were found. The incidence of THA is increasing, and the incidence of TKA is increasing at a greater rate.


The complementarity-determining region sequences in IgY antivenom hypervariable regions.
The data presented in this article are related to the research article entitled "Development of IgY antibodies against anti-snake toxins endowed with highly lethal neutralizing activity" (da Rocha et al., 2017) [1]. Complementarity-determining region (CDR) sequences are variable antibody (Ab) sequences that respond with specificity, duration and strength to identify and bind to antigen (Ag) epitopes. B lymphocytes isolated from hens immunized with Bitis arietans (Ba) and anti-Crotalus durissus terrificus (Cdt) venoms and expressing high specificity, affinity and toxicity neutralizing antibody titers were used as DNA sources. The VLF1, CDR1, CDR2, VLR1 and CDR3 sequences were validated by BLASTp, and values corresponding to IgY VL and VH anti-Ba or anti-Cdt venoms were identified, registered [Gallus gallus IgY Fv Light chain (GU815099)/Gallus gallus IgY Fv Heavy chain (GU815098)] and used for molecular modeling of IgY scFv anti-Ba. The resulting CDR1, CDR2 and CDR3 sequences were combined to construct the three - dimensional structure of the Ab paratope.


Chromatin integration labeling for mapping DNA-binding proteins and modifications with low input.
Cell identity is determined by the selective activation or silencing of specific genes via transcription factor binding and epigenetic modifications on the genome. Chromatin immunoprecipitation (ChIP) has been the standard technique for mapping the sites of transcription factor binding and histone modification. Recently, alternative methods to ChIP have been developed for addressing the increasing demands for low-input epigenomic profiling. Chromatin integration labeling (ChIL) followed by sequencing (ChIL-seq) has been demonstrated to be particularly useful for epigenomic profiling of low-input samples or even single cells because the technique amplifies the target genomic sequence before cell lysis. After labeling the target protein or modification in situ with an oligonucleotide-conjugated antibody (ChIL probe), the nearby genome sequence is amplified by Tn5 transposase-mediated transposition followed by T7 RNA polymerase-mediated transcription. ChIL-seq enables the detection of the antibody target localization under a fluorescence microscope and at the genomic level. Here we describe the detailed protocol of ChIL-seq with assessment methods for the key steps, including ChIL probe reaction, transposition, in situ transcription and sequencing library preparation. The protocol usually takes 3 d to prepare the sequencing library, including overnight incubations for the ChIL probe reaction and in situ transcription. The ChIL probe can be separately prepared and stored for several months, and its preparation and evaluation protocols are also documented in detail. An optional analysis for multiple targets (multitarget ChIL-seq) is also described. We anticipate that the protocol presented here will make the ChIL technique more widely accessible for analyzing precious samples and facilitate further applications.


Odor-related bulbar EEG spatial pattern analysis during appetitive conditioning in rabbits.
Mildly thirsty rabbits were classically conditioned by reinforcement with water to give a discriminative licking response to the presentation of odors. The jaw movement component of the licking conditioned response (JM CR) was elicited only by the reinforced odor; an increase in the relative frequency of sniffing (RR CR) occurred to both reinforced (CS+) and nonreinforced (CS-) odors. Oscillatory electroencephalographic bursts of high-frequency (40-80 Hz) potentials were recorded epidurally from the lateral olfactory bulb with 64-electrode arrays (8 X 8, 3.5 X 3.5 mm) chronically implanted. Emphasis was on comparing bursts during odor presentation with bursts preceding odor arrival on each trial. A "detection" burst was characterized as occurring immediately after odor arrival and before the sniff response. "Discrimination" bursts occurred during the RR CR and before the JM CR onset. Significant air-odor burst differences (together with sniffing) occurred through up to six sessions for both CS+ and CS- odors for "discrimination" bursts but not for "detection" bursts.


AFM probing of polymer/nanofiller interfacial adhesion and its correlation with bulk mechanical properties in a poly(ethylene terephthalate) nanocomposite.
The interfacial adhesion between polymer and nanofiller plays an important role in affecting the properties of nanocomposites. The detailed relationship between interfacial adhesion and bulk properties, however, is unclear. In this work, we developed an atomic force microscopy (AFM)-based abrasive scanning methodology, as applied to model laminate systems, to probe the strength of interfacial adhesion relevant to poly(ethylene terephthalate) (PET)/graphene or clay nanocomposites. Graphite and mica substrates covered with ∼2 nm thick PET films were abrasively sheared by an AFM tip as a model measurement of interfacial strength between matrix PET and dispersed graphene and clay, respectively. During several abrasive raster-scan cycles, PET was shear-displaced from the scanned region. At temperatures below the PET glass transition, PET on graphite exhibited abrupt delamination (i.e., full adhesive failure), whereas PET on mica did not; rather, it exhibited a degree of cohesive failure within the shear-displaced layer. Moreover, 100-fold higher force scanning procedures were required to abrade through an ultimate "precursor" layer of PET only ∼0.2-0.5 nm thick, which must be largely disentangled from the matrix polymer. Thus, the adhesive interface of relevance to the strength of clay-filler nanocomposites is between matrix polymer and strongly bound polymer. At 90 °C, above the bulk PET glass transition temperature, the PET film exhibited cohesive failure on both graphite and mica. Our results suggest that there is little difference in the strength of the relevant interfacial adhesion in the two nanocomposites within the rubbery dynamic regime. Further, the bulk mechanical properties of melt mixed PET/graphene and PET/clay nanocomposites were evaluated by dynamic mechanical analysis. The glassy dynamic storage modulus of the PET/clay nanocomposite was higher than that of PET/graphene, correlating with the differences in interfacial adhesion probed by AFM.


Selective management of arterial occlusion with low-dose streptokinase.
Fibrinolytic therapy has been reported as a limited aid in limb salvage. It is allegedly fraught with complications and pitfalls; however, the usage of low-dose streptokinase has never totally been explored. The purpose of this study was to examine the role of low-dose streptokinase in arterial occlusion. Nineteen patients (12 men and 7 women) with an average age of 68 years (range 37 to 79 years) and a total of 22 limbs under study were treated with low-dose streptokinase (initial intravenous dose of 10,000 units and a subsequent dose of 5,000 to 10,000 units/hour) for 1 to 3 days. Seven of the patients underwent further operative intervention and four underwent angioplasty. Seven patients had diabetes controlled by insulin. Results were assessed clinically by angiography and by noninvasive measurement of distal pressure. Within 30 days of low-dose streptokinase therapy, four patients died from a myocardial infarction that was thought to be part of their total disease process. Limited salvage occurred in 19 of 22 limbs at risk. Ten patients (12 extremities) underwent subsequent balloon angioplasty or bypass surgery. There were three amputations. One patient received a below-knee amputation rather than an expected above-knee amputation, one had a below-knee amputation, and one had an above-knee amputation. In all cases, the patency or lack thereof was confirmed by angiography. The mean ankle to brachial pressure indices increased from 0.07 +/- 0.15 to 0.64 +/- 0.14 after therapy. There were no prolonged hospital stays due to complications in any of the patients. Selective infusions of low-dose streptokinase lyse thrombi, open collaterals, and provide an opportunity for extended surgery and angioplasty, increasing limb salvage without the risks of coagulopathy and bleeding that may occur in full-dose thrombolysis.


A prospective pilot trial of ablation of Barrett's esophagus with low-grade dysplasia using stepwise circumferential and focal ablation (HALO system).
Yearly surveillance endoscopy is carried out for Barrett's esophagus with low-grade dysplasia (LGD) so that progression to high-grade dysplasia and adenocarcinoma can be detected at the earliest stage. The aim of the study was to assess the long-term safety and effectiveness of circumferential ablation followed by focal ablation (HALO system) for eliminating Barrett's esophagus and LGD. Patients with 2 - 6 cm of Barrett's esophagus with histology demonstrating LGD on their last two sequential endoscopies over the previous 2 years and confirmed by two pathologists were enrolled in this prospective, single-center trial. Circumferential ablation was carried out at baseline and at 4 months (if residual Barrett's esophagus present). Endoscopy with 4-quadrant biopsies every 1 cm was performed at 1, 3, 6, 12, and 24 months. After 1 year, focal ablation was applied to any visible Barrett's esophagus or irregularity of the squamocolumnar junction. Patients received lansoprazole 30 mg bid. Complete responses for dysplasia (CR-dysplasia) and intestinal metaplasia (CR-IM) at 2-year follow-up, with complete response defined as "all biopsies negative for dysplasia or intestinal metaplasia" were the main outcomes. Ten patients (nine men, mean age 66.9 years, range 48 - 79) with confirmed LGD (median 4.4 cm, range 3 - 6) underwent circumferential ablation with focal ablation after 1 year as necessary. At 2 years, CR-dysplasia was 100 % and CR-IM was 90 %. There were no strictures or buried intestinal metaplasia at follow-up. A stepwise regimen of circumferential ablation followed by focal ablation appears to eradicate intestinal metaplasia (90 % CR-IM) and dysplasia (100 % CR-dysplasia) at 2-year follow-up in this trial, without stricture formation or buried intestinal metaplasia.


Studies on the psychosomatic functioning of ill-health according to eastern and Western medicine. 2. Anxiety-affinitive constitution associated with qi, blood, and body fluid--diagnostic and therapeutic methods.
The objective of this investigation was to identify characteristics of psychosomatic function in medical students (N = 62, mean age, 23.3, SD, 1.7 years) whose ill-health was related to unbalanced qi, blood, and body fluid, and to develop a diagnosis and treatment method for these conditions. Our study revealed complicated characteristics. At the psychological level, these characteristics are stress-related emotional disturbances, including anxiety, insomnia and anergy, and the lowering of social function. At the physiological level, these characteristics are associated with high complexity of fractal dimension of eye (horizontal) and respiratory (thoracic) movements correlated to STA1-trait anxiety. Thus, the three psychosomatic characteristics related to unbalanced qi, blood, and body fluid suggest the concept of an anxiety-affinitive constitution, also described as the equivalent of ill-health. This indicates that diagnosis and treatment of this type of constitution has the potential to be useful for both the prevention of stress-related and life-style disease, and the treatment of current disease.


