Differential effects of docosahexaenoic acid on contractions and L-type Ca2+ current in adult cardiac myocytes.
Beneficial effects of n-3 polyunsaturated fatty acids in Ca2+ overload have been attributed to blockade of L-type Ca2+ current (I(Ca-L)). However, cardiac contractions may be maintained despite block of I(Ca-L). This study investigates the cellular basis by which docosahexaenoic acid (DHA), a representative n-3 polyunsaturated fatty acid, inhibits I(Ca-L) while preserving contraction. Experiments were conducted in adult guinea pig ventricular myocytes with Na+ currents blocked. Contractions initiated by the voltage-sensitive release mechanism (VSRM) and calcium-induced calcium release (CICR) triggered by I(Ca-L), were activated separately with voltage clamp techniques. DHA (10 microM) inhibited I(Ca-L) and CICR contractions but not VSRM contractions. CICR contractions exhibited a bell-shaped voltage-dependence. However, in the presence of DHA, only contractions with a sigmoidal voltage-dependence characteristic of the VSRM remained. These contractions exhibited inactivation properties characteristic of the VSRM. DHA abolished I(Ca-L) elicited by test steps from -40 mV. Block was voltage-dependent, as residual I(Ca-L) was elicited by steps from -70 mV. Cd2+ inhibited residual current, but not contractions initiated by the same activation steps. Preservation of VSRM contractions during block of I(Ca-L), may explain the ability of n-3 polyunsaturated fatty acids to inhibit Ca2+ influx while preserving cardiac contractile function.


A self-determination theory-based self-myofascial release program in older adults with myofascial trigger points in the neck and back: A pilot study.
To examine the effectiveness and adherence to a self-determination theory (SDT)-based self-myofascial release (SMR) program in older adults with myofascial trigger points (MTrPs), and to investigate the factors that influence participant behavioral change while conducting the program in a home setting. An explanatory mixed-method design was used to evaluate a 12-week SDT-based SMR program, including a 4-week group-based education and practice (EP) phase and an 8-week home-based self-management (SM) phase. Pain intensity on palpation and sensitivity to pain were assessed at baseline and the post EP and post SM phase. Focus group interviews were conducted at the post SM phase. Fifteen participants completed the study. Pain intensity and sensitivity to pain significantly improved at the post SM phase compared with the baseline. Adherence increased during the SM phase compared with that during the EP phase. Four main themes emerged as factors that influenced participant behavioral change: 1) "awareness of the effectiveness"; 2) "a sense of duty to perform the exercise"; 3) "obedience to expert instruction"; and 4) "lack of friendship." These results support the effectiveness of an SDT-based SMR program for the treatment of MTrPs and in motivating older adults to participate in the program.


Proteomics in the Study of Bacterial Keratitis.
Bacterial keratitis is a serious ocular infection that can cause severe visual loss if treatment is not initiated at an early stage. It is most commonly caused by Staphylococcus aureus, Pseudomonas aeruginosa, Streptococcus pneumoniae, or Serratia species. Depending on the invading organism, bacterial keratitis can progress rapidly, leading to corneal destruction and potential blindness. Common risk factors for bacterial keratitis include contact lens wear, ocular trauma, ocular surface disease, ocular surgery, lid deformity, chronic use of topical steroids, contaminated ocular medications or solutions, and systemic immunosuppression. The pathogenesis of bacterial keratitis, which depends on the bacterium-host interaction and the virulence of the invading bacterium, is complicated and not completely understood. This review highlights some of the proteomic technologies that have been used to identify virulence factors and the host response to infections of bacterial keratitis in order to understand the disease process and develop improved methods of diagnosis and treatment. Although work in this field is not abundant, proteomic technologies have provided valuable information toward our current knowledge of bacterial keratitis. More studies using global proteomic approaches are warranted because it is an important tool to identify novel targets for intervention and prevention of corneal damage caused by these virulent microorganisms.


[A novel phenotype (CD 4+, Leu 7+) in large granular lymphocyte leukemia: a case report].
We report a case of a 72-year-old man with large granular lymphocyte (LGL) leukemia. Immunophenotypical analysis of the abnormal cells showed the following results: CD 2+, CD 3+, CD 4+, CD 8-, CD 11+, CD 16-, Leu 7+. These cells had natural killer (NK) activity, responded to PHA and recombinant interleukin-2 (rIL-2), and showed neither helper nor suppressor function in B-cell differentiation. Molecular genetical analysis showed monoclonal rearrangement of T-cell receptor beta-chain gene, indicating they are of T-cell origin. These findings provide information on biological characteristics of normal CD 4+, Leu 7+ cells.


[Congenital total ectropion of upper lid].
Two cases with congenital total ectropion of the upper eyelids are reported (1 bilateral and 1 unilateral). There were no associated ocular or general abnormalities nor any apparent causes. One child was born normally, the other by cesarean section. The disease is not caused by difficult labor through natural birth passages. The condition is usually cured by conservative therapy. If surgery is carried out, it should be performed as early as possible in order to rule out secondary infections, amblyopia, epidermization of the conjunctiva, etc.


Differential labeling of the pinealocytes and pineal interstitial cells by a series of monoclonal antibodies to human pineal body.
Ten hybridomas producing monoclonal antibodies against pineal antigens were established by hybridizing mouse myeloma cells with spleen cells from BALB/c mice immunized with human pineal body homogenate. Seven antibodies immunohistochemically reacted with the pinealocytes and three reacted with the pineal interstitial cells. According to the antibodies applied, the pinealocytes were immunostained in a variable manner; granularly with PP1, PP4 and PP6 antibodies, diffusely with PP2 and PP5, membraneously with PP3, and apically with PP7. The PI1 and P12 antibodies immunolabeled most of the interstitial cells, but PX1 immunolabeled only a small population of these cells. An immunoblotting study indicated that single or multiple polypeptides of the pineal homogenate constituted the antigen epitopes for these antibodies. Most antibodies also immunoreacted with several cell types of the extra-pineal tissues, thus these antibodies are not specific to the human pineal body. This series of monoclonal antibodies should be available for immunohistochemical studies involving the normal and pathological human pineal body.


Existence of T cells manifesting self-reactivity indistinguishable from alloreactivity.
The studies reported here were designed to analyze the phenotypic characteristics of self-reactive T lymphocytes induced in culture by allogeneic effect factor (AEF), as well as the control of their functional activities by the major histocompatibility complex (MHC). Unprimed T cells cultured with AEF in the absence of exogenous stimulating target cells become activated against self-antigens, as evidenced by their ability to manifest two distinct activities. First, such cells could lyse syngeneic target cells. This cytolytic activity was directed against H-2K antigens and was mediated by Lyt-2+ T cells. Second, the AEF-activated T cells could be stimulated in a secondary culture to high levels of proliferative activity by irradiated syngeneic spleen cells. The stimulator cells in this syngeneic mixed lymphocyte reaction (MLR) were found to be Thy-1-negative, Ia-positive splenic adherent cells. Stimulation in the secondary syngeneic MLR was provided by I-region specificities, and the majority of the proliferating cells were Lyt-1+ cells. Finally, AEF-induced T cells were effective in serving as effectors of graft-vs-host reactions in vivo in syngeneic recipients. These results prove that, under appropriate conditions, murine T lymphocytes can display aggressive patterns of self-reactivity that are similar in both quantity and quality to the classical patterns of alloreactivity and may have great significance for our understanding of MHC recognition processes.


Potential clinical use of cardiopulmonary exercise testing in obstructive sleep apnea hypopnea syndrome.
There is growing evidence linking obstructive sleep apnea hypopnea syndrome (OSAHS) with multiple cardiovascular and metabolic diseases. Exercise testing is generally available and routinely used to provide valuable information on cardiopulmonary function in healthy and diseased populations. This review summarizes and integrates recent findings on exercise testing in OSAHS and discusses the potential mechanisms that may contribute to the responses that seem to differentiate these patients from apparently healthy subjects and patients with other cardiopulmonary diseases. Although exercise testing is widely used in the evaluation and diagnosis of coronary artery disease patients, recent studies showed distinctive cardiopulmonary responses in OSAHS that raise the possibility of similar applications in this disorder, as well. Several studies illustrated in this review found that OSAHS patients have a reduced exercise capacity, as shown by low peak oxygen uptake achieved. Also, their exercise HR response was reported as significantly lower than in healthy peers, suggesting chronotropic incompetence. Exercise blood pressure response were atypical as well. OSAHS patients had increased systolic and diastolic BP during exercise and a persistently elevated systolic BP during the early post-exercise recovery period. Possible explanations for these responses include cardiac dysfunction, impaired muscle metabolism, chronic sympathetic over-activation, and endothelial dysfunction. Early identification of OSAHS using cardiopulmonary exercise testing (CPXT) shows promise for selecting patients at risk for this disorder in the clinical setting. A uniform definition and measurement of OSAHS together with more rigorous trials are necessary to establish the utility of exercise responses in clinical settings.


Epidermolysis bullosa acquisita associated with epidermal-binding circulating antibodies.
Epidermolysis bullosa acquisita (EBA) is a rare, immunobullous disease, characterized by circulating and tissue-bound antibodies against type VII collagen (C7) of anchoring fibrils in the cutaneous basement membrane zone. These antibodies localize to the dermal aspect of salt-split skin on indirect and direct immunofluorescence (IMF). We report two patients with clinical features of EBA, in whom circulating IgG antibodies bound to the epidermal aspect of salt-split skin. In both patients direct IMF of salt-split perilesional skin revealed dermal IgG deposits, and direct immunogold immunoelectron microscopy showed antibody deposits in the region of anchoring fibrils. Their serum failed to react with epidermal or dermal extracts on Western immunoblotting. Epidermal-binding antibodies have not been reported previously in association with EBA, and the IMF findings in these cases suggest the development of autoantibodies to additional epidermal-associated antigens. Target antigen heterogeneity has been reported in most other immunobullous diseases, and may be a hitherto unrecognized feature of EBA.


MicroRNA-31 Emerges as a Predictive Biomarker of Pathological Response and Outcome in Locally Advanced Rectal Cancer.
Neoadjuvant chemoradiotherapy (CRT) followed by total mesorectal excision has emerged as the standard treatment for locally advanced rectal cancer (LARC) patients. However, many cases do not respond to neoadjuvant CRT, suffering unnecessary toxicities and surgery delays. Thus, identification of predictive biomarkers for neoadjuvant CRT is a current clinical need. In the present study, microRNA-31 expression was measured in formalin-fixed paraffin-embedded (FFPE) biopsies from 78 patients diagnosed with LARC who were treated with neoadjuvant CRT. Then, the obtained results were correlated with clinical and pathological characteristics and outcome. High microRNA-31 (miR-31) levels were found overexpressed in 34.2% of cases. Its overexpression significantly predicted poor pathological response (p = 0.018) and worse overall survival (OS) (p = 0.008). The odds ratio for no pathological response among patients with miR-31 overexpression was 0.18 (Confidence Interval = 0.06 to 0.57; p = 0.003). Multivariate analysis corroborated the clinical impact of miR-31 in determining pathological response to neoadjuvant CRT as well as OS. Altogether, miR-31 quantification emerges as a novel valuable clinical tool to predict both pathological response and outcome in LARC patients.


Immunopathogenesis of central nervous system fungal infections.
Fungal infections of the central nervous system (CNS) evoke humoral and cellular immune responses with the scope to enable the host to eliminate the pathogen. Immunopathogenesis of CNS fungal infections remains incompletely understood, with most of our understanding coming from studies on experimentally infected animals. However, activation of brain resident cells combined with relative expression of immunoenhancing and immunosuppressing cytokines and chemokines may play a determinant role and partially explain immunopathogenesis of CNS fungal infections.


Diversity of Vi-related antigens in the microcapsule of Salmonella typhi.
Two new antigenic acidic polysaccharides, Vi-P and Vi-C, were isolated from the microcapsule of Salmonella typhi by a very mild procedure. The antigens were purified to serological homogeneity, and it was found that each of them shares with Vi antigen one of its two serological determinants (a different one in each case). One of the antigens Vi-C, was also isolated from Escherichia coli B, which is not a Vi-producing strain.


Risk Stratification for Covert Invasive Cancer Among Patients Referred for Colonic Endoscopic Mucosal Resection: A Large Multicenter Cohort.
Among patients with large colorectal sessile polyps or laterally spreading lesions, it is important to identify those at risk for submucosal invasive cancer (SMIC). Lesions with overt endoscopic evidence of SMIC are referred for surgery, although those without these features might still contain SMIC that is not visible on endoscopic inspection (covert SMIC). Lesions with a high covert SMIC risk might be better suited for endoscopic submucosal dissection than for endoscopic mucosal resection (EMR). We analyzed a group of patients with large colon lesions to identify factors associated with SMIC, and examined lesions without overt endoscopic high-risk signs to determine factors associated with covert SMIC. We performed a prospective cohort study of consecutive patients referred for EMR of large sessile or flat colorectal polyps or laterally spreading lesions (≥20 mm) at academic hospitals in Australia from September 2008 through September 2016. We collected data on patient and lesion characteristics, outcomes of procedures, and histology findings. We excluded serrated lesions from the analysis of covert SMIC due to their distinct phenotype and biologic features. We analyzed 2277 lesions (mean size, 36.9 mm) from 2106 patients (mean age, 67.7 years; 53.2% male). SMIC was evident in 171 lesions (7.6%). Factors associated with SMIC included Kudo pit pattern V, a depressed component (0-IIc), rectosigmoid location, 0-Is or 0-IIa+Is Paris classification, non-granular surface morphology, and increasing size. After exclusion of lesions that were obviously SMIC or serrated, factors associated with covert SMIC were rectosigmoid location (odds ratio, 1.87; P = .01), combined Paris classification, surface morphology (odds ratios, 3.96-22.5), and increasing size (odds ratio, 1.16/10 mm; P = .012). In a prospective study of 2106 patients who underwent EMR for large sessile or flat colorectal polyps or laterally spreading lesions, we associated rectosigmoid location, combined Paris classification and surface morphology, and increasing size with increased risk for covert malignancy. Rectosigmoid 0-Is and 0-IIa+Is non-granular lesions have a high risk for malignancy, whereas proximally located 0-Is or 0-IIa granular lesions have a low risk. These findings can be used to inform decisions on which patients should undergo endoscopic submucosal dissection, EMR, or surgery. ClinicalTrials.gov, Number: NCT02000141.


Determination of hexamethylene-based isocyanates in spray-painting operations. Part 1. Evaluation of a polyurethane foam sponge sampler.
A polyurethane foam (PUF) sponge was mounted in a cassette sampler and evaluated as a sorbent for the collection of hexamethylene diisocyanate (HDI) monomer and HDI-based oligomers. Recovery studies indicated 112 +/- 34% average recovery of HDI monomer and 92 +/- 9% and 97 +/- 25% average recovery of HDI-based oligomers when using impregnated PUF sponges. The PUF sponge was also evaluated during actual spray-painting operations. In a series of side-by-side sampling events, an impinger filled with 1-(2-methoxyphenyl)piperazine (MOP) in toluene was compared directly with a cassette sampler containing a PUF sponge impregnated with MOP or 1-(9-anthracenylmethyl)piperazine (MAP) in dimethyl sulfoxide (DMSO). For the analysis of HDI-based oligomer, there is no significant difference (p < 0.05, n = 7) in the air concentration when sampling with either the PUF sponge cassette or the impinger. The results are significant because they indicate that a PUF sponge, which is more convenient than an impinger, may be used for the collection of HDI-based oligomer generated during spray-painting operations.


Possible association between suicide committed under influence of ethanol and a variant in the AUTS2 gene.
rs6943555 in AUTS2 has been shown to modulate ethanol consumption. We hypothesized that rs6943555 might be associated with completed suicide. We genotyped rs6943555 in 625 completed suicides and 3861 controls using real-time TaqMan Allelic Discrimination Assay. All individuals were Polish Caucasians. We detected an association between suicide and rs6943555 A allele (OR = 1.17, P = 0.018 for allelic comparison, OR = 1.24, P = 0.013 for dominant, and OR = 1.18, P = 0.020 for co-dominant model of inheritance). The association remained significant after adjusting for age and gender (co-dominant: P = 0.002 and dominant model: P = 0.001). After stratifying suicides according to blood ethanol concentration (BAC≤ 20 mg/dl and BAC > 20 mg/dl) the association remained significant only for cases who committed suicide under influence of alcohol (co-dominant: OR = 1.37, P = 0.004 and dominant model: OR = 1.45, P = 0.006). To validate this finding we genotyped another cohort of 132 cases. We reproduced the association between rs6943555 A allele and suicide under influence of ethanol (allelic comparison: OR = 1.55, P = 0.023; co-dominant : OR = 1.54, P = 0.031; dominant model: OR = 1.84, P = 0.015). Analyzing pooled suicides with BAC >20 mg/dl (N = 300) we found the association of rs6943555 A allele not only vs. controls (allelic OR = 1.41, P = 0.00029) but also vs. cases with BAC ≤ 20 mg/dl (N = 449, allelic OR = 1.33, P = 0.019). In our study rs6943555 A allele is associated with suicide committed after drinking ethanol shortly before death. The rs6943555 A allele may be linked to adverse emotional reaction to ethanol, which could explain the association with lower consumption in general population as well as the predisposition to suicide under influence of ethanol.


Nondestructive determination of pacemaker sense amplifier passband.
Most artificial cardiac pacemakers incorporate sense amplifiers to detect intrinsic heart activity in order to eliminate the possibility of competition between the artificial and natural pacemakers. When artificial pacemakers fail prematurely, the failure cause should be determined so that systematic failure modes can be identified and corrected. The failure analysis of any sophisticated electronic product is difficult; failure analysis of a cardia pacemaker is complicated by the sealing technologies encountered. Because access to the circuitry of implantable devices is impeded by the packaging of the device, and because the packaging may have influenced the failure, nondestructive testing techniques must be used extensively. This paper reports on a method for nondestructive determination of the pacemaker sense amplifier with a (sin x)/x waveform to which a continuous wave sinusoid is added. The amplifier passband is characterized by increasing the frequency of the sinusoid in increments of 5 Hertz and determining the amplifier sensitivity at each step.


Electrodepositing DNA Self-Assembled Monolayers on Au: Detailing the Influence of Electrical Potential Perturbation and Surface Crystallography.
The preparation of DNA self-assembled monolayers (SAMs) on single-crystal gold bead electrodes using an applied potential is evaluated with in situ electrochemical fluorescence microscopy. Applying a constant deposition potential or a square-wave potential perturbation during the formation of DNA SAMs is compared for two different modification methods: DNA SAM formation on a clean gold surface followed by alkythiol backfilling (as is typically done in the literature) or via thiol-exchange on an alkylthiol-modified gold surface. DNA SAMs prepared from a chloride-containing deposition buffer were not significantly different when using either square-wave potential perturbation or at a constant applied potential even when considering different surface crystallographies. Greater variations were observed when applying more positive potentials for both DNA thiol-exchange and DNA adsorption on clean Au. Our results suggest that using either a constant potential or a square-wave potential perturbation for 5 min both create defects by weakening the gold-thiol interaction. When the deposition is performed with the adsorption of chloride ions from the electrolyte, the electrodeposition results in a similar increase in DNA coverage when compared to depositions performed at open circuit potentials.


A comprehensive overview on electro-active biofilms, role of exo-electrogens and their microbial niches in microbial fuel cells (MFCs).
Microbial fuel cells (MFCs) are biocatalyzed systems which can drive electrical energy by directly converting chemical energy using microbial biocatalyst and are considered as one of the important propitious technologies for sustainable energy production. Much research on MFCs experiments is under way with great potential to become an alternative to produce clean energy from renewable waste. MFCs have been one of the most promising technologies for generating clean energy industry in the future. This article summarizes the important findings in electro-active biofilm formation and the role of exo-electrogens in electron transfer in MFCs. This study provides and brings special attention on the effects of various operating and biological parameters on the biofilm formation in MFCs. In addition, it also highlights the significance of different molecular techniques used in the microbial community analysis of electro-active biofilm. It reviews the challenges as well as the emerging opportunities required to develop MFCs at commercial level, electro-active biofilms and to understand potential application of microbiological niches are also depicted. Thus, this review is believed to widen the efforts towards the development of electro-active biofilm and will provide the research directions to overcome energy and environmental challenges.


Homology Modeling of 5-alpha-Reductase 2 Using Available Experimental Data.
5-Alpha-reductase 2 is an interesting pharmaceutical target for the treatment of several diseases, including prostate cancer, benign prostatic hyperplasia, male pattern baldness, acne, and hirsutism. One of the main approaches in computer aided drug design is structure-based drug discovery. However, the experimental 3D structure of 5-alpha-reductase 2 is not available at present. Therefore, a homology modeling method and molecular dynamics simulation were used to develop a reliable model of 5-alpha-reductase 2 for inhibitor pose prediction and virtual screening. Despite the low sequence identity between the target and template sequences, a useful 3D model of 5-alpha-reductase 2 was generated by the inclusion of experimental data.


High-Resolution 3-T Endorectal Prostate MRI: A Multireader Study of Radiologist Preference and Perceived Interpretive Quality of 2D and 3D T2-Weighted Fast Spin-Echo MR Images.
The goal of this study was to compare the perceived quality of 3-T axial T2-weighted high-resolution 2D and high-resolution 3D fast spin-echo (FSE) endorectal MR images of the prostate. Six radiologists independently reviewed paired 3-T axial T2-weighted high-resolution 2D and 3D FSE endorectal MR images of the prostates of 85 men in two sessions. In the first session (n = 85), each reader selected his or her preferred images; in the second session (n = 28), they determined their confidence in tumor identification and compared the depiction of the prostatic anatomy, tumor conspicuity, and subjective intrinsic image quality of images. A meta-analysis using a random-effects model, logistic regression, and the paired Wilcoxon rank-sum test were used for statistical analyses. Three readers preferred the 2D acquisition (67-89%), and the other three preferred the 3D images (70-80%). The option for one of the techniques was not associated with any of the predictor variables. The 2D FSE images were significantly sharper than 3D FSE (p < 0.001) and significantly more likely to exhibit other (nonmotion) artifacts (p = 0.002). No other statistically significant differences were found. Our results suggest that there are strong individual preferences for the 2D or 3D FSE MR images, but there was a wide variability among radiologists. There were differences in image quality (image sharpness and presence of artifacts not related to motion) but not in the sequences' ability to delineate the glandular anatomy and depict a cancerous tumor.


Pregnancy after heart transplant: update and case report.
A literature review of 22 cases of pregnancy following cardiac transplantation up to 1995 and a case report are presented here. A 30 year old woman, gravida 3, para 1, contacted us for obstetric care at 8 weeks gestation, about 55 months after orthotopic cardiac transplantation. The transplant had been performed for a familial dilative cardiomyopathy, which had become manifest during her previous pregnancy. The course of the current gestation was uneventful. The patient's cardiovascular function was good throughout the pregnancy. Immunosuppressive therapy, the dose of which was increased during pregnancy, included cyclosporine and azathioprine. Because of an increase in the patient's plasma uric acid concentration and an initial rise in her blood pressure, despite therapy, a repeat Caesarean section was performed at 37 weeks gestation. A female baby weighing 2330 g, Apgar scores 7/9, was delivered. Mother and infant were discharged on postoperative day 15 and are doing well 14 months postpartum. Through a review of literature and our case, the issues and problems related to pregnancy after a heart transplant are discussed, in particular the maternal-fetal risks, management, therapy, delivery, neonatal problems and follow-up postpartum of mother and baby.


[Length of stay in medical departments. Similarities and differences in Denmark].
The relation between the length of stay after admission to a medical ward, the available resources, and the quality of the results is not well established. There is no documentation that allocation of resources results in improved quality. In Denmark we have recently focused on the quality of cancer treatment and have allocated resources without any evidence that it will improve survival, whereas less attention has been paid to less prestigious diseases. Length of stay can be an indicator of quality, as we operate with an efficient work process as a goal. But it is not a goal by itself, as only when coupled with cure or improvement in the disease can it be worth aiming at. We therefore compared the length of stay in Danish Departments of Internal Medicine to look for differences or similarities. MATERIAL AN METHODS: The homepage of the Danish National Board of Health, www.tal.dk (now terminated) was visited and data drawn for analyses. Six days seems to be the average length of stay in most departments, with some extreme deviations. A tendency towards a short stay in the department of Cardiology and a long term stay in the Geriatric Department was found as expected, but again extreme deviations were seen. No typical pattern was seen in the length of stay. A short stay is not attractive in itself, only when combined with a high quality of care and a healthy economy. Conversely, too short a stay can be risky if it is because of overcrowding and this must be prevented.


Smart Floor with Integrated Triboelectric Nanogenerator As Energy Harvester and Motion Sensor.
A smart floor is demonstrated by integrating a square-frame triboelectric nanogenerator (SF-TENG) into a standard wood floor. The smart floor has two working modes based on two pairs of triboelectric materials: one is purposely chosen polytetrafluoroethylene films and aluminum (Al) balls, and the other is the floor itself and the objects that can be triboelectrically charged, such as basketball, shoe soles, and Scotch tape, etc. Utilizing the Al balls enclosed inside shallow boxes, the smart floor is capable of harvesting vibrational energy and, hence, provides a nonintrusive way to detect sudden falls in elderly people. In addition, when the basketball is bounced repeatedly on the floor, the average output voltage and current are 364 ± 43 V and 9 ± 1 μA, respectively, and 87 serially connected light-emitting diodes can be lit up simultaneously. Furthermore, the friction between the triboelectrically chargeable objects and the floor can also induce an alternating current output in the external circuit without the vibration of the Al balls. Normal human footsteps on the floor produce a voltage of 238 ± 17 V and a current of 2.4 ± 0.3 μA. Therefore, this work presents a smart floor with built-in SF-TENG without compromising the flexibility and stability of the standard wood floor and also demonstrates a way to harvest ambient energy solely by using conventional triboelectric materials in our daily life.


Promoting active engagement in health research: lessons from an undergraduate gerontology capstone course.
With National Institutes of Health/National Institute of Aging (NIH/NIA) (R15/AREA) funding, the authors offered a four-credit hour undergraduate research course that was cross-listed in gerontology and sociology. This capstone course was aimed at providing students with the opportunity to (1) gain knowledge about diabetes and racial/ethnic disparities in the management of the illness and (2) develop expertise in secondary data analysis, using the Behavioral Risk Factor Surveillance System (BRFSS) data set. Each student designed and conducted her or his own research project and, working in teams, created a team poster and presentation. The authors examine student pretest/posttest questionnaire data, rubric-based assessment of students' work, and mid- and end-of-the-semester student evaluations to highlight three distinct aspects of the course: (1) skills acquired by students, (2) students' evaluation of the course, and (3) successes and challenges of implementing the course.


Susceptibility of bovine macrophages to infectious bovine rhinotracheitis virus infection.
Infectious bovine rhinotracheitis virus replicated in cultured bovine alveolar macrophages (AM). However, yields of infectious virus were low, with maximum titers approximately 100 times that of the residual inoculum. Immunofluorescence and electron microscopic studies indicated that the majority of macrophages produced viral antigen, but after infection at a multiplicity of 0.1, only 4.1% of AM produced infectious centers. Virus-infected AM culture supernatants possessed interfering activity, probably due to interferon. Incubation of fresh AM with these fluids rendered them refractory to infection. Although AM from infectious bovine rhinotracheitis virus-immune and -susceptible donors were equally permissive and their susceptibility was unaltered by incubation with bacterial lipopolysaccharide, bovine mammary macrophages which were elicited with lipopolysaccharide became nonpermissive when further incubated for 48 h with 1 microgram of lipopolysaccharide per ml. Under these conditions, infected mammary macrophages failed to synthesize viral DNA, and there was reduced synthesis of "late" viral polypeptides.


Systematic review of interventions aimed at reducing hookah pipe use: Implications for practitioners and clinicians.
Globally, tobacco ranks as one of the major risk factors for death, disease and disability. While strong measures have been implemented to reduce cigarette use, there are alternative ways to smoke tobacco, such as the hookah pipe. Hookah pipe use appears to pose a significant public health concern and has serious short- and long-term health consequences for users and those exposed to second-hand smoke. To date, few studies have reviewed hookah pipe interventions beyond the efficacy-based paradigm. To systematically review interventions aimed at reducing hookah pipe use through the RE-AIM framework (reach, efficacy, adoption, implementation and maintenance of results) in order to provide a practical means of evaluating interventions. A systematic review spanning 12 databases identified studies aimed at reducing hookah pipe use. All methodological types of intervention studies that were peer reviewed and in the English language were considered for inclusion. The quality of each study was assessed. Ten studies were deemed eligible. For each study, data were extracted using the RE-AIM framework. All studies focused solely on the smoker, and their recruitment strategies were described. Eight studies reported meeting their objectives. Overall, the studies presented limited information regarding adoption success. The interventions were mainly supportive, educational or counselling sessions. Only five studies reported on the maintenance of results post intervention. Interventions focusing on reducing hookah pipe use are limited. Counselling and educational support sessions seem to be the most feasible and potentially successful approaches for intervention.


Pericapillary spongy sheaths in the human spleen. An immunohistological study.
Antisera to extracts of human hyaline cartilage allow distinct visualization of extracellular structures of adventitial sheaths around arterial capillaries in the red pulp and marginal zone in the human spleen. These pericapillary sheaths have a prominently spongy character indicating their essential filter function. In childhood they are most marked. In premature and stillborn infants they sometimes occupy whole stretches of pulp cords, whereas in old age they are frequently diminished to small formations lacking a distinctly spongy structure.


Predicting Flow in the Pediatric Emergency Department: Are Holidays Lighter?
The aim of this study was to determine whether patient volume in an urban pediatric emergency department (ED) can be predicted based on holidays and thus aid in staffing and resource allocation. Log-in dates and times were obtained for all patients seen in an urban pediatric ED between July 1, 2006, and June 30, 2013. Visits were coded for the day of the week, tour (ie, shift), and season and whether they occurred on a holiday or nonholiday. Comparisons between the median number of patient visits on holidays versus nonholidays by day of the week, tour, and season were performed. Additional comparisons on 5 Monday holidays as well as New Year's Day, Thanksgiving, and Christmas Day were also performed. Data were presented as medians with interquartile ranges. Group comparisons were performed via using Mann-Whitney U tests and Kruskal-Wallis tests (α = 0.05, 2 tailed). There were 223,677 total patient visits, with a mean yearly census of 31,954. The median daily volume was 85, peaking on Mondays (median, 99). The summer season demonstrated the fewest number of patient visits (median, 74) relative to the other seasons (medians, 89-91). Compared with nonholidays, there were fewer patient visits on Thanksgiving and Christmas Day and in the late afternoon and evening on other individual holidays. Fewer patient visits on Thanksgiving and Christmas Days, as well as during the late afternoon/evening on several other holidays, point to the possibility of small adjustments to staffing in ways that can more efficiently balance demand with available resources.


Immunohistochemical study of a canine neurofibroma.
Accurate diagnostic approaches to differentiate peripheral nerve sheet tumours from others have not been firmly established. The aim of this case report was to diagnose neurofibroma using a combination of diagnostic imaging, histopathology and immunohistochemistry, which were applied to a canine neurofibroma arising in the left mandible. The tumour was surgically excised and examined histologically. Round or spindle cells, with elongated, dense and homogenous chromatin and pale cytoplasm typical of Schwann cells in an abundant fibromyxomatous stroma, with ruby collagen fibres were seen. Immunohistochemistry demonstrated that S-100 and vimentin were more than 70% positive. Neurofibroma may therefore be recognisable using markers such as S-100 and vimentin.


Maternal antenatal anxiety and children's behavioural/emotional problems at 4 years. Report from the Avon Longitudinal Study of Parents and Children.
Animal experiments suggest that maternal stress and anxiety during pregnancy have long-term effects on the behaviour of the offspring. To test the hypothesis that antenatal maternal anxiety predicts behavioural problems at age 4 years. Data were collected on multiple antenatal and postnatal assessments of maternal anxiety and depression, antenatal and obstetric risks, psychosocial risks and children's behavioural/emotional problems (n=7448). Antenatal maternal anxiety predicted behavioural/emotional problems in boys (OR=2.14, 95% CI 1.48-3.10) and girls (OR=1.88, 95% CI 1.3-2.69) after accounting for covariates. When covarying maternal anxiety up to 33 months postnatally, antenatal anxiety continued to predict total problems in boys (OR=1.56, 95% CI 1.02-2.41) and girls (OR=1.51, 95% CI 1.22-2.81). There could be a direct effect of maternal mood on foetal brain development, which affects the behavioural development of the child.


Analysis of Conjunctival Sac Microbiome in Dry Eye Patients With and Without Sjögren's Syndrome.
To analyze the conjunctival sac microbial communities in patients with Sjögren's syndrome-associated dry eyes (SSDE) and non-Sjögren's syndrome-associated dry eyes (NSSDE), compared with normal controls (NC). Conjunctival sac swab samples from 23 eyes of SSDE, 36 eyes of NSSDE, and 39 eyes of NC were collected. The V3-V4 region of the 16S ribosomal RNA (rRNA) gene high-throughput sequencing was performed on an Illumina MiSeq platform and analyzed using Quantitative Insights Into Microbial Ecology (QIIME). Alpha diversity was employed to analyze microbiome diversity through Chao1 and Shannon indexes. Beta diversity was demonstrated by the principal coordinates analysis (PCoA) and Partial Least Squares Discrimination Analysis (PLS-DA). The relative abundance was bioinformatically analyzed at the phylum and genus levels. The alpha diversity was lower in patients with dry eye disease (Shannon index: NC vs. SSDE: P = 0.020, NC vs. NSSDE: P = 0.029). The beta diversity showed divergent microbiome composition in different groups (NC vs. SSDE: P = 0.001, NC vs. NSSDE: P = 0.001, NSSDE vs. SSDE: P = 0.005). The top 5 abundant phyla were Firmicutes, Proteobacteria, Actinobacteriota, Bacteroidota, and Cyanobacteria in all three groups. The top five abundant genera included Acinetobacter, Staphylococcus, Bacillus, Corynebacterium, and Clostridium_sensu_stricto_1. The relative microbiome abundance was different between groups. The Firmicutes/Bacteroidetes (F/B) ratio was 6.42, 7.31, and 9.71 in the NC, NSSDE, and SSDE groups, respectively (NC vs. SSDE: P = 0.038, NC vs. NSSDE: P = 0.991, SSDE vs. NSSDE: P = 0.048). The diversity of conjunctival sac microbiome in patients with NSSDE and SSDE was diminished compared with NC. The main microbiome at the phylum and genus level were similar between groups, but the relative abundance had variations. The Firmicutes/Bacteroidetes ratio was higher in the SSDE group.


Netherton syndrome with ichthyosis linearis circumflexa and trichorrhexis invaginatum.
Netherton syndrome is a rare, autosomal recessive disorder that is characterized by congenital ichthyosis, trichorrhexis invaginata, and atopic diathesis. Ichthyosis presents at birth with erythroderma and subsequently evolves into ichthyosis linearis circumflexa; hair shaft abnormalities tend to present later. The disorder is caused by loss-of-function mutations in the SPINK5 (serine protease inhibitor Kazal-type 5) gene that encodes LEKTI (lympho-epithelial Kazal-type related inhibitor), which is a protease inhibitor that counteracts epidermal proteases involved in desquamation. Use of topical medications is limited by potential for systemic absorption and toxicity in the setting of a defective skin barrier. Therapeutic options include topical glucocorticoids and retinoids, oral retinoids, and narrowband ultraviolet B phototherapy. Topical tacrolimus has been shown to be efficacious and may be used safely with careful laboratory monitoring.


Chemokines in tumor immunotherapy.
The chemokines are a family of small molecules that mediate cell migration, activation, differentiation, angiogenesis, and perhaps other functions. The chemokines have been classified by their amino acid composition, functional activity, and receptor binding properties. The chemokines receptors are 7 transmembrane G proteins and there is considerable redundancy in ligand specificity. The role of chemokines in cancer is not well understood, but there is accumulating evidence that they play a major role in both tumorigenesis and the host immune response to tumors. Thus, chemokines and their receptors represent potential therapeutic targets for drug development. This article will briefly review the current understanding of chemokines biology of defined chemokines that are thought to be involved in tumor growth, metastasis, and the host immune response against cancer.


ADAPTATION TO SEASONALITY IN A CRICKET: PATTERNS OF PHENOTYPIC AND GENOTYPIC VARIATION IN BODY SIZE AND DIAPAUSE EXPRESSION ALONG A CLINE IN SEASON LENGTH.
This paper investigates patterns of phenotypic variation in the striped ground cricket (Allonemobious fasciatus) along a cline in season length and tests the hypothesis that variation in body size and diapause propensity is the result of diversifying selection due to different local conditions. We examined 83 populations and found that A. fasciatus produced a single generation per year (univoltine) north of 37°N latitude and was bivoltine south of 35°30'N. Body size generally increased with increasing season length, with a sudden drop in the region corresponding to the transition from univoltine to bivoltine life cycles, reflecting the division of total season length in two within-bivoltine populations. We reared ten populations in our laboratory and found that much of the interpopulation variance in body size observed in the field could be attributed to genetic differences. Diapause expression also varied significantly among populations and was strongly correlated with season length. The heritability of body size did not differ between populations, but full-sib estimates greatly exceeded parent-offspring estimates (h po2=0.15±0.05; h fs2=0.45±0.04) suggesting that there are important nonadditive genetic effects. The heritability of diapause expression, determined from analysis of full sibs, varied significantly between populations (0.33 ± 0.10 to 1.31 ± 0.21) with an average of 0.74 ± 0.16. Body size and diapause expression were genetically correlated in transition-zone populations, but not in univoltine or bivoltine populations. Our findings support the suggestion that clinal variation in body size and diapause expression in the striped ground cricket reflect adaptation to season length.


[Radiolabelled peptides in the diagnosis and therapy of tumours].
In the last two decades, radiolabelled receptor-specific peptides have profiled themselves as excellent tools that have expressively increased the diagnostic and therapeutical possibilities of tumours predominantly of neuroendocrine origin. The aim of this review paper is to transparently inform the Czech scientific fraternity about the significance and limitations of the use of this group of radiopharmaceuticals in clinical practice.


The Heterogeneity of Immune Cell Infiltration Landscape and Its Immunotherapeutic Implications in Hepatocellular Carcinoma.
Immunotherapy, closely associated with immune infiltration and tumor mutation burden (TMB), is emerging as a promising strategy for treating tumors, but its low response rate in hepatocellular carcinoma (HCC) remains a major challenge. Herein, we applied two algorithms to uncover the immune infiltration landscape of the immune microenvironment in 491 HCC patients. Three immune infiltration patterns were defined using the CIBERSORT method, and the immune cell infiltration (ICI) scores were established using principal component analysis. In the high ICI score group, the activation of the Wnt/β-catenin pathway was significantly enriched and expressions of immune checkpoint genes increased, which showed a pessimistic outcome. The low ICI score group was characterized by increased TMB and enrichment of metabolism-related pathways. Further analysis found that the ICI score exhibited a significant difference in age ≥65/age <65, grade I/grade II-IV, and response to immunotherapy. Moreover, the CTNNB1 mutation status was found to be closely associated with prognosis and immunotherapeutic efficiency, significantly affecting the ICI score and TMB, which might be regarded as a potential marker for the treatment of HCC. The evaluation of immune infiltration patterns can improve the understanding of the tumor immune microenvironment and provide new directions for the study of individualized immunotherapy strategies for HCC.


[The role of inhalation chambers in the treatment of asthma].
Inhalation chambers (spacers), interposed between the aerosol doser and the patient's mouth take 3 forms: lengthened tubes, large volume plastic sacs and conical chamber in the shape of a pear. Their chief advantages are: A greater proportion of the drug reaches the airways, as the deposition in the oropharynx is reduced. Co-ordination of lung and hand, a major obstacle to the correct use of aerosol-dosers, is no longer necessary.


Inhibition of type 1 human immunodeficiency virus replication by a tat antagonist to which the virus remains sensitive after prolonged exposure in vitro.
The transactivator of transcription, Tat, of human immunodeficiency virus type 1 (HIV-1) is required for viral replication. Inhibition of Tat function could have the potential to keep integrated provirus in dormancy. In the presence of Tat, Ro 24-7429, an analog of Ro 5-3335, inhibited expression of indicator genes controlled by the HIV-1 long terminal repeat promoter in transient transfection assays and in a constitutive cell line at noncytotoxic concentrations. Reduction of steady-state mRNA of the indicator gene by the compound correlated with reduction of the gene product in the constitutive cell line. Ro 24-7429 has broad activity against several strains of HIV-1 in different cell lines, peripheral blood lymphocytes, and macrophages (IC90 = 1-3 microM). Importantly, Ro 24-7429 inhibited viral replication in both acute and chronic infection in vitro, a characteristic expected of a Tat antagonist and not shared by viral reverse transcriptase inhibitors. Consistent with this, the compound reduced cell-associated viral RNA and proteins and partially restored cell-surface CD4 in chronically infected cells. After 2 years of continued weekly passage of the virus in fresh CEM cells grown in the presence of the compound at 1 or 10 microM, the virus did not develop resistance to the drug. These results indicate that the compound's action might involve a cellular factor.


[An example of internet-based quality assurance in rheumatology].
In Germany, patient care and medical progress have become increasingly influenced by quality assurance and quality management and also by a rapid increase in knowledge and information. Thus, modern information management achieves high relevance in medicine, too. The internet provides a fascinating medium with its open architecture and interaction possibilities offering new, trailblazing perspectives. This article shows examples of the current use of the internet for quality assurance at the RheumaNet, which functions as a presentation platform for the competence network for systemic inflammatory rheumatic diseases ('KN-Rheuma') in Germany. The RheumaNet has already contributed to achieving quality assurance by supplying extensive, valuable and reliable scientific information. Other innovative interactive and quality assuring applications have been developed, tested and implemented in the system. Future applications will deal with standardised online documentation modules, and aids for patient self-management are on their way.


Understanding contextual influences of community reintegration among injured servicemembers.
As part of a larger mixed-methods research project investigating the influence of contextual factors on community reintegration (CR), this qualitative study sought to understand the subjective experiences of injured servicemembers and their perception of how contextual factors influenced their CR. More specifically, this article addresses how the influences of contextual factors differ between injured servicemembers with different levels of CR. Using a phenomenological framework, semistructured interviews were conducted with nine injured, community-dwelling servicemembers with low, moderate, and high levels of CR (three per category). Participants provided in-depth descriptions of the contextual barriers and facilitators of CR. Thematic analysis indicated the importance of social support and personal factors (e.g., self-efficacy, personal motivation) as the primary means for being reintegrated into their homes and communities. Other themes indicated factors that had an indirect but important influence on CR, including adapted sports, recreation, and other social programs; rehabilitation programs and therapists; school, work, and volunteering; and organizations and policies in developing social supports and personal factors. Comparisons between servicemembers indicated participants with low CR described many more contextual barriers and far fewer contextual facilitators to reintegration than those with high CR. Those with moderate CR were unique in that they described many facilitators and barriers to reintegration.


Multiple factors contribute to acetylcholine-induced renal afferent arteriolar vasodilation during myogenic and norepinephrine- and KCl-induced vasoconstriction. Studies in the isolated perfused hydronephrotic kidney.
Acetylcholine (ACh) elicits vasodilation by releasing a number of endothelium-derived relaxing factors (EDRFs). We used the isolated perfused hydronephrotic rat kidney to examine the characteristics of ACh-induced vasodilation of renal afferent arterioles during different types of underlying vasoconstriction. Basal arteriolar tone was increased by either elevating perfusion pressure to 180 mm Hg (myogenic), administering 0.3 mumol/L norepinephrine (NE), or elevating medium potassium concentration to 30 mmol/L (KCl). ACh (10 mumol/L) completely reversed myogenic and NE-induced vasoconstriction and reversed KCl-induced vasoconstriction by 80 +/- 5%. However, whereas ACh produced a sustained vasodilation during KCl- and NE-induced vasoconstriction, only a transient reversal of myogenic vasoconstriction was observed, and myogenic tone recovered within 5 to 10 minutes. ACh-induced vasodilation of arterioles preconstricted with KCl was markedly inhibited by either indomethacin (100 mumol/L) or nitro-L-arginine (100 mumol/L) and was completely abolished by pretreatment with both inhibitors. In contrast, indomethacin and nitro-L-arginine had no effect on the transient response to ACh observed during pressure-induced vasoconstriction. In vessels preconstricted with NE, nitro-L-arginine converted the normally sustained response to ACh to a transient vasodilation, which was refractory to both nitric oxide synthase and cyclooxygenase inhibition. Since this component was not observed during KCl-induced vasoconstriction, it may reflect the actions of an, as yet unidentified, endothelium-derived hyperpolarizing factor (EDHF). Our findings thus suggest that prostanoids, nitric oxide, and EDHF all contribute to ACh-induced renal afferent arteriolar vasodilation and that the relative contributions of these individual EDRFs depends on the nature of the underlying renal vascular tone.


Effect of a Medicaid Accountable Care Collaborative on 30-Day Hospital Readmission Rates.
Hospital readmission within 30 days is undesirable and costly. Most programs and studies have focused on the Medicare population and readmission prevention through discharge planning; less is understood about how Medicaid might reduce readmissions to improve outcomes and control program costs. The objective of this study was to estimate the relationship between the Colorado Medicaid Accountable Care Collaborative (ACC) and 30-day hospital readmission rates. A difference-in-differences design was used to compare 30-day readmissions before and after Medicaid members were enrolled in the ACC program using 2 different control groups: Medicaid members not enrolled and commercially insured. The authors used Probit regressions at the hospital level, controlling for patient characteristics, and clustered errors at the provider level. The study sample included Colorado adults ages 19-64 with qualifying hospital discharge. Analysis data included Medicaid and commercial payer administrative claims data (2009-2015) from Colorado's All-Payer Claims Database. The ACC program significantly reduced 30-day readmissions among Colorado Medicaid patients. Participation in the ACC program reduced the probability of a 30-day readmission by 1.4% (P < 0.001), with the largest effect among maternity and delivery patients. Because the majority of Medicaid members are female, even after Medicaid expansion, and Medicaid covers a disproportionate share of complex births, maternity and delivery readmissions are a fruitful area for reducing Medicaid expenditures. To reduce readmissions, Medicaid programs will need to develop interventions specific to their populations.


Vibronic Coupling and Excitation Transfer in Hydrogen-Bonded Molecular Dimers: A Quantum Dynamical Analysis.
A brief pedagogic rederivation is given of basic exciton coupling theory, taking the nuclear coordinates to be fixed. This is then extended to take variations of these coordinates into account by adopting suitable multimode coupling models and extracting the transfer of excitation energy from the populations of the locally excited states. The dynamical problem thus defined is solved numerically in a fully quantal manner. Two doubly hydrogen bonded dimers of (hetero)aromatic systems are selected as representative cases whose electronic excitation spectra have been analyzed previously based on ab initio data, and good agreement with experiment has been found. The numerical calculations of the electronic populations reveal a complex time dependence of the excitation transfer that is far from being oscillatory or exponential. For localized excitation, the short-time behavior can be understood in terms of the quenched excitonic energy splitting, while for delocalized excitation a complex time dependence with rapidly changing features results. Some of these can be interpreted in terms of the vibronic structure of the excitation spectra. The importance of the quenched excitonic splitting for the short-time behavior of the excitation energy transfer is emphasized.


Fungal infections in corn picker hand injury.
Hand injuries caused by corn pickers are relatively rare but in most cases extensive, with massive tissue destruction. Severe wounds sustained during agricultural work are contaminated, with high incidence of infection. The aim of the study was to determine the frequency and type of fungal infection in corn picker injuries and their impact on the course and outcome of treatment. Corn picker hand injuries for the period 2006-2012 were analyzed. After setting up clinical suspicion, direct examination of repeated swabs and histopathological analysis of biopsy material were done in order to detect fungi. From the total number of 60 patients, there was a fungal infection in nine of them (which makes 15% of the total number of patients). Aspergillus spp. was isolated in seven patients, Candida spp. in three, and Mucor spp. in one patient. None of the patients had increased risk factors for developing a fungal infection. In most cases, there was loss of graft and tissue necrosis in previously normally look- ing wound, after seven or more days. All patients were treated with repeated surgical debridement and concomitant parenteral and topical application of appropriate antifungal agents. There was no need for reamputation in any patient. A high degree of suspicion and a multidisciplinary approach are needed for early diagnosis of fungal infection. Confirmation of diagnosis and the initiation of surgical and appropriate antifungal therapy are essential for a successful outcome.


Assessing the operation of secure care programs in New York State facilities.
In 1980 New York State's Office of Mental Health began operation of a program designed to provide a secure treatment unit at each of the 23 state psychiatric centers. As part of a research project to assess the operation of the units, demographic and hospitalization data were gathered on all clients residing on, and admitted to, the 14 operational units over a five-month period in 1982. Clinical data and information on program operation were also obtained. Results indicated that the units were generally functioning as planned, primarily serving young male civil patients referred for assaultive behavior. The patients were significantly more likely to have been involved in incidents of dangerous behavior and to have been in restraint or seclusion than were patients on comparison wards. The study also found that the secure units had been effective in reducing the rate of such incidents for the patients served. However, some data suggested the presence of an inappropriate population on certain units.


Treating pain in the older person.
Clinical guidance on the management of pain in elderly patients is presented. The way in which pain presents in elderly people and how it differs form other segments of the population are discussed.


[Molecular mechanisms underlying the formation of neuromuscular junction].
The neuromuscular junction (NMJ) is a synapse between a motor neuron and skeletal muscle. The contraction of skeletal muscle is controlled by the neurotransmitter acetylcholine (ACh), which is released from the motor nerve terminal. To achieve efficient neuromuscular transmission, acetylcholine receptors (AChRs) must be densely clustered on the muscle membrane of the NMJ. Failure of AChR clustering is associated with disorders of neuromuscular transmission such as congenital myasthenic syndromes (CMS) and myasthenia gravis (MG). Motoneuronal agrin and muscle-specific receptor tyrosine kinase (MuSK) are known to play essential roles in the formation and maintenance of NMJs in the central region of each muscle. However, it had been unclear how agrin activates MuSK. Recent studies have elucidated the roles of several key molecules, including the cytoplasmic adaptor protein Dok-7 and LDL receptor-related protein 4 (Lrp4), in agrin-induced MuSK activation. Moreover, new evidence indicates that cyclin-dependent kinase 5 (Cdk5) regulates postsynaptic differentiation. In this review, we summarize the latest developments in molecular mechanisms underlying NMJ formation in vertebrates.


The effects of ice application over the vastus medialis on the activity of quadriceps femoris assessed by muscle function magnetic resonance imaging.
The purpose of this study was to investigate the effect of ice application for the muscle vastus medialis (VM) on the activation pattern of the quadriceps femoris muscle during repetitive knee extensions using muscle function magnetic resonance imaging (mfMRI) technique. Seven men underwent transverse relaxation time (T2)-weighted magnetic resonance imaging (spin echo, TR/TE=1500/25, 80 ms, 10 mm slice thickness and gap) of their right thigh at rest and immediately after isotonic knee extension exercise with 5 sets of 10 repetitions at a load equal to 70% of their 10 repetitions with and without skin cooling. Cooling over surface skin of the VM was carried out for 3 min before and during 60-s of each rest interval between the knee extension exercise. The relative change in T2 of the muscle vastus intermedius increased significantly more by skin cooling than the control (p<0.01), but not the muscle rectus femoris (RF), muscle vastus lateralis, and VM. These results suggest that selective skin cooling combined with repeated muscle contraction facilitates the activation of other synergistic muscles, making this technique useful for activating the agonist muscles expected for injured muscle in training and rehabilitation.


Clinical and Basic Studies on Therapeutic Efficacy of Herbal Medicines against Mycobacterial Infections.
The high incidence of tuberculosis (TB) in developing countries, the resurgence of TB in industrialized countries, and the worldwide increase in the prevalence of Mycobacterium avium complex infections are important global health concerns. However, the development of novel antimycobacterial drugs is currently making very slow progress. Therefore, it is considered that devising improved administration protocols for clinical treatment against intractable mycobacteriosis using existing chemotherapeutics is more practical than awaiting the development of new antimycobacterial drugs. The regulation of host immune responses using immunoadjunctive agents may increase the efficacy of antimicrobial treatment against mycobacteriosis. In particular, the mild and long-term up-regulation of host immune reactions against mycobacterial pathogens using herbal medicines may be beneficial for such immunoadjunctive therapy. This review focuses on the current status regarding basic and clinical studies on protocols using herbal medicines, including medicinal plants, useful for the clinical treatment of intractable mycobacterial infections.


Workmen's Compensation Act; some aspects of interest to California physicians.
This article was prepared by Mr. William M. Whelan, Director of Special Services, California Medical Association, under the supervision of Dr. Francis J. Cox, Chairman of the Medical Services Commission of the Association, and Mr. Howard Hassard, the Association's Legal Counsel. It is intended as a brief synopsis of the California Workmen's Compensation Law as it applies to the physician in private practice. It is not an exhaustive treatment of the subject. A physician who desires to acquaint himself in detail with California industrial practice should consult the article entitled "The Physician's Role in Workmen's Compensation," California Medicine, 82:352-362, April, 1955. Inquiries regarding industrial medicine should be addressed to Mr. William M. Whelan, California Medical Association, 450 Sutter St., San Francisco 8.


[Expression of Type 3 Acid Sensitive Ion Channels in Bladder of OAB Rat Model].
To investigate the expression of type 3 acid-sensing ion channels (ASIC3) in bladder tissue of over active bladder (OAB) rat model. Sixty adult female rats were randomly divided into control group (intraperitoneal injection of 0.9% sodium chloride), GAB group (intraperitoneal injection of cyclophosphamide) and the intervention group (OAB rats treated with ASIC3 inhibitor amiloride). The rats underwent urodynamic testing. The bladder tissues were collected for pathological examination, while the expressions of ASIC3 were measured by the methods of immunohistochemistry, RT-PCR and Western blot. Urodynamic study found that the rats in control group had no significant contraction instability in both storage and voiding stages. Compared with the control group, OAB group and intervention group showed instability of visible contraction in urine storage stage, with shorter micturition interval (P < 0.01) and increased frequency of urination (P < 0.01). Compared with the OAB group, the intervention group showed significantly prolonged micturition interval (P < 0.05) and reduced frequency of urination (P < 0.05). Pathologic examination showed rat bladder mucosal damage in both OAB group and intervention group. Immunohistochemistry found the expression of ASIC3 on bladder mucosa. RT-PCR and Western blot showed significantly higher expression of ASIC3 in OAB group (P < 0.01), but the expression of ASIC3 decreased in intervention group after adding ASIC3 inhibitor. CONCLUSION ASIC3 expresses mainly on bladder mucosa. The gene and protein expression of ASIC3 in rat bladder tissue of OAB rats is higher, which can be significantly decreased by ASIC inhibitor. The symptoms of OAB reduce after intervention, which demonstrates the increased expression of ASIC3 in bladder tissue is closely related to bladder detrusor.


The role of aggression-related early maladaptive schemas and schema modes in aggression in a prisoner sample.
Contemporary social-cognitive aggression theory and extant empirical research highlights the relationship between certain Early Maladaptive Schemas (EMSs) and aggression in offenders. To date, the related construct of schema modes, which presents a comprehensive and integrated schema unit, has received scant empirical attention. Furthermore, EMSs and schema modes have yet to be examined concurrently with respect to aggressive behavior. This study examined associations between EMSs, schema modes, and aggression in an offender sample. Two hundred and eight adult male prisoners completed self-report psychological tests measuring their histories of aggression, EMSs, and schema modes. Regression analyses revealed that EMSs were significantly associated with aggression but did not account for a unique portion of variance once the effects of schema modes were taken into account. Three schema modes, Enraged Child, Impulsive Child, and Bully and Attack, significantly predicted aggression. These findings support the proposition that schema modes characterized by escalating states of anger, rage, and impulsivity characterize aggressive offenders. In this regard, we call attention to the need to include schema modes in contemporary social-cognitive aggression theories, and suggest that systematic assessment and treatment of schema modes has the potential to enhance outcomes with violent offenders.


Vascular smooth muscle function is associated with initiation and processing speed in patients with atherosclerotic vascular disease.
We previously reported a relationship between forearm resistance vessel function and global neuropsychological performance in patients with atherosclerotic vascular disease (AVD). This study was conducted to determine the relationships among vascular smooth muscle function, endothelial function, and initiation and processing speed in this sample. Participants were 80 individuals with AVD. Resistance vessel function was measured before and after infusion of vasoactive agents. Neuropsychological assessment included measures of estimated premorbid cognitive function, current global cognitive function, initiation, and processing speed. Vascular smooth muscle function was significantly associated with the initiation/processing speed composite score [R-Square Change = .152; F Change (1,71) = 16.61; p < .001], above and beyond the variance accounted for by age, education, premorbid cognitive function, and endothelium-dependent vascular function. This relationship remained significant when controlling for current level of global cognitive functioning and 10 vascular risk factors. Endothelium-dependent vascular function was not significantly associated with test performance. Decreased vascular smooth muscle function in forearm resistance vessels was significantly associated with relatively poor initiation and processing speed in individuals with AVD. With additional research, measures of vascular function might become useful in the early identification of those individuals at greatest risk for vascular-related cognitive dysfunction.


Vaccines and risk of lymphoedema--a case report of a breast cancer patient.
Vaccinations have been linked to lymphoedema but there is no quality scientific evidence to support or refute a causative relationship. We report on a case of a breast cancer patient who developed lymphoedema following vaccination in her 'at risk' arm. She had previously undergone mastectomy and axillary clearance but did not have lymphoedema before the vaccinations. The risk of lymphoedema is still present for many years following breast surgery. Patients who are at risk of lymphoedema should be warned to report persistent swelling after vaccination so that they can be referred early for physiotherapy intervention if required.


Surgical resection of esophagogastric junction stromal tumor: How to protect the cardiac function.
Various surgical procedures have been described for gastrointestinal stromal tumors (GISTs) at the esophagogastric junction (EGJ) close to the Z-line. However, surgery for EGJ-GIST involving Z-line has been rarely reported. To introduce a novel technique called conformal resection (CR) for open resection of EGJ-GIST involving Z-line. In this retrospective study, 43 patients having GISTs involving Z-line were included. The perioperative outcomes of patients receiving CR (n = 18) was compared with that of proximal gastrectomy (PG) (n = 25). CR was successfully performed in all the patients with negative microscopic margins. The mean operative time, time to first passage of flatus, and postoperative hospital stay was significantly shorter in the CR group (P < 0.05), while the intraoperative blood loss was similar in the two groups. The postoperative gastroesophageal reflux as diagnosed by esophageal 24-h pH monitoring and quality of life at 3 mo were significantly in favor of CR compared to PG (both P < 0.001). The 5-year disease-free survival between the two groups was similar (P = 0.163). The cut- off value for the determination of CR or PG was 7.0 mm above the Z-line (83.33% sensitivity, 84.00% specificity, 83.72% accuracy). CR is safe and feasible for EGJ-GIST located within 7.0 mm above the Z-line.


Scenario of a dirty bomb in an urban environment and acute management of radiation poisoning and injuries.
In the new security environment, there is a clear and present danger of terrorists using non-conventional weapons to inflict maximum psychological and economic damage on their targets. This article examines two scenarios of radiation contamination and injury, one accidental in nature leading to environmental contamination, and another of deliberate intent resulting in injury and death. This article also discusses the management of injury from radiological dispersion devices or dirty bombs, with emphasis on the immediate aftermath as well as strategy recommendations.


[Review for treatment effect and signaling pathway regulation of kidney-tonifying traditional Chinese medicine on osteoporosis].
The treatment effect and signaling pathway regulation effects of kidney-tonifying traditional Chinese medicine on osteoporosis have been widely studied, but there is no systematic summary currently. This review comprehensively collected and analyzed the traditional Chinese medicines on the treatment and signaling pathway regulation of osteoporosis in recent ten years, such as Epimedii Folium, Drynariae Rhizoma, Cnidii Fructus, Eucommiae Cortex, Psoraleae Fructus and Dipsaci Radix. Based on the existing findings, the following conclusions were obtained: ①kidney-tonifying traditional Chinese medicine treated osteoporosis mainly through BMP-Smads, Wnt/β-catenin, MAPK, PI3K/AKT signaling pathway to promote osteoblast bone formation and through OPG/RANKL/ RANK, estrogen, CTSK signaling pathway to inhibit osteoclasts of bone resorption. Epimedii Folium, Drynariae Rhizoma, Cnidii Fructus and Psoraleae Fructus up-regulated the expression of key proteins and genes of BMP-Smads and Wnt/β-catenin signaling pathways to promote bone formation. Epimedii Folium, Drynariae Rhizoma, Cnidii Fructus, Eucommiae Cortex, Psoraleae Fructus and Dipsaci Radix inhibited the bone resorption by mediating the OPG/RANKL/RANK signaling pathway. ②Kidney-tonifying traditional Chinese medicine prevented and treated osteoporosis through a variety of ways: icariin in Epimedii Folium, naringin in Drynariae Rhizoma, osthole in Cnidii Fructus and psoralen in Psoraleae Fructus can regulate BMP-Smads, Wnt/β-catenin signaling pathway to promote bone formation, but also activate OPG/RANKL/RANK, CTSK and other signaling pathways to inhibit bone resorption. ③The crosstalk of the signaling pathways and the animal experiments of the traditional Chinese medicine on the prevention and treatment of osteoporosis as well as their multi-target mechanism and comprehensive regulation need further clarification.


Cellular Trafficking of Sn-2 Phosphatidylcholine Prodrugs Studied with Fluorescence Lifetime Imaging and Super-resolution Microscopy.
While the in vivo efficacy of Sn-2 phosphatidylcholine prodrugs incorporated into targeted, non-pegylated lipid-encapsulated nanoparticles was demonstrated in prior preclinical studies, the microscopic details of cell prodrug internalization and trafficking events are unknown. Classic fluorescence microscopy, fluorescence lifetime imaging microscopy, and single-molecule super-resolution microscopy were used to investigate the cellular handling of doxorubicin-prodrug and AlexaFluor™-488-prodrug. Sn-2 phosphatidylcholine prodrugs delivered by hemifusion of nanoparticle and cell phospholipid membranes functioned as phosphatidylcholine mimics, circumventing the challenges of endosome sequestration and release. Phosphatidylcholine prodrugs in the outer cell membrane leaflet translocated to the inner membrane leaflet by ATP-dependent and ATP-independent mechanisms and distributed broadly within the cytosolic membranes over the next 12 h. A portion of the phosphatidylcholine prodrug populated vesicle membranes trafficked to the perinuclear Golgi/ER region, where the drug was enzymatically liberated and activated. Native doxorubicin entered the cells, passed rapidly to the nucleus, and bound to dsDNA, whereas DOX was first enzymatically liberated from DOX-prodrug within the cytosol, particularly in the perinuclear region, before binding nuclear dsDNA. Much of DOX-prodrug was initially retained within intracellular membranes. In vitro anti-proliferation effectiveness of the two drug delivery approaches was equivalent at 48 h, suggesting that residual intracellular DOX-prodrug may constitute a slow-release drug reservoir that enhances effectiveness. We have demonstrated that Sn-2 phosphatidylcholine prodrugs function as phosphatidylcholine mimics following reported pathways of phosphatidylcholine distribution and metabolism. Drug complexed to the Sn-2 fatty acid is enzymatically liberated and reactivated over many hours, which may enhance efficacy overtime.


Asymmetric synthesis of bioactive hydrodibenzofuran alkaloids: (-)-lycoramine, (-)-galanthamine, and (+)-lunarine.
Divergent route: a direct C-C bond-forming approach to the key aryl-substituted all-carbon quaternary stereogenic center present in bioactive hydrodibenzofuran alkaloids has been discovered. This approach involves an unprecedented organocatalytic enantioselective Michael addition of α-cyanoketones with acrylates and was used in a novel and divergent synthetic strategy for the title compounds in asymmetric fashion.


Calculation of inspired oxygen fraction during anaesthesia based on awake oxygen saturation.
One hundred ASA grade 1 or 2 patients were studied to assess the use of awake oxygen saturation to determine the necessary inspired oxygen fraction during anaesthesia. The inspired oxygen fraction was adjusted gradually to the lowest possible value to maintain the pre-operative oxygen saturation at a constant level. Normocapnic ventilation was maintained and analgesia was provided with 0.5mg.kg-1 of pethidine given intravenously. In addition to routine monitoring and measurement (electrocardiograph, oxygen saturation, expired carbon dioxide concentration and noninvasive blood pressure), arterial samples for blood gas analysis and venous samples for lactate and pyruvate levels were taken when awake and 30 min after achieving a steady state with a minimum inspired oxygen fraction. The mean inspired oxygen fraction required in these patients was 20.91 (SD 1.92%) ranging from 18-25%. The arterial pH were 7.34 (SD 4.04) (awake) and 7.35 (SD 3.15) (after 30 min), the partial pressure of oxygen 13.17 (SD 1.97) (awake) and 13.83 (SD 1.6 kPa) (after 30 min) and the partial pressure of carbon dioxide and base excess were normal. Serum lactate levels were 1.04 (SD 0.25) (awake) and 1.15 (SD 0.48) (after 30 min) mmol.l-1, whilst pyruvate levels were 0.1 (SD 0.02) (awake) and 0.12 (SD 0.21) (after 30 min) mmol.l-1. Patients' recovery and postoperative course were uneventful.


Assessment of health-related quality of life and how it predicts the outcome of pegylated interferon and ribavirin therapy for chronic hepatitis C.
Chronic infection with hepatitis C virus (HCV) decreases health-related quality of life (HRQOL). The present study was planned to investigate the impact of HRQOL of patients with chronic hepatitis C (CHC) on the outcomes of therapy with pegylated interferon and ribavirin (RBV), in addition to IL28B polymorphisms. The present study enrolled 228 CHC patients and assessed their HRQOLs prospectively with the 36-item short-form health survey. The patients with CHC have lower physical HRQOL status than the general population (P = 0.037, the Z-test). The patients with advanced liver diseases exhibited further decreases in HRQOL (P = 0.036, Spearman's rank correlation coefficient). The score of total HRQOL was significantly lower in the group with sustained virological response (SVR) to the therapy with pegylated interferon and RBV than the non-SVR group (P = 0.031, the Mann-Whitney U-test), with significantly lower scores of mental component and its comprising subscales in the SVR group. Stepwise multivariate logistic regression analysis showed that low HRQOL score ≤ 400 points was significantly associated with SVR (odds ratio = 2.4, P = 0.013), independently from high platelet counts, low HCV RNA, favorable single-nucleotide polymorphism type of IL28B, and HCV serotype 2. The patients with low HRQOL score will have significantly less decrease in HRQOL score by 4 weeks of the treatment than those with high HRQOL score at baseline (P = 0.0045). HRQOL is one of the significant predictor of the outcomes of therapy with pegylated interferon and RBV independently from IL28B polymorphism.


Secretogranin III Selectively Promotes Vascular Leakage in the Deep Vascular Plexus of Diabetic Retinopathy.
Diabetic retinopathy (DR), a leading cause of vision loss in working-age adults, induces mosaic patterns of vasculopathy that may be associated with spatial heterogeneity of intraretinal endothelial cells. We recently reported that secretogranin III (Scg3), a neuron-derived angiogenic and vascular leakage factor, selectively binds retinal vessels of diabetic but not healthy mice. Here, we investigated endothelial heterogeneity of three retinal vascular plexuses in DR pathogenesis and the therapeutic implications. Our unique in vivo ligand binding assay detected a 22.7-fold increase in Scg3 binding to retinal vessels of diabetic mice relative to healthy mice. Functional immunohistochemistry revealed that Scg3 predominantly binds to the DR-stressed CD31- deep retinal vascular plexus but not to the relatively healthy CD31+ superficial and intermediate plexuses within the same diabetic retina. In contrast, VEGF bound to healthy and diabetic retinal vessels indiscriminately with low activity. FITC-dextran assays indicated that selectively increased retinal vascular leakage coincides with Scg3 binding in diabetic mice that was independent of VEGF, whereas VEGF-induced leakage did not distinguish between diabetic and healthy mice. Dose-response curves showed that the anti-Scg3 humanized antibody (hAb) and anti-VEGF aflibercept alleviated DR leakage with equivalent efficacies, and that the combination acted synergistically. These findings suggest: (i) the deep plexus is highly sensitive to DR; (ii) Scg3 binding to the DR deep plexus coincides with the loss of CD31 and compromised endothelial junctions; (iii) anti-Scg3 hAb alleviates vascular leakage by selectively targeting the DR-stressed deep plexus within the same diabetic retina; (iv) combined anti-Scg3 and anti-VEGF treatments synergistically ameliorate DR through distinct mechanisms.


Genome Sequence of Streptococcus phocae subsp. salmonis Strain C-4T, Isolated from Atlantic Salmon (Salmo salar).
Streptococcus phocae subsp. salmonis is a fish pathogen that has an important impact on the Chilean salmon industry. Here, we report the genome sequence of the type strain C-4(T) isolated from Atlantic salmon (Salmo salar), showing a number of interesting features and genes related to its possible virulence factors.


Exploring the best predictors of fluid responsiveness in patients with septic shock.
To evaluate respiratory variations in carotid and brachial peak velocity and other hemodynamic parameters to predict responsiveness to fluid challenge. A prospective observational study was performed on mechanically ventilated patients with septic shock. Outcomes included the measurements of central venous pressure, intrathoracic blood volume index, stroke volume variation (SVV), pleth variability index(PVI), and ultrasound assessments of respiratory variations in inferior vena cava diameter (ΔIVC), carotid Doppler peak velocity (ΔCDPV), and brachial artery peak velocity (ΔVpeak brach). All patients received 200 mL normal saline challenge. There were 27 responders and 22 non-responders. Responders had higher SVV, PVI, ΔIVC, ΔCDPV, and ΔVpeak brach measurements. In addition, all these measurements had statistically significant linear correlations with changes in cardiac index (CI).When responders were defined by ΔCI≥10%, receiver operating characteristics (ROC) curve analysis showed that fluid responsiveness could be predicted:11.5% optimal cut-off 1evels of SVV with sensitivity of 75% and specificity of 85%, 15.5% optimal cut-off 1evels of PVI with sensitivity of 65% and specificity of 80%, 20.5% optimal cut-off 1evels of ΔIVC with sensitivity of 67% and specificity of 77%, 13% optimal cut-off 1evels of ΔCDPV with sensitivity of 78%% and specificity of 90%, 11.7% optimal cut-off 1evels of ΔVpeak brach with sensitivity of 70% and specificity of 80%. Ultrasound assessment of ΔIVC and ΔVpeak brach, especially ΔCDPV, could predict fluid responsiveness and might be recommended as a continuous and noninvasive method to monitor functional hemodynamic parameter in mechanically ventilated patients with septic shock.


The study of endogenous hepatocyte growth factor in the pathogenesis of intracranial aneurysms.
Inflammation as a significant influence factor plays an important role in the formation and rupture of intracranial aneurysms. However, based on plenty of related studies, it is believed that the hepatocyte growth factor (HGF) is able to prevent vascular inflammation. This paper, therefore, explored the role and mechanism of endogenous HGF in the pathogenesis of intracranial aneurysms. 16 blood samples were collected from the intracranial aneurysms and the lumens of the femoral artery of 16 patients. Comparison and quantitative detection of HGF serum concentrations in an aneurysm and femoral artery samples according to the immune assay based on Luminex were followed. The tissue of superficial temporal artery (STA) and ruptured or unruptured intracranial aneurysm from the patients (n=10) who were performed surgical clipping of craniotomy was then collected. The intracranial aneurysm model was induced by surgery on adult c57/B16 mouse and grouping administration of c-Met antagonist PF-04217903 or its solvent DMSO for 3 weeks. Then, the brains of the experimental mouse were dissected and examined whether there were intracranial aneurysms and/or subarachnoid hemorrhage (SAH). The procedures followed by treatment of human endothelial cells cultured in vitro, smooth muscle cells and monocytes with HGF and PF-04217903 lipopolysaccharide (LPS). Through Real-time fluorescence quantitative PCR, with ΔΔCt methods, we used the expressions of β-actin normalized inflammatory factor [intercellular adhesion molecule-1 (ICAM-1)], vascular cell adhesion molecule-1 (VCAM-1), E-selectin, tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), monocyte chemoattractant protein-1 (MCP-1), cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2) and transforming growth factor-β (TGF-β). It was found that the concentration of HGF (1076±656) pg/ml from the blood collected from human intracranial aneurysms was significantly higher than that from the femoral artery (196±436) pg/ml (p<0.01). Experimental mouse treated with PF-04217903 (c-Met antagonist) and in control group were induced to form intracranial aneurysms. C-Met antagonists did not alter the formation of intracranial aneurysms (p>0.05), but significantly increased the occurrence of subarachnoid hemorrhage and reduced the survival rate of mice (p<0.05). HGF attenuated the expression of VCAM-1 (p<0.05) and E-selectin (p<0.05) in human aortic endothelial cells CONCLUSIONS: The plasma HGF levels were elevated in intracranial aneurysms, and the HGF and c-Met were expressed in STA and intracranial aneurysms. In the treatment of intracranial aneurysms, HGF signaling pathway reduced inflammation in endothelial cells and prevented the rupture of intracranial aneurysm through c-Met.


Experiences of Social Support Among Chinese Women with Breast Cancer: A Qualitative Analysis Using a Framework Approach.
BACKGROUND Breast cancer and its treatment provoke a series of emotional changes in patients during their breast cancer journeys. Social support is critical in helping women cope with their negative emotional responses. However, few studies have described the experiences of women with breast cancer within the Chinese context. This qualitative study explored the experiences of Chinese women with breast cancer regarding social support. MATERIAL AND METHODS This qualitative study was based on constructivism epistemology. Chinese women with breast cancer were invited to interview between June and August 2016. Purposive sampling was used, and the women were recruited until data saturation was reached (n=25). RESULTS We found that all participants expressed the importance of social support during their breast cancer journeys. The thematic framework of social support was identified, which included the following 4 interrelated themes: providers, types of support, outcomes of support, and challenges for care. CONCLUSIONS Social support is important in the health care of women living with breast cancer. Healthcare professionals should provide more individualized support and care to women during this vulnerable period.


The Brazilian research and teaching center in biomedicine and aerospace biomedical engineering.
The recent engagement of Brazil in the construction and utilization of the International Space Station has motivated several Brazilian research institutions and universities to establish study centers related to Space Sciences. The Pontificia Universidade Catolica do Rio Grande do Sul (PUCRS) is no exception. The University initiated in 1993 the first degree course training students to operate commercial aircraft in South America (the School of Aeronautical Sciences. A further step was the decision to build the first Brazilian laboratory dedicated to the conduct of experiments in ground-based microgravity simulation. Established in 1998, the Microgravity Laboratory, which was located in the Instituto de Pesquisas Cientificas e Tecnologicas (IPCT), was supported by the Schools of Medicine, Aeronautical Sciences and Electrical Engineering/Biomedical Engineering. At the end of 2006, the Microgravity Laboratory became a Center and was transferred to the School of Engineering. The principal activities of the Microgravity Centre are the development of research projects related to human physiology before, during and after ground-based microgravity simulation and parabolic flights, to aviation medicine in the 21st century and to aerospace biomedical engineering. The history of Brazilian, and why not say worldwide, space science should unquestionably go through PUCRS. As time passes, the pioneering spirit of our University in the aerospace area has become undeniable. This is due to the group of professionals, students, technicians and staff in general that have once worked or are still working in the Center of Microgravity, a group of faculty and students that excel in their undeniable technical-scientific qualifications.


Relationship between clinical signs and postmortem test status in cattle experimentally infected with the bovine spongiform encephalopathy agent.
Various clinical protocols have been developed to aid in the clinical diagnosis of classical bovine spongiform encephalopathy (BSE), which is confirmed by postmortem examinations based on vacuolation and accumulation of disease-associated prion protein (PrPd) in the brain. The present study investigated the occurrence and progression of sixty selected clinical signs and behaviour combinations in 513 experimentally exposed cattle subsequently categorised postmortem as confirmed or unconfirmed BSE cases. Appropriate undosed or saline inoculated controls were examined similarly and the data analysed to explore the possible occurrence of BSE-specific clinical expression in animals unconfirmed by postmortem examinations. Based on the display of selected behavioural, sensory and locomotor changes, 20 (67%) orally dosed and 17 (77%) intracerebrally inoculated pathologically confirmed BSE cases and 21 (13%) orally dosed and 18 (6%) intracerebrally inoculated but unconfirmed cases were considered clinical BSE suspects. None of 103 controls showed significant signs and were all negative on diagnostic postmortem examinations. Signs indicative of BSE suspects, particularly over-reactivity and ataxia, were more frequently displayed in confirmed cases with vacuolar changes in the brain. The display of several BSE-associated signs over time, including repeated startle responses and nervousness, was significantly more frequent in confirmed BSE cases compared to controls, but these two signs were also significantly more frequent in orally dosed cattle unconfirmed by postmortem examinations. The findings confirm that in experimentally infected cattle clinical abnormalities indicative of BSE are accompanied by vacuolar changes and PrPd accumulation in the brainstem. The presence of more frequently expressed signs in cases with vacuolar changes is consistent with this pathology representing a more advanced stage of disease. That BSE-like signs or sign combinations occur in inoculated animals that were not confirmed as BSE cases by postmortem examinations requires further study to investigate the potential causal relationship with prion disease.


Development and Assessment of a Horizontally Integrated Biological Sciences Course Sequence for Pharmacy Education.
To design and assess a horizontally integrated biological sciences course sequence and to determine its effectiveness in imparting the foundational science knowledge necessary to successfully progress through the pharmacy school curriculum and produce competent pharmacy school graduates. A 2-semester course sequence integrated principles from several basic science disciplines: biochemistry, molecular biology, cellular biology, anatomy, physiology, and pathophysiology. Each is a 5-credit course taught 5 days per week, with 50-minute class periods. Achievement of outcomes was determined with course examinations, student lecture, and an annual skills mastery assessment. The North American Pharmacist Licensure Examination (NAPLEX) results were used as an indicator of competency to practice pharmacy. Students achieved course objectives and program level outcomes. The biological sciences integrated course sequence was successful in providing students with foundational basic science knowledge required to progress through the pharmacy program and to pass the NAPLEX. The percentage of the school's students who passed the NAPLEX was not statistically different from the national percentage.


Aη-α and Aη-β peptides impair LTP ex vivo within the low nanomolar range and impact neuronal activity in vivo.
Amyloid precursor protein (APP) processing is central to Alzheimer's disease (AD) etiology. As early cognitive alterations in AD are strongly correlated to abnormal information processing due to increasing synaptic impairment, it is crucial to characterize how peptides generated through APP cleavage modulate synapse function. We previously described a novel APP processing pathway producing η-secretase-derived peptides (Aη) and revealed that Aη-α, the longest form of Aη produced by η-secretase and α-secretase cleavage, impaired hippocampal long-term potentiation (LTP) ex vivo and neuronal activity in vivo. With the intention of going beyond this initial observation, we performed a comprehensive analysis to further characterize the effects of both Aη-α and the shorter Aη-β peptide on hippocampus function using ex vivo field electrophysiology, in vivo multiphoton calcium imaging, and in vivo electrophysiology. We demonstrate that both synthetic peptides acutely impair LTP at low nanomolar concentrations ex vivo and reveal the N-terminus to be a primary site of activity. We further show that Aη-β, like Aη-α, inhibits neuronal activity in vivo and provide confirmation of LTP impairment by Aη-α in vivo. These results provide novel insights into the functional role of the recently discovered η-secretase-derived products and suggest that Aη peptides represent important, pathophysiologically relevant, modulators of hippocampal network activity, with profound implications for APP-targeting therapeutic strategies in AD.


Study on the effect of peripheral kisspeptin administration on basal and glucose-induced insulin secretion under fed and fasting conditions in the adult male rhesus monkey (Macaca mulatta).
Kisspeptin (KP)-Kiss1r, a ligand-receptor pair, has recently been implicated as a pivotal regulator of the neuroendocrine reproductive axis. KISS1 (encoding KP) as well as KISS1R (encoding receptor for KP) are expressed in several peripheral tissues including the pancreas. But the specific role of KP in the physiology of pancreas is still incompletely deciphered. This study was designed to examine the effect of peripheral KP administration on basal and glucose-induced plasma insulin (an important pancreatic hormone) secretion under fed and fasting conditions in the adult male rhesus monkey. A set of 4 chair-restraint habituated intact adult male rhesus monkeys were assigned to receive intravenous bolus administration of human kisspeptin-10 (KP10, 50 μg), and vehicle (1 ml) in normal fed and fasting conditions without or with glucose infusions. Plasma concentrations of insulin were measured by using a specific IRMA. Glucose infusion significantly stimulated plasma insulin levels (p<0.005). Vehicle administration did not affect both basal and glucose stimulated insulin in fed as well as in fasting condition. KP10 administration had no effect on the basal insulin levels in both fed and fasting as compared to pretreatment or vehicle treatment levels, while it significantly heightened glucose stimulated insulin levels (p<0.05) in both fed and fasted monkeys. The present results show that KP administration does not affect the basal secretion of insulin under both fed and fasting condition while potentiated the glucose-induced insulin levels in the adult male rhesus monkey. Therefore, these findings suggest a potential role of KP in the physiology of pancreas.


Systemic Sclerosis Presenting With Frank Exhibition of Mizutani's Sign.
Systemic sclerosis is an autoimmune connective tissue disease (AICTD) known for its hallmark feature of fibrosis affecting the skin, blood vessels, and viscera. The maintenance of the extracellular matrix (ECM) involves fibroblasts and other cells, which play a vital role in the degradation and replacement of damaged proteins such as collagens with new ones. The continuous stimulation of fibroblasts results in the overproduction of extracellular matrix proteins, leading to the progression of fibrosis. Although the exact etiology of scleroderma is not clear, the onset of the condition has been attributed to genetic and environmental factors. Excessive collagen buildup in the dermis is the telltale sign of the disease. Clinicians face significant challenges in managing systemic sclerosis. Management is based on reducing or eliminating complaints to improve organ function, and frequently, multidisciplinary involvement is required. The aim of this case report is to emphasize the importance of the recognition of Mizutani's sign, which makes it prudent to rule out the presence of systemic sclerosis.