Management of non-variceal upper gastrointestinal bleeding: role of endoscopic ultrasound-guided treatments.
Non-variceal upper gastrointestinal bleeding (NVUGIB) is a common type of upper gastrointestinal emergency with high risk of life-threatening conditions. Nowadays some standard guidelines for the treatments of NVUGIB have been established based on endoscopic therapies, including injection of glues or sclerosing agents, coiling, band ligation, and thermal therapies. Nevertheless, some patients are refractory to standard endoscopic treatments. We have noticed that endoscopic ultrasound (EUS)-guided treatments have been performed by some endoscopists in certain conditions. This review aims to evaluate the role of EUS-guided treatments in the management of NVUGIB. We performed a MEDLINE/PubMed search, and relevant studies were extracted and examined. According to the existing literature, the most common lesions were Dieulafoy's lesion, pancreatic pseudoaneurysms, and gastrointestinal stromal tumors. EUS-guided treatments mainly include injection, mechanical therapies, and combined therapies, and seem to be a promising technique in the management of NVUGIB, especially for refractory bleeding.


Early embryonic death of glutamate carboxypeptidase II (NAALADase) homozygous mutants.
Glutamate carboxypeptidase II (EC 22.214.171.124) catalyzes the hydrolysis (Km = 0.2 microM) of the neuropeptide N-acetylaspartylglutamate to yield N-acetylaspartate and glutamate and also serves as a high-affinity folate hydrolase in the gut, cleaving the polyglutamate chain to permit the absorption of folate. N-acetylaspartylglutamate is an agonist at the mGluR3 metabotropic receptor and a source of extracellular glutamate through hydrolysis by glutamate carboxypeptidase II. Given the important role of glutamate in brain development and function, we were interested in the effects of a null mutation of glutamate carboxypeptidase II that would potentiate the effects of N-acetylaspartylglutamate. The PGK-Neomycin cassette was inserted to delete exons 9 and 10, which we previously demonstrated encode for the zinc ligand domain essential for enzyme activity. Successful germline transmission was obtained from chimeras derived from embryonic stem cells with the targeted mutation of glutamate carboxypeptidase II. Homozygous null mutants did not survive beyond embryonic day 8. Folate supplementation of the heterozygous mothers did not rescue the homozygous embryos. Mice heterozygous for the null mutation appeared grossly normal and expressed both mutated and wild-type mRNA but the activity of glutamate carboxypeptidase II is comparable to the wild-type mice. The results indicate that the expression of glutamate carboxypeptidase II is upregulated when one allele is inactivated and that its activity is essential for early embryogenesis.


Nurses' pay in Japan: market forces vs. institutional constraints.
To analyse Japan's labour market for nurses and determine reasons for the continuing excess demand. Japan has long been experiencing a shortage of nurses. The situation has been worsening over the past few years, as is reflected in the growing media coverage of the issue. We constructed an economic model of wage setting for Japanese nurses and analysed those wages applying standard labour economics theories. We constructed a nurse labour market data base from various public sets and estimated a few alternative wage functions from this data base. We then interpreted these parameters and the differences of some parameters by function to make an evaluation of relative importance of labour market forces and policies on the setting of the Japanese nurse wages. The government's move to improve the nursing staff-inpatient ratio and the shorter inpatient hospital stays have had a positive impact on the wages of registered nurses (RNs) and licensed practicing nurses (LPNs). Yet, the nursing labour market imbalance remains. The findings show that individual hospitals and clinics could take three steps to help fill the nursing vacancies. First, they could introduce a reorientation program for those nurses no longer in the labour market. Second, they could restructure the working arrangements for those nurses with family responsibilities. Third, they could be instrumental in having the current wage system reassessed.


Sports drinks, exercise training, and competition.
A plethora of investigations examining fluid intake before, during, and after training and competition have suggested that a lack of adequate fluid intake will impair or decrease physical performance. Depending upon the type of training or competition, individuals training for prolonged endurance events should drink fluids containing carbohydrates and electrolytes during and after training or competition. Inadequate hydration will cause significant decrements in performance, increase thermal stress, reduce plasma volume, accelerate fatigue, and possibly cause injuries associated with fluid and sweat loss. However, overdrinking may cause Na+ depletion and in some cases lead to hyponatremia. Maintaining proper hydration before, during, and after training and competition will help reduce fluid loss, maintain performance, lower submaximal exercise heart rate, maintain plasma volume, and reduce heat stress, heat exhaustion, and possibly heat stroke.


The ultrastructure of the dermo-epidermal junction in lichen planus.
The ultrastructure of the dermo-epidermal junctional area in biopsy material from 5 patients suffering from lichen planus has been studied during treatment with steroids. Tannic acid was used on the tissue blocks in order to provide high and diversified contrast for electron microscopy. The changes observed in the basal cells consisted mainly of degeneration of the mitochondria and disorganization of the tonofilaments. No ultrastructural changes were seen in the basal lamina, apart from occasional gaps, whose significance for pigment incontinence in old lichen planus lesions is discussed. Cellular infiltration was seen in the dermis, while the ultrastructure of the collagen fibrils of the papillary layer was normal. It is suggested that degeneration of mitochondria with subsequent disturbance of the organization and fixation of tonofilaments are events in the pathogenesis of the condition.


Nurses' work experiences in hospital wards with single rooms: An integrative review.
To evaluate evidence that examined nurses' work experiences in hospital wards with single rooms. The research question was 'What does the research tell us about nurses' work experiences in hospital wards with single rooms?' In the last decades, new hospital builds have moved towards including a high proportion of single rooms. Yet, single rooms create 'complex environments' that impact the nurses. A structured integrative review was undertaken of empirical evidence. Original, peer-reviewed articles, written in English, were sourced from four databases: CINAHL, PubMed, Embase and Web of Science. The initial searches were performed in April 2021 and repeated in December 2022. Quality appraisal was undertaken using the Mixed Methods Appraisal Tool. A narrative synthesis approach was used to analyse the data. Reporting was guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Twelve studies, published between 2006 and 2022, with an international origin, and representing n = 826 nurses, were included in this review. The synthesis revealed mixed perspectives about nurses' work experiences in wards with single rooms. Whilst single rooms are 'all good in theory (and) a good idea', the reality was quite different. Synthesised findings are presented in four categories: (i) aesthetics and the physical space, (ii) privacy vs. isolation, (iii) safety, which includes situational awareness and (iv) communication and collaboration. This review describes how single rooms affects nurses' work experience. Whilst nurses shared multiple concerns about single rooms and the challenges they also acknowledged patient preference for the privacy and space afforded by single rooms. Findings from this review highlight the need for careful planning to maintain and strengthen teamwork, prevent nurses' sense of working in isolation, as well as creating opportunities for mentorship, and collaboration among nurses when working in single-room settings.


Grading and characterization of soft tissue tumors on magnetic resonance imaging: the value of an expert second opinion report.
To retrospectively compare the accuracy of the initial MRI (magnetic resonance imaging) report of referring radiologists and the second opinion report. MRI of 155 patients presenting with a soft tissue tumor (STT) in a single large community center were referred for inclusion in the Belgian Soft Tissue Neoplasm Registry (BSTNR). The initial report and the second opinion report were made independently. Histopathology (gold standard) was obtained in 90 patients (group 1). In 65 patients, the diagnosis was made by the combination of clinical findings and/or follow-up (group 2). In group 1, the concordance in grading and tissue-specific (TS) diagnosis between the referring center (RC) and expert center (EC) was reviewed. In group 1, MR grading yields a sensitivity of 100% and a specificity of 89% in the EC. The sensitivity was 88% and the specificity 81% in the RC. The accuracy was significantly higher in the EC (92%) compared to the RC (83%) (p = 0.039). The TS diagnosis was correct in 50% versus 38.5% of malignant tumors and in 71.8% versus 51.6% of benign tumors in the EC and RC respectively. A second opinion report increases the accuracy in the diagnosis of STT on MRI. • A second opinion MRI report increases the overall accuracy in the diagnosis of soft tissue tumors. • There is a good overall agreement in MR grading between the referring and expert institution. • In the expert center, there were fewer false-negative and false-positive diagnoses. • MRI performs better in the tissue-specific diagnosis of benign versus malignant STT.


Iron supplementation during pregnancy, anemia, and birth weight: a randomized controlled trial.
The need for prophylactic iron during pregnancy is uncertain. We tested the hypothesis that administration of a daily iron supplement from enrollment to 28 wk of gestation to initially iron-replete, nonanemic pregnant women would reduce the prevalence of anemia at 28 wk and increase birth weight. Between June 1995 and September 1998, 513 low-income pregnant women in Cleveland were enrolled in the study before 20 wk of gestation. Of these, 275 had a hemoglobin concentration >/= 110 g/L and a ferritin concentration >/= 20 micro g/L and were randomly assigned to receive a monthly supply of capsules containing either 30 mg Fe as ferrous sulfate or placebo until 28 wk of gestation. At 28 and 38 wk of gestation, women with a ferritin concentration of 12 to < 20 micro g/L or < 12 micro g/L received 30 and 60 mg Fe/d, respectively, regardless of initial assignment. Almost all the women received some supplemental iron during pregnancy. We obtained infant birth weight and gestational age at delivery for 117 and 96 of the 146 and 129 women randomly assigned to receive iron and placebo, respectively. Compared with placebo, iron supplementation from enrollment to 28 wk of gestation did not significantly affect the overall prevalence of anemia or the incidence of preterm births but led to a significantly higher mean (+/- SD) birth weight (206 +/- 565 g; P = 0.010), a significantly lower incidence of low-birth-weight infants (4% compared with 17%; P = 0.003), and a significantly lower incidence of preterm low-birth-weight infants (3% compared with 10%; P = 0.017). Prenatal prophylactic iron supplementation deserves further examination as a measure to improve birth weight and potentially reduce health care costs.