Hair analysis in toxicology.
Morphological, serological and chemical examination of human hair for medical purposes was initiated some decades ago. In the 1960s and 1970s, hair analysis was used to evaluate exposure to toxic heavy metals. At this time, examination of hair for organic substances, especially drugs, was not possible because analytical methods were not sensitive enough. Since the early 1980s, the development of highly sensitive and specific assay methods such as radioimmunoassay or gas chromatography/mass spectrometry has permitted the analysis of organic substances trapped in hair. This, theoretically, offered the possibility of revealing an individual's recent history of drug exposure beginning at sampling day and dating back over a period of weeks or months. The present review aims to summarise the various applications that have been published.


Mastectomy and immediate breast reconstruction in the elderly: Trends and outcomes.
Immediate breast reconstruction after mastectomy may confer more complication rates in the elderly. Therefore, granular analysis of postmastectomy complications in women aged ≥65 years may help formulate clinical guidelines to improve patient selection and outcomes. We identified patients undergoing mastectomy with or without immediate reconstruction from our breast surgery database (2014-2018). Complications requiring treatment were compared between patients aged ≥65 and <65 years. A total of 1,721 mastectomies were performed in 1,698 patients; 85.8% had a 30-day follow-up. Of these patients, 968 (65.6%) had immediate breast reconstruction, of whom 95 (9.8%) were aged ≥65 years. Among patients aged ≥65 years, 27.6% underwent mastectomy with immediate breast reconstruction compared with 77.1% of women aged <65 years (P < .001). Overall complication rates were not greater for older compared with younger mastectomy patients but were for older versus younger patients who had mastectomy with immediate breast reconstruction (12.6% vs 6.8%; P = .04). Hematoma requiring reoperation was more frequent in patients aged ≥65 years (5.3% vs 0.9%; P = .006). Necrosis (5.3% vs 2.6%; P = .18) and 30-day unplanned readmissions (7.4% vs 4.0%; P = .18) were not greater. Despite low overall postoperative complication rates, we found some clinically relevant differences between older and younger patients after mastectomy with immediate breast reconstruction. Additional investigation of contributing factors may help further refine patient selection. In the interim, elderly patients should be counseled on their somewhat greater risk of postoperative complications to facilitate shared decision making.


Quad bike related trauma in Ireland.
A quad bike or an all-terrain vehicle is a four-wheeled powered vehicle generally designed for off-road use. They are widely used for farm-related work and more recently for recreational purposes. The potential for serious injury and death with quad bike use is a growing public health concern. There is an inherent instability in their design and they are typically used on rugged terrain characterised by dangerous driving surfaces. This study examines quad bike related trauma in Ireland using a national trauma registry to identify patient demographics, injury mechanism and type, treatments received and outcomes. All quad bike related trauma cases recorded on the Major Trauma Audit (MTA), National Office of Clinical Audit in Ireland for the period 2014-2019 were gathered and analysed. There were 69 cases identified and 63 (91 %) of these were male. The median (IQR) age was 27 (19 - 49.1). There were 25 % (n = 17) aged 0-18 years, 64 % (n = 44) aged 19-65 and 12 % (n = 8) aged greater than 65 years. The median injury severity score (ISS) was 10 (IQR 9-22). The most severely injured body region was the head (n = 21, 30 %). No helmet use was recorded in 50 % (n = 34) of cases. October recorded the highest number of cases (n = 9, 13 %), and Sunday was the most common day (n = 17, 25 %). The median length of hospital stay was five days (IQR 3-9). One patient died after arrival to hospital. Quad bike related trauma predominantly affects a young male cohort with serious injury characteristics. A sizeable proportion of patients are under 18 years of age. This data can better inform national policies and public awareness campaigns targeting this trauma subset. The head was the most common severely injured body region, highlighting the potential need for legislative intervention regarding mandatory helmet use. A large cohort of patients required transfer for definitive care which has implications for trauma care pathways and advocates for the development of an integrated trauma system in Ireland.


Dengue Patients Treated with Doxycycline Showed Lower Mortality Associated to a Reduction in IL-6 and TNF Levels.
To determine the effect of doxycycline treatment on cytokine levels, including tumor necrosis factor (TNF) and interleukin 6 (IL-6), and mortality in dengue patients at high risk of complication. A group of dengue hemorrhagic fever patients (n=231) were randomized to receive either standard supportive care or supportive care in addition to oral doxycycline twice daily for 7 days. Dengue virus infection was confirmed by PCR using multiple primers. Serum samples were obtained at days 0, 3, 5 and 7 and tested for levels of TNF and IL-6. Doxycycline-treated group presented a 46% lower mortality than that observed in the untreated group (11.2% [13/116] vs 20.9% [24/115], respectively, p=0.05). Moreover, administration of doxycycline resulted in a significant (p<0.01) decrease in levels of TNF and IL-6 versus controls in the tests performed during follow-up (day 3, 5 and 7). Patients who died in both groups possessed significantly (p<0.01) higher levels of TNF and IL-6 compared to those who survived at all-time points. The above findings suggest that doxycycline can provide a clinical benefit to dengue patients at high risk of complications. This effect could be mediated by decreasing pro-inflammatory cytokine levels.


Expanded ensemble predictions of absolute binding free energies in the SAMPL9 host-guest challenge.
As part of the SAMPL9 community-wide blind host-guest challenge, we implemented an expanded ensemble workflow to predict absolute binding free energies for 13 small molecules against pillar[6]arene. Notable features of our protocol include consideration of a variety of protonation and enantiomeric states for both host and guests, optimization of alchemical intermediates, and analysis of free energy estimates and their uncertainty using large numbers of simulation replicates performed using distributed computing. Our predictions of absolute binding free energies resulted in a mean absolute error of 2.29 kcal mol-1 and an R2 of 0.54. Overall, results show that expanded ensemble calculations using all-atom molecular dynamics simulations are a valuable and efficient computational tool in predicting absolute binding free energies.


Genes determining pathogenicity to pea are clustered on a supernumerary chromosome in the fungal plant pathogen Nectria haematococca.
Three genes that contribute to the ability of the fungus Nectria haematococca to cause disease on pea plants have been identified. These pea pathogenicity (PEP) genes are within 25 kb of each other and are located on a supernumerary chromosome. Altogether, the PEP gene cluster contains six transcriptional units that are expressed during infection of pea tissue. The biochemical function of only one of the genes is known with certainty. This gene, PDA1, encodes a specific cytochrome P450 that confers resistance to pisatin, an antibiotic produced by pea plants. The three new PEP genes, in addition to PDA1, can independently increase the ability of the fungus to cause lesions on pea when added to an isolate lacking the supernumerary chromosome. Based on predicted amino acid sequences, functions for two of these three genes are hypothesized. The deduced amino acid sequence of another transcribed portion of the PEP cluster, as well as four other open reading frames in the cluster, have a high degree of similarity to known fungal transposases. Several of the features of the PEP cluster -- a cluster of pathogenicity genes, the presence of transposable elements, and differences in codon usage and GC content from other portions of the genome -- are shared by pathogenicity islands in pathogenic bacteria of plants and animals.


Asymptomatic carotid bruit.
Cerebrovascular events are responsible for high morbidity and mortality, and carotid atherosclerosis with vascular stenosis is a major etiological factor in cerebrovascular disease. Carotid bruit is an important marker of generalized atherosclerosis. On the basis of good quality studies, we can conclude that it indicates an increased risk of cerebrovascular events and acute myocardial infarction, with the degree of carotid stenosis and presence of ischemic heart disease as the most important predictive factors. Management can be medical (risk factor modification and antiplatelet therapy) or surgical (endarterectomy). In this review article we briefly discuss the management of asymptomatic carotid bruit based on the main studies published in the last few years addressing cardiovascular event prevention in carotid atherosclerosis.


The effect of testosterone and season on prodynorphin messenger RNA expression in the preoptic area-hypothalamus of the ram.
Testosterone and season influence mRNA expression for the opioid, enkephalin, in the preoptic area and hypothalamus of rams. Dynorphin is another opioid which has been shown to play a role in the control of reproductive function in females. We now report effects of season and testosterone on the expression of prodynorphin mRNA in the hypothalamus of the ram. Castrated adult Romney Marsh rams (5/group) received vehicle or testosterone propionate (i.m.) during either the 'breeding' season or 'non-breeding' season. Prodynorphin mRNA expression was quantified in the hypothalami by in situ hybridisation. Testosterone treatment increased prodynorphin mRNA expression in the supraoptic nucleus and the bed nucleus of the stria terminalis in the breeding season but not during the non-breeding season. Prodynorphin mRNA expression was also higher in the breeding season than in the non-breeding season in the caudal preoptic area, paraventricular nucleus and accessory supraoptic nucleus, irrespective of treatment. No effects of treatment were observed in any other regions of the hypothalamus. We conclude that testosterone and season regulate prodynorphin mRNA expression in a region-specific manner, which may influence seasonal changes in reproductive function.


Treatment of blood with a pathogen reduction technology using ultraviolet light and riboflavin inactivates Ebola virus in vitro.
Transfusion of plasma from recovered patients after Ebolavirus (EBOV) infection, typically called "convalescent plasma," is an effective treatment for active disease available in endemic areas, but carries the risk of introducing other pathogens, including other strains of EBOV. A pathogen reduction technology using ultraviolet light and riboflavin (UV+RB) is effective against multiple enveloped, negative-sense, single-stranded RNA viruses that are similar in structure to EBOV. We hypothesized that UV+RB is effective against EBOV in blood products without activating complement or reducing protective immunoglobulin titers that are important for the treatment of Ebola virus disease (EVD). Four in vitro experiments were conducted to evaluate effects of UV+RB on green fluorescent protein EBOV (EBOV-GFP), wild-type EBOV in serum, and whole blood, respectively, and on immunoglobulins and complement in plasma. Initial titers for Experiments 1 to 3 were 4.21 log GFP units/mL, 4.96 log infectious units/mL, and 4.23 log plaque-forming units/mL. Conditions tested in the first three experiments included the following: 1-EBOV-GFP plus UV+RB; 2-EBOV-GFP plus RB only; 3-EBOV-GFP plus UV only; 4-EBOV-GFP without RB or UV; 5-virus-free control plus UV only; and 6-virus-free control without RB or UV. UV+RB reduced EBOV titers to nondetectable levels in both nonhuman primate serum (≥2.8- to 3.2-log reduction) and human whole blood (≥3.0-log reduction) without decreasing protective antibody titers in human plasma. Our in vitro results demonstrate that the UV+RB treatment efficiently reduces EBOV titers to below limits of detection in both serum and whole blood. In vivo testing to determine whether UV+RB can improve convalescent blood product safety is indicated.


Validation of the Implementation Climate Scale (ICS) in substance use disorder treatment organizations.
One critical factor in the implementation of evidence-based practice (EBP) in substance use disorder treatment organizations is an inner organizational context that clearly supports implementation efforts. The Implementation Climate Scale (ICS) has been developed to allow researchers and organizations to assess climate for EBP implementation in health and allied health service organizations. The ICS consists of 18 items and measures six dimensions of implementation climate: focus on EBP, educational support for EBP, recognition for EBP, rewards for EBP, selection for EBP, and selection for openness. The ICS was initially developed in a mental health context; thus, the goal of this study was to provide initial validation of the ICS in substance use disorder (SUD) treatment settings. Confirmatory factor analysis (CFA) was used to assess the psychometric functioning of the ICS using survey data from 326 providers in 65 teams in SUD treatment programs. Cronbach's alpha was examined to assess internal consistency of the ICS, and individual and team level construct-based validity was examined by comparing its correlations with service climate, molar climate, and organizational change. We found evidence for the reliability, factor structure, and validity of the ICS in SUD services. The psychometric functioning of the ICS in SUD treatment settings was comparable to that found in mental health contexts. The ICS is a brief and pragmatic tool for researchers to better understand a critical antecedent for implementation effectiveness in SUD treatment and for organizational leaders in SUD treatment organizations to evaluate the extent to which providers perceive that their organization supports EBP implementation.


[Japanese anger expression styles and their interpersonal influence].
The purpose of the present study was to investigate Japanese anger expression styles and their influence on interpersonal relationships. In the initial study, 239 undergraduates were asked to complete a questionnaire which assessed seven distinct anger expression styles. The results indicated that the participants most often employed three anger expression styles including hyojo-kucho (nonverbal), tohmawashi (implicit), and itsumodori (none). In the second study, 162 undergraduates were asked to watch these three anger expression styles portrayed on videotape. Participants rated the degree to which the actor in the videotape felt angry and their impressions toward male or female actors in either higher, lower, or equal status, same-sex situations. The findings indicated that the effect on interpersonal relationships varied across the three different expression styles. This study has important implications for understanding Japanese anger expression in interpersonal, and perhaps cross-cultural, relationships.


A Cluster of Paediatric Invasive Group A Streptococcal and Chicken Pox Infections.
An increase in invasive group A streptococcus (GAS) cases referred to the paediatric infectious disease (PID) department of the Children's University Hospital (CUH), Temple Street, prompted review of all invasive GAS cases in 2016. All of the 10 cases identified occurred over a 16-week period from February to June, of which 6 (60%) required admission to the paediatric intensive care unit. The median length of stay was 21.5 days. Seven had active chickenpox infection at diagnosis. This study highlights the significant morbidity of invasive GAS in children in Ireland. Most cases were associated with a vaccine preventable illness, which should prompt reappraisal of the absence of varicella vaccine from the national immunisation schedule in Ireland.


[Role adaptation process of elementary school health teachers: establishing their own positions].
The purpose of this study was to explore and identify patterns from the phenomenon of the role adaptation process in elementary school health teachers and finally, suggest a model to describe the process. Grounded theory methodology and focus group interviews were used. Data were collected from 24 participants of four focus groups. The questions used were about their experience of role adaptation including situational contexts and interactional coping strategies. Transcribed data and field notes were analyzed with continuous comparative analysis. The core category was 'establishing their own positions', an interactional coping strategy. The phenomenon identified by participants was confusion and wandering in their role performance. Influencing contexts were unclear beliefs for their role as health teachers and non-supportive job environments. The result of the adaptation process was consolidation of their positions. Pride as health teachers and social recognition and supports intervened to produce that result. The process had three stages; entry, growth, and maturity. The role adaptation process of elementary school health teachers can be explained as establishing, strengthening and consolidating their own positions. Results of this study can be used as fundamental information for developing programs to support the role adaptation of health teachers.


Diagnostic approach to patients with tinnitus.
Tinnitus, a common symptom encountered in family medicine, is defined as the perception of noise in the absence of an acoustic stimulus outside of the body. Because tinnitus is a symptom and not a disease, its underlying cause must be determined to best help patients. Although tinnitus is often idiopathic, sensorineural hearing loss is the most common identified cause. It can also be caused by other otologic, vascular, neoplastic, neurologic, pharmacologic, dental, and psychological factors. More serious causes, such as Meniere disease or vestibular schwannoma, can be excluded during the evaluation. History and physical examination of the head, eyes, ears, nose, throat, neck, and neurologic system guide subsequent evaluation. Almost all patients with tinnitus should undergo audiometry with tympanometry, and some patients require neuroimaging or assessment of vestibular function with electronystagmography. Supportive counseling should begin during the initial evaluation to help patients cope with tinnitus. Counseling may also improve the chances of successful subsequent treatment.


[Suicide by electrocution--2 case reports].
Suicides by electrocution are extremely rare in our country. In these cases, specific or characteristic external lesions caused through contact with conductors at the sites of entry and exit of the current, as well as general autopsy findings, and excluding the other possible causes of death, are important to elucidate them. Dilemma if death was suicidal, homicidal or accidental in manner, could be solved through good police investigation, and properly explained circumstantial events. Herein, we reported two cases of suicidal deaths, caused by electrocution. In the first case, it was a male, age of 32, who wrapped the electrical cord around his wrists, and killed himself by plugging it in. In second case, it was a female, age of 46, abused by her husband, who committed suicide by putting the switched hear-dryer into the water in bathtub.


Arteriovenous anastomoses in the skin of the Weddell Seal, Leptonychotes weddelli.
Arteriovenous anastomoses of epithelioid type were demonstrated in Weddell seal skin. The majority occurred just beneath the epidermis and among the hair follicles. There was no significant variation in density of these anastomoses between body and flipper skin. These observations suggest that arteriovenous anastomoses are important in thermoregulation in the Weddell seal, particularly as heat dissipating structures when the animal is out of the water, and that the entire body surface is involved rather than specific regions such as the flippers.


Intracellular Accumulation of Staphylopine Can Sensitize Staphylococcus aureus to Host-Imposed Zinc Starvation by Chelation-Independent Toxicity.
The host restricts the availability of zinc to prevent infection. To overcome this defense, Staphylococcus aureus and Pseudomonas aeruginosa rely on zincophore-dependent zinc importers. Synthesis of the zincophore staphylopine by S. aureus and its import are both necessary for the bacterium to cause infection. In this study, we sought to elucidate how loss of zincophore efflux impacts bacterial resistance to host-imposed zinc starvation. In culture and during infection, mutants lacking CntE, the staphylopine efflux pump, were more sensitive to zinc starvation imposed by the metal-binding immune effector calprotectin than those lacking the ability to import staphylopine. However, disruption of staphylopine synthesis reversed the enhanced sensitivity phenotype of the ΔcntE mutant to calprotectin, indicating that intracellular toxicity of staphylopine is more detrimental than the impaired ability to acquire zinc. Unexpectedly, intracellular accumulation of staphylopine does not increase the expression of metal importers or alter cellular metal concentrations, suggesting that, contrary to prevailing models, the toxicity associated with staphylopine is not strictly due to intracellular chelation of metals. As P. aeruginosa and other pathogens produce zincophores with similar chemistry, our observations on the crucial importance of zincophore efflux are likely to be broadly relevant.IMPORTANCEStaphylococcus aureus and many other bacterial pathogens rely on metal-binding small molecules to obtain the essential metal zinc during infection. In this study, we reveal that export of these small molecules is critical for overcoming host-imposed metal starvation during infection and prevents toxicity due to accumulation of the metal-binding molecule within the cell. Surprisingly, we found that intracellular toxicity of the molecule is not due to chelation of cellular metals.


Inhibition of return in the visual field: the eccentricity effect is independent of cortical magnification.
Inhibition of return (IOR) as an indicator of attentional control is characterized by an eccentricity effect, that is, the more peripheral visual field shows a stronger IOR magnitude relative to the perifoveal visual field. However, it could be argued that this eccentricity effect may not be an attention effect, but due to cortical magnification. To test this possibility, we examined this eccentricity effect in two conditions: the same-size condition in which identical stimuli were used at different eccentricities, and the size-scaling condition in which stimuli were scaled according to the cortical magnification factor (M-scaling), thus stimuli being larger at the more peripheral locations. The results showed that the magnitude of IOR was significantly stronger in the peripheral relative to the perifoveal visual field, and this eccentricity effect was independent of the manipulation of stimulus size (same-size or size-scaling). These results suggest a robust eccentricity effect of IOR which cannot be eliminated by M-scaling. Underlying neural mechanisms of the eccentricity effect of IOR are discussed with respect to both cortical and subcortical structures mediating attentional control in the perifoveal and peripheral visual field.


The diffusion coefficient of caffeine through agar gels containing a hyaluronic acid-protein complex. A model system for the study of the permeability of connective tissues.
A hyaluronic acid-protein complex was embedded into agar gel. This gel complex resembles in some respects the physiological situation in connective tissue, but still permits precise physicochemical measurements to be made. The diffusion coefficient of caffeine into and from such gels has been measured as a function of both agar and hyaluronate concentration. The value for the diffusion coefficient of caffeine was also measured by using a Gouy type diffusiometer. From both types of measurement the value for D (Fick) for caffeine when extrapolated to zero caffeine and agar concentrations agreed at (6.79+/-0.01)x10(-6)cm(2).s(-1) at 25 degrees C. Although agar concentration had only a small effect on caffeine diffusion, hyaluronic acid caused a large decrease in caffeine diffusion co-efficient. The presence of the hyaluronic acid-protein complex within the gel tended to oppose gel syneresis, a concentration of 1.7mg/ml abolishing the effect and higher concentrations reversing it. The possible physiological implications of these results are discussed.


[Application of autocartilage for treatment of tracheostenosis with chondromalacia].
Reconstruction of the stenotic part of the trachea with chondromalacia was made with semicircular autocartilage. The operation included two stages: creation of a semiring of rib autocartilage in abdominal tissues (stage I), implantation of the semiring to tracheal walls (stage II). Reception of the autocartilage was confirmed morphologically. According to 5 year follow-up, a stable positive result was obtained in 14 of 18 patients.


Atmospheric effects on voice command intelligibility from acoustic hail and warning devices.
Voice command sound pressure levels (SPLs) were recorded at distances up to 1500 m. Received SPLs were related to the meteorological condition during sound propagation and compared with the outdoor sound propagation standard ISO 9613-2. Intelligibility of received signals was calculated using ANSI S3.5. Intelligibility results for the present voice command indicate that meteorological condition imposes little to no effect on intelligibility when the signal-to-noise ratio (SNR) is low (<-9 dB) or high (>0 dB). In these two cases the signal is firmly unintelligible or intelligible, respectively. However, at moderate SNRs, variations in received SPL can cause a fully intelligible voice command to become unintelligible, depending on the meteorological condition along the sound propagation path. These changes in voice command intelligibility often occur on time scales as short as minutes during upward refracting conditions, typically found above ground during the day or upwind of a sound source. Reliably predicting the intelligibility of a voice command in a moderate SNR environment can be challenging due to the inherent variability imposed by sound propagation through the atmosphere.


Phosphoribosylamidotransferase: regulation of activity in virus-induced murine leukemia by purine nucleotides.
Infection with Friend leukemia virus causes a marked increase in the activity of splenic phosphoribosylamidotransferase in mice. Intraperitoneal injection of purine nucleotides and their free bases inhibits this enzyme. This is the first example of the control of phosphoribosylamidostransferase in vivo in the mammalian system as well as in virus-induced leukemia. Experiments in vitro support the findings in vivo.


The Earned Income Tax Credit and Intimate Partner Violence.
Intimate partner violence (IPV) is a serious public health problem in the United States with adverse consequences for affected individuals and families. Recent reviews of the literature suggest that economic policies should be further investigated as part of comprehensive strategies to address IPV. The Earned Income Tax Credit (EITC) is the nation's largest anti-poverty program for working parents, and especially benefits low-income women with children, who experience an elevated risk of IPV. The EITC may prevent IPV by offering financial resources; such resources may help individuals experiencing IPV leave abusive relationships or address IPV risk factors, thereby preventing entry into abusive relationships. However, the association between EITC generosity and IPV has not been previously examined. We used state-level and individual-level datasets to examine the association between EITC generosity and IPV. Our state-level data source was the nationally representative National Crime Victimization Survey (NCVS; N = ~ 95,000 households per year). For NCVS, we used a difference-in-difference approach to investigate the relationship between state EITC generosity and IPV rates. We also used individual-level longitudinal data from the Fragile Families and Child Well-being Study (n = 13,422 person-waves). Using this cohort of US families at higher risk for IPV, we evaluated associations between estimated EITC benefits based on the mother's state of residence and number of children and self-reported IPV. In both state- and individual-level analyses, no significant association between state EITC benefits and IPV was found. Factors that may account for these null findings include program ineligibility for individuals who separate from abusive spouses. Future research efforts should more closely examine EITC policy implementation processes and the lived experience of participating in anti-poverty programs for people experiencing IPV.


Polytopic multiplexing.
Polytopic multiplexing is a new method of overlapping holograms that, when combined with other multiplexing techniques, can increase the capacity of a volume holographic data storage system by more than a factor of 10. This is because the method makes possible the effective utilization of thick media. An experimental demonstration of this technique is also presented.


A Personal Health Record System for Diabetes Care Conforming to the ISO 16527 Interoperability Requirements.
A Personal Health Record (PHR) is a health information repository controlled and managed directly by a patient or his/her custodian, or a person interested in his/her own health. PHR System's adoption and compliance with international standards is foremost important because it can help to meet international, national, regional or institutional interoperability and portability policies. In this paper, an interoperable PHR System for supporting the control of type 2 diabetes mellitus is proposed, which meets the mandatory interoperability requirements proposed in the Personal Health Record System Functional Model standard (ISO 16527). After performing a detailed analysis of different applications and platforms for the implementation of electronic Personal Health Records, the adaptation of the Indivo Health open source platform was completed. Interoperability functions were added to this platform by integrating the Mirth Connect platform. The assessment of the platform's interoperability capabilities was carried out by a group of experts, who verified the interoperability requirements proposed in the ISO 16527 standard.


Protection of ovarian function by two distinct methods of ovarian shielding for young female patients who receive total body irradiation.
To prevent ovarian dysfunction due to total body irradiation, we started ovarian shielding at our center (Saitama Medical Center, Jichi Medical University (SMC-JMU)) with a long source axis distance, which is different from the original method used at the University of Tokyo Hospital (UTH). We retrospectively analyzed the outcome of eight patients with a median age of 20.5 years from SMC-JMU and compared the results with the published data for eight patients with a median age of 22 years from UTH. The recovery of ovarian function was observed in five and six patients, respectively. The cumulative incidence of ovarian recovery, while treating relapse and death without ovarian recovery as competing risks, was 68.8 % at 2 years after transplantation in the total population, and there was no statistically significant difference between the two institutions (p = 0.85). Age and the history of previous chemotherapy did not affect the incidence of ovarian recovery. Two patients from each center had a relapse of leukemia. Overall, among the 11 patients who have survived without relapse, only one has not achieved ovarian recovery. In conclusion, ovarian shielding with both methods strongly protected ovarian function. However, we should continue to monitor the relapse rate among patients who undergo this procedure.


Treatment Outcome and Follow-up of Tuberculosis Patients Put on Directly Observed Treatment Short-course Under Rural Health Training Center, Paithan, Aurangabad in India.
Revised National Tuberculosis Control Program (RNTCP) was found successful in achieving its objectives; still there is concern of relapse cases and defaulters. The aim of this study is to know the treatment outcome, to assess the reasons for relapse, default, death of patient and to assess the follow-up status of tuberculosis (TB) patients put on directly observed treatment short-course (DOTS). This cross-sectional survey was conducted in 140 TB patients put on DOTS during year 2005-2007 under Rural Health Training Center, Paithan. The personal interview was carried out by an investigator with pre-tested questionnaire during month of July-August 2008. Out of total 140, 125 TB cases could be traced: Category I 48% (60/125), Category II 16% (20/125) and Category III 36% (45/125). Cure rate among Category I was calculated to be 61.7% (37/60). Defaulters were observed to be 18.3% (11/60), 25% (5/20) and 20% (9/45) among Category I, Category II and Category III respectively. Death rate was higher (5%) among patients of Category II. During the follow-up visit, 82.4% (103/125) were found to be alive while 17.6% (22/125) dead. A total of 18 deaths were related with TB and its sequelae. Around 20% (5/25) defaulted because of feeling of well-being. During the follow-up visit, 5.8% (6/103) were again put on DOTS. Defaulters were high in present study. The majority of patients left the treatment due to feeling well. This can be tackled by effective counseling. Higher percentage of the patients showed improvement in their weight after completion of DOTS treatment. More emphasis was to be given toward existing TB patients to get successful results of RNTCP.


Association Between Chronic Tension-Type Headache Coexistent with Chronic Temporomandibular Disorder Pain and Limitations in Physical and Emotional Functioning: A Case-Control Study.
To assess the association between chronic tension-type headache coexistent with chronic temporomandibular disorder (TMD) pain and severe limitations in physical and emotional functioning. Sample size estimation was used to determine that this case-control study should include 126 subjects. Subjects suffering from chronic TMD who were aged between 18 and 68 were recruited in routine clinical practice. Of the 126 included subjects, 63 had TMD pain associated with chronic tension-type headache (cases) and 63 had TMD pain without a history of tension-type headache (controls). Clinical diagnosis of TMD was made according to the Research Diagnostic Criteria for TMD (RDC/TMD) Axis I criteria, and clinical diagnosis of headache was made according to the International Classification of Headache (ICHD-II). RDC/TMD Axis II criteria were applied to record the scores from the Graded Chronic Pain Scale (GCPS) and the Symptoms Checklist-90-Revised Depression (SCL-DEP) and Somatization (SCL-SOM) scales. A logistic regression analysis was used to assess the relationship between TMD pain with chronic tension-type headache and high levels of depression and somatization severity as scored on the SCLDEP and SCL-SOM scales, respectively, and high pain-related disability (GCPS grade III or IV). Data were adjusted to take into account age, gender, time since TMD pain onset, chronic TMD pain intensity, and characteristic pain intensity. The presence of chronic tension-type headache was significantly associated with severe SCL-DEP (odds ratio [OR] = 7.2; P < .001), severe SCLSOM (OR = 13.8; P < .001), and high pain-related disability (OR = 9.7; P < .001). This study provides evidence of associations between the clinical diagnosis of chronic tension-type headache coexistent with chronic TMD pain and key aspects of physical and emotional functioning reflected in severe depression, severe somatization, and high pain-related disability.


Knocking Out OsPT4 Gene Decreases Arsenate Uptake by Rice Plants and Inorganic Arsenic Accumulation in Rice Grains.
Arsenic (As) accumulation in rice grains poses health risk to humans. Plants including rice take up arsenate (AsV) by phosphate transporters. In this study, rice phosphate transporter OsPT4 (OsPht1;4) was investigated based on two independent T-DNA insertion mutants of OsPT4 (M1 and M2), which displayed stronger AsV resistance than wild types WT1 and WT2. When cultivated in medium (+P or -P) with AsV, ospt4 mutants accumulated 16-32% lower As in plants, suggesting that OsPT4 mediates AsV uptake. Analysis of the xylem sap showed that AsV concentrations in ospt4 mutants was 20-40% lower than WT controls under -P condition, indicating OsPT4 may also mediate AsV translocation. Moreover, kinetics analysis showed that ospt4 mutants had lower AsV uptake rates than the WT controls, further proving that OsPT4 functions as an AsV transporter in rice. When grown in flooded soils with As, AsV concentrations in rice grains of ospt4 mutants decreased by 50-55%. More importantly, knocking out OsPT4 in M1 and M2 reduced inorganic As accumulation in rice grains by 20-44%, significant for controlling As exposure risk from rice. Taken together, our findings revealed a critical role of OsPT4 in AsV uptake and translocation in rice. Knocking out OsPT4 effectively decreased inorganic As accumulation in rice grains, shedding light on engineering low-As rice to enhance food safety.


Evolution of a highly active and enantiospecific metalloenzyme from short peptides.
Primordial sequence signatures in modern proteins imply ancestral origins tracing back to simple peptides. Although short peptides seldom adopt unique folds, metal ions might have templated their assembly into higher-order structures in early evolution and imparted useful chemical reactivity. Recapitulating such a biogenetic scenario, we have combined design and laboratory evolution to transform a zinc-binding peptide into a globular enzyme capable of accelerating ester cleavage with exacting enantiospecificity and high catalytic efficiency (k cat/K M ~ 106 M-1 s-1). The simultaneous optimization of structure and function in a naïve peptide scaffold not only illustrates a plausible enzyme evolutionary pathway from the distant past to the present but also proffers exciting future opportunities for enzyme design and engineering.


Knowledge, attitude and practices towards visceral leishmaniasis among HIV patients: A cross-sectional study from Bihar, India.
In the Indian state of Bihar, visceral leishmaniasis (VL) is a major public health issue that has been aggravated by the rising incidence of new Human immunodeficiency virus (HIV) infections. In endemic areas, the risk of VL infections in patients living with HIV (PLHIV) is higher. It is important to investigate the disease-related knowledge, attitude, and practices (KAP) of PLHIV in Bihar in order to monitor HIV/VL co-infection. Adequate knowledge, a positive attitude, and good practices for VL control are essential to stamp out the disease. This study investigated the KAP towards VL in HIV patients attending antiretroviral therapy (ART) clinic at ICMR-RMRIMS, Patna. A questionnaire based cross-sectional study was performed among 120 HIV patients aged ≥18 years, to evaluate their KAP regarding visceral leishmaniasis. For the KAP indicators, each correct answer received a score of 1, while unsure and incorrect responses received a score of 0. Descriptive statistics and logistic regression were used for the analysis. Data analysis was performed using Statistical Package for the Social Sciences (SPSS) version 27. The study population had a male (68.30%) preponderance with a mean age of 37.03 years ± 9.80 years of standard deviation. The majority (93.30%) of the study participants had previously heard about VL. Only 32.10% of those who had heard about VL knew that the disease was transmitted by the sandfly. Most (80.40%) of the study respondents were ignorant of the sandfly breeding grounds. The vast majority (75.90%) had no idea how to recognize sandflies and were unaware of their biting time, leishmaniasis transmission season, and preventive practices. Although PLHIV are vulnerable to VL, only 27.70% of them agreed that VL is a fatal disease if untreated, and 42.90% believed they wear not at risk of developing the disease. Regarding the control methods of sandflies, 28.60% of participants did not use any methods to avoid sandfly bites. The multivariable analysis revealed that occupation and family history were the two independent predictor variables of the knowledge index. Age and gender were significantly associated with attitude towards VL. Participants working as laborers had significantly lesser odds (AOR: 0.248, 95% CI: 0.073-0.844) to follow good preventive practices. There were significantly higher odds of having good practice among participants aged 18-40 years (AOR: 6.866, 95% CI: 1.694-27.834) and those residing in urban areas (AOR: 4.159, 95% CI: 1.317-13.139) than their peers. Overall, 27.7% of respondents were knowledgeable, 41.1% had a positive mindset, and 33.9% had strong VL preventive habits, according to the study. The study determined a remarkable gap in the knowledge attitude and practices towards VL among PLHIV. This underscores the need of augmented health education initiatives for PLHIV in endemic areas for good VL awareness and preventive practices.


Dermatomyositis and pregnancy. Case report and review of the literature.
Dermatomyositis is a rare disease complicating pregnancy. We treated a patient in whom two pregnancies were complicated by dermatomyositis. In the first of the two gestations, a mild form of the disease arose in the last trimester. In the second gestation, the disease was inactive following treatment with 0.3 mg/kg/day prednisolone. Both the mother and two children have since been doing well.


[Influence of halidor on experimental bronchospasm].
Through local stimulation of various structures of medulla oblongata a centrogenic bronchial spasm was simulated in acute tests on cats. A peripheral bronchial spasm was reporduced by stimulating the peripheral length of the vagus. An experimental bronchial spasm caused by activation of reticular nuclei and of a single fascicular nucleus halidor suppressed with doses half as large as the ones needed to inhibit the peripheral spasm. An application of halidor to the ground of the fourth ventricle tended to immediately lessen the intensity of the bronchial spasm, this suggesting a central component in the action of the drug.


The haemodynamic basis of lung congestion during exercise in heart failure with preserved ejection fraction.
Increases in extravascular lung water (EVLW) during exercise contribute to symptoms, morbidity, and mortality in patients with heart failure and preserved ejection fraction (HFpEF), but the mechanisms leading to pulmonary congestion during exercise are not well-understood. Compensated, ambulatory patients with HFpEF (n = 61) underwent invasive haemodynamic exercise testing using high-fidelity micromanometers with simultaneous lung ultrasound, echocardiography, and expired gas analysis at rest and during submaximal exercise. The presence or absence of EVLW was determined by lung ultrasound to evaluate for sonographic B-line artefacts. An increase in EVLW during exercise was observed in 33 patients (HFpEFLW+, 54%), while 28 (46%) did not develop EVLW (HFpEFLW-). Resting left ventricular function was similar in the groups, but right ventricular (RV) dysfunction was two-fold more common in HFpEFLW+ (64 vs. 31%), with lower RV systolic velocity and RV fractional area change. As compared to HFpEFLW-, the HFpEFLW+ group displayed higher pulmonary capillary wedge pressure (PCWP), higher pulmonary artery (PA) pressures, worse RV-PA coupling, and higher right atrial (RA) pressures during exercise, with increased haemoconcentration indicating greater loss of water from the vascular space. The development of lung congestion during exercise was significantly associated with elevations in PCWP and RA pressure as well as impairments in RV-PA coupling (area under the curve values 0.76-0.84). Over half of stable outpatients with HFpEF develop increases in interstitial lung water, even during submaximal exercise. The acute development of lung congestion is correlated with increases in pulmonary capillary hydrostatic pressure that favours fluid filtration, and systemic venous hypertension due to altered RV-PA coupling, which may interfere with fluid clearance. NCT02885636.


Variations in immunofluorescent antibody response against Trichobilharzia and Schistosoma antigens in compatible and incompatible hosts.
Schistosome cercariae are able to penetrate into the skin of various vertebrate hosts. However, in contrast to the compatible host, the infection of incompatible hosts results in the death of parasites at various intervals post-infection. In order to compare the immune responses in both types of host infected with Trichobilharzia regenti, Trichobilharzia szidatior Schistosoma mansoni, antibody responses against various T. regenti, T. szidatiand S. mansonischistosome developmental stages were studied. Indirect immunofluorescence tests (IFAT) demonstrated no species-specific reactivity of human, mouse or duck immune sera with cercarial surfaces. Study of the cercarial glands also gave no significant results. However, differences were found in schistosomular and adult antigens: only the sera of compatible hosts recognised schistosomular and adult gut associated antigens in homologous as well as heterologous systems. Based on the presented data, our study supports the use of IFAT for the serological differentiation of schistosomiasis and cercarial dermatitis caused by bird schistosomes.


Providing nutritional support for patients with cancer cachexia.
Malnutrition is the single most common secondary diagnosis for patients with advanced cancer, and can affect up to 85% of patients. Anorexia and weight loss affect up to 80% of patients and are responsible for death in up to 20% of cases. Cancer cachexia is a feature of advanced cancer characterised by anorexia and a progressive loss of body weight, reduced immune response, poor treatment response, and poor quality of life. Providing effective nutritional support for patients who experience cancer cachexia at the end of life is very challenging and requires a multidisciplinary team approach to consider the implications beyond the patient's dietary needs being met. Evidence suggests that health professionals have limited understanding of cachexia and are often at a loss as to how to manage patients who experience this severe form of weight loss. The purpose of this article is to examine the quality of life of patients with advanced cancer who experience cachexia. The article covers the aetiology and management of the condition as well as current treatment methods and management strategies. In particular, it emphasises the advantages of the Macmillan approach to weight and eating. This approach focuses on the social aspects of eating and weight gain, indicating the importance of considering the effects of malnutrition on both the patient and the carer.


Evaluation and application of the CROPGRO-soybean model for determining optimum sowing windows of soybean in the Nigeria savannas.
Soybean production is limited by poor soil fertility and unstable rainfall due to climate variability in the Nigeria savannas. There is a decline in the amount and duration of rainfall as one moves from the south to north of the savanna zones. The use of adapted soybean varieties and optimum sowing windows are avenues to increase productivity in the face of climate variability. Crop simulation models can be used as tools for the evaluation of alternative management options for a particular location, including fertilizer application rates, plant density, sowing dates and land use. In this study, we evaluated the performance of the Cropping System Model (CSM)-CROPGRO-Soybean to determine optimum sowing windows for three contrasting soybean varieties (TGX1835-10E, TGX1904-6F and TGX1951-3F) cultivated in the Nigeria savannas. The model was calibrated using data from ten field experiments conducted under optimal conditions at two sites (BUK and Dambatta) in Kano in the Sudan savanna (SS) agro-ecology over four growing seasons. Data for model evaluation were obtained from independent experiment for phosphorus (P) response trials conducted under rainfed conditions in two locations (Zaria and Doguwa) in the northern Guinea savanna (NGS) zone. The model calibration and evaluation results indicated good agreement between the simulated and observed values for the measured parameters. This suggests that the CROPGRO-Soybean model was able to accurately predict the performance of soybean in the Nigeria savannas. Results from long-term seasonal analysis showed significant differences among the agro-ecologies, sowing windows and the soybean varieties for grain yield. Higher yields are simulated among the soybean varieties in Zaria in the NGS than in Kano the SS and Jagiri in the southern Guinea savanna (SGS) agro-ecological zones. Sowing from June 1 to July 5 produced optimal yield of TGX1951-3F and TGX1835-10E beyond which yield declined in Kano. In Zaria and Jagiri the simulated results show that, sowing from June 1 to July 12 are appropriate for all the varieties. The variety TGX1951-3F performed better than TGX1904-6F and TGX1835-10E in all the agro-ecologies. The TGX1951-3F is, therefore, recommended for optimum grain yield in the savannas of northern Nigeria. However, the late maturing variety TGX1904-6F is not recommended for the SS due to the short growing season in this zone.


Magnetic cell delivery for peripheral arterial disease: A theoretical framework.
Our aim was to compare different magnet arrangements for magnetic cell delivery to human lower leg arteries and investigate the theoretical targeting efficiency under realistic flow conditions as a possible treatment after angioplasty. Additionally the potential of scaling down or translating the magnetic actuation device for preclinical studies was explored. Using finite element methods, the magnetic field distribution was calculated in 3D for the optimization of magnet arrangements. Computational fluid dynamics simulations were performed for the human posterior tibial artery with the geometry and boundary condition data derived from magnetic resonance imaging (MRI) studies. These simulations were used to trace the trajectories of cells for an optimized magnet arrangement. Additionally the behavior of cells close to the vessel wall was investigated using a fluid-structure interaction model. The optimal magnet for the lower leg arteries was a Halbach cylinder k3 variety (12 elements with 900 rotation steps for the magnetization orientation). With this magnet, numerical simulations predict a targeting efficiency of 6.25% could be achieved in the posterior tibial artery for cells containing 150 pg iron. Similar simulations, which were scaled down to rabbit dimensions while keeping the forces acting on a cell constant, lead to similar predicted targeting efficiencies. Fluid dynamic and fluid-structure interaction simulations predict that magnetically labeled cells within a 0.5% radii distance to the vessel wall would be attracted and remain at the wall under physiological flow conditions. First pass capture of magnetically labeled cells under pulsatile flow conditions in human lower leg arteries leads to low targeting efficiencies. However, this can be increased to almost 100% by stopping the blood flow for 5 min. A magnetic actuation device can be designed for animal models that generate magnetic forces achievable for cells in human leg arteries.


Self-assembling peptide-polymer hydrogels designed from the coiled coil region of fibrin.
Biomaterials constructed from self-assembling peptides, peptide derivatives, and peptide-polymer conjugates are receiving increasing attention as defined matrices for tissue engineering, controlled therapeutic release, and in vitro cell expansion, but many are constructed from peptide structures not typically found in the human extracellular matrix. Here we report a self-assembling biomaterial constructed from a designed peptide inspired by the coiled coil domain of human fibrin, the major protein constituent of blood clots and the provisional scaffold of wound healing. Targeted substitutions were made in the residues forming the interface between coiled coil strands for a 37-amino acid peptide from human fibrinogen to stabilize the coiled coil peptide bundle, while the solvent-exposed residues were left unchanged to provide a surface similar to that of the native protein. This peptide, which self-assembled into coiled coil dimers and tetramers, was then used to produce triblock peptide-PEG-peptide bioconjugates that self-assembled into viscoelastic hydrogel biomaterials.


[Acute transverse myelopathy associated to S. aureus: a difficult differential diagnosis].
Acute myelopathy includes a group of diseases with an important associated morbidity, thus early diagnosis and treatment is important. The most frequent etiology is extramedullary compression. Magnetic resonance (MR) is the most suitable procedure in this type of disease since it also offers information on extramedullar lesions and makes it possible to assess spine involvement. We present the case of a 57 year-old man who was admitted because of back pain for several weeks and systemic infection due to S. aureus. Later, he suffered a sudden neurological deficit with spine involvement but without compressive images on the MRI. We discuss the differential diagnosis among intramedullary abscess, epidural abscess, acute transverse myelitis and spondylodiscitis associated to acute myelopathy. We carry out a brief review of the medical literature on diagnosis criteria of those entities.


Reducing inappropriate ESR testing with computerized clinical decision support.
Laboratory test overutilization increases health care costs, leads to unwarranted investigations, and may have a negative impact on health outcomes. The American Society of Clinical Pathology, in its Choosing Wisely Campaign, advocates that inflammation be investigated with C-reactive protein (CRP) instead of Erythrocyte Sedimentation Rate (ESR). London Health Sciences Centre (LHSC), a tertiary care hospital organization in Ontario, Canada, set a goal to reduce inappropriate ESR orders by 50%. After developing appropriateness criteria for ESR, we used a series of PDSA cycles to reduce inappropriate ESR ordering and analyzed our results with an interrupted time series design. Our intervention began with an educational bulletin and moved to city-wide implementation of computerized Clinical Decision Support (CDS). After implementation, ESR orders decreased by 40% from 386 orders per week to 241 orders per week. Our results are supported by previous literature on the effectiveness of CDS in reducing overutilization and suggest that provider habit is a significant contributor to inappropriate ordering.


[Microsporogenesis y microgametogenesis de annatto (Bixa orellana L.)].
A series of buds of increasing maturity were individually sampled in order to examine cytological events of annatto (Bixa orellana L.), genotype Portuguesa. They were fixed in Carnoy II at 12:30 am, time of the highest rate of meiotic division. Three stain solutions were attempted. In the microspores mother cells, the use of acetic orcein 1% resulted in a good nucleus coloration and sharpness. In contrast, a well chromosome resolution was achieved with the application of propionic carmin 2%. The pollen grain mother cells (n = 8 chromosomes) at metaphase I were found in floral buds of 0.5 to 0.6 cm long; tetrad stage in buds of 0.6 to 0.7 cm long, uninucleate stage of microspores in buds of 0.7 to 0.8 cm long and the binucleate stage (pollen) in buds longer than 0.8 cm. Microphotographies showing the sequence of meiotic division (microsporogenesis) and subsequent mitosis to originate pollen grains were included.


The role of different toothpastes on preventing dentin erosion: an SEM and AFM study®.
The aim of the present in vitro study was the evaluation of new formulation toothpastes on preventing dentin erosion produced by a soft drink (Coca Cola®), using atomic force microscopy (AFM) and scanning electron microscopy (SEM). Fifty dentin specimens were divided in treatment and control halves and were than assigned to 5 groups of 10 specimens each: group 1a: intact dentin, group 1b: dentin + soft drink, group 2a: intact dentin + Biorepair Plus-Sensitive Teeth®, group 2b: dentin + soft drink + Biorepair Plus-Sensitive Teeth®, group 3a: intact dentin + Biorepair Plus-Total Protection®, group 3b: dentin + soft drink + Biorepair Plus-Total Protection®, group 4a: intact dentin + Sensodyne Repair & Protect®, group 4b: dentin + soft drink + Sensodyne Repair & Protect®, group 5a: intact dentin + Colgate Sensitive Pro Relief®, group 5b: dentin + soft drink + Colgate Sensitive Pro Relief®. The surface of each specimen was imaged by AFM and SEM. Comparing specimens of group a and b (no demineralization and demineralization), a statistically significant difference (p < 0.01) in Rrms values was registered. Comparing b groups, all the analyzed toothpastes tended to remineralize the dentine surface in different extent. Biorepair Plus-Total Protection® and Sensodyne Repair & Protect® provided higher protective effect against dentin demineralization.


The increase of perceived exertion, aches and pain in the legs, heart rate and blood lactate during exercise on a bicycle ergometer.
This study was designed to show the general increase in perceived exertion, perception of aches or pain in the legs, heart rate (HR), and blood lactate, and the covariance between these variables during bicycle ergometer work, and to describe individual differences both within and between power levels by testing a large group (28 male students). Estimates of perceived exertion and feelings of aches or pain in the legs were recorded using Borg's category-ratio scale (CR-10). The subjects were tested with a stepwise increase of power levels with 40 W increments up to a voluntary maximum. Though HR increases fairly linearly with power, the other variables follow positively accelerating functions with exponents of about 1.6-2 for the perceptual variables, and an exponent of about 3 for blood lactate. The results from the 8 most fit subjects could be described in the same way as for the whole group except for blood lactate, where there was a need to include a threshold value (b), that, together with a rest value (a), shows the starting point of the function (R = a + c(W - Wo)n). The data support the idea that a combination of heart rate and blood lactate is a better predictor of perceived exertion and feelings of aches and pain in the legs, than is each of the single physiological variables taken alone.


Treatment of cancer of the base of the tongue and glosso-epiglottic region: a multicenter Italian survey. GLOCC Group. Gruppo di Lavoro in Oncologia Cervico Cefalica.
The current treatment options for cancer of the base of the tongue and glosso-epiglottic region are surgery, radiotherapy, or a combination of both modalities. Comparisons between different modalities are not common in the literature, and a real standard of treatment has not yet been established. The purpose of our study was to evaluate the results of treatment in a large series of patients from 18 Italian institutions in relation to the main treatment adopted. The present study is a retrospective survey. The series was divided into a combined surgery group and a radiotherapy group. The Kaplan-Meier method and the log-rank test were used for survival calculations and comparisons. Eight hundred patients were registered (25.7% stage III and 62% stage IV), 336 in the surgery and 372 in the radiotherapy group. Conventional fractionation was adopted in almost all cases. The five-year overall and disease free survival of the whole series was 32% and 38%, respectively. Survival was slightly better for patients with tumors of the glosso-epiglottic region than for those with a tumor of the base of the tongue. Five-year disease-free survival was 55% for patients treated with surgery +/- radiochemotherapy and 26% for those submitted to radiotherapy alone or in combination with chemotherapy. As far as the total dose and the treatment duration were concerned, only 26% of the patients of the radiotherapy group met the established criteria of adequacy, but in patients with adequate radiation the control rate was better only for small tumors (T1-T2). The results in patients treated with surgery +/- postoperative radiotherapy were similar to or better than those reported in the best series in the literature. By contrast, the survival rate of irradiated patients was lower than those reported by other centers.


Humoral immunity directed against tumor-associated antigens as potential biomarkers for the early diagnosis of cancer.
Over the past decade, it has been demonstrated that cancer is immunogenic, and multiple tumor antigens have been identified in cancer patients. It is now possible to potentially harness the immune response elicited by cancer growth as a potential diagnostic tool. Humoral immunity, or the development of autoantibodies against tumor-associated proteins, may be used as a marker for cancer exposure. Unlike circulating proteins that are shed by bulky tumors, serum autoantibodies are detectable even when antigen expression is minimal. This paper will review the methods used for tumor antigen discovery and overview what is known about autoantibodies targeting common cancer antigens with a focus on breast cancer. Data will be presented modeling the use of tumor antigen associated autoantibodies as a breast cancer diagnostic. The endogenous humoral immune response present in cancer patients may allow the identification of individuals exposed to the malignant transformation of somatic cells.


Depression and loneliness of older adults in Europe and Israel after the first wave of covid-19.
Epidemic control measures that aim to introduce social distancing help to decelerate the spread of the COVID-19 pandemic. However, their consequences in terms of mental well-being might be negative, especially for older adults. While existing studies mainly focus on the time during the first lockdown, we look at the weeks afterward in order to measure the medium-term consequences of the first wave of the pandemic. Using data from the SHARE Corona Survey, we include retired respondents aged 60 and above from 25 European countries plus Israel. Combining SHARE data with macro-data from the Oxford COVID-19 Government Response Tracker allows us to include macro-indicators at the country level, namely the number of deaths per 100,000 and the number of days with stringent epidemic control measures, in addition to individual characteristics. The findings show that both macro-indicators are influential for increased feelings of sadness/depression, but that individual factors are crucial for explaining increased feelings of loneliness in the time after the first lockdown. Models with interaction terms reveal that the included macro-indicators have negative well-being consequences, particularly for the oldest survey participants. Additionally, the results reveal that especially those living alone had a higher risk for increased loneliness in the time after the first COVID-19 wave. The online version contains supplementary material available at 10.1007/s10433-021-00640-8.


Quercetin, a Promising Clinical Candidate for The Prevention of Contrast-Induced Nephropathy.
Iodinated contrast media (CM) are the leading cause of acute renal failure of toxic origin. Between 21% and 50% of patients that receive them develop contrast-induced nephropathy (CIN). All prophylactic measures used so far have failed to provide effective prevention. Since oxidative stress is involved in the damage, a possible preventive strategy could be the administration of antioxidant substances, such as quercetin. This compound has shown renoprotective effects in experimental studies. The aim of this study was to evaluate whether quercetin may be helpful in preventing CIN in patients undergoing coronary catheterization. A clinical phase II study was conducted. Patients were distributed in two groups, namely, CM (patients who only received contrast media) and CM+Q (patients who were pretreated with quercetin orally for 3-5 days). Results showed less incidence of CIN in the CM+Q group, possibly due to glomerular protection, evidenced by a lower increase in serum creatinine and albuminuria; and a lower decrease in the glomerular filtration rate (GFR). Furthermore, in this group, the relative risk of developing CIN observed in patients that received a high dose of contrast media was inferior. In conclusion, this is the first study that demonstrates that quercetin is a promising safe candidate in preventing CIN.


Prostatic androgen-repressed message-1 as a regulator of adipocyte differentiation in the mouse.
Adipocyte differentiation is an important aspect in energy homeostasis. Although the regulation of adipocyte differentiation is relatively well understood, the underlying molecular mechanism remains unclear. In this study, subcutaneous and epididymal adipose tissues were used to study the differential expression of associated genes. We found that the expression level of mouse homologue of rat prostatic androgen-repressed message-1 (mPARM-1) gene was higher in subcutaneous, perirenal and mesenteric adipose tissues than in epididymal adipose tissue. In mouse subcutaneous, perirenal, and mesenteric adipose tissues, the expression level of this gene was higher in adipocytes than in non-adipocyte cells, i.e. stromal-vascular cells. Furthermore, mPARM-1 mRNA expression was up-regulated in subcutaneous, mesenteric, and epididymal adipose tissues of mice fed a high-fat diet compared to those fed a normal-fat diet. Expression level of mPARM-1 mRNA increased in the early stage of the chemically induced adipocyte differentiation, preceding the increase in peroxisome proliferator-activated receptor-gamma 2 (PPAR-gamma2) mRNA. Tumor necrosis factor-alpha (TNF-alpha), an inhibitor of adipocyte differentiation, reduced the expression of mPARM-1 mRNA in differentiated 3T3-L1 cells and subsequently down-regulated the expression of adipogenic genes, including PPAR-gamma2, leptin and adipogenin. Moreover, knockdown of mPARM-1 expression with siRNA reduced lipid accumulation and the expression levels of PPAR-gamma2 and adipocyte protein 2 mRNAs, which suggest that the degree of adipocyte differentiation of 3T3-L1 cells has been reduced. These results indicate that mPARM-1 might be involved in the regulation of fat accumulation and adipocyte differentiation.


Allergens in pollen from mugwort (Artemisia vulgaris L.). II. Characterization of a crude and a partly purified extract of mugwort pollen with particular emphasis on the glycoprotein allergen Ag7.
A crude and a partly purified extract of mugwort pollen were characterized with particular emphasis on the glycoprotein allergen Ag7. Crossed immunoaffinoelectrophoresis with immobilized Con A in the intermediate gel demonstrated binding of Ag7 to this lectin, indicating that Ag7 contains terminal alpha-D-mannopyranosyl and/or alpha-D-glucopyranosyl residues. Crossed immunoaffinoelectrophoresis with free Con A in the first-dimension gel demonstrated microheterogeneity in the carbohydrate moiety of the allergen. Crossed radioimmunoelectrophoresis analysis using sera from 26 mugwort-allergic patients indicated that Ag7 is an important allergen in mugwort pollen. Heat stability experiments demonstrated the presence of at least three heat-resistant allergens, one of these being Ag7. Crossed immunoelectrofocusing indicated a pI value for Ag7 of 4.3.


Pseudodistance measures for recognition of curved objects.
A method for the description and identification of curved objects is described in this paper. The shape of a curved object is considered as a surface which is an accumulation of horizontal section boundaries. This is described by the coefficients of a Fourier series expansion of the proposed representative function. Each complicated feature of the shape of the object is decomposed into five simple features: elongatedness, horizontal strain, section shape, torsion, and displacement. Differences of objects as patterns are defined as pseudodistances of corresponding features. Some essential properties such as completeness of the pseudodistance family are explained theoretically. Finally, experimental results of identification of wooden block models and a doll are displayed.


Vascular graft sealants.
Although the use of vascular graft sealants is primarily intended to decrease the porosity of grafts upon implantation, sealants also may serve to passivate polymeric surfaces or act as a temporary scaffold for cell attachment and subsequent graft healing. The safety and efficacy of vascular grafts sealed with albumin, collagen, and gelatin have been established through many preclinical and clinical studies. Such products have been used in clinical practice since the mid-1980s. Any differences in the long-term human healing response to these sealants and the clinical relevance of such differences can be assessed only as the time of implantation increases and the data are evaluated.


A Model to Incorporate the bHLH Transcription Factor OsIRO3 within the Rice Iron Homeostasis Regulatory Network.
Iron (Fe) homeostasis in plants is governed by a complex network of regulatory elements and transcription factors (TFs), as both Fe toxicity and deficiency negatively impact plant growth and physiology. The Fe homeostasis network is well characterized in Arabidopsis thaliana and remains poorly understood in monocotyledon species such as rice (Oryza sativa L.). Recent investigation of the rice Fe homeostasis network revealed OsIRO3, a basic Helix-Loop-Helix (bHLH) TF as a putative negative regulator of genes involved in Fe uptake, transport, and storage. We employed CRISPR-Cas9 gene editing to target the OsIRO3 coding sequence and generate two independent T-DNA-free, loss-of-function iro3 mutants in rice cv. Nipponbare. The iro3 mutant plants had similar phenotype under nutrient-sufficient conditions and had stunted growth under Fe-deficient conditions, relative to a T-DNA free, wild-type control (WT). Under Fe deficiency, iro3 mutant shoots had reduced expression of Fe chelator biosynthetic genes (OsNAS1, OsNAS2, and OsNAAT1) and upregulated expression of an Fe transporter gene (OsYSL15), relative to WT shoots. We place our results in the context of the existing literature and generate a model describing the role of OsIRO3 in rice Fe homeostasis and reinforce the essential function of OsIRO3 in the rice Fe deficiency response.


Stimulation of proteoglycan synthesis in explants of porcine articular cartilage by recombinant osteogenic protein-1 (bone morphogenetic protein-7).
Osteogenic protein-1 (also known as bone morphogenetic protein-7) is a member of the bone morphogenetic protein family. Bone morphogenetic proteins and related members of the TGF-beta (transforming growth factor-beta) superfamily are involved in the development and repair of bone. Recombinant bone morphogenetic proteins induce the formation of new cartilage and bone at heterotopic sites. We investigated the influence of recombinant osteogenic protein-1 (at doses of three, ten, thirty, or 100 nanograms per milliliter) on the synthesis and release of proteoglycans and the maintenance of a steady-state concentration of proteoglycans in explants of porcine articular cartilage that were maintained in chemically defined serum-free medium. We found a dose-dependent stimulation of proteoglycan synthesis and a concurrent decrease in the rate of release of proteoglycans from the explants. The size of the proteoglycan monomers and the composition of the glycosaminoglycan chains in the untreated articular cartilage were similar to those in the articular cartilage treated with osteogenic protein-1. The capacity of the newly synthesized proteoglycan monomers to form aggregates with exogenous hyaluronic acid was found to be similar to that of proteoglycans in bovine nasal cartilage. Our results demonstrated that osteogenic protein-1 stimulated the synthesis of proteoglycans and diminished the release of proteoglycans from explants of porcine articular cartilage. The maintenance and repair of articular cartilage is a formidable challenge in clinical orthopaedics. The stimulation of proteoglycan synthesis by osteogenic protein-1 (bone morphogenetic protein-7) in explants of cartilage maintained in chemically defined serum-free medium implies that recombinant osteogenic protein-1 may play a role in the maintenance of a steady-state concentration of proteoglycans in articular cartilage, a desirable prerequisite for optimum repair of cartilage. Osteogenic protein-1 can initiate the formation of cartilage from mesenchymal cells. Once new cartilage has formed at the site of repair, osteogenic protein-1 also may maintain the synthesis of proteoglycans.


Evaluation of increased subclinical atherosclerosis risk with carotid intima-media thickness and pulse wave velocity in inflamatory bowel disease.
A significant increase in accelerated atherosclerosis risk have determined in chronic inflammatory diseases. Recent studies have suggested a pathophysiological link between inflamatory bowel disease (IBD) and atherosclerosis; for which carotid intima-media thickness (CIMT) and pulse wave velocity (PWV) has been considered as an early marker. The aim of this study was to determine the presence of early atherosclerosis in IBD patients without clinically diagnosed cardiovascular disease and any coincident risk factors for atherosclerosis. 40 IBD patients who are in remission and without known atherosclerosis and also without any risk factors for atherosclerosis (17 Crohn's disease and 23 ulcerative colitis ) and 40 healthy subjects for control group involved in the study. The measurement of bilateral CIMT and carotis-femoral PWV have done in patients and control groups. Significant differences existed between control subjects and patients with IBD in the values of PWV (5.97±0.54 vs. 7.17±0.92 m/sn; p<0.001), maximum CIMT (0.76±0.06 vs. 0.86±0.11 mm; p<0.001) and mean CIMT (0.66±0.06 vs 0.74±0.09 mm; p<0.001). In the correlation analysis, a positive correlation has determined between PWV and maximum CIMT and mean CIMT ( p<0.001, r=0.75 / p<0.001, r=0.74 respectively ). IBD patients have an increased risk of subclinical atherosclerosis than healty controls as showed by greater values of CIMT and PWV.


Histochemical studies in experimental portal-systemic encephalopathy.
Results of a histochemical study of glutamic dehydrogenase in experimental portal-systemic encephalopathy with hyperammonemia indicate that the enzyme's activity in brain was increased in all stages of the encephalopathy, and this increase appeared to be localized exclusively in astrocytes. The results are consistent with the view that the astrocyte has a critical role in ammonia metabolism in brain, probably in ammonia detoxification. The findings, moreover, indicate that one pool of glutamate, possibly the small pool, is located in the astrocyte.


Isolated intracranial rosai-dorfman disease involving the meninges: report of a rare case.
Sinus histiocytosis with massive lymphadenopathy or Rosai-Dorfman disease (RDD) is a reactive condition of unknown etiology, characterised by a proliferation of histiocytes exhibiting emperipolesis of lymphocytes and plasma cells. It usually presents as bilateral painless cervical lymphadenopathy. Extranodal RDD without nodal disease is seen in 23% of the cases. Intracranial RDD occurs in less than 5% of the total number of patients with extranodal disease. Isolated intracranial RDD in the absence of nodal disease is exceptional. We report a case of Rosai-Dorfman disease with isolated intracranial involvement. A 38-year-old man came with long-standing headache and the magnetic resonance imaging (MRI) scan showed features of meningioma. The histopathology revealed sheets of histiocytes displaying emperipolesis. These histiocytes were S100 positive but CD1a and epithelial membrane antigen negative.


The possible role of capillary cerebral amyloid angiopathy in Alzheimer lesion development: a regional comparison.
Recent studies have observed beta-amyloid-positive capillaries in lesion-prone regions of Alzheimer's disease (AD) brains. It is possible that there is a pathogenic link between neurofibrillary tangles (NFTs) and/or senile plaques (SPs) and altered capillary structure/function. In this study, we examined and compared brain tissue from a frequently observed NFT abundant area, the superior temporal cortex (ST), and a comparatively much NFT sparser area, the calcarine cortex (COC), in ten AD and ten normal adult control brain samples. We recorded the densities of NFTs, and beta-amyloid(8-17,40,42) peptide forms in SPs, capillaries and large vessels [cerebral amyloid angiopathy (CAA)] in these areas. Our results demonstrated that there was a significant difference between the means of NFT and SP beta(8-17,40) lesions when comparing the ST and COC cortical regions in both AD and control brains. In AD brains, we observed a positive correlation between NFTs and SPs in both regions, and between NFTs and beta-amyloid-positive capillaries and CAA vessels, particularly in the calcarine cortex. In addition, significant correlations were observed between some SP beta-amyloid peptide forms and CAA beta(42), in particular, in both regions. These new observations support the view that there are regional (focal) differences in the presence of each AD lesion, and that there may be a pathogenic relationship between the development of AD lesions and beta-amyloid-positive vessels. The data are also consistent with the concept that a focally dysfunctional blood-brain barrier (BBB) that is unable to regulate the influx/efflux of neurotoxic amyloid peptides may participate in the pathogenesis of AD lesions.


Increased incidence of rare codon clusters at 5' and 3' gene termini: implications for function.
The process of translation can be affected by the use of rare versus common codons within the mRNA transcript. Here, we show that rare codons are enriched at the 5' and 3' termini of genes from E. coli and other prokaryotes. Genes predicted to be secreted show significant enrichment in 5' rare codon clusters, but not 3' rare codon clusters. Surprisingly, no correlation between 5' mRNA structure and rare codon usage was observed. Potential functional roles for the enrichment of rare codons at terminal positions are explored.


Improved culture conditions for the growth and detection of Borrelia from human serum.
In this report we present a method to cultivate Borrelia spirochetes from human serum samples with high efficiency. This method incorporates improved sample collection, optimization of culture media and use of matrix protein. The method was first optimized utilizing Borrelia laboratory strains, and later by demonstrating growth of Borrelia from sera from fifty seropositive Lyme disease patients followed by another cohort of 72 Lyme disease patients, all of whom satisfied the strict CDC surveillance case definition for Lyme disease. The procedure resulted in positive cultures in 47% at 6 days and 94% at week 16. Negative controls included 48 cases. The positive identification of Borrelia was performed by immunostaining, PCR, and direct DNA sequencing.


Beckwith-Wiedemann syndrome.
Beckwith-Wiedemann syndrome (BWS) is an imprinting disorder characterized by overgrowth, tumor predisposition, and congenital malformations. Approximately 85% of reported BWS cases are sporadic, while the remaining 15% are familial. BWS is caused by epigenetic or genomic alterations which disrupt genes in one or both of the two imprinted domains on chromosome 11p15.5. In each domain, an imprinting center regulates the expression of imprinted genes in cis. Normally in domain 1, insulin-like growth factor 2 (IGF2) and the untranslated mRNA H19 are monoallelically expressed. In BWS, increased expression of IGF2 occurs via several mechanisms. In domain 2, CDKN1C, a growth repressor, and an untranslated RNA, KCNQ1OT1, are normally expressed monoallelically. In cases of BWS, several mechanisms result in reduced expression of CDKN1C. Recent reports of BWS cases have identified mutations outside the chromosome 11p15.5 critical region, thereby broadening the challenges in the diagnosis and genetic counseling of individuals and families with BWS.