Midazolam and its effect on vital signs and behavior in children under conscious sedation in dentistry.
Midazolam is a short acting sedative with small number of adverse effects. Administered orally, it is currently the most common form of conscious sedation in children. The objective of this paper is to describe effect of midazolam administered to children during dental treatment on their vital signs, and to monitor changes in children's behavior. We described values of vital signs and behavior in 418 sedations conducted in 272 children between 1-12 years of age. To achieve the following results, we used data from 272 all first-time sedations. After administration of midazolam arterial blood pressure and blood oxygen saturation decreased by values which were not clinically significant. The heart rate increased, with values staying within the limits of physiological range. The speed of onset of midazolam's clinical effects depends on age and dose. The lower age and dose correlated with the higher behavior score. The effectiveness of midazolam treatment is 97.8 %. Unwillingness of child to receive midazolam is predictor for disruptive behavior during sedation. 1.8 % of all sedation cases showed paradoxical reactions. The administration of midazolam in dose of 0.5 mg per 1 kg of child's body weight is safe and could be recommended for dental treatment in pediatric dentistry.


State regulatory enforcement and nursing home termination from the medicare and medicaid programs.
Nursing homes certified by the Medicare and/or Medicaid program are subject to federally mandated and state-enforced quality and safety standards. We examined the relationship between state quality enforcement and nursing home terminations from the two programs. Using data from a survey of state licensure and certification agencies and other secondary databases, we performed bivariate and multivariate analyses on the strength of state quality regulation in 2005, and nursing home voluntary terminations (decisions made by the facility) or involuntary terminations (imposed by the state) in 2006-2007. Involuntary terminations were rarely imposed by state regulators, while voluntary terminations were relatively more common (2.16 percent in 2006-2007) and varied considerably across states. After controlling for facility, market, and state covariates, nursing homes in states implementing stronger quality enforcement were more likely to voluntarily terminate from the Medicare and Medicaid programs (odds ratio = 1.53, p = .018). Although involuntary nursing home terminations occurred rarely in most states, nursing homes in states with stronger quality regulations tend to voluntarily exit the publicly financed market. Because of the consequences of voluntary terminations on patient care and access, state regulators need to consider the effects of increased enforcement on both enhanced quality and the costs of termination.


HMIS and decision-making in Zambia: re-thinking information solutions for district health management in decentralized health systems.
At the onset of health system decentralization as a primary health care strategy, which constituted a key feature of health sector reforms across the developing world, efficient and effective health management information systems (HMIS) were widely acknowledged and adopted as a critical element of district health management strengthening programmes. The focal concern was about the performance and long-term sustainability of decentralized district health systems. The underlying logic was that effective and efficient HMIS would provide district health managers with the information required to make effective strategic decisions that are the vehicle for district performance and sustainability in these decentralized health systems. However, this argument is rooted in normative management and decision theory without significant unequivocal empirical corroboration. Indeed, extensive empirical evidence continues to indicate that managers' decision-making behaviour and the existence of other forms of information outside the HMIS, within the organizational environment, suggest a far more tenuous relationship between the presence of organizational management information systems (such as HMIS) and effective strategic decision-making. This qualitative comparative case-study conducted in two districts of Zambia focused on investigating the presence and behaviour of five formally identified, different information forms, including that from HMIS, in the strategic decision-making process. The aim was to determine the validity of current arguments for HMIS, and establish implications for current HMIS policies. Evidence from the eight strategic decision-making processes traced in the study confirmed the existence of different forms of information in the organizational environment, including that provided by the conventional HMIS. These information forms attach themselves to various organizational management processes and key aspects of organizational routine. The study results point to the need for a radical re-think of district health management information solutions in ways that account for the existence of other information forms outside the formal HMIS in the district health system.


Mouse mutants lacking the type 2 IGF receptor (IGF2R) are rescued from perinatal lethality in Igf2 and Igf1r null backgrounds.
The cation-dependent and cation-independent mannose 6-phosphate receptors (CD- and CI-MPRs) bind the phosphomannosyl recognition marker of lysosomal hydrolases, but in mammals the latter also interacts with insulin-like growth factor II (IGF-II). While IGF signaling is mediated by the type 1 IGF receptor (IGF1R), the type 2 receptor (IGF2R/CI-MPR) serves IGF-II turnover. Mouse mutants inheriting maternally a targeted disruption of the imprinted Igf2r gene, which is normally expressed only from the maternal allele, have increased serum and tissue levels of IGF-II and exhibit overgrowth (135% of normal birthweight) and generalized organomegaly, kinky tail, postaxial polydactyly, heart abnormalities, and edema. These mutants usually die perinatally, but a small minority can survive depending on genetic background and can occasionally reproduce, except for some females characterized by an imperforate vagina and hydrometrocolpos. Consistent with the hypothesis that lethality in the absence of IGF2R-mediated turnover is caused by excess of IGF-II overstimulating IGF1R, Igf2r mutants are completely rescued when they carry a second mutation eliminating either IGF-II or IGF1R. Normal embryonic development of the Igf1r/Igf2r double mutants, which differ from wild-type siblings only in the pattern of postnatal growth, appears to occur by signaling of IGF-II, being in excess, through a genetically identified unknown receptor, since triple mutants lacking IGF1R, IGF2R, and IGF-II are nonviable dwarfs (30% of normal size). In contrast with the Igf2r/Igf2 double mutants, mice lacking IGF2R/CI-MPR and CD-MPR survive in an IGF-II null background at a very low frequency and only for a few postnatal weeks, indicating that the mannose 6-phosphate-mediated lysosomal enzyme trafficking is essential for viability.


Stable physical activity tracking during children's guided active play.
Physical activity (PA) decreases during childhood with PA tracking statistics showing moderate coefficients in early childhood moving to poor coefficients in late childhood. The age-related instability of PA tracking is attributed to variations in age-related PA behaviors when quantifying PA in different settings (in/out of school, sports camps, and habitual PA). This study has examined the stability of age-related PA for children (from 7 to 11 years) during self-paced guided active play (GAP) sessions separated by 12 months. Children (n = 65) recruited from community camps in two consecutive years were assessed for growth and PA participation during GAP sessions (1 h.d-1 on 2 d.wk-1) using cooperative games. Accelerometer outputs were used to quantify PA and estimate energy expenditure (EE) and moderate-to-vigorous PA (MVPA). Tracking statistics were assessed by Spearman coefficients (r) and agreement scores for percentile rankings (Kappa (k)) after a 1-year interval. Grouped data for PA tracking (EE) over the 1-year interval showed strong coefficients (r = 0.88, p = 0.001) and moderate agreement scores (k = 0.54). Boys and girls showed similar results. During the 1-year interval, the MVPA tracking coefficient was r = 0.54 (p = 0.01) with a moderate k score of 0.47. Age-related PA (EE) tracking coefficients at 7 (r = 0.90), 8 (r = 0.88), 10 (r = 0.82), and 11 (r = 0.83) years showed strong coefficients except at 9 years (r = 0.51). Children's age-related PA tracking (EE and MVPA) is stable during self-paced GAP assessed over a 1-year interval. Since PA tracking is stable in self-paced GAP, GAP should be included in children's PA intervention strategies to improve health and fitness.


Natural flow regimes, nonnative fishes, and native fish persistence in arid-land river systems.
Escalating demands for water have led to substantial modifications of river systems in arid regions, which coupled with the widespread invasion of nonnative organisms, have increased the vulnerability of native aquatic species to extirpation. Whereas a number of studies have evaluated the role of modified flow regimes and nonnative species on native aquatic assemblages, few have been conducted where the compounding effects of modified flow regimes and established nonnatives do not confound interpretations, particularly at spatial and temporal scales that are relevant to conservation of species at a range-wide level. By evaluating a 19-year data set across six sites in the relatively unaltered upper Gila River basin, New Mexico, USA, we tested how natural flow regimes and presence of nonnative species affected long-term stability of native fish assemblages. Overall, we found that native fish density was greatest during a wet period at the beginning of our study and declined during a dry period near the end of the study. Nonnative fishes, particularly predators, generally responded in opposite directions to these climatic cycles. Our data suggested that chronic presence of nonnative fishes, coupled with naturally low flows reduced abundance of individual species and compromised persistence of native fish assemblages. We also found that a natural flow regime alone was unlikely to ensure persistence of native fish assemblages. Rather, active management that maintains natural flow regimes while concurrently suppressing or excluding nonnative fishes from remaining native fish strongholds is critical to conservation of native fish assemblages in a system, such as the upper Gila River drainage, with comparatively little anthropogenic modification.


Small Area Analysis of Veterans Affairs Mental Health Services Data.
To identify geographic variation in mental health service use in the Department of Veterans Affairs (VA), the authors constructed utilization-based VA mental health service areas (MHSAs) for outpatient treatment and mental health referral regions (MHRRs) for residential and acute inpatient treatment. MHSAs are empirically derived geographic groupings of one or more counties containing one or more VA outpatient mental health clinics. For each county within an MHSA, patients received most of their VA-provided outpatient mental health care within that MHSA. MHSAs were aggregated into MHRRs according to where VA users in each MHSA received most of their residential and acute inpatient mental health care. Attribution loyalty was evaluated with the localization index-the fraction of VA users living in each geographic area who used their designated MHSA and MHRR facility. Variation in outpatient mental health visits and in acute inpatient and residential mental health stays was determined for the 2008-2018 period. A total of 441 MHSAs were aggregated to 115 MHRRs (representing 3,909,080 patients with 52,372,303 outpatient mental health visits). The mean±SD localization index was 59.3%±16.4% for MHSAs and 67.8%±12.7% for MHRRs. Adjusted outpatient mental health visits varied from a mean of 0.88 per year in the lowest quintile of MHSAs to 3.14 in the highest. Combined residential and acute inpatient days varied from 0.29 to 1.79 between the lowest and highest quintiles. MHSAs and MHRRs validly represented mental health utilization patterns in the VA and displayed considerable variation in mental health service provision across different locations.


[Identification of Nodular Gastritis among Patients Diagnosed with Lymphofollicular Gastritis on a Gastric Biopsied Specimen].
Nodular gastritis (NG) is a well-known endoscopic finding observed in patients with a Helicobacter pylori infection, which may lead to invasive gastric cancer. Lymphofollicular gastritis consists of lymphoid follicles or lymphoid cell aggregates, and is common in children. The aim of this study was to identify patients with NG from those in whom gastric biopsied specimens showed lymphoid follicles and lymphoid cell aggregates. Subjects, whose gastric biopsy specimens showed lymphoid follicles or lymphoid cell aggregates, were included in this study. The inclusion criterion was that they underwent a serum pepsinogen assay on the day of upper gastrointestinal endoscopy. NG was diagnosed if the endoscopy findings revealed regular-sized, multiple, colorless subepithelial nodules. Among 108 subjects who showed lymphoid follicles or lymphoid cell aggregates, 13 (12.0%) revealed NG on endoscopy, and all these subjects showed positive Giemsa staining. Patients diagnosed with NG were younger (p=0.012) and showed a female predominance (p=0.001) compared to those without NG. The mean serum pepsinogen levels were higher (p=0.001) and lymphoid follicle-dominant subjects were more common (p<0.001) in the NG subjects than in those without NG. Logistic regression analysis revealed a younger age (p=0.041) and female gender (p=0.002) to be significant independent risk factors for NG. NG should be distinguished from lymphofollicular gastritis because only 12% of patients showing gastric biopsy findings of lymphoid follicles and lymphoid cell aggregates demonstrated NG on endoscopy. NG is an endoscopic finding that is more common in women and in the younger population, irrespective of the biopsy findings and gastric secretory ability.


miR-3189-targeted GLUT3 repression by HDAC2 knockdown inhibits glioblastoma tumorigenesis through regulating glucose metabolism and proliferation.
Epigenetic regulations frequently appear in Glioblastoma (GBM) and are highly associated with metabolic alterations. Especially, Histone deacetylases (HDACs) correlates with the regulation of tumorigenesis and cell metabolism in GBM progression, and HDAC inhibitors report to have therapeutic efficacy in GBM and other neurological diseases; however, GBM prevention and therapy by HDAC inhibition lacks a mechanism in the focus of metabolic reprogramming. HDAC2 highly express in GBM and is analyzed in TCGA/GEPIA databases. Therefore, HDAC2 knockdown affects GBM cell death. Analysis of RNA sequencing and qRT-PCR reveals that miR-3189 increases and GLUT3 decreases by HDAC2 knockdown. GBM tumorigenesis also examines by using in vivo orthotopic xenograft tumor models. The metabolism change in HDAC2 knockdown GBM cells measures by glucose uptake, lactate production, and OCR/ECAR analysis, indicating that HDAC2 knockdown induces GBM cell death by inhibiting GLUT3. Notably, GLUT3 was suppressed by increasing miR-3189, demonstrating that miR-3189-mediated GLUT3 inhibition shows an anti-tumorigenic effect and cell death by regulating glucose metabolism in HDAC2 knockdown GBM. Our findings will demonstrate the central role of HDAC2 in GBM tumorigenesis through the reprogramming of glucose metabolism by controlling miR-3189-inhibited GLUT3 expression, providing a potential new therapeutic strategy for GBM treatment.


Mandibular reconstruction with a fibular osteocutaneous free flap in an 8-month-old girl with a 12-year follow-up.
The purpose of this article is to describe a case of an 8-month-old girl who was diagnosed with a melanotic neuroectodermal tumor and was submitted to a right hemimandibulectomy and immediate reconstruction with a fibular osteocutaneous free flap. At 12-year follow-up, the longest reported in a patient this young, the transferred bone had grown much like the native mandible, and the patient had adequate mandibular contour and function. No revisions were needed, although orthopedic surgery was performed to correct an ankle valgus deviation on the donor leg. It is the opinion of the authors that microsurgical mandible reconstruction in very young patients is efficient and that the surrounding structures contribute to the remodeling of the bone segment to achieve characteristics similar to those of the native mandible.


Making pre-school children wear masks is bad public health.
Children are not small adults. This is a critical point that many pediatricians and other child health professionals get bored of saying, yet it does seem to need repeating. While children have the lowest risk from COVID-19 directly, they risk suffering the indirect impacts of policy decisions, many of which appear to have been made with next to no explicit consideration of their interests. Public health interventions should not only be about infectious disease control, they should consider a broad set of outcomes. In addition, they ought to consider vulnerability, including that in early childhood - a time when young children's brains are developing rapidly and are most susceptible to adversity. We believe that mandating masking of pre-school children is not in line with public health principles, and needs to be urgently re-considered.


Evaluation and treatment of dyspareunia.
Dyspareunia affects 8-22% of women at some point during their lives, making it one of the most common pain problems in gynecologic practice. A mixture of anatomic, endocrine, pathologic, and emotional factors combine to challenge the diagnostic, therapeutic, and empathetic skills of the physician. New understandings of pain in general require new interpretations concerning the origins of pain during intercourse, but also provide new avenues of treatment. The outcomes of medical and surgical treatments for common gynecologic problems should routinely go beyond measures of coital possibility, to include assessment of coital comfort, pleasure, and facilitation of intimacy. This review will discuss aspects of dyspareunia, including anatomy and neurophysiology, sexual physiology, functional changes, pain in response to disease states, and pain after gynecologic surgical procedures.


Visco- and poroelastic contributions of the zona pellucida to the mechanical response of oocytes.
Probing mechanical properties of cells has been identified as a means to infer information on their current state, e.g. with respect to diseases or differentiation. Oocytes have gained particular interest, since mechanical parameters are considered potential indicators of the success of in vitro fertilisation procedures. Established tests provide the structural response of the oocyte resulting from the material properties of the cell's components and their disposition. Based on dedicated experiments and numerical simulations, we here provide novel insights on the origin of this response. In particular, polarised light microscopy is used to characterise the anisotropy of the zona pellucida, the outermost layer of the oocyte composed of glycoproteins. This information is combined with data on volumetric changes and the force measured in relaxation/cyclic, compression/indentation experiments to calibrate a multi-phasic hyper-viscoelastic model through inverse finite element analysis. These simulations capture the oocyte's overall force response, the distinct volume changes observed in the zona pellucida, and the structural alterations interpreted as a realignment of the glycoproteins with applied load. The analysis reveals the presence of two distinct timescales, roughly separated by three orders of magnitude, and associated with a rapid outflow of fluid across the external boundaries and a long-term, progressive relaxation of the glycoproteins, respectively. The new results allow breaking the overall response down into the contributions from fluid transport and the mechanical properties of the zona pellucida and ooplasm. In addition to the gain in fundamental knowledge, the outcome of this study may therefore serve an improved interpretation of the data obtained with current methods for mechanical oocyte characterisation.


Clustered Nyström method for large scale manifold learning and dimension reduction.
Kernel (or similarity) matrix plays a key role in many machine learning algorithms such as kernel methods, manifold learning, and dimension reduction. However, the cost of storing and manipulating the complete kernel matrix makes it infeasible for large problems. The Nyström method is a popular sampling-based low-rank approximation scheme for reducing the computational burdens in handling large kernel matrices. In this paper, we analyze how the approximating quality of the Nyström method depends on the choice of landmark points, and in particular the encoding powers of the landmark points in summarizing the data. Our (non-probabilistic) error analysis justifies a "clustered Nyström method" that uses the k-means clustering centers as landmark points. Our algorithm can be applied to scale up a wide variety of algorithms that depend on the eigenvalue decomposition of kernel matrix (or its variant), such as kernel principal component analysis, Laplacian eigenmap, spectral clustering, as well as those involving kernel matrix inverse such as least-squares support vector machine and Gaussian process regression. Extensive experiments demonstrate the competitive performance of our algorithm in both accuracy and efficiency.


Therapeutic options for resistant lupus nephritis.
To summarize the therapeutic options for proliferative and membranous lupus nephritis that is resistant to conventional treatment. Treatment trials in human lupus nephritis from years 1985 to 2005 that have been published in the English literature were searched by Medline using the keywords "lupus," "nephritis," "glomerulonephritis," "renal," "refractory," "resistant," "recalcitrant," "cyclophosphamide," "mycophenolate," "cyclosporin," "tacrolimus," "leflunomide," "intravenous immunoglobulin," "apheresis," "plasmapheresis," "immunoadsorption," "marrow transplantation," "stem cell transplantation," "immunoablative," "rituximab," and "biologics." Laboratory, histological, and nonrenal lupus studies were excluded. There is no universal definition of treatment resistance in lupus nephritis. Controlled trials in refractory lupus nephritis are largely unavailable. Open-labeled studies have reported success of newer immunosuppressive drugs, immunomodulatory therapies, and the biological agents such as mycophenolate mofetil (MMF), calcineurin inhibitors, leflunomide, intravenous immunoglobulin, immunoadsorption, and rituximab in the treatment of cyclophosphamide (CYC) resistant proliferative lupus nephritis. More aggressive CYC regimens have been used in lupus nephritis, but at the expense of more toxicities. For membranous lupus nephritis (MLN), a combination of corticosteroids with either azathioprine, chlorambucil, cyclosporin A, MMF, or CYC is initially effective in two-thirds of patients. More aggressive and costly regimens should be reserved for truly refractory disease with persistent nephrotic syndrome or declining renal function. Evidence regarding the efficacy of MMF in refractory MLN is conflicting and controlled trials are necessary to resolve the controversy. The treatment of refractory lupus nephritis remains anecdotal. An international consensus in the renal response criteria should be developed and validated so that controlled trials can be performed to compare the efficacy of various treatment modalities.


A novel polymer-free ciglitazone-coated vascular stent: in vivo and ex vivo analysis of stent endothelialization in a rabbit iliac artery model.
Peroxisome proliferator-activated receptor-gamma (PPARg) agonists have known pleiotropic cardiovascular effects with favourable properties in vascular remodeling, and specifically in suppression of vascular smooth muscle cell proliferation. A novel vascular stent coating using the PPARg ligand ciglitazone (CCS) was investigated regarding its effects on endothelialization after 7 and 28 days. Microporous bare metal stents (BMS) were coated with ciglitazone by ultrasonic flux with a load of 255 μg ciglitazone/stent. SixteenNew Zealand white rabbits, fed a with high cholesterol diet, underwent stent implantation in both iliac arteries. Everolimus-eluting stents (EES) and BMS were comparators. Histology (CD 31 immunostaining, confocal and scanning electron microscopy, morphometry) was performed after 7 and 28 days and by OCT (optical coherence tomography) in vivo after 28 days. Microscopy showed comparable results with near complete endothelialization in CCS and BMS (%CD31 above stent struts after 7 days: 67.92±36.35 vs. 84.48±23.86; p = 0.55; endothel % above stent struts: 77.22±27.9 vs. 83.89±27.91; p = 0.78). EES were less endothelialized with minimal fibrin deposition, not found in BMS and CCS (% CD 31 above struts after 28 days, BMS: 100.0±0.0 vs. EES: 95.9±3.57 vs. CCS: 100.0±0.0; p = 0.0292). OCT revealed no uncovered struts in all stents after 28 days. Polymer-free coating with ciglitazone, a PPARg agonist is feasible and stable over time. Our data prove unimpaired endothelial coverage of a ciglitazone-coated vascular stent system by histology and OCT. Thus, this PPARg agonist coating deserves further investigation to evaluate its potency on local neointimal suppression.


Mesothelioma and Colorectal Cancer: Report of Four Cases with Synchronous and Metachronous Presentation.
There is evidence that asbestos could play a role in the carcinogenesis of digestive cancers. The presence of asbestos fibres in histological samples from gastric, biliary, colon cancers has been reported, but the mechanism is still controversial. It has been hypothesised that asbestos reaches these sites, especially through contaminated water; however, some experimental studies have shown that the inhaled fibres are mobile, so they can migrate to many organs, directly or via blood and lymph flow. We report four unusual cases of colorectal cancers in patients with a long history of asbestos exposure who also developed synchronous or metachronous mesothelioma. We evaluated the roles of BRCA associated protein-1 (BAP1) and cyclin-dependent kinase inhibitor 2A (CDKN2A) in colon cancer and mesothelioma to support the hypothesis that BAP-1 and CDKN2A are tumour suppressor genes involved in disease progression, recurrence, or death in both digestive cancers and mesothelioma. Potentially, these markers may be used as predictors of worse prognosis, but we also stress the importance of clinical surveillance of exposed patients because asbestos could induce cancer in any organ.


Characterization of pathogenic fungi genomes using pulsed field gel electrophoresis.
Pulsed field gel electrophoresis (PFGE) has been firstly introduced in characterization of the pathogenic fungi Penicillium marneffei and Exophiala dermatitidis genomes. The numbers and sizes of their chromosomes have been detected. Polymorphism was identified on the smallest chromosome of E. dermatitidis. The result shows that PFGE for characterization of large molecular DNA pathogenic fungi is very suitable, it is more simple and more efficacy. The result also shows the diversity of pathogenic fungi is relative common even in rare occurred pathogenic fungi such as E. dermatitidis.


Controlled trial of two keto acid supplements on renal function, nutritional status, and bone metabolism in uremic patients.
In this matched, controlled study, two different types of EAA/KA supplements were compared in uremic patients fed a 30 g protein restricted diet. The patients were paired for age, sex, and underlying renal disease. The supplement with the higher BCKA content resulted in an improvement of renal function, bone metabolism, and a normalization of plasma BCAA concentrations. With both supplements, adequate nutritional status of the patients was maintained. We conclude that the BCKA content of the supplement is of considerable importance for uremic patients on low protein diets.


Adventitial delivery of nanoparticles encapsulated with 1α, 25-dihydroxyvitamin D3 attenuates restenosis in a murine angioplasty model.
Percutaneous transluminal angioplasty (PTA) of stenotic arteriovenous fistulas (AVFs) is performed to maintain optimal function and patency. The one-year patency rate is 60% because of venous neointimal hyperplasia (VNH) and venous stenosis (VS) formation. Immediate early response gene X-1 (Iex-1) also known as Ier3 increases in response to wall shear stress (WSS), and can cause VNH/VS formation in murine AVF. In human stenotic samples from AVFs, we demonstrated increased gene expression of Ier3. We hypothesized that 1α, 25-dihydroxyvitamin D3, an inhibitor of IER3 delivered as 1α, 25-dihydroxyvitamin D3 encapsulated in poly lactic-co-glycolic acid (PLGA) nanoparticles loaded in Pluronic F127 hydrogel (1,25 NP) to the adventitia of the stenotic outflow vein after PTA would decrease VNH/VS formation by reducing Ier3 and chemokine (C-C motif) ligand 2 (Ccl2) expression. In our murine model of AVF stenosis treated with PTA, increased expression of Ier3 and Ccl2 was observed. Using this model, PTA was performed and 10-μL of 1,25 NP or control vehicle (PLGA in hydrogel) was administered by adventitial delivery. Animals were sacrificed at day 3 for unbiased whole genome transcriptomic analysis and at day 21 for immunohistochemical analysis. Doppler US was performed weekly after AVF creation. At day 3, significantly lower gene expression of Ier3 and Ccl2 was noted in 1,25 NP treated vessels. Twenty-one days after PTA, 1,25 NP treated vessels had increased lumen vessel area, with decreased neointima area/media area ratio and cell density compared to vehicle controls. There was a significant increase in apoptosis, with a reduction in CD68, F4/80, CD45, pro-inflammatory macrophages, fibroblasts, Picrosirius red, Masson's trichrome, collagen IV, and proliferation accompanied with higher wall shear stress (WSS) and average peak velocity. IER3 staining was localized to CD68 and FSP-1 (+) cells. After 1,25 NP delivery, there was a decrease in the proliferation of α-SMA (+) and CD68 (+) cells with increase in the apoptosis of FSP-1 (+) and CD68 (+) cells compared to vehicle controls. RNA sequencing revealed a decrease in inflammatory and apoptosis pathways following 1,25 NP delivery. These data suggest that adventitial delivery of 1,25 NP reduces VNH and venous stenosis formation after PTA.


Galantamine and Environmental Enrichment Enhance Cognitive Recovery after Experimental Traumatic Brain Injury But Do Not Confer Additional Benefits When Combined.
Environmental enrichment (EE) enhances cognition after traumatic brain injury (TBI). Galantamine (GAL) is an acetylcholinesterase inhibitor that also may promote benefits. Hence, the aims of this study were to assess the efficacy of GAL alone (standard [STD] housing) and in combination with EE in adult male rats after TBI. The hypothesis was that both therapies would confer motor, cognitive, and histological benefits when provided singly, but that their combination would be more efficacious. Anesthetized rats received a controlled cortical impact or sham injury, then were randomly assigned to receive GAL (1, 2, or 3 mg/kg; intraperitoneally [i.p.]) or saline vehicle (VEH; 1 mL/kg; i.p.) beginning 24 h after surgery and once daily for 21 days (experiment 1). Motor (beam-balance/walk) and cognitive (Morris water maze [MWM]) assessments were conducted on post-operative Days 1-5 and 14-19, respectively. Cortical lesion volumes were quantified on Day 21. Sham controls were better versus all TBI groups. No differences in motor function or lesion volumes were observed among the TBI groups (p > 0.05). In contrast, GAL (2 mg/kg) enhanced MWM performance versus VEH and GAL (1 and 3 mg/kg; p < 0.05). In experiment 2, GAL (2 mg/kg) or VEH was combined with EE and the data were compared with the STD-housed groups from experiment 1. EE alone enhanced motor performance over the VEH-treated and GAL-treated (2 mg/kg) STD-housed groups (p < 0.05). Moreover, both EE groups (VEH or GAL) facilitated spatial learning and reduced lesion size versus STD + VEH controls (p < 0.05). No additional benefits were observed with the combination paradigm, which does not support the hypothesis. Overall, the data demonstrate that EE and once daily GAL (2 mg/kg) promote cognitive recovery after TBI. Importantly, the combined therapies did not negatively affect outcome and thus this therapeutic protocol may have clinical utility.


Do hypermobile subjects without pain have alteration to the feedback mechanisms controlling the shoulder girdle?
It has been reported that hypermobile subjects have proprioceptive deficits. However, it remains unclear whether pain-free subjects with hypermobility also have deficits. Ten subjects with hypermobility and nine without hypermobility were recruited following ethical approval and informed consent. Shoulder mobility, joint position sense (JPS) and a reflex of trapezius evoked from arm afferents were compared. There was greater shoulder mobility in the hypermobile group (p = 0.004). There were no differences in shoulder JPS between the groups (p = 0.27), although, the hypermobile group displayed a larger degree of variability (p = 0.014). Finally, there were no differences in the latency of upper and lower trapezius reflexes evoked from arm afferents (p = 0.86 and 0.98, respectively). In a group of people with hypermobility without shoulder problems, there was no difference in either shoulder JPS or reflex latency when compared with a non- hypermobile group. The relevance of pain to proprioceptive deficits is discussed.


Value of magnetic resonance cholangiopancreatography in the diagnosis of biliary abnormalities in postcholecystectomy patients: a probabilistic cost-effectiveness analysis of diagnostic strategies.
Endoscopic retrograde cholangiopancreatography (ERCP) is considered the gold standard for imaging of the biliary tract but is associated with complications. Less invasive imaging techniques, such as magnetic resonance cholangiopancreatography (MRCP), have a much lower complication rate. The accuracy of MRCP is comparable to that of ERCP, and MRCP may be more effective and cost-effective, particularly in cases for which the suspected prevalence of disease is low and further intervention can be avoided. A model was constructed to compare the effectiveness and cost-effectiveness of MRCP and ERCP in patients with a previous history of cholecystectomy, presenting with abdominal pain and/or abnormal liver function tests. Diagnostic accuracy estimates came from a systematic review of MRCP. A decision analytic model was constructed to represent the diagnostic and treatment pathway of this patient group. The model compared the following two diagnostic strategies: (i) MRCP followed with ERCP if positive, and then management based on ERCP; and (ii) ERCP only. Deterministic and probabilistic analyses were used to assess the likelihood of MRCP being cost-effective. Sensitivity analyses examined the impact of prior probabilities of common bile duct stones (CBDS) and test performance characteristics. The outcomes considered were costs, quality-adjusted life years (QALYs), and cost per additional QALY. The deterministic analysis indicated that MRCP was dominant over ERCP. At prior probabilities of CBDS, less than 60 percent MRCP was the less costly initial diagnostic test; above this threshold, ERCP was less costly. Similarly, at probabilities of CBDS less than 68 percent, MRCP was also the more effective strategy (generated more QALYs). Above this threshold, ERCP became the more effective strategy. Probabilistic sensitivity analyses indicated that, in this patient group for which there is a low to moderate probability of CBDS, there was a 59 percent likelihood that MRCP was cost-saving, an 83 percent chance that MRCP was more effective with a higher quality adjusted survival, and an 83 percent chance that MRCP had a cost-effectiveness ratio more favorable than dollars 50,000 per QALY gained. Costs and cost-effectiveness are dependent upon the prior probability of CBDS. However, probabilistic analysis indicated that, with a high degree of certainty, MRCP was the more effective and cost-effective initial test in postcholecystectomy patients with a low to moderate probability of CBDS.


Mode of Action of the Toxin from Pseudomonas phaseolicola: I. Toxin Specificity, Chlorosis, and Ornithine Accumulation.
The specificity of the Pseudomonas phaseolicola toxin for enzyme inhibition and its relationship to toxin-induced chlorosis in bean leaves (Phaseolus vulgaris L.) was examined. The toxin showed no significant inhibitory activity against glutamine synthetase, glutamine transferase, carbamyl phosphate synthetase, aspartate carbamoyltransferase, or arginase at concentrations 100-fold higher than that needed to inhibit ornithine carbamoyltransferase by 50%.Protection from and reversal of toxin-induced chlorosis in bean leaves was attempted with several amino acids. Aside from protection with l-citrulline which was previously reported, only l-arginine-HCl and to a minor extent l-leucine and l-glutamine showed protection from chlorosis. l-Citrulline and l-arginine-HCl (but not l-glutamine and l-leucine) also reversed toxin-induced chlorosis.Ultrastructurally, cells from toxin-treated chlorotic tissues showed no observable changes as compared to nontreated tissues. This, together with the ability of the two amino acids to reverse chlorosis, indicated that the toxin causes a reversible biochemical lesion in treated tissue.While tissues from bean plants inoculated with P. phaseolicola showed a large accumulation of ornithine, toxin-treated tissues showed no accumulation of ornithine. The latter finding indicated that in addition to the ornithine carbamoyltransferase inhibitor, the pathogen may produce inhibitors of other ornithine metabolizing enzymes in inoculated tissues.


Notch signaling during development requires the function of awd, the Drosophila homolog of human metastasis suppressor gene Nm23.
The Drosophila abnormal wing discs (awd) belongs to a highly conserved family of genes implicated in metastasis suppression, metabolic homeostasis and epithelial morphogenesis. The cellular function of the mammalian members of this family, the Nm23 proteins, has not yet been clearly defined. Previous awd genetic analyses unraveled its endocytic role that is required for proper internalization of receptors controlling different signaling pathways. In this study, we analyzed the role of Awd in controlling Notch signaling during development. To study the awd gene function we used genetic mosaic approaches to obtain cells homozygous for a loss of function allele. In awd mutant follicle cells and wing disc cells, Notch accumulates in enlarged early endosomes, resulting in defective Notch signaling. Our results demonstrate that awd function is required before γ-secretase mediated cleavage since over-expression of the constitutively active form of the Notch receptor in awd mutant follicle cells allows rescue of the signaling. By using markers of different endosomal compartments we show that Notch receptor accumulates in early endosomes in awd mutant follicle cells. A trafficking assay in living wing discs also shows that Notch accumulates in early endosomes. Importantly, constitutively active Rab5 cannot rescue the awd phenotype, suggesting that awd is required for Rab5 function in early endosome maturation. In this report we demonstrate that awd is essential for Notch signaling via its endocytic role. In addition, we identify the endocytic step at which Awd function is required for Notch signaling and we obtain evidence indicating that Awd is necessary for Rab5 function. These findings provide new insights into the developmental and pathophysiological function of this important gene family.


Hyperfunctioning intrathyroidal parathyroid carcinoma.
Intrathyroidal parathyroid carcinoma is an exceedingly rare cause of primary hyperparathyroidism with difficulties in the diagnosis and management. We report a case of hypercalcemia from intrathyroidal parathyroid carcinoma in a 63-year-old Saudi female. She was diagnosed 2 years earlier with osteoporosis in a primary care clinic and was on alendronate since then. This year she was noted to have hypercalcemia, but in retrospect she had more than 10 years history of multiple medical problems related to hypercalcemia. Parathyroid 99mTc-SestaMIBI scintigraphy revealed parathyroid adenoma in the left inferior parathyroid gland. She had successful video-assisted parathyroidectomy that relieved most of her symptoms. The extreme rarity of such a case, the interesting clinical presentation and review of the literature are discussed.


Kinetics and mechanisms of cholesterol gallstone dissolution.
The purpose of this paper is to review the past and current in vitro studies aimed at understanding the mechanisms of cholesterol gallstone dissolution in bile. As is pointed out, there has been considerable progress in this area during the past 15 years with regard to the physical chemistry of the dissolution process.


Associations Between Genetic Variants of NADPH Oxidase-Related Genes and Blood Pressure Responses to Dietary Sodium Intervention: The GenSalt Study.
The aim of this study was to comprehensively test the associations of genetic variants of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-related genes with blood pressure (BP) responses to dietary sodium intervention in a Chinese population. We conducted a 7-day low-sodium intervention followed by a 7-day high-sodium intervention among 1,906 participants in rural China. BP measurements were obtained at baseline and each dietary intervention using a random-zero sphygmomanometer. Linear mixed-effect models were used to assess the additive associations of 63 tag single-nucleotide polymorphisms in 11 NADPH oxidase-related genes with BP responses to dietary sodium intervention. Gene-based analyses were conducted using the truncated product method. The Bonferroni method was used to adjust for multiple testing in all analyses. Systolic BP (SBP) response to high-sodium intervention significantly decreased with the number of minor T allele of marker rs6967221 in RAC1 (P = 4.51 × 10-4). SBP responses (95% confidence interval) for genotypes CC, CT, and TT were 5.03 (4.71, 5.36), 4.20 (3.54, 4.85), and 0.56 (-1.08, 2.20) mm Hg, respectively, during the high-sodium intervention. Gene-based analyses revealed that RAC1 was significantly associated with SBP response to high-sodium intervention (P = 1.00 × 10-6) and diastolic BP response to low-sodium intervention (P = 9.80 × 10-4). These findings suggested that genetic variants of NADPH oxidase-related genes may contribute to the variation of BP responses to sodium intervention in Chinese population. Further replication of these findings is warranted.


Acute infectious urticaria: clinical and laboratory analysis in nineteen patients.
We treated 19 Japanese patients with acute urticaria presumably caused by infection during the five years from 1994 to 1998. The patients' ages ranged from 2 to 66 years (8 males and 11 females). Most of them had urticaria, angioedema, high fever, neutrophilia, and high serum levels of C reactive protein (CRP). The skin rash lasted more than 24 hours. In four patients, a flow cytometric analysis revealed that the percentage of circulating T cells bearing T-cell receptor V beta 3 was decreased during the active stage and that this decrease was sustained for at least 2 to 3 weeks. This suggests that certain T-cell populations were numerically altered in association with the occurrence of the disease. A retrospective review indicated that the combination therapy with corticosteroid and antibiotics was more effective than the single use of either agent.


A new isolate of hepatitis B virus from the Philippines possibly representing a new subgenotype C6.
Hepatitis B virus (HBV) genotypes and subgenotypes show distinct geographical prevalence. A genotyping analysis of 28 samples from asymptomatic HBV carriers from the Philippines gave a distribution of HBV genotypes as expected from a previous study: 54% B (15/28), C5 18% (5/28), 14% D (4/28), 7% A1 (2/28). In addition, 7% (2/28) of the samples showed a double infection with genotypes B and D. One of the isolates sequenced completely, ph105, did not group into one of the known subgenotypes after phylogenetic analysis. Ph105 formed a separate clade in genotype C. With a genome length of 3,215 nt. and a serological subtype adr, ph105 exhibited the main features of most genotype C strains. However, ph105 differed by 4.1-7.2% from HBV subgenotypes C1 to C5 when comparing the nucleotide sequence of whole genomes. With only 4.1% difference ph105 was most closely related to subgenotype C2. SimPlot analysis gave no indication for recombination with known HBV genotypes. Ph105 fulfils all criteria for a new subgenotype C6.


[Pathogenesis of thrombosis in JAK2V617F myeloproliferative neoplasms].
BCR-ABL negative myeloproliferative neoplasms are acquired hematologic diseases characterized by blood cell proliferation and that include polycythemia vera (PV), essential thrombocytemia (ET) and primary myelofibrosis (PMF). Occurring of venous and arterial thrombosis is the main complication of these diseases. Risk factors for thrombosis are individuals older than 60 and history of thrombosis. The mechanisms leading to thrombosis are complex and involve several blood compartments, plasmatic factors and endothelial cells. Over the last years, new actors of thrombosis have been discovered.


Predictors of sentinel lymph node metastasis in melanoma.
Several studies have examined the correlation between patient and tumour characteristics and sentinel lymph node (SLN) metastasis in patients with melanoma. Although most studies have identified Breslow thickness as an important factor, results for other variables have been conflicting. Much of this variability is probably because of differences in measurement techniques and reporting practices at different institutions. We sought to identify the predictors of SLN melanoma metastasis in our institution and patient population. We performed a retrospective chart review of 348 patients with malignant melanoma who underwent SLN biopsy at a single institution from January 1999 to April 2007. We compared multiple variables related to patient demographics, primary tumour characteristics and SLN characteristics between patients in the positive and negative SLN groups. Breslow thickness and nodular tumour type were independent factors significantly correlated with a positive SLN biopsy result in our study. Head and neck tumour location correlated with a lower likelihood of positive SLN status in univariate but not multivariate analyses. This study confirms the status of Breslow thickness as a reproducible predictor of positive SLN status. We also found that nodular type was predictive of positive SLN status, an outcome that has not been reported by others.


Skeletal and cardiac muscle pericytes: Functions and therapeutic potential.
Pericytes are periendothelial mesenchymal cells residing within the microvasculature. Skeletal muscle and cardiac pericytes are now recognized to fulfill an increasing number of functions in normal tissue homeostasis, including contributing to microvascular function by maintaining vessel stability and regulating capillary flow. In the setting of muscle injury, pericytes contribute to a regenerative microenvironment through release of trophic factors and by modulating local immune responses. In skeletal muscle, pericytes also directly enhance tissue healing by differentiating into myofibers. Conversely, pericytes have also been implicated in the development of disease states, including fibrosis, heterotopic ossication and calcification, atherosclerosis, and tumor angiogenesis. Despite increased recognition of pericyte heterogeneity, it is not yet clear whether specific subsets of pericytes are responsible for individual functions in skeletal and cardiac muscle homeostasis and disease.


Regulatory requirements (CLIA '88, JCAHO, CAP) for decentralized testing.
All decentralized testing is regulated according to the Clinical Laboratory Improvement Amendments of 1988. Two organizations, the Joint Commission on Accreditation of Health Care Organizations and the College of American Pathologists, have received deemed status for their voluntary standards from the Health Care Financing Administration. Deemed status means that the organizations' voluntary standards meet or exceed the federal requirements. The decentralized testing sites can exercise several options in determining which organization, and hence which set of standards, will be used to regulate their testing processes. In this article, the authors outline the various regulatory requirements, provide insight into the relationship of each, and offer a framework for decentralized testing sites to follow to meet the requirements.


Values in environmental research: Citizens' views of scientists who acknowledge values.
Scientists who perform environmental research on policy-relevant topics face challenges when communicating about how values may have influenced their research. This study examines how citizens view scientists who publicly acknowledge values. Specifically, we investigate whether it matters: if citizens share or oppose a scientist's values, if a scientist's conclusions seem contrary to or consistent with the scientist's values, and if a scientist is assessing the state of the science or making a policy recommendation. We conducted two 3x2 factorial design online experiments. Experiment 1 featured a hypothetical scientist assessing the state of the science on the public-health effects of exposure to Bisphenol A (BPA), and Experiment 2 featured a scientist making a policy recommendation on use of BPA. We manipulated whether or not the scientist expressed values and whether the scientist's conclusion appeared contrary to or consistent with the scientist's values, and we accounted for whether or not subjects' values aligned with the scientist's values. We analyzed our data with ordinary least squares (OLS) regression techniques. Our results provide at least preliminary evidence that acknowledging values may reduce the perceived credibility of scientists within the general public, but this effect differs depending on whether scientists and citizens share values, whether scientists draw conclusions that run contrary to their values, and whether scientists make policy recommendations.


Induction by chronic autoimmune arthritis in DBA/1 mice by oral administration of type II collagen and Escherichia coli lipopolysaccharide.
We have developed a new model of autoimmune arthritis in DBA/1 mice by feeding chick type II collagen (CII) for 2-3 week intervals over a 15 week period. Clinically evident arthritis occurred in 8/10 mice receiving native CII (nCII; 100 micrograms/mouse) alone at 9-13 weeks. Arthritis was aggravated by the further ingestion of CII, while remission occurred after withdrawal of the CII. Heat-denatured CII (dCII; 200 micrograms/mouse) was also arthritogenic if co-administered with ovoinhibitor (OVI; 2 mg/mouse), a proteinase inhibitor. Co-oral administration of lipopolysaccharide (LPS; 10 micrograms/mouse) with CII enhanced the antibody production and T-cell responses to CII, and induced a more chronic arthritis that progressed spontaneously without further administration of CII or LPS. Long-term oral administration of LPS alone also induced a mild arthritis characterized by destruction of bone rather than cartilage. These observations suggest that abnormal gastrointestinal absorption of dietary mimic antigens and intestinal bacterial toxins can potentially disrupt self-tolerance mechanisms, thereby precipitating or exacerbating autoimmune disease in genetically susceptible individuals.


Myofascial pain: diagnosis and management.
Clinical understanding and management of myofascial pain is overlooked frequently when dealing with pain. Myofascial pain is defined as pain or autonomic phenomena referred from active trigger points, with associated dysfunction. The trigger point is a focus of hyperirritability in the muscle that, when compressed, is locally tender and, if sensitized, gives rise to referred pain and tenderness. The pain quality is dull or achy and associated with autonomic changes. Myofascial pain is poorly understood, which results too often in underdiagnosis and poor management. The pathogenesis likely has a central mechanism with peripheral clinical manifestations. The therapy for myofascial pain requires enhancing central inhibition through pharmacology or behavioral techniques and simultaneously reducing peripheral inputs through physical therapies including exercises and trigger point-specific therapy.


Effects of Ionizing Radiation on Physical Properties of Peripherally Inserted Central Catheter.
Peripherally inserted central catheter (PICC) has been widely used to treat cancer patients. It is unknown whether or not it can be applied safely during radiotherapy. The study aimed to investigate the direct effects of gamma radiation on physical properties of PICC. A total of 60 catheters were included in this study. Thirty PICCs were exposed to a radiation field, and another 30 PICCs received radiation in a 3-cm homogeneity water equivalent phantom and then were irradiated. Each group was divided into three subgroups: 10 PICCs were given conventional fractionation, 2 Gy per fraction, 5 fractions per week; 10 PICCs were continuously given hypofractionation, 10 Gy per fraction, for 6 weeks; and 10 PICCs were given mock radiation as controls. The physical properties of these catheters were analyzed after radiation. None of the PICCs leaked under 300-kPa airflow pressure lasting 15 seconds. Fracture force values and liquid velocity values of all PICCs were within the normal range. The liquid velocity values of the control groups were higher than the two groups that received radiation (P < 0.05), and there was no difference between the two irradiation groups (P > 0.05). There were no statistical differences among the conventional fractionation group, hypofractionation group, and control group when compared to the fracture force values in two parts (P > 0.05). The physical property of PICC is quite stable with a clinically relevant dose of gamma radiation. It is likely that PICC can be used safely in patients receiving radiotherapy, although further in vivo and clinical studies are required.


The van der Waals potential of the magnesium dimer.
The ground state van der Waals potential of the magnesium dimer is described by the Tang-Toennies potential model, which requires five essential parameters. Among them, the three dispersion coefficients C(6), C(8), and C(10) are available from accurate ab initio calculations. The other two are the Born-Mayer parameters in A exp(-bR). In this paper, we show that A and b can be determined from the self-consistent Hartree-Fock calculations and the experimental dissociation energy D(0). The predicted well depth D(e) and equilibrium distance R(e) are in nearly perfect agreement with the experiment. In fact, the entire potential energy curve, which is given by a single analytic function, is in excellent agreement with the pointwise potential energies constructed from the spectroscopic measurements in the interval of 6a(0)-14a(0) and in good agreement with the experimental repulsive potential determined from Franck-Condon factors of the bound-free transitions for R less than 6a(0). The reduced potential of Mg(2) is analyzed in terms of its components, and the number of terms in the dispersion series necessary for convergence is investigated.


Addition of anaerobic tanks to an oxidation ditch system to enhance removal of phosphorus from wastewater.
The oxidation ditch has been used for many years all over the world as an economic and efficient wastewater treatment technology. It can remove COD, nitrogen and a part of phosphorus efficiently. In the experiment described, a pilot scale Pasveer oxidation ditch system has been tested to investigate the removal of phosphorus from wastewater. The experimental results showed that influent total phosphorus(TP) was removed for 35%-50%. After this, two anaerobic tanks with total volume of 11 m3 were added to the system to release phosphorus. As a result, the TP removal efficiency increased by about 20%. At an anaerobic HRT of about 6 hours, a TP removal efficiency of 71% was achieved.


Psychometric Testing of the Chinese Version of the Coping and Adaptation Processing Scale-Short Form in Adults With Chronic Illness.
Adaptive capacity may serve as an indicator of the individuals' coping behaviors toward illness management and may contribute to day-to-day living with chronic illness and improved quality of life. Practical and well-constructed instruments for measuring adaptation have not been adequately explored. An English 15-item Coping and Adaptation Processing-Short Form (CAPS-SF) for assessing adaptation has been created and validated in line with the underlying tenets of Coping and Adaptation Processing theory, but there is no applicable Chinese version. The CAPS-SF was translated and culturally adapted into simplified Chinese. Among Chinese adults with chronic illness, 81 patients were selected for cultural adaptation and 288 patients were approached for psychometric testing. Content validity was evaluated by an expert panel. Construct validity was tested by confirmatory factor analysis. Concurrent validity and predictive validity were analyzed by Spearman correlation coefficient. Reliability was assessed by internal consistency and test-retest coefficients. Floor/ceiling effect was calculated. Adequate content validity was ensured by the expert panel. A four-factor structure (resourceful and focused, self-initiated and knowing-based, physical and fixed, and positive and systematic) describing individuals' coping strategies was identified and verified. Concurrent validity and predictive validity were demonstrated by strong correlations with the confrontation of coping mode (r = 0.46) and a quality-of-life measure (r = 0.58). The McDonald's omega coefficient of total scale was 0.82. Split-half reliability and test-retest reliability were 0.87 and 0.87. No floor/ceiling effect was present. The Chinese version CAPS-SF is a theoretically based and culturally acceptable instrument with sound psychometric properties. Further studies are advocated to refine its four-factor structure.


The people behind the papers - Nathalie Rion and Markus Rüegg.
In development and during regeneration in adults, muscle fibres develop from muscle progenitor cells, and the proliferation, differentiation and fusion of these progenitors needs to be tightly controlled and co-ordinated. A new paper in Development studies the role of the mTOR protein in this process using genetic deletions that target either of the two protein complexes mTOR functions in. We caught up with lead author Nathalie Rion and her supervisor Markus Rüegg, Professor of Neurobiology at Biozentrum, University of Basel, to find out more about the work.


Proliferating or differentiating stimuli act on different lipid-dependent signaling pathways in nuclei of human leukemia cells.
Previous results have shown that the human promyelocytic leukemia HL-60 cell line responds to either proliferating or differentiating stimuli. When these cells are induced to proliferate, protein kinase C (PKC)-beta II migrates toward the nucleus, whereas when they are exposed to differentiating agents, there is a nuclear translocation of the alpha isoform of PKC. As a step toward the elucidation of the early intranuclear events that regulate the proliferation or the differentiation process, we show that in the HL-60 cells, a proliferating stimulus (i.e., insulin-like growth factor-I [IGF-I]) increased nuclear diacylglycerol (DAG) production derived from phosphatidylinositol (4,5) bisphosphate, as indicated by the inhibition exerted by 1-O-octadeyl-2-O-methyl-sn-glycero-3-phosphocholine and U-73122 (1-[6((17 beta-3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl]-1H-pyrrole-2,5-dione), which are pharmacological inhibitors of phosphoinositide-specific phospholipase C. In contrast, when HL-60 cells were induced to differentiate along the granulocytic lineage by dimethyl sulfoxide, we observed a rise in the nuclear DAG mass, which was sensitive to either neomycin or propranolol, two compounds with inhibitory effect on phospholipase D (PLD)-mediated DAG generation. In nuclei of dimethyl sulfoxide-treated HL-60 cells, we observed a rise in the amount of a 90-kDa PLD, distinct from PLD1 or PLD2. When a phosphatidylinositol (4,5) bisphosphate-derived DAG pool was generated in the nucleus, a selective translocation of PKC-beta II occurred. On the other hand, nuclear DAG derived through PLD, recruited PKC-alpha to the nucleus. Both of these PKC isoforms were phosphorylated on serine residues. These results provide support for the proposal that in the HL-60 cell nucleus there are two independently regulated sources of DAG, both of which are capable of acting as the driving force that attracts to this organelle distinct, DAG-dependent PKC isozymes. Our results assume a particular significance in light of the proposed use of pharmacological inhibitors of PKC-dependent biochemical pathways for the therapy of cancer disease.


Letter naming and letter writing reversals in children with dyslexia: momentary inefficiency in the phonological and orthographic loops of working memory.
Given mounting evidence for working memory impairments in dyslexia, letter reversals during rapid automatic letter naming (phonological loop) or rapid automatic letter writing (orthographic loop) may reflect momentary inefficiency of working memory. Few of the children, with or without dyslexia, in a multi-generational family genetics study, produced reversals, but those with dyslexia produced more than those without dyslexia. Working-memory component predictors (word storing and processing units, phonological and orthographic loops, and executive functions) in regressions differentiated children with dyslexia (average age 11) who did and did not make reversals, predicted the number of reversals on specific letter naming or letter writing tasks, and explained unique variance in reading and writing outcomes. Although reversals are not a hallmark defining feature of dyslexia, children who produce reversals may benefit from instruction designed to develop specific working memory components and their efficient coordination in time.


Early-Life Respiratory Infections in Infants with Cow's Milk Allergy: An Expert Opinion on the Available Evidence and Recommendations for Future Research.
Acute respiratory infections are a common cause of morbidity in infants and young children. This high rate of respiratory infections in early life has a major impact on healthcare resources and antibiotic use, with the associated risk of increasing antibiotic resistance, changes in intestinal microbiota composition and activity and, consequently, on the future health of children. An international group of clinicians and researchers working in infant nutrition and cow's milk allergy (CMA) met to review the available evidence on the prevalence of infections in healthy infants and in those with allergies, particularly CMA; the factors that influence susceptibility to infection in early life; links between infant feeding, CMA and infection risk; and potential strategies to modulate the gut microbiota and infection outcomes. The increased susceptibility of infants with CMA to infections, and the reported potential benefits with prebiotics, probiotics and synbiotics with regard to improving infection outcomes and reducing antibiotic usage in infants with CMA, makes this a clinically important issue that merits further research.


Sleep-prolonging effect of Coriandrum sativum hydro-alcoholic extract in mice.
The present study was planned to investigate sleep-prolonging effect of C. sativum. The hydro-alcoholic extract (HAE) and its three fractions namely water (WF), ethyl acetate (EAF) and N-butanol (NBF) were prepared from C. sativum aerial parts and administrated to mice. Also, the possible cytotoxicity of the extracts was tested using cultured PC12 cells. The HAE, EAF and NBF significantly prolonged sleep duration. Only the NBF could significantly decrease sleep latency. No decrease in the neuronal surviving was observed either by HAE or by its fractions. The present data indicate that C. sativum exert sleep-prolonging action without major neurotoxic effect.


Trap and nonradiative centers in Ba₃Si₆O₁₂N₂:Eu²⁺ phosphors observed by thermoluminescence and two-wavelength excited photoluminescence methods.
We have studied trap centers and nonradiative (NRR) recombination centers in a Ba3Si6O12N2:Eu2+ (BSON), one of promising materials for efficient and stable phosphors in white LED lamp applications. The energy distribution of four trap centers was obtained by thermo-luminescence (TL) with the excitation energy of 5.59eV. By superposing a below-gap excitation light of 1.77eV and observing the intensity change of the 5d-4f emission of Eu2+ centered at 2.36eV in our two-wavelength excited photoluminescence (TWEPL) measurement, both transient and steady state enhancement were observed. Such peculiar behavior of photo-stimulation is attributed to the coexistence of trap centers and NRR centers: the photoexcitation of electrons from trap centers generates the transient component, while that from NRR centers maintains the steady state component. An optical detection of relatively faint contribution of defects became possible in order to improve further the reliability and efficiency of phosphor materials.


Free-viewing multi-stimulus eye tracking task to index attention bias for alcohol versus soda cues: Satisfactory reliability and criterion validity.
Cognitive -motivational models point to attention bias (AB) as an important factor in the persistence of problematic drinking behavior. Unfortunately, the measures that have been used to examine AB in addiction typically showed poor psychometric properties. To bring research on AB a critical step further it would be crucial to develop tasks with acceptable reliability and construct validity. Recently, Lazarov and colleagues (2016) developed a multi-stimulus free-viewing task (participants were free to look at any part of the screen and there was no secondary task involved) that showed excellent psychometric properties in the context of social anxiety as well as depression. We, therefore, adapted this task and examined its psychometric quality within the context of alcohol use. Participants with varying levels of alcohol use (N = 100) were presented with 54 matrices each containing 8 alcoholic and 8 non-alcoholic drinks. Each matrix was presented for 6 s. First fixation (100 ms) location and latency and total dwell time were assessed for alcohol and soda pictures. Assessment of AB, craving, and alcohol use (problems) was repeated after 3-8 days. Specifically, the dwell-time based AB-measure showed excellent internal reliability and considerable stability. Supporting the validity of the current AB-measures, it was found that participants with higher scores on craving and alcohol problems (i) dwelt longer on alcohol stimuli, and (ii) more often showed a first fixation on alcohol, whereas (iii) stronger craving was associated with shorter latency of first alcohol fixations. The AB-measure showed promising psychometric properties. Thus, this free-viewing eye-tracking task seems a welcome new tool for being used in future research on AB in addiction.


CYTOKINOGENESIS DISORDERS IN MECHANISMS OF THE EXPERIMENTAL PERODONTITIS DEVELOPMENT AND THEIR CORRECTION BY FLAVONOL.
The aim: Evaluation of changes in proinflammatory and anti-inflammatory units of the cytokine profile in the mechanisms of development of experimental bacterial-immune periodontitis and elucidation of the effect of flavonol quercetin on its parameters. Materials and methods: Experimental periodontitis was caused by introducing into the tissues of the periodontal complex a mixture of microorganisms diluted with egg protein. In order to enhance the immune response, a complete Freund's adjuvant was injected into the rat's paw at the same time. For correction, intramuscular injections of water-soluble quercetin at a dose of 100 mg / kg body weight were performed for 7 days (7th to 14th day). Results: The use of flavonol quercetin led to a decrease in the serum content of experimental animals with pro-inflammatory cytokines. With regard to anti-inflammatory cytokines, their content in the blood of animals during the development of this simulated inflammatory process changed in the opposite direction. Quercetin effectively eliminated the imbalance of the immune system and increased the level of IL-10 and IL-4 in the serum. After injections of quercetin, the relation of pro- and anti-inflammatory cytokines in the serum of animals on 14th day of the study was reduced compared to their content in rats that did not receive correction. Conclusions: The formation and course of experimental bacterial-immune periodontitis is accompanied by a complex of pathological changes in immunocytokinogenesis, which is manifested by a progressive increase in serum concentrations of proinflammatory cytokines and a decrease in anti-inflammatory cytokines. Flavonol quercetin reduces the concentration of pro-inflammatory and increases the content of anti-inflammatory cytokines.


More After Hours Medical Service: 'pillars' of success.
This study aimed to identify and explore the factors that are crucial to the successful operation of rural after-hours medical services. It sought to determine the attributes that contribute toward the successful operation of after-hours medical services in rural towns. It drew on computer-assisted telephone interviews with stakeholders, and operational, demographic and financial data. The findings were brought together and analysed within an integrated framework for the guidance of policy makers. In a rural setting, the most important factors for a successful after-hours medical service are related to, 'place', 'process', 'people' and 'time'. These need to be integrated through effective management of relationships.


Phosphorylation and inhibition of type III adenylyl cyclase by calmodulin-dependent protein kinase II in vivo.
Inhibition of type III adenylyl cyclase (III-AC) by intracellular Ca2+ in vivo provides a mechanism for attenuation of hormone-stimulated cAMP signals in olfactory epithelium, heart, and other tissues (Wayman, G. A., Impey, S., and Storm, D. R. (1995) J. Biol. Chem. 270, 21480-21486). Although the mechanism for Ca2+ inhibition of III-AC in vivo has not been defined, inhibition is not mediated by Gi, cAMP-dependent protein kinase, or protein kinase C. However, Ca2+ inhibition of III-AC is antagonized by KN-62, a CaM-dependent kinase inhibitor. In addition, constitutively activated CaM kinase II inhibits the enzyme. These data suggest that CaM kinase II regulates the activity of III-AC by direct phosphorylation or by an indirect mechanism involving phosphorylation of a protein that inhibits III-AC. Here we report that III-AC is phosphorylated in vivo when intracellular Ca2+ is increased and that phosphorylation is prevented by CaM-dependent kinase inhibitors. Site-directed mutagenesis of a CaM kinase II consensus site (Ser-1076 to Ala-1076) in III-AC greatly reduced Ca2+-stimulated phosphorylation and inhibition of III-AC in vivo. These data support the hypothesis that Ca2+ inhibition of III-AC is due to direct phosphorylation of the enzyme by CaM kinase II in vivo.


Spinal block complications in obstetrics and gynecology patients.
To determine spinal complications during and after surgery in obstetrics and gynecological patients. We conducted a descriptive study in Al-Wahda and Aden Teaching Hospitals in Aden, Yemen from March 2004 to March 2005. One hundred and fifty obstetrics and gynecological patients were enrolled. Before and during surgery, pulse and blood pressure was monitored, and patients were observed for any complications of spinal anesthesia, for example, hypotension, nausea, vomiting, shivering, and total spinal block. Post operatively, the patients were followed to identify post-spinal headache, urine retention, neuralgia, back pain, and respiratory failure. Results of complications were related by applying statistical test. Hypotension during surgery was established at a very high percentage of 82%. This could be due to lack of preloading of the patients before spinal block. Vomiting was 61%, nausea 56%, shivering 30%, and total spinal anesthesia 2%. Post operatively, 77.3% patients had post spinal headache, which lasted 4 days, compared with patients who had been applied with non-cutting disposable needles. Urine retention was 38.7%, while back pain and neuralgia was 21.3% each, and respiratory failure was 1.3%. Hypotension was traced in a very high percentage of cases due to unawareness and ignorance of pre-anesthetic intravenous fluid loading by concerned staff. Post spinal headache was the second most common complication due to the usage of large, cutting, non-disposable needles.


Comparative genomics of dairy-associated Staphylococcus aureus from selected sub-Saharan African regions reveals milk as reservoir for human-and animal-derived strains and identifies a putative animal-related clade with presumptive novel siderophore.
Staphylococcus aureus infection is considered to be a neglected tropical disease with huge impact on human and animal health alike. Dairy production in sub-Saharan Africa (SSA) relies heavily on various animals such as cows, goats, and camels, depending on the region. S. aureus causes mastitis and exhibits high prevalence in raw milk. The population structure including genotypic and phenotypic traits of dairy S. aureus in relation to animal and human isolates is, however, unknown for SSA. In this work, 20 S. aureus dairy isolates from East and West Africa were selected for comparative genomics and phenotypic analysis. Comparing their population structure revealed a large diversity of different origins suggesting milk to be a reservoir for human and animal strains alike. Furthermore, a novel putative siderophore was detected in multiple strains in a distinct animal-clade with strains of global origin. This putative siderophore shares a high genetic identity with that from Streptococcus equi suggesting possible horizontal gene transfer. These findings combined with the virulence genes harbored by these dairy-derived strains such as pvl, human evasion factor scn, various enterotoxin, leucocidin and antibiotic resistance genes, stresses the need for an integrative One Health approach to tackle the problem of S. aureus infections in animals and humans in sub-Saharan Africa.


The prescription of direct oral anticoagulants in the elderly: An observational study of 19 798 Ambulatory subjects.
Direct oral anticoagulants (DOACs) are increasingly prescribed to elderly people, but the epidemiologic data for this population remains scarce. We compared the elderly population taking DOACs and those not taking DOACs (noDOAC). We included individuals over 75 years old, affiliated to Mutualité Sociale Agricole of Burgundy (a French regional health insurance agency), who had been refunded for a prescribed DOAC between 1st and 30th September 2017. The DAOC group (DAOCG) and noDOAC group (noDOACG) were compared in terms of demographic conditions, registered chronic diseases (RCD), and number and types of prescribed drugs. In the DOACG, we compared the type of prescribing physician and laboratory monitoring for novel prescriptions (initial) and prescription refills (≥ 3 months). Of the 19 798 included patients, 1518 (7.7%) were prescribed DAOCs and 18 280 (92.3%) were not. Mean and median age was 85 years in the 2 groups (DOACG and noDOACG). In the DOACG, there were more men (50% vs 40.2%), more RCD (88.9% vs 68.7%) and more drugs per prescription (6 ± 2.8 vs 5 ± 2.9) (All P < .01). The DOACG also took more antihypertensive drugs. The most commonly prescribed DOACs were apixaban (42.9%) followed by rivaroxaban (38.4%) and dabigatran (18.6%). Complete blood count, serum creatinine and coagulation function tests were requested for 69.4%, 75% and 22.2%, respectively, of patients prescribed DAOCs. The DOACG had more RCD and drugs per prescription than the noDOACG; routine laboratory monitoring was insufficient. What's known Platelet aggregation inhibitors (low-dose) are recommended for secondary prevention of cardiovascular events in patients suffering from symptomatic atherosclerosis. The main risk of this treatment is bleeding. What's new A prescription for platelet aggregation inhibitors was found in 34% of geriatric inpatients in this prospective study. Compliance to guidelines was better for symptomatic peripheral artery disease than for primary prevention in accordance with recent publications. Geriatric comorbidities had no impact on the prescription of platelet aggregation inhibitors. Underuse of platelet aggregation inhibitors was observed in 11.3% of cases and overuse in 13.7% of cases.


Mapping Buried Hydrogen-Bonding Networks.
We map buried hydrogen-bonding networks within self-assembled monolayers of 3-mercapto-N-nonylpropionamide on Au{111}. The contributing interactions include the buried S-Au bonds at the substrate surface and the buried plane of linear networks of hydrogen bonds. Both are simultaneously mapped with submolecular resolution, in addition to the exposed interface, to determine the orientations of molecular segments and directional bonding. Two-dimensional mode-decomposition techniques are used to elucidate the directionality of these networks. We find that amide-based hydrogen bonds cross molecular domain boundaries and areas of local disorder.


Appearance of Membrane-bound Iron-Sulfur Centers and the Photosystem I Reaction Center during Greening of Barley Leaves.
Dark-grown barley (Hordeum vulgare) etioplasts were examined for their content of membrane-bound iron-sulfur centers by electron paramagnetic resonance spectroscopy at 15K. They were found to contain the high potential iron-sulfur center characterized (in the reduced state) by an electron paramagnetic resonance g value of 1.89 (the "Rieske" center) but did not contain any low potential iron-sulfur centers. Per mole of cytochrome f, dark-grown etioplasts and fully developed chloroplasts had the same content of the Rieske center. During greening of etioplasts under continuous light, low potential bound iron-sulfur centers appear. In addition, the photosystem I reaction center, as measured by the photooxidation of P700 at 15K, also became functional; during greening the appearance of a photoreducible low potential iron-sulfur center paralleled the appearance of P700 photoactivity.These findings indicate the close association of the low potential iron-sulfur centers with the photosystem I reaction center; they also support the concept that the development of stable charge separation in the photosystem I reaction center requires, in addition to P700, a low potential iron-sulfur center.


Lectin binding pattern of Hodgkin disease-derived cell lines in comparison to other human cell lines.
The three Hodgkin disease-derived cell lines L 428, L 540, and L 591 were characterized in their carbohydrate epitope composition by a panel of lectins. Nine other human cell lines were tested in comparison to the Hodgkin (H) and Sternberg Reed (SR) cells: promyelocytic (HL 60), lymphoblastoid, myeloma, histiocytic lymphoma (U 937), and other non-Hodgkin lymphoma cell lines. Twenty-four different fluoresceinated lectins bound to the Hodgkin and other cell lines in different percentages of positive cells and with varying intensities. Lotus lectin and a monoclonal anti-Lewis blood group X antibody showed very similar binding patterns (L 428, L 540, HL 60, U 937). Soybean agglutinin stained only L 428 and L 540, although nearly all were positive after neuraminidase treatment. Cell lysis of the three H cell lines resulted in a very similar electrophoretic mobility pattern of proteins. In addition, staining of transblotted glycoproteins with biotinylated concanavalin A by avidin peroxidase reaction revealed corresponding bands. Differences were seen with Lotus staining. In summary, the origin of H cells is still unknown, but there is obviously some relationship in the glycoconjugate profile to the myelohistiocytic lineage.


The potential of advanced MR techniques for precision radiotherapy of glioblastoma.
As microscopic tumour infiltration of glioblastomas is not visible on conventional magnetic resonance (MR) imaging, an isotropic expansion of 1-2 cm around the visible tumour is applied to define the clinical target volume for radiotherapy. An opportunity to visualize microscopic infiltration arises with advanced MR imaging. In this review, various advanced MR biomarkers are explored that could improve target volume delineation for radiotherapy of glioblastomas. Various physiological processes in glioblastomas can be visualized with different advanced MR techniques. Combining maps of oxygen metabolism (CMRO2), relative cerebral blood volume (rCBV), vessel size imaging (VSI), and apparent diffusion coefficient (ADC) or amide proton transfer (APT) can provide early information on tumour infiltration and high-risk regions of future recurrence. Oxygen consumption is increased 6 months prior to tumour progression being visible on conventional MR imaging. However, presence of the Warburg effect, marking a switch from an infiltrative to a proliferative phenotype, could result in CMRO2 to appear unaltered in high-risk regions. Including information on biomarkers representing angiogenesis (rCBV and VSI) and hypercellularity (ADC) or protein concentration (APT) can omit misinterpretation due to the Warburg effect. Future research should evaluate these biomarkers in radiotherapy planning to explore the potential of advanced MR techniques to personalize target volume delineation with the aim to improve local tumour control and/or reduce radiation-induced toxicity.


Ambient virtual scribes: Mutuo Health's AutoScribe as a case study of artificial intelligence-based technology.
Studies show that clinicians are increasingly burning out in large part from the clerical burden associated with using Electronic Medical Record (EMR) systems. At the same time, recently developed health data analytic algorithms struggle with poor quality free-text entered data in these systems. We developed AutoScribe using artificial intelligence-based natural language processing tools to automate these clerical tasks and to output high-quality EMR data. In this article, we describe the benefits and drawbacks of our technology. Furthermore, we describe how we are positioning our company's culture within the existing healthcare system and suggest steps leaders of the system should consider in order to ensure that potentially transformative artificial intelligence-based technologies like ours are optimally adopted.


[Three-dimensional reconstruction of carp brain tissue and brain electrodes for biological control].
In order to accurately implant the brain electrodes of carp robot for positioning and navigation, the three-dimensional model of brain structure and brain electrodes is to be proposed in the study. In this study, the tungsten electrodes were implanted into the cerebellum of a carp with the aid of brain stereotaxic instrument. The brain motor areas were found and their three-dimensional coordinate values were obtained by the aquatic electricity stimulation experiments and the underwater control experiments. The carp brain and the brain electrodes were imaged by 3.0 T magnetic resonance imaging instrument, and the three-dimensional reconstruction of carp brain and brain electrodes was carried out by the 3D-DOCTOR software and the Mimics software. The results showed that the brain motor areas and their coordinate values were accurate. The relative spatial position relationships between brain electrodes and brain tissue, brain tissue and skull surface could be observed by the three-dimensional reconstruction map of brain tissue and brain electrodes which reconstructed the three-dimensional structure of brain. The anatomical position of the three-dimensional reconstructed brain tissue in magnetic resonance image and the relationship between brain tissue and skull surface could be observed through the three-dimensional reconstruction comprehensive display map of brain tissue. The three-dimensional reconstruction model in this study can provide a navigation tool for brain electrodes implantation.


Sonic Rhinoplasty: Review and Updated Uses.
The ultrasonic bone aspirator (UBA) allows for precision and provides ease of use in multiple steps of cosmetic and functional rhinoplasties. Its use has previously been described; however, since the publication of many studies the UBA has been improved and its applications for rhinoplasty have been modified and expanded. Both bony and cartilaginous modifications to the nose can be aided with the use of the UBA. From our experience, patient results have subjectively been found to be more acceptable, if not better, than with the use of other rhinoplasty instruments.


A randomized, double-blinded, placebo-controlled oral challenge study to evaluate the allergenicity of commercial, food-grade fish gelatin.
Recent interest in the labeling of foods and food proteins derived from allergenic sources necessitates determination of the potential allergenicity of such food ingredients. Fish gelatin is extracted from the skin of fish species known to elicit allergic reactions in sensitized individuals. To determine the allergenicity of fish gelatin by double-blinded, placebo-controlled food challenges (DBPCFC) in clinically fish-allergic individuals. Thirty fish-allergic patients diagnosed according to the EAACI Guidelines were included (age 9-50 years). Skin prick tests (SPT) and Histamine Release tests (HR) were performed with fish gelatin and codfish, and codfish-specific IgE was measured. All patients underwent DBPCFC with a cumulative dose of 14.61 g fish gelatin. In all 30 patients SPT, HR, and specific IgE to codfish were positive. SPT and HR with fish gelatin were positive in 3/30 and 7/30, respectively. One patient showed mild reaction to placebo and no reaction to the active challenge. Two patients reported mild subjective reactions to active challenge. Upon re-challenge one of them described subjective symptoms again to the active challenge (7.61 g cumulated dose of fish gelatin) with no reaction to placebo, while the other experienced very mild subjective symptoms to placebo and nothing to the active. The proportion of truly sensitive patients was estimated to 0.03 in the total study group. None of 30 fish allergic patients reacted adversely to the ingestion of 3.61 g cumulative dose of fish gelatin. In this study fish gelatin presents no risk to fish-allergic patients at the doses typically used. Statistically, these results indicate that there is 95% certainty that 90% of fish-allergic consumers will not react to ingestion of a 3.61 g cumulative dose of fish gelatin.


21-Hydroxy-6,19-oxidoprogesterone: a novel synthetic steroid with specific antiglucocorticoid properties in the rat.
In the rat, the conformationally highly bent steroid 21-hydroxy-6, 19-oxidoprogesterone efficiently displaces [3H]corticosterone from thymus-glucocorticoid receptors and blocks type II receptors in kidney cytosols but competes with neither [3H]aldosterone for kidney-mineralocorticoid receptors nor [3H]progesterone for uterus-progesterone receptors. It evokes Na+ retention only at very high doses (approximately 100 microg/100 g of rat weight) and is unable to induce tyrosine aminotransferase or to increase glycogen deposits in rat liver. When coincubated with corticosterone or dexamethasone, 2.5 microM 21OH-6OP inhibits 80% of tyrosine aminotransferase induction. It may therefore be used experimentally as an antiglucocorticoid virtually lacking mineralocorticoid or glucocorticoid properties as well as affinity for mineralocorticoid or progesterone receptors.


[Bronchial endoscopy for the diagnosis of tuberculous mediastinal adenopathies].
The aim of this retrospective study was to evaluate the yield of bronchial endoscopy for the diagnosis of tuberculous mediastinal adenopathies. We analyzed the results in 200 procedures in patients with tuberculous mediastinal adenopathies. Mediastinal tuberculous adenopathies were found in 6% of the patients with tuberculosis diagnosed during the same period. Mean age of the patients was 30.5 years, and the sex ratio was 1.5. Bronchial endoscopy improved the diagnostic yield of the bronchial aspiration fluid (22% versus 11% without endoscopy). This method allowed positive diagnosis of tuberculosis in 164 patients (82%) by visualizing specific lesions such as compressions, granulations, and gangliobronchial fistulae. Histological confirmation was obtained in 72 (79%) patients among 91 biopsy specimens. Bronchial endoscopy remains a crucial exploration for the diagnosis of mediastinal tuberculous adenopathy, even in HIV-infected patients, because in our series, among 101 treated patients, 99 were HIV positive (98%).


[The drugs for H. pylori eradication therapy].
H. pylori eradication significantly inhibited ulcer recurrence in Japanese peptic ulcer patients. In Japan, 12 months after treatment, gastric ulcers had recurred in 11.4% of those with successful H. pylori eradication and 64.5% of those with unsuccessful H. pylori eradication. Duodenal ulcers had recurred in 6.8% of patients for whom H. pylori eradication was successful and in 85.3% of patients in whom eradication failed. About long-term study, 4 years after treatment, gastric ulcers had recurred in 9.3% of those with successful H. pylori eradication and duodenal ulcers recurrence was occurred in 6.2% of those. The annual recurrence rates of gastric, duodenal ulcer were 2.3% and 1.6%, respectively. However, in current Japan, the decrease of the primary eradication rate is reported by the increase of clarithromycin-resistant strains. The increase of metronidazole-resistant strains used for the second eradication is not recognized so far, but in future, increase is concerned about. Therefore, the making of the regimen of the third-line eradication therapy is needed now.


Determination of the time origin by the maximum entropy method in time-domain terahertz emission spectroscopy.
We have developed a scheme for determining the time origin by the maximum entropy method (MEM) in time-domain terahertz (THz) emission spectroscopy. By applying the MEM to trial damped sinusoidal waveforms, we confirmed that the MEM gives true phase shifts across the resonance features and that its inherent uncertainty in determining the time origin is +/-15 fs for 100-fs-class excitation/sampling optical pulses. Furthermore, when the MEM was applied to a THz waveform recorded experimentally with