Drug-stimulated nucleotide trapping in the human multidrug transporter MDR1. Cooperation of the nucleotide binding domains.
The human multidrug transporter (MDR1 or P-glycoprotein) is an ATP-dependent cellular drug extrusion pump, and its function involves a drug-stimulated, vanadate-inhibited ATPase activity. In the presence of vanadate and MgATP, a nucleotide (ADP) is trapped in MDR1, which alters the drug binding properties of the protein. Here, we demonstrate that the rate of vanadate-dependent nucleotide trapping by MDR1 is significantly stimulated by the transported drug substrates in a concentration-dependent manner closely resembling the drug stimulation of MDR1-ATPase. Non-MDR1 substrates do not modulate, whereas N-ethylmaleimide, a covalent inhibitor of the ATPase activity, eliminates vanadate-dependent nucleotide trapping. A deletion in MDR1 (Delta amino acids 78-97), which alters the substrate stimulation of its ATPase activity, similarly alters the drug dependence of nucleotide trapping. MDR1 variants with mutations of key lysine residues to methionines in the N-terminal or C-terminal nucleotide binding domains (K433M, K1076M, and K433M/K1076M), which bind but do not hydrolyze ATP, do not show nucleotide trapping either with or without the transported drug substrates. These data indicate that vanadate-dependent nucleotide trapping reflects a drug-stimulated partial reaction of ATP hydrolysis by MDR1, which involves the cooperation of the two nucleotide binding domains. The analysis of this drug-dependent partial reaction may significantly help to characterize the substrate recognition and the ATP-dependent transport mechanism of the MDR1 pump protein.


Neuronal cadherin (NCAD) increases sensory neurite formation and outgrowth on astrocytes.
We examined the neurite outgrowth of sensory neurons on astrocytes following the genetic deletion of N-cadherin (NCAD). Deletion abolished immunostaining for NCAD and the other classical cadherins, indicating that NCAD is likely the only classical cadherin expressed by astrocytes. Only 38% of neurons grown on NCAD-deficient astrocytes for 24 h produced neurites, as compared to 74% of neurons grown on NCAD-expressing astrocytes. Of the neurons that produced neurites, those grown on NCAD-deficient astrocytes had a mean total length of 378 μm, as compared to 1093 μm for neurons grown on NCAD-expressing astrocytes. Thus, the loss of NCAD greatly impairs the formation and extension neurites on astrocytes.


[ACTH in the plasma and cerebrospinal fluid in patients with multiple sclerosis].
In 1984 and at the beginning of 1985 the authors carried out radioimmunoassays (SORIN-CIS kit) the plasma levels of ACTH in 116 multiple sclerosis patients (m-52, f-64) and in 10 cases this radioimmunoassay was done in the cerebrospinal fluid (m-5, f-5). The control group comprised 90 patients with ischialgia and neuroses. The normal value in the plasma was from 0 to 80.86 pg/ml, and in the fluid it was from 0 to 77.08 pg/ml. In multiple sclerosis patients the plasma ACTH level was from 0 to 286.9 pg/ml, in the cerebrospinal fluid from 0 to 89 pg/ml. The values of ACTH were significantly higher in multiple sclerosis patients, mainly in males. In the fluid the level of ACTH was significantly higher in the studied patients. No significant differences in ACTH levels were found between males and females with multiple sclerosis, and in the control group this level was higher in females. Raised ACTH level was found mainly in multiple sclerosis with lung duration of the disease (10 years) at the time of exacerbations. The authors continue studies on the axis hypothalamus-hypophysis-adrenals, on various hormones, prostaglandins, beta-endorphin, biochemical markers, cAMP, cCMP, arylosulphatase A and B MBC etc.


[Functional recovery of rat facial-facial anastomosis model].
To observe the recovery process of facial behavior and function in rat, and then to supply reliable functional parameters for the researches in such fields. Rat models of facial nerve paralysis were set up by sectioning and anastomosis of facial nerve. The behavioral change included whisker movement and blink reflex were observed weekly. Electroneurography (ENoG) and blink reflex (BR) were examined dynamically and all data were analyzed by statistic soft ware. Postoperatively, the whisker movement ceased, blink reflex was lost or sluggish but the fibrillation of vibrissae appeared. Whisker movement and evoke blink reflex were seen 1-2 months following operation gradually, which subsequently increased in intensity and frequency. Mass contraction of the periauricular muscles were observed at the same time as eye closure 2 month following operation. The latency of compound muscle action potential (CMAP) at experimental side began to prolong at 21 day, reached climax at 1 month and was stabilized at 3-4 month postoperatively, but it could not get full recovery. The latencies of 28-63 day were longer than other time points (P<0.05). The amplitude and intensity didn't change characteristically. The R1 can be observed repetitively, which disappeared at 7-14 day and gradually recovered 1 month following operation. At experimental side, the R1-type wave (R1oris) in orbicularis oris could be observed at the same time as R1 recorded 2 month following operation, which indicated the facial synkinesis, one hyperkinetic post-paralytic sequela happened. Then the latency of both R1 and R1oris decreased concomitantly. There were correlations between them, but only the significant difference of R1oris latency presented between 2 month and other time points (P<0.05). It is concluded that the methods of ENoG and BR could examine the recovery process of facial movement, which would help studying the pathophysiological mechanism of facial nerve injury and regeneration after being revised.


Periodontal Status and Some Variables among Pregnant Women in a Nigeria Tertiary Institution.
Gingival changes during pregnancy have been well-documented. The prevalence of gingivitis in pregnant women has reportedly ranged from 30% to 100%. Increase in both the rate of estrogen metabolism and synthesis of prostaglandins by the gingiva contributed to the gingival changes observed during pregnancy. In effect increased prevalence of dental caries, gingivitis, periodontitis and tooth mobility may be encountered in pregnancy. The purpose of the study was to determine the association of some variables and the periodontal status in a sample of pregnant women attending the Ante Natal Clinic (ANC) of Lagos State University Teaching Hospital (LASUTH), Ikeja, Lagos. Women at various stages of pregnancy, attending the ANC of LASUTH, constituted the target population. The questionnaire was administered on each patient followed by dental examinations. Periodontal status was assessed using the community periodontal index (CPI) of treatment needs. Oral hygiene status was evaluated according to Green and Vermilion simplified oral hygiene index (OHI-S). The association between the CPI scores; OHI-S scores and variables such as trimester and dental visits were statistically significant. This study indicated that the gestational age of pregnancy and dental visits have a definite impact on the periodontal status. Oral health education should be included as an integral part of antenatal care to increase the women awareness. This would improve the mothers' dental care-seeking behavior.


Reduced Functional Connectivity in Adults with Persistent Post-Concussion Symptoms: A Functional Near-Infrared Spectroscopy Study.
Concussion, or mild traumatic brain injury (mTBI), accounts for ∼80% of all TBIs across North America. The majority of mTBI patients recover within days to weeks; however, 14-36% of the time, acute mTBI symptoms persist for months or even years and develop into persistent post-concussion symptoms (PPCS). There is a need to find biomarkers in patients with PPCS, to improve prognostic ability and to provide insight into the pathophysiology underlying chronic symptoms. Recent research has pointed toward impaired network integrity and cortical communication as a biomarker. In this study we investigated functional near-infrared spectroscopy (fNIRS) as a technique to assess cortical communication deficits in adults with PPCS. Specifically, we aimed to identify cortical communication patterns in prefrontal and motor areas during rest and task, in adult patients with persistent symptoms. We found that (1) the PPCS group showed reduced connectivity compared with healthy controls, (2) increased symptom severity correlated with reduced coherence, and (3) connectivity differences were best distinguishable during task and in particular during the working memory task (n-back task) in the right and left dorsolateral prefrontal cortex (DLPFC). These data show that reduced brain communication may be associated with the pathophysiology of mTBI and that fNIRS, with a relatively simple acquisition paradigm, may provide a useful biomarker of this injury.


Extracorporeal transient distal penile corporoglanular shunt in early ischemic priapism treatment.
Ischemic priapism, which is a compartment syndrome, needs urgent treatment in order to nourish corpora cavernosa. As the first step, the aspiration of blood and/or the irrigation of the cavernosal bodies are performed to prevent fibrotic activity and secure erectile capability. While performing aspiration and irrigation, there are some risks of the procedure in which most refrained one is cardiovascular side effects of adrenergic agonists. We aimed to evaluate extracorporeal transient distal penile corporoglanular shunt technique in place of aspiration/ irrigation techniques for early ischemic priapism treatment. In this transient shunt technique, a sterile closed system blood collection set (BD Vacutainer, Cat. No.: 367282; NJ, USA), which has two 21G needles, was used. The length of the needle and tubing was 19 mm. (0.75 inch) and 178 mm. (7 inches), respectively. This blood collection set was designed to be used not only for blood collection but can also be used for short term infusions (maximum 2 hours). Ten patients out of fifteen with early ischemic priapism were successfully treated with this transient shunt technique. The permanent detumescence achieved in the first 10 minutes in nine out of fifteen patients.No additional procedure needed after the disappearance of rigidity in successfully treated patients. The permanent detumescence achieved in the first 10 minutes in nine out of fifteen patients. We demonstrated that this extracorporeal transient shunt technique gets some advantages over aspiration and irrigation in early ischemic priapism treatment. Our results indicate thatthe presented technique to be offered for the patients with an ischemic priapism episode of no more than 7 hours.


Pediatric sutureless circumcision: an effective and cost efficient alternative.
Circumcision is the most commonly performed surgical procedures in male children. Maine is one of 18 states in the United States which does not pay for neonatal circumcisions. The aim of this study was to perform outcomes and cost analysis of a sutureless circumcision technique versus circumcision using sutures. Specifically, we evaluated Dermaflex (2-octyl cyanoacrylate, 2-OCA) surgical glue circumcision as a cost effective, faster, and safe alternative to traditional suture circumcision. Our study was a non-randomized series. We collected the operative details prospectively, abstracted clinical outcomes retrospectively, and performed data analysis retrospectively. One hundred and twenty-six circumcisions were performed by two pediatric urologists over a 1 year period. Suture circumcisions were performed exclusively during the first 6 months, and 2-OCA glue circumcisions were performed during the second 6 months. Billing charges were analyzed to extrapolate variable costs between the two surgical procedures. The technique used to perform the sutureless circumcision was a modification of the standard sleeve technique, with the use of monopolar diathermy instead of scalpel, and application of 2-OCA glue to approximate tissue edges. From Jan 2013 to Jan 2014, 72 patients underwent circumcision with suture, and 54 patients underwent circumcision with 2-OCA glue. Mean age in the glue group was 61 months (range 8-202 months), and 50 months in the suture group (range 5-215 months), p = 0.19. All cases were performed under general anesthesia, as outpatient surgery. Mean operative cut time was 18.4 min for the glue group, and 28.6 min for the suture group (p < 0.01). The 10.2 min operative time difference translated to a $378 cost savings per glue circumcision case. Complication rates were not statistically significant between the two groups. The use of 2-OCA tissue adhesive for sutureless circumcision is an alternative to the standard technique. It results in faster operative times, with a significant cost savings, while maintaining comparable complication rates to the standard suture technique. This is a viable, less expensive surgical option for patients whose circumcisions are not covered by Medicaid.


Non-physical violence: a risk factor for physical violence in health care settings.
This research study assessed the extent to which non-physical violence is a risk factor for physical violence against workers in health care settings. More than 600 nursing staff, other clinical providers, and non-clinical staff in two health care settings completed a cross-sectional survey. For the preceding 12-month period, 72.8% of workers reported at least one incident of non-physical violence and 21.3% reported at least one incident of physical violence. Workers who had experienced non-physical violence were 7.17 times more likely to experience physical violence than those who had not. Both patients and employees were perpetrators of non-physical and physical violence. These results indicate efforts to prevent or reduce physical violence against health care workers need to focus on non-physical as well as physical violence and employee as well as patient perpetrators.


The ultrasonic evaluation of the carotid intima-media thickness and its relation to risk factors of atherosclerosis in normal and diabetic population.
High-resolution ultrasound provides an excellent tool for the non-invasive assessment of the severity of atherosclerosis. It allows the measurement of the common carotid artery (CCA) intima media thickness (IMT) which has been found to be a feasible and reliable method for the evaluation of the progression and regression of the disease. The aim of this study was to evaluate the influence of risk factors of atherosclerosis on the mean CCA IMT in both normal and non-insulin dependent diabetic (NIDDM) individuals and to determine the effect of diabetes as a major atherosclerotic risk factor on the CCA IMT. Four hundred and eighty-four subjects were studied, 244 normal individuals and 240 non insulin dependent diabetic patients. The right and left CCA IMT were measured using high resolution ultrasonography. Both in the normal and diabetic individuals, the mean CCA IMT was found to increase linearly with age (p < 0.01), was directly related to total serum cholesterol and triglyceride and inversely related to HDL-cholesterol (p < 0.01). Multiple linear regression analysis showed the most important risk factor influencing the CCA IMT and hence early athrosclerosis to be the presence of diabetes, followed by serum HDL-cholesterol (inverse relation), total cholesterol, age and serum triglyceride. This study has shown that high resolution ultrasonography can be used to evaluate the effect to risk factors on early atherosclerosis and could be used to monitor future clinical trails aiming to modify the progression of atherosclerosis in the population.


Dissipative energy loss within the left ventricle detected by vector flow mapping in diabetic patients with controlled and uncontrolled blood glucose levels.
Diabetes mellitus (DM) is related to increased risks of cardiovascular diseases, such as myocardial infarction, diabetic cardiomyopathy and secondary hypertension. Dissipative energy loss (EL) derived from vector flow mapping (VFM) is thought to reflect the efficiency of blood flow and has been deemed to be an index for the evaluation of left ventricular function. Our study aimed to investigate the value of dissipative EL in diabetic patients with controlled and uncontrolled blood glucose by VFM. Eighty-eight patients with DM and 58 age-matched healthy controls were recruited. All of the patients received echocardiography examinations. VFM analyses were executed to calculate the EL values according to the apical four-chamber examinations from the left ventricle (LV) view. Our results showed that diastolic EL was compromised in the controlled-blood glucose (59.19 mV/m vs. 32.68 mV/m, p = 0.039) patients and was more dramatically increased in the uncontrolled blood glucose group (88.84 mV/m vs. 32.68 mV/m, p < 0.001) compared with the healthy controls. The impairment of systolic EL was observed only in the uncontrolled blood glucose patients (39.65 mV/m vs. 20.29 mV/m, p < 0.001) and not in the controlled blood glucose patients (29.25 mV/m vs. 20.29 mV/m, p = 0.072). Multivariate backward stepwise linear regression analysis revealed that the HbA1c level was independently related to the diastolic EL (β = 0.233, p = 0.026) and systolic EL (β = 0.237, p = 0.023). VFM is feasible and reproducible for assessing LV dissipative EL in DM patients with normal LVEF values in whom diastolic EL may be a more vulnerable indicator of early LV cardiac dysfunction in patients with DM. However, LV systolic EL may be a sensitive indicator of preclinical LV dysfunction for patients with DM with uncontrolled blood glucose levels. Uncontrolled blood glucose, which is independently correlated with subclinical LV dysfunction, may lead to increases in systolic EL and diastolic EL in LV.


Struggling toward reward: Recent experience of anhedonia interacts with motivation to predict reward pursuit in the face of a stressful manipulation.
Anhedonia, or the loss of interest and/or pleasure, is a core symptom of depression. Individuals experiencing anhedonia have difficulty motivating themselves to pursue rewarding stimuli, which can result in dysfunction. Action orientation is a motivational factor that might interact with anhedonia to potentially buffer against this dysfunction, as action-oriented individuals upregulate positive affect to quickly motivate themselves to complete goals in the face of stress. The Effort-Expenditure for Rewards Task (EEfRT) is a promising new method for examining differences in motivation in individuals experiencing anhedonia. In the EEfRT, participants choose either easier tasks associated with smaller monetary rewards or harder tasks associated with larger monetary rewards. We examined the relationship between action orientation and EEfRT performance following a negative mood induction in a sample with varying levels of anhedonia. There were two competing hypotheses: (1) action orientation would act as a buffer against anhedonia such that action-oriented individuals, regardless of anhedonic symptoms, would be motivated to pursue greater rewards despite stress, or (2) anhedonia would act as a debilitating factor such that individuals with elevated anhedonic symptoms, regardless of action orientation, would not pursue greater rewards. We examined these hypotheses via Generalized Estimating Equations and found an interaction between anhedonia and action orientation. At low levels of anhedonia, action orientation was associated with effort for reward, but this relationship was not present at high levels of anhedonia. Thus, at low levels of anhedonia, action orientation acted as a buffer against stress, but at high levels, anhedonia debilitated action orientation so that it was no longer a promotive factor.


Factor VIII epitopes recognized with inhibitory monoclonal antibodies.
To test whether anti-idiotypic immunoregulation of factor VIII(FVIII)-inhibiting antibodies could be feasible in hemophiliacs, we assayed the minimal number and range of immunogenic, functional FVIII epitopes to which a series of murine anti-FVIII monoclonal antibodies (MAb) were directed. Rabbit anti-idiotypic sera to 7 MAb were prepared and used in competitive immunoradiometric assays to test Id similarities among 36 murine MAb. At least 12 immunogenic and functional epitopes were found on the FVIII molecule. The large range of target loci for FVIII inhibitors will make their immunoregulation by anti-idiotypic methods difficult.


Restoration of diabetes-induced abnormal local Ca2+ release in cardiomyocytes by angiotensin II receptor blockade.
Stimulation of local renin-angiotensin system and increased levels of oxidants characterize the diabetic heart. Downregulation of ANG II type 1 receptors (AT(1)) and enhancement in PKC activity in the heart point out the role of AT(1) blockers in diabetes. The purpose of this study was to evaluate a potential role of an AT(1) blocker, candesartan, on abnormal Ca(2+) release mechanisms and its relationship with PKC in the cardiomyocytes from streptozotocin-induced diabetic rats. Cardiomyocytes were isolated enzymatically and then incubated with either candesartan or a nonspecific PKC inhibitor bisindolylmaleimide I (BIM) for 6-8 h at 37 degrees C. Both candesartan and BIM applied on diabetic cardiomyocytes significantly restored the altered kinetic parameters of Ca(2+) transients, as well as depressed Ca(2+) loading of sarcoplasmic reticulum, basal Ca(2+) level, and spatiotemporal properties of the Ca(2+) sparks. In addition, candesartan and BIM significantly antagonized the hyperphosphorylation of cardiac ryanodine receptor (RyR2) and restored the depleted protein levels of both RyR2 and FK506 binding protein 12.6 (FKBP12.6). Furthermore, candesartan and BIM also reduced the increased PKC levels and oxidized protein thiol level in membrane fraction of diabetic rat cardiomyocytes. Taken together, these data demonstrate that AT(1) receptor blockade protects cardiomyocytes from development of cellular alterations typically associated with Ca(2+) release mechanisms in diabetes mellitus. Prevention of these alterations by candesartan may present a useful pharmacological strategy for the treatment of diabetic cardiomyopathy.


A case of Bloom syndrome with conjunctival telangiectasia.
Bloom syndrome is a rare genodermatosis characterized by photosensitivity, telangiectasias, growth retardation and malignancies. Eye findings have rarely been mentioned in case reports of this syndrome. We report a child with Bloom syndrome who had pronounced bulbar conjunctival telangiectasia originally diagnosed as episcleritis. Bulbar telangiectasia are frequently described in other genodermatoses such as ataxia telangiectasia and hereditary hemorrhagic telangiectasia, but are infrequently noted in Bloom syndrome. Previously described eye findings in Bloom syndrome are reviewed and the differential diagnosis of bulbar telangiectasia is discussed.


The impact of temperature and relative humidity on spatiotemporal patterns of infant bronchiolitis epidemics in the contiguous United States.
Infant bronchiolitis is primarily due to infection by respiratory syncytial virus (RSV), which is highly seasonal. The goal of the study is to understand how circulation of RSV is impacted by fluctuations in temperature and humidity in order to inform prevention efforts. Using data from the Military Health System (MHS) Data Repository (MDR), we calculated rates of infant bronchiolitis for the contiguous US from July 2004 to June 2013. Monthly temperature and relative humidity were extracted from the National Climate Data Center. Using a spatiotemporal generalized linear model for binomial data, we estimated bronchiolitis rates and the effects of temperature and relative humidity while allowing them to vary over location and time. Our results indicate a seasonal pattern that begins in the Southeast during November or December, then spreading in a Northwest direction. The relationships of temperature and humidity were spatially heterogeneous, and we find that climate can partially account for early onset or longer epidemic duration. Small changes in climate may be associated with larger fluctuations in epidemic duration.


The evaluation of chronic progressive external ophthalmoplegia with computerized tomography.
Chronic progressive external ophthalmoplegia is characterised by limitation of ocular motility in all directions of gaze and ptosis. Innervational or myogenic factors were claimed to be responsible for this motility disorder. The aim of this study was to investigate the extraocular muscles in CPEO with computerized tomography in an attempt to distinguish extraocular muscle morphology caused by this disorder from that occurring in normal individuals. Eighteen orbits from 9 patients diagnosed with CPEO were included in the study. Axial and coronal scans were obtained for CT evaluation of extraocular muscles and the dimensions of extraocular muscles were measured. The control group consisted of 40 orbits belonging to 20 individuals and, the results were compared with a student's t test. The thickness (the vertical dimension of vertical recti and the horizontal dimension of horizontal recti) of all rectus muscles was significantly decreased in comparison with the control group, whereas the width (the horizontal dimension of vertical recti and the vertical dimension of horizontal recti) was similar in both the diseased and normal orbits. In all the rectus muscles of the diseased orbits, the normal fusiform shape was lost and the muscles appeared as thin bands. The differentiation of CPEO from other myogenic and neurogenic disorders may present difficulty, and a cluster of criteria are required for a final diagnosis. CT has proven to be a valuable tool in assessing extraocular muscles [1, 2]. In this study, an extreme atrophy of all rectus muscles was demonstrated by means of CT. This diagnostic method may consequently contribute to a proper diagnosis of CPEO.


Fine needle aspiration cytology of cystic hypersecretory carcinoma of the breast. A case report.
Cystic hypersecretory carcinoma (CHC) of the breast is a rare variant of intraductal carcinoma. It is characterized by a multicystic, yellow-brown lesion with gelatinous material grossly and cystically dilated ducts with an eosinophilic secretion microscopically. The histologic or cytologic features can be deceptively bland. A 37-year-old female presented with an 8-cm-diameter, firm mass in the breast. Radical mastectomy was performed after fine needle aspiration (FNA). The moderately cellular smear had a characteristic background of proficient, intensely staining secretion with bubbling. The cellular components were various, ranging from sheets of benign hyperplastic ductal cells to three-dimensional clusters or papillae of frankly malignant ductal cells, with varying degrees of secretory activity. The background consisted of inflammatory cells, naked nuclei and foamy histiocytes. The cytologic findings correlated well with the histologic features of the tumor, which showed both micropapillary intraductal carcinoma with apocrine metaplasia and focal high grade invasive carcinoma in a background of cystic hypersecretory hyperplasia. This was the first reported case of FNA cytology of an invasive form of CHC. CHC has characteristic features on FNA, and so a reliable diagnosis can be made.


Description of an optimized ChIP-seq analysis pipeline dedicated to genome wide identification of E4F1 binding sites in primary and transformed MEFs.
This Data in Brief report describes the experimental and bioinformatic procedures that we used to analyze and interpret E4F1 ChIP-seq experiments published in Rodier et al. (2015) [10]. Raw and processed data are available at the GEO DataSet repository under the subseries # GSE57228. E4F1 is a ubiquitously expressed zinc-finger protein of the GLI-Kruppel family that was first identified in the late eighties as a cellular transcription factor targeted by the adenoviral oncoprotein E1A13S (Ad type V) and required for the transcription of adenoviral genes (Raychaudhuri et al., 1987) [8]. It is a multifunctional factor that also acts as an atypical E3 ubiquitin ligase for p53 (Le Cam et al., 2006) [2]. Using KO mouse models we then demonstrated that E4F1 is essential for early embryonic development (Le Cam et al., 2004), for proliferation of mouse embryonic cell (Rodier et al., 2015), for the maintenance of epidermal stem cells (Lacroix et al., 2010) [6], and strikingly, for the survival of cancer cells (Hatchi et al., 2007) [4]; (Rodier et al., 2015) [10]. The latter survival phenotype was p53-independent and suggested that E4F1 was controlling a transcriptional program driving essential functions in cancer cells. To identify this program, we performed E4F1 ChIP-seq analyses in primary Mouse Embryonic Fibroblasts (MEF) and in p53(-/-), H-Ras(V12)-transformed MEFs. The program directly controlled by E4F1 was obtained by intersecting the lists of E4F1 genomic targets with the lists of genes differentially expressed in E4F1 KO and E4F1 WT cells (Rodier et al., 2015). We describe hereby how we improved our ChIP-seq analyses workflow by applying prefilters on raw data and by using a combination of two publicly available programs, Cisgenome and QESEQ.


ESNOQ, proteomic quantification of endogenous S-nitrosation.
S-nitrosation is a post-translational protein modification and is one of the most important mechanisms of NO signaling. Endogenous S-nitrosothiol (SNO) quantification is a challenge for detailed functional studies. Here we developed an ESNOQ (Endogenous SNO Quantification) method which combines the stable isotope labeling by amino acids in cell culture (SILAC) technique with the detergent-free biotin-switch assay and LC-MS/MS. After confirming the accuracy of quantification in this method, we obtained an endogenous S-nitrosation proteome for LPS/IFN-gamma induced RAW264.7 cells. 27 S-nitrosated protein targets were confirmed and using our method we were able to obtain quantitative information on the level of S-nitrosation on each modified Cys. With this quantitative information, over 15 more S-nitrosated targets were identified than in previous studies. Based on the quantification results, we found that the S-nitrosation levels of different cysteines varied within one protein, providing direct evidence for differences in the sensitivity of cysteine residues to reactive nitrosative stress and that S-nitrosation is a site-specific modification. Gene ontology clustering shows that S-nitrosation targets in the LPS/IFN-gamma induced RAW264.7 cell model were functionally enriched in protein translation and glycolysis, suggesting that S-nitrosation may function by regulating multiple pathways. The ESNOQ method described here thus provides a solution for quantification of multiple endogenous S-nitrosation events, and makes it possible to elucidate the network of relationships between endogenous S-nitrosation targets involved in different cellular processes.


Probiotics and prebiotics in chronic inflammatory bowel diseases.
The prokaryotic and eukaryotic cells of the colon exist in a highly complex, but harmonious relationship. Disturbances in this remarkable symbiosis can result in the development of inflammatory bowel diseases (IBD). Although the etiology of IBD is not entirely understood, it is known that the chronic inflammation of Crohn's disease, ulcerative colitis and chronic pouchitis are a result of an overly aggressive immune response to the commensal intestinal flora in genetically susceptible hosts. Recent studies have enhanced our ability to understand the interaction between the host and its intestinal microflora and the role the microflora plays in maintaining intestinal homeostasis. As we begin to understand the benefits conferred to the intestine by the microflora, the notion of modifying the composition of the bacterial load to improve human health has arisen. A significant body of research now exists investigating the role of probiotics and prebiotics in ameliorating chronic intestinal inflammation. This article will begin with an overview of the role of the commensal microflora in maintaining mucosal immune homeostasis, and how a dysregulated immune response to the intestinal microflora results in IBD. This will be followed by a summary of the use of probiotics and prebiotics in experimental and human IBD.


Multifunctional nanoparticle composites: progress in the use of soft and hard nanoparticles for drug delivery and imaging.
With continued advancements in nanoparticle (NP) synthesis and in the interfacing of NPs with biological systems has come the exponential growth in the use of NPs for therapeutic drug delivery and imaging applications. In recent years, the advent of NP multifunctionality-the ability to perform multiple, disparate functions on a single NP platform-has garnered much excitement for the potential realization of highly functional NP-mediated drug delivery for use in the clinical setting. This Overview will survey the current state of the art (reports published within the last 5 years) of multifunctional NPs for therapeutic drug delivery, imaging or a combination thereof. We provide extensive examples of both soft (micelles, liposomes, polymeric NPs) and hard (noble metals, quantum dots, metal oxides) NP formulations that have been used for multimodal drug delivery and imaging. The criteria for inclusion, herein, is that there must be at least two therapeutic drug cargos or imaging agents or a combination of the two. We next offer an assessment of the cytotoxicity of therapeutic NP constructs in biological systems. We then conclude with a forward-looking perspective on how we expect this field to develop in the coming years. WIREs Nanomed Nanobiotechnol 2017, 9:e1466. doi: 10.1002/wnan.1466 For further resources related to this article, please visit the WIREs website.


Inactivated Sendai virus strain Tianjin induces apoptosis in breast cancer MCF-7 cells by promoting caspase activation and Fas/FasL expression.
Virotherapy represents a promising new approach for treating cancer. Here the authors have analyzed the effect of ultraviolet-inactivated Sendai virus strain Tianjin (UV-Tianjin) on human breast cancer MCF-7 cells in vitro and in vivo. In vitro, UV-Tianjin inhibited the proliferation of MCF-7, MDA-MB-231, and T47D breast cancer cell lines, although MCF-7 cells were most susceptible to UV-Tianjin treatment. Hoechst staining and flow cytometric analysis of UV-Tianjin-treated MCF-7 cells revealed that UV-Tianjin induced apoptosis in a dose-dependent manner. Moreover, UV-Tianjin treatment resulted in reductions in the mitochondria membrane potential of MCF-7 cells and regulated the levels and activities of Bcl-2, Bax, cyt c, caspases, Fas, and Fas ligand (FasL). In vivo, UV-Tianjin inhibited the growth of MCF-7 tumors in nude mice and increased tumor cell apoptosis compared with saline-treated controls. In addition, the percentage of tumor cells positive for cleaved versions of caspase-7, caspase-8, and caspase-9 was higher in UV-Tianjin-treated tumors than in saline-treated controls. In summary, UV-Tianjin exhibited the antitumor activity in human breast cancer MCF-7 cells both in vitro and in vivo. The UV-Tianjin treatment seemed to induce apoptosis by activating both the mitochondrial and death receptor apoptotic pathways.


Optimization of extraction of phenolic compounds from flax shives by pressurized low-polarity water.
Pressurized low-polarity water (PLPW) extraction of phenolic compounds from flax shive was investigated using statistically based optimization and the "one-factor-at-a-time" method. Extraction variables examined using central composite design (CCD) included temperature, flow rate, and NaOH concentration of the extracting water. Extraction of phenolic compounds including p-hydroxybenzaldehyde, vanillic acid, syringic acid, vanillin, acetovanillone, and feruric acid was affected by temperature and NaOH concentration; and extraction of all phenolic compounds, except ferulic acid, increased with temperature and NaOH concentration of the extracting water. Flow rate had little effect on concentration of phenolic compounds at equilibrium, but the extraction rate at the early phase was higher for higher flow rates. The mechanism of PLPW extraction of flax shive phenolics was also investigated using a two-site kinetic model and a thermodynamic model. To determine the extraction mechanism, flow rate was varied from 0.3 to 4.0 mL/min while temperature and NaOH concentration were fixed at 180 degrees C and 0.47 M, respectively. The flow rate tests showed the extraction rates of total phenolic (TP) compounds increased with flow rate and can be described by a thermodynamic model. The results from the thermodynamic model demonstrated that a K(D) value of 30 agreed with the experimental data in the flow rate range of 0.3-4.0 mL/min. When the effect of the three independent variables was evaluated simultaneously using CCD, a maximum TP concentration of 5.8 g/kg of dry flax shive (DFS) was predicted from the combination of a high temperature (230.5 degrees C), a high initial concentration of NaOH (0.63 M), and a low flow rate (0.7 mL/min). Maximum TP concentration of 5.7 g/kg of DFS was obtained from extraction conditions of 180 degrees C, 0.3 or 0.5 mL/min, and 0.47 M NaOH at equilibrium. A second-order regression model generated by CCD predicted a maximum TP concentration of 5.8 g/kg of DFS under the same extraction conditions, which is well matched with the results from experimental data.


A new genus and species of Sclerodactylidae (Echinodermata: Holothuroidea: Sclerothyoninae) from the Pacific coast of Panama, and assignment of Neopentamera anexigua to Sclerothyoninae.
Paulayellus gustavi, a new sclerodactylid genus and species, is described from the Pacific coast of Panama. The new genus and species is assigned to the subfamily Sclerothyoninae based on a suite of characters, which include the radial and interradial plates of the calcareous ring united at the base only. Paulayellus gen. nov. differs from the other Sclerothyoninae genera in having posterior processesof radial plates undivided. Additionally, differs from Sclerothyone, Thandarum and Neopentamera in having knobbed buttons, plates and cups in the body wall (whereas the body wall is furnished only with tables and plates in Sclerothyone, Temparena and Thandarum, and only with knobbed buttons and plates in Neopentamera). The new genus is, so far, monotypic. The also monotypic genus Neopentamera proved to have the radial and the interradial plates of the calcareous ring united at the base only, as typically found in the Sclerothyoninae, and is therefore transferred to that subfamily. The discovery of a new genus in the Sclerothyoninae and the transfer of Neopentamera required the amendation of the diagnosis for the subfamily. A key to the Sclerothyoninae is given.


Contributions to Arabinogalactan Protein Analysis.
Arabinogalactan proteins (AGPs) are important plant proteoglycans involved in many development processes. In roots, AGPs occur in the cell wall of root cells and root cap-derived cells as well as in the secreted mucilage. Detection, localization , and quantification techniques are therefore essential to unravel the AGP diversity of structures and functions. This chapter details root-adapted immunocytochemical methods using monoclonal antibodies, and a collection of biochemical analysis protocols using β-D-glucosyl Yariv reagent for comprehensive AGP characterization.


HPLC study of oxidation products of hydroethidine in chemical and biological systems: ramifications in superoxide measurements.
Methods for the detection and quantitation of hydroethidine (HE) and its oxidation products by HPLC analysis are described. Synthetic methods for preparation of authentic standards (2-hydroxyethidium and diethidium) are provided. Potential applications of the HPLC methods to chemical and biological systems are discussed. Specific examples of chromatograms obtained using UV-Vis absorption, fluorescence, electrochemical, and mass spectrometry detectors are provided. The development of a dual electrochemical and fluorescence detection methodology and its applications are described. The HPLC-based method enables analyses of HE and its oxidation products such as ethidium and the dimeric products of HE. The ramifications of HPLC measurement of HE and its oxidation products in the detection and quantitation of 2-hydroxyethidium, the diagnostic marker product of superoxide and HE, in the intracellular milieu are discussed. Similarly, mitochondria-targeted HE conjugated to a triphenylphosphonium group (Mito-HE or Mito-SOX) also forms oxidation products (dimers of Mito-HE and Mito-E+) that can affect the detection and quantitation of 2-hydroxy-mito-ethidium, the diagnostic marker product of Mito-HE and superoxide in mitochondria.


Intelligent Textiles with Comfort Regulation and Inhibition of Bacterial Adhesion Realized by Cross-Linking Poly(n-isopropylacrylamide-co-ethylene glycol methacrylate) to Cotton Fabrics.
Comfort regulation and inhibition of bacterial adhesion to textiles is realized by cross-linking thermoresponsive random copolymer to the cotton fabrics. By introduction of ethylene glycol methacrylate (EGMA) monomers into n-isopropylacrylamide (NIPAM) with a molar ratio of 2:18, the obtained random copolymer poly(n-isopropylacrylamide-co-ethylene glycol methacrylate), abbreviated as P(NIPAM-co-EGMA), presents a transition temperature (TT) of 40 °C in an aqueous solution with a concentration of 1 mg/mL. Because of the additional EGMA in the copolymer, the obtained P(NIPAM-co-EGMA) shows a glass transition temperature (Tg) of 0 °C, which is much lower than that of pure PNIPAM (Tg = 140 °C). Therefore, the introduction of P(NIPAM-co-EGMA) into the cotton fabrics will have little influence on the softness of the fabrics. Due to the cross-linked P(NIPAM-co-EGMA) layer on the cotton fabrics, the porosity of the polymer layer can be adjusted by varying the external temperature below or above TT, showing that regulation of the air and moisture permeability as well as the body comfort are feasible in the cotton fabrics cross-linked with P(NIPAM-co-EGMA). In addition, the cross-linked P(NIPAM-co-EGMA) layer is capable of absorbing moisture in the ambient atmosphere to form a hydrated layer on top, which can inhibit bacterial adhesion to the textiles.


Origins of pluripotent stem cells.
Different types of pluripotent stem cells can be identified and cultured in vitro. Here an overview is presented of the various pluripotent stem cells types. Embryonal carcinoma (EC) cells that have been cultured in vitro provided the groundwork for future pluripotent cell cultures. Conditions established for these cells such as culture on a feeder layer of mouse embryonic fibroblasts and the importance of fetal calf serum were initially also used for the culture of mouse embryonic stem (ES) cells derived from the inner cell masses of blastocysts. Embryonic stem cells derived from human blastocysts were found to require different conditions and are cultured in the presence of activin and basic fibroblast growth factor. Recently pluripotent stem cells have also been derived from mouse peri-implantation epiblasts. Since these epiblast stem cells (EpiSCs) require the same conditions as the human ES cells it has been suggested that human ES cells are more similar to mouse EpiSCs than to mouse ES cells. Pluripotent cell lines have also been derived from migratory primordial germ cells and spermatogonial stem cells. The creation of pluripotent stem cells from adult cells by the introduction of reprogramming transcription factors, so-called induced pluripotent stem (iPS) cells allowed the derivation of patient-specific pluripotent stem cells without the need of creation of a human blastocyst after cloning by somatic cells nuclear transfer. Recently it has become clear however that iPS cells may be quite different to ES cells in terms of epigenetics.


Degree of Soft Tissue Injury is a Major Determinant of Successful Arterial Repair in the Extremity: A New Classification of Extremity Arterial Injury?
This study aimed to investigate outcomes after extremity arterial injury repair and examined the association between outcomes and the degree of soft tissue injury and vascular repair methods. A retrospective study was conducted on 106 patients (108 cases) who underwent emergent microsurgical repair of extremity arterial injury due to trauma and non-perfusion of the affected extremity. The cases were divided into three groups by degree of associated soft tissue injuries: (A) adequate soft tissue coverage over the injured major vessels after radical debridement, (B) inadequate soft tissue coverage over the injured major vessels after radical debridement, and (C) radical debridement was not feasible due to unclear extent of injured soft tissue. Differences in vascular repair methods and outcomes among the three groups were analyzed. In Group A (n = 61), microvascular suture and vessel graft achieved 95.1% and 85.0% successful limb reperfusion, respectively. In Group B (n = 31), vessel reconstruction with flap coverage achieved 100% successful reperfusion. Vessel graft achieved 28.6% successful limb reperfusion, while there were no cases of successful reperfusion using microvascular sutures. In Group C (n = 16), no vascular repair method achieved successful reperfusion. There were significant differences among the three groups in successful reperfusion (p < 0.001) and limb salvage (p < 0.001). The extent of associated soft tissue injury was associated with different vascular repair methods and outcomes. We propose a new system for classifying these injuries according to the degree of associated soft tissue injury.


Long- and short-haul travel by air: issues for people with diabetes on insulin.
To determine what problems are experienced by people with diabetes mellitus traveling abroad using insulin, whether appropriate and consistent advice is available to them, and if necessary, how this advice could be improved or enhanced. Census study by self-administered questionnaire of patients with diabetes who use insulin attending an outpatient clinic. Grampian Diabetes Centre, Woolmanhill Hospital, Aberdeen. A total of 493 patients using insulin who attended the clinic in Aberdeen over a period of 3 months. Determination of number of patients experiencing problems during travel, of number of patients seeking advice prior to travel and whether it was helpful, and of where respondents would like to access advice. About 10% of respondents experienced problems while traveling, mostly due to hypoglycemia. Most patients want more advice to be available at the clinic. Long-haul travelers were more likely to ask clinic staff for advice and were more willing to use a clinic Web site (70%) to access information about travel than those traveling shorter distances (54%). Patient education may help to reduce the incidence of problems related to travel in those with diabetes mellitus. More than 95% of patients were happy with the advice relating to travel health at the clinic but would like more to be available. It would be useful to improve the consistency of advice within the clinic, and this advice should be readily accessible by all, including fellow healthcare professionals such as General Practitioners (GPs), practice nurses, and travel clinic staff.


Association of thyroid-stimulating hormone and cardiovascular risk factors.
Thyroid hormone plays an important role in regulating the lipid and glucose metabolism. Previously, much attention has been drawn to define the pathophysiological relationship between thyroid dysfunction and the incidence of cardiovascular diseases (CVDs). While the conditions of overt hypothyroidism and subclinical hypothyroidism were both emphasized, the association between CVD risks and the deregulated circulating thyroid-stimulating hormone (TSH) level remains to be elucidated. Nevertheless, multiple TSH-mediated physiological adaptations, including alteration of the serum lipids, body mass index, blood pressure and insulin sensitivity, have led to the difficulty of clearly examining the association between the TSH level and CVD prevalence. The current review aims to 1) summarize the evidence for the role of thyroid dysfunction and TSH abnormality in CVD pathogenesis and 2) explore the possible underlying molecular mechanisms of TSH-mediated cardiovascular pathology in hopes of providing better therapeutic strategies for the patients with deregulated TSH.


A conceptual model of cognitive deficits in chronic heart failure.
To describe a conceptual model to guide studies of cognitive deficits among patients with heart failure. The conceptual framework of cognitive deficits in chronic heart failure is based on theoretical and empirical literature about (a) the pathophysiology of heart failure, (b) the pathophysiology of cognitive deficits, and (c) health-related quality of life. Other variables that may cause or contribute to cognitive deficits include age, the relative contributions of multiple comorbid conditions, hypertension, and depressive symptoms. Covariates that might influence cognitive deficits (medications, gender, and education) are also included in the model. The most prominent cognitive deficits are believed to occur in domains of attention, working memory, memory, learning, executive function, and psychomotor speed. The main outcome variable is health-related quality of life, which is believed to be influenced by circulatory insufficiency and cognitive deficits. The conceptual model described in this paper is a framework for testing cognitive deficits that occur in heart failure. After validation through empirical testing, the model may be useful in developing interventions for patients with heart failure whose care is complicated by cognitive deficits.


Defence responses regulated by jasmonate and delayed senescence caused by ethylene receptor mutation contribute to the tolerance of petunia to Botrytis cinerea.
Ethylene and jasmonate (JA) have powerful effects when plants are challenged by pathogens. The inducible promoter-regulated expression of the Arabidopsis ethylene receptor mutant ethylene-insensitive1-1 (etr1-1) causes ethylene insensitivity in petunia. To investigate the molecular mechanisms involved in transgenic petunia responses to Botrytis cinerea related to the ethylene and JA pathways, etr1-1-expressing petunia plants were inoculated with Botrytis cinerea. The induced expression of etr1-1 by a chemical inducer dexamethasone resulted in retarded senescence and reduced disease symptoms on detached leaves and flowers or intact plants. The extent of decreased disease symptoms correlated positively with etr1-1 expression. The JA pathway, independent of the ethylene pathway, activated petunia ethylene response factor (PhERF) expression and consequent defence-related gene expression. These results demonstrate that ethylene induced by biotic stress influences senescence, and that JA in combination with delayed senescence by etr1-1 expression alters tolerance to pathogens.


A multitrophic approach to monitoring the effects of metal mining in otherwise pristine and ecologically sensitive rivers in northern Canada.
It is not known if current chemical and biological monitoring methods are appropriate for assessing the impacts of growing industrial development on ecologically sensitive northern waters. We used a multitrophic level approach to evaluate current monitoring methods and to determine whether metal-mining activities had affected 2 otherwise pristine rivers that flow into the South Nahanni River, Northwest Territories, a World Heritage Site. We compared upstream reference conditions in the rivers to sites downstream and further downstream of mines. The endpoints we evaluated included concentrations of metals in river water, sediments, and liver and flesh of slimy sculpin (Cottus cognatus); benthic algal and macroinvertebrate abundance, richness, diversity, and community composition; and various slimy sculpin measures, our sentinel forage fish species. Elevated concentrations of copper and iron in liver tissue of sculpin from the Flat River were associated with high concentrations of mine-derived iron in river water and copper in sediments that were above national guidelines. In addition, sites downstream of the mine on the Flat River had increased algal abundances and altered benthic macroinvertebrate communities, whereas the sites downstream of the mine on Prairie Creek had increased benthic macroinvertebrate taxa richness and improved sculpin condition. Biological differences in both rivers were consistent with mild enrichment of the rivers downstream of current and historical mining activity. We recommend that monitoring in these northern rivers focus on indicators in epilithon and benthic macroinvertebrate communities due to their responsiveness and as alternatives to lethal fish sampling in habitats with low fish abundance. We also recommend monitoring of metal burdens in periphyton and benthic invertebrates for assessment of exposure to mine effluent and causal association. Although the effects of mining activities on riverine biota currently are limited, our results show that there is potential for effects to occur with proposed growth in mining activities.


Monitoring intraventricular pressure using an implanted reservoir in head injured patients.
Intracranial pressure monitoring facilitates the management of patients with severe craniocerebral trauma. The advantages of monitoring from the intraventricular space are outweighed by the increased incidence of infections with this technique. A system using an implanted Rickham reservoir attached to an intraventricular catheter with exchangeable external connections has been used successfully for monitoring intracranial pressure in 34 of 35 consecutive head-injured patients, with one minor infection.


[The role of telomerase activity in non-invasive diagnostics of bladder cancer].
To evaluate the potentials of determining the telomerase activity (TA) in the cellular material of the urine for noninvasive diagnosis of bladder cancer (BC). Evaluation of TA was performed in the urine of 48 patients with bladder cancer (study group) before and after transurethral resection of the bladder wall (n=38), an open resection of the bladder (n=4), and cystectomy (n=6). TA was also evaluated in 48 tumor tissue samples obtained from these patients during removal of the bladder tumor. Each sample of the tumor tissue was separated into two parts, one of which was subjected to histological examination, and the latter was used to determine the telomerase activity. In all cases, the diagnosis of bladder cancer was confirmed morphologically. Determination of TA in the samples was performed by the modified TRAP-method (telomerase repeat amplification protocol), RT-PCR, PCR, and electrophoresis. As a control, cell material of the urine and tissue in 12 patients with chronic cystitis was investigated. TA before surgery was found in 45 (93.75%) of 48 samples of cellular material of the urine from patients with suspected bladder cancer. BC was histologically verified in all patients in this group. In the postoperative period, TA was not observed in the 48 samples of cellular material of the urine from patients with BC. In the control group of patients with histologically verified cystitis, weak TA was determined only in one sample of cellular material of the urine. The analysis indicates statistically significant predominance of patients with bladder cancer in case of TA in the urine (P=0.001). TA was detected in all samples of tumor tissue. We also analyzed the dependence of TA levels in urine and tissue on the degree of BC differentiation. In patients with highly differentiated BC, mean AT in the cellular materials of the urine was 0,61% (n=15), in patients with moderately differentiated BC - 0.95% (n=23), in patients with low-grade bladder cancer - 1.33% (n=10); in other words, increase in the TA levels with decreasing the degree of differentiation was observed. This finding can be used in the prognosis of the course of disease based on determining the TA level in these patients. Preliminary data indicate the possibility of use of determining the TA in cellular material of the urine for the diagnosis and monitoring of bladder cancer recurrence.


In pursuit of empowerment: Sensei Nellie Kleinsmidt, race and gender challenges in South Africa.
This chapter traces the way in which Nellie Kleinsmidt, known as the grandmother of karate in Africa, has negotiated discriminatory practices and overcome race and gender-related struggles, including the struggle to free the female body, in pursuit of empowerment. It explores her expectations and the constraints and frustrations she experienced, as well as the many contributions she has made to women's karate in South Africa. Nellie Kleinsmidt's karate career, which began in 1965, coincided with the early developments of South African karate. As a woman of colour her life and karate career were significantly shaped by apartheid legislation. It divided the country into areas of occupancy and residency according to race and was designed to prevent contact between the people of the government defined race groups. Black karate-kas were prohibited by law from practising karate in white designated areas. Lack of facilities and qualified instructors in areas allocated to Kleinsmidt's race group meant that she received very little formal karate instruction between 1966 and 1973. Soon after, she met Johan Roux, a white male. He was to become her chief karate instructor and life-long companion. They defied the apartheid legislation and in 1978 set up home together. They organized defiance campaigns, resisting the pressures from government to close their dojo because of its non-racial policies. Freeing her body at the broader political level involved the abolition of the race categories and all other apartheid legislation which impacted on her life choices and experiences. Initially this struggle and that of freeing her body occurred simultaneously. In her ongoing struggle against gender discrimination in the sport, it was in karate that Nellie Kleinsmidt could strive for the personal empowerment she sought. She could however not translate this into freedom in South African society itself. The impact of apartheid legislation together with the imposition of a sports moratorium by the South African Council on Sports (SACOS), hindered the growth of Nellie Kleinsmidt's karate career, yet she managed to obtain her sixth Dan Black Belt in 1998. This was a remarkable achievement given the constraints she had to overcome. In karate, Kleinsmidt was often viewed as a female first. The problem of female access is exacerbated by the overwhelming number of male instructors perpetuating the notion that the martial arts are inherently male sports. Accessing the various levels of karate has involved claiming physical and symbolic space on the dojo floor as well as involvement in the decision-making arenas of karate. In 1992 with the unification of karate in South Africa, Sensei Nellie began to extend her involvement with the refereeing arena and jointly established a Women's Karate Forum in her province. She has subsequently become a South African national referee and has earned the status of continental judge with the Union of African Karate Federation (UFAK). Nellie Kleinsmidt is the first and only woman of colour to have been appointed to the Referee's Board of South Africa and the only woman of colour in Africa to have obtained a sixth Dan Black belt.


High pressure effects in high-field asymmetric waveform ion mobility spectrometry.
High-Field Asymmetric Waveform Ion Mobility Spectrometry (FAIMS) is an analytical technique based on the principle of non-linear electric field dependence of coefficient of mobility of ions for separation that was originally conceived in the Soviet Union in the early 1980s. Being well developed over the past decades, FAIMS has become an efficient method for the separation and characterization of gas-phase ions at ambient pressure, often in air, to detect trace amounts of chemical species including explosives, toxic chemicals, chemical warfare agents and other compounds. However the resolution of FAIMS and ion separation capability need to be improved for more applications of the technique. The effects of above-ambient pressure varying from 1 to 3 atm on peak position, resolving power, peak width, and peak intensity are investigated theoretically and experimentally using micro-fabricated planar FAIMS in purified air. Peak positions, varying with pressure in a way as a function of dispersion voltage, could be simplified by expressing both compensation and dispersion fields in Townsend units for E/N, the ratio of electric field intensity (E) to the gas number density (N). It is demonstrated that ion Townsend-scale peak positions remain unchanged for a range of pressures investigated, implying that the higher the pressure is, stronger compensation and separation fields are needed within limits of air breakdown field. Increase in pressure is found to separate ions that could not be distinguished in ambient pressure, which could be interpreted as the differentials of ions' peak compensation voltage expanded wider than the dilation of peak widths leading to resolving power enhancement with pressure. Increase in pressure can also result in an increase in peak intensity.


The many guises of amyloidosis. Clinical presentations and disease associations.
Amyloidosis occurs in association with many diseases and can also be idiopathic. It is usually a systemic disease with variable presentations. The diagnosis should be suspected in patients with unexplained proteinuria, cardiomyopathy, congestive heart failure, peripheral neuropathy, carpal tunnel syndrome, macroglossia, or hepatosplenomegaly. Amyloidosis generally has a poor prognosis and responds poorly to therapy. Much needs to be learned about its pathogenesis and treatment possibilities.


Climatic controls of ecohydrological responses in the highlands of northern Ethiopia.
Climate variability and recurrent droughts have a strong negative impact on agricultural production and hydrology in the highlands northern Ethiopia. Since the 1980s, numerous mitigation and land rehabilitation measures have been implemented by local and national authorities to reduce these impacts, are often poorly effective. As underlying reason may be that controlling relationships between climate and ecohydrology at medium-sized catchments (10-10,000km2) of semi-arid highlands are not well known. We investigated trends and relationships in precipitation, temperature, streamflow, and net primary productivity (NPP). The results were mixed, with both significant increasing and decreasing trends for temperature and streamflow. Precipitation time series did not show a significant trend for the majority of stations, both over the years and over each season, except for a few stations. A time series indicated a significant abrupt increase of NPP in annual, seasonal and monthly timescale. Cross-correlation and regression analysis indicate precipitation and maximum temperature were the dominant climatic variables in the Geba catchment for streamflow and NPP. In view of these results, also land use and land cover change over the past three decades was analysed as a possible factor of importance, as human intervention, may affect streamflow and NPP. Factors that mainly correlate with streamflow and NPP are precipitation and maximum temperature. Important interventions that appear beneficial for these responses are construction of micro-dams, soil and water conservation and ecological restoration measures. The awareness that interactions can be quite different in semi-arid and semi-humid regions, as well as in upstream and downstream areas, should be reflected in management aimed at sustainable water and land resources use.


Empirically mapping the subspecialties of cardiovascular-interventional technology.
As the practice of cardiovascular interventional technology (CVIT) has evolved over the last 50 years, so has the role of radiographers employed in this specialty. In 1991, the American Registry of Radiologic Technologists (ARRT) initiated a certification program to recognize radiologic technologists practicing in CVIT. The certification program consisted of a single examination that covered all aspects of CVIT (e.g., neurologic, cardiac, genitourinary). In 2000, the ARRT conducted a study to investigate further the nature of subspecialization occurring within CVIT. A comprehensive job analysis questionnaire was developed that consisted of 137 clinical activities organized into 19 general domains of practice. The questionnaire was completed by a national sample of 848 radiologic technologists working in CVIT, who indicated the frequency with which they performed each of the 137 activities. Responses were subjected to cluster analysis to classify technologists into homogeneous groups corresponding to different CVIT subspecialties. Results indicated that CVIT consists of two major subspecialties: one corresponding to cardiac procedures and one corresponding to procedures involving organ systems other than the heart. Other smaller subspecialties also emerged from the cluster analysis. A multidimensional scaling of the profiles suggested that CVIT subspecialization can be explained by two dimensions: (1) whether the procedures are diagnostic or interventional and (2) the type of organ system involved. The findings are discussed in terms of their implications for education, certification, and performance evaluation.


How adults construct evening meals. Scripts for food choice.
The evening meal is an important regular event in the lives of many people. Understanding how people cognitively construct evening meals can provide insight into social and behavioral processes that are used in food choice. Schema theory provided a framework to explore cognitive constructions as scripts that guide behavior for the evening meal. A grounded theory approach was used to explore participants' evening meal scripts. Qualitative interviews with 32 adults were conducted and analyzed using the constant comparative method. Analysis revealed that participants' evening meal scripts were guided and shaped by dominant values and general expectations about food and eating in this context. Evening meal scripts included sequentially ordered behaviors characterized as strategies providing a general guide for behaviors and procedures that include relatively specific details about how the behavior will occur within the context. Eight different kinds of scripts emerged from the analysis including Provider, Family Cook, Head of the table, Egalitarian, Struggler, Just eat, Anything goes, and Entertainer. The exploration of food choice scripts provides insight into links between cognitions and behaviors that may influence dietary intake. Future investigations should examine these scripts with different participants, in different settings, and for different eating contexts.


Cysteines and Disulfide-Bridged Macrocyclic Mimics of Teixobactin Analogues and Their Antibacterial Activity Evaluation against Methicillin-Resistant Staphylococcus Aureus (MRSA).
Teixobactin is a highly potent cyclic depsipeptide which kills a broad range of multi-drug resistant, Gram-positive bacteria, such as Methicillin-resistant Staphylococcus aureus (MRSA) without detectable resistance. In this work, we describe the design and rapid synthesis of novel teixobactin analogues containing two cysteine moieties, and the corresponding disulfide-bridged cyclic analogues. These analogues differ from previously reported analogues, such as an Arg10-teixobactin, in terms of their macrocyclic ring size, and feature a disulfide bridge instead of an ester linkage. The new teixobactin analogues were screened against Methicillin-resistant Staphylococcus aureus and Methicillin-sensitive Staphylococcus aureus. Interestingly, one teixobactin analogue containing all l-amino acid building blocks showed antibacterial activity against MRSA for the first time. Our data indicates that macrocyclisation of teixobactin analogues with disulfide bridging is important for improved antibacterial activity. In our work, we have demonstrated the unprecedented use of a disulfide bridge in constructing the macrocyclic ring of teixobactin analogues.


Loss of the transcription factor RBPJ induces disease-promoting properties in brain pericytes.
Sufficient vascular supply is indispensable for brain development and function, whereas dysfunctional blood vessels are associated with human diseases such as vascular malformations, stroke or neurodegeneration. Pericytes are capillary-associated mesenchymal cells that limit vascular permeability and protect the brain by preserving blood-brain barrier integrity. Loss of pericytes has been linked to neurodegenerative changes in genetically modified mice. Here, we report that postnatal inactivation of the Rbpj gene, encoding the transcription factor RBPJ, leads to alteration of cell identity markers in brain pericytes, increases local TGFβ signalling, and triggers profound changes in endothelial behaviour. These changes, which are not mimicked by pericyte ablation, imperil vascular stability and induce the acquisition of pathological landmarks associated with cerebral cavernous malformations. In adult mice, loss of Rbpj results in bigger stroke lesions upon ischemic insult. We propose that brain pericytes can acquire deleterious properties that actively enhance vascular lesion formation and promote pathogenic processes.


Yeast, rye, and calf histones. Similarities and differences detected by electrophoretic and immunological methods.
Yeast histones H2A, H2B, and H3 were purified using the standard histone purification procedures of differential solubility and exclusion chromatography. Yeast histone H4 was isolated by the same methods in a fraction containing one other major protein component. The four yeast core histones were identified by their reactions with antisera against rye and (or) calf histone fractions as well as by their electrophoretic, chromatographic, and solubility properties. The immunological distances between yeast H2B and rye and calf H2B fractions are substantial, as is the rye-calf distance for H2B. The immunological distance between yeast H2A and rye H2A is also large and is similar to the rye H2A - calf H2A distance. On the other hand, the immunological distance between yeast H3 and rye and calf H3 is much greater than that between rye H3 and calf H3. These and other results indicate that yeast H3 differs appreciably from the H3 of higher eucaryotes.


[Primary Sjögren's syndrome and hypokalaemic paralysis--case report].
We report a case of hypokalaemic quadriparesis in 31-year old woman in whom the discovery of distal renal tubular acidosis led to the diagnosis of primary Sjögren's syndrome. Hypokalaemic paralysis as initial manifestation of primary Sjögren's syndrome is rare, but when it occurs it may precede symptoms of xerostomia and xerophthalmia. The diagnosis of primary Sjögren's syndrome should be considered in young women who present with progressive weakness, hypokalaemia and metabolic acidosis.


Adjustments of γδ T Cells in the Lung of Schistosoma japonicum-Infected C56BL/6 Mice.
Many kinds of lymphocytes are involved in Schistosoma japonicum (S. japonicum) infection-induced disease. γδ T cells comprise a small number of innate lymphocytes that quickly respond to foreign materials. In this study, the role of γδ T cells in the lung of S. japonicum-infected C56BL/6 mice was investigated. The results demonstrated that S. japonicum infection induces γδ T cell accumulation in the lung, expressing higher levels of CD25, MHCII, CD80, and PDL1, and lower levels of CD127 and CD62L (P < 0.05). The intracellular cytokines staining results illustrated higher percentages of IL-4-, IL-10-, IL-21-, and IL-6-producing γδ T cells and lower percentages of IFN-γ-expressing γδ T cells in the lung of infected mice (P < 0.05). Moreover, the granuloma size in lung tissue was significantly increased in Vδ-/- mice (P < 0.05). In the lung of S. japonicum-infected Vδ-/- mice, both type 1 and type 2 immune responses were decreased significantly (P < 0.05). In addition, the expression of CD80 and CD69 on B cells was decreased significantly (P < 0.05), and the SEA-specific antibody was markedly decreased (P < 0.05) in the blood of infected Vδ-/- mice. In conclusion, this study indicates that γδ T cells could adjust the Th2 dominant immune response in the lung of S. japonicum-infected mice.


Time in mind.
Streamlining care can reduce morbidity and mortality from stroke. Nurses in Merseyside have organised services so that patients with suspected stroke are fast-tracked through the system.


Purification, characterization and fine sugar specificity of a N-Acetylgalactosamine specific lectin from Adenia hondala.
Plant lectins are gaining interest because of their interesting biological properties. Several Adenia species, that are being used in traditional medicine to treat many health ailments have shown presence of lectins or carbohydrate binding proteins. Here, we report the purification, characterization and biological significance of N-Acetyl galactosamine specific lectin from Adenia hondala (AHL) from Passifloraceae family. AHL was purified in a single step by affinity chromatography on asialofetuin Sepharose 4B column, characterized and its fine sugar specificity determined by glycan array analysis. AHL is human blood group non specific and also agglutinates rabbit erythrocytes. AHL is a glycoprotein with 12.5% of the carbohydrate, SDS-PAGE, MALDI-TOF-MS and ESI-MS analysis showed that AHL is a monomer of 31.6 kDa. AHL is devoid of DNase activity unlike other Ribosome inactivating proteins (RIPs). Glycan array analysis of AHL revealed its highest affinity for terminal lactosamine or polylactosamine of N- glycans, known to be over expressed in hepatocellular carcinoma and colon cancer. AHL showed strong binding to human hepatocellular carcinoma HepG2 cells with MFI of 59.1 expressing these glycans which was effectively blocked by 93.1% by asialofetuin. AHL showed dose and time dependent growth inhibitory effects on HepG2 cells with IC50 of 4.8 μg/ml. AHL can be explored for its clinical potential.


Natural history of chronic granulomatous disease.
An analysis of the patient characteristics, clinical course, and therapy of 52 patients with chronic granulomatous disease (CGD) was carried out through a multinstitutional questionnaire survey in order to further define the natural history of this disorder of phagocyte microbicidal function. The results suggest that CGD is characterized by significant heterogeneity in clinical course and prognosis. The age at diagnosis, severity of disease, or early death in an affected sibling does not seem to be of value in predicting the prognosis for individual patients with CGD. A more detailed, large-scale multicenter study and the establishment of a patient registry is recommended.


Avirulent Bacillus anthracis Strain with Molecular Assay Targets as Surrogate for Irradiation-Inactivated Virulent Spores.
The revelation in May 2015 of the shipment of γ irradiation-inactivated wild-type Bacillus anthracis spore preparations containing a small number of live spores raised concern about the safety and security of these materials. The finding also raised doubts about the validity of the protocols and procedures used to prepare them. Such inactivated reference materials were used as positive controls in assays to detect suspected B. anthracis in samples because live agent cannot be shipped for use in field settings, in improvement of currently deployed detection methods or development of new methods, or for quality assurance and training activities. Hence, risk-mitigated B. anthracis strains are needed to fulfill these requirements. We constructed a genetically inactivated or attenuated strain containing relevant molecular assay targets and tested to compare assay performance using this strain to the historical data obtained using irradiation-inactivated virulent spores.


[Quality of life of patients with gastric tube anastomosis after proximal gastrectomy in adenocarcinoma of esophagogastric junction].
To compare postoperative quality of life (QOL) of patients receiving proximal gastrectomy (PG) for adenocarcinoma of gastroesophagealjunction (AEG) throughgastric tube anastomosis and traditional esophagogastrostomy. Between January 2010 and February 2011, 112 patients were diagnosed as AEG in our hospital. All patients underwent curative operations. Two post-PG alimentary tract reconstruction methods were adopted: gastric tube anastomosis (n = 60) and traditional direct anastomosis (n = 52). The European Organization for Research and Treatment of Cancer (EORTC) Quality of life Questionnaire Core-30 (EORTC QLQ-C30) and QLQ-STO22 were used to assess QOL of those patients before and two years after operations. There were no statistically significant differences between the two groups of patients in clinical and pathologic characteristics, clinical pathological characteristics and preoperative QOL (P > 0.05). Two years after operations, the patients receiving traditional direct anastomosis showed higher scores in reflux, body image, and nausea and vomiting compared with those receiving gastric tube anastomosis. No statistical differences were found between the two groups of patients in general health, physical function, role function, fatigue and pain (P > 0.05). Gastric tube reconstruction could improve the postoperative QOL of AEG patients.


Detailed analysis of polymer response to delivery balloon expansion of drug-eluting stents versus bare metal stents.
We sought to describe the response of the polymer surface of drug-eluting stents (DES) to delivery balloon expansion, including quantitation of any resulting detached microparticles. We expanded the US Food and Drug Administration (FDA)-approved first- and second-generation DES in a vacuum filtration system and used optical and scanning electron microscopy to image the polymer surface, filters and delivery balloons. DES were expanded under a range of conditions, from in vitro conditions used for FDA regulatory submissions to human in vivo conditions. Dispersive Raman spectroscopy was used for definitive identification of microparticles. All polymer surfaces were topographically disturbed over an average of 4.6%-100% of the surface area imaged. Disturbances ranged from deformation (including peeling) to complete delamination. The dimensions of detached microparticles were 2-350 μm. The extent and nature of surface disturbances and microparticles were primarily a function of polymer composition (p<0.001 for 8/10 disturbance types/locations) and were independent of expansion condition (p=0.100 to 0.989 for 9/10 disturbance types/locations). Balloon expansion of first- and second-generation DES disturbs the polymer surface and can cause detachment of microparticles; each is functionally related to the specific polymer but not to expansion condition. Disturbance "roughness" and detached microparticles may contribute to DES limitations.


[Role of autologous bone marrow transplantation in cancer chemotherapy].
Over the past 9 years, total number of 147 patients with various types of malignant solid tumors were treated 220 times with high-dose chemotherapy supported by autologous bone marrow transplantation. Two most frequently used chemotherapeutic protocols were: cyclophosphamide 1,600 mg/m2 + adriamycin 80 mg/m2 + ACNU 3 mg/kg and cyclophosphamide 1,600-2,400 mg/m2 + adriamycin 80 mg/m2 + CDDP 100-120 mg/m2. There were 89 patients with advanced and/or recurrent diseases. The overall response (CR + PR) rate was 44.1% with the complete response (CR) rate, being 11.8% among 68 evaluable patients in this group. The most favorable response was obtained in breast cancer patients with 77.3% response rate and 13.6% CR rate. Nearly 50% of patients with gastric, lung, gynecological and pediatric malignancies responded, whereas poor responses were observed in the cases of pancreato-biliary, colorectal, esophageal cancers and melanoma. In 8 complete responders, three are alive and well without any evidence of disease 5 years after the treatment. There were 58 patients who underwent this treatment in adjuvant settings. There are 5 patients with breast cancer who have been followed over 5 years after treatment. All of them are alive and well without any demonstrable diseases. Four of them were in stage IIIa and histologically examined axillary nodes were positive in 14/15, 11/17, 37/44, 22/25. Autologous bone marrow transplantation seems to be instrumental in shortening the period of myelosuppression, thus allowing safe dose escalation in chemotherapy. Adequacy of cryopreserved marrow as marrow inoculum was ascertained with mononuclear cell count, cellular viability, CFU-GM, CFU-E, BFU-E and CFU-Mk.


The prevalence of undernutrition among students attending traditional Ethiopian orthodox Tewahedo church schools in northwest Ethiopia.
Undernutrition is a major public health concern affecting the health, growth, development, and academic performance of adolescents studying in school. During this crucial period, dietary patterns have a vital impact on lifetime nutritional status and health. The problem of undernutrition among particular groups of adolescents attending traditional schools has not previously been studied. Therefore, this study aimed to assess the prevalence of undernutrition and associated factors among adolescents aged 10-19 years attending Orthodox Church schools in northwest Ethiopia. An institution-based, cross-sectional study design was employed, with data collected from March 1 to 30, 2021. A simple random sampling technique was used to recruit a total of 848 male attendees of traditional schools. Data were collected via an interviewer-administered semi-structured questionnaire. The nutritional status of participants was assessed using anthropometric measurements. The WHO Anthroplus software was used for analysis. Both bivariable and multivariable logistic regression analyses were conducted to identify the factors associated with nutritional status. The degree of association between the independent variables and the dependent variable was assessed using odds ratios, reported with 95% confidence intervals, and a threshold of p ≤ 0.05. The prevalence of undernutrition was found to be 61.3% [95% CI: 58.1, 64.6]. The likelihood of developing undernutrition was elevated among those adolescents who were following the traditional school levels of dikuna (AOR = 4.3, 95% CI = 1.3, 13.6), kinne (AOR = 4.5, 95% CI = 1.4, 14.6), aquaquame (AOR = 9.9, 95% CI = 2.5, 39.88), tirguame (AOR = 6.4, 95% CI = 1.6, 25.6), and among those whose mothers had no formal education [AOR = 3.7, 95% CI: 1.2, 12.8]. In contrast, those adolescents who always washed their hands after a toilet visit had lower odds of undernutrition than their counterparts [AOR = 0.7, 95%CI: 0.5, 0.98]. More than three out of five participating male adolescents were undernourished. Thus, to improve the nutritional status of adolescents studying in traditional church schools, extensive health education for these adolescents is essential. Moreover, the establishment of well-resourced traditional religious school, equipped for the provision of an adequate, diversified diet, is important. Developing the habit of handwashing after visiting the toilet and before and after food preparation is also recommended for adolescent students.


Comparative effects of di(n-butyl) phthalate exposure on fetal germ cell development in the rat and in human fetal testis xenografts.
Phthalate exposure induces germ cell effects in the fetal rat testis. Although experimental models have shown that the human fetal testis is insensitive to the steroidogenic effects of phthalates, the effects on germ cells have been less explored. We sought to identify the effects of phthalate exposure on human fetal germ cells in a dynamic model and to establish whether the rat is an appropriate model for investigating such effects. We used immunohistochemistry, immunofluorescence, and quantitative real-time polymerase chain reaction to examine Sertoli and germ cell markers on rat testes and human fetal testis xenografts after exposure to vehicle or di(n-butyl) phthalate (DBP). Our study included analysis of germ cell differentiation markers, proliferation markers, and cell adhesion proteins. In both rat and human fetal testes, DBP exposure induced similar germ cell effects, namely, germ cell loss (predominantly undifferentiated), induction of multinucleated gonocytes (MNGs), and aggregation of differentiated germ cells, although the latter occurred rarely in the human testes. The mechanism for germ cell aggregation and MNG induction appears to be loss of Sertoli cell-germ cell membrane adhesion, probably due to Sertoli cell microfilament redistribution. Our findings provide the first comparison of DBP effects on germ cell number, differentiation, and aggregation in human testis xenografts and in vivo in rats. We observed comparable effects on germ cells in both species, but the effects in the human were muted compared with those in the rat. Nevertheless, phthalate effects on germ cells have potential implications for the next generation, which merits further study. Our results indicate that the rat is a human-relevant model in which to explore the mechanisms for germ cell effects.


Improved gas-jet based extreme ultraviolet, soft X-ray laser plasma source.
We present a new nozzle design for an improved brilliance of laser-produced gas plasmas emitting in the soft X-ray and extreme ultraviolet spectral regime. A rotationally asymmetric gas jet is formed by employing two closely adjacent nozzles facing each other under the angle of 45°. The generated three-dimensional gas density distribution is tomographically analyzed using a Hartmann-Shack wavefront sensor. A comparison with numerical simulations accomplishes an optimization of the nozzle arrangement. The colliding gas jets create an optimized gas distribution with increased density, leading to a significant brilliance enhancement of the extreme ultraviolet, soft X-ray plasma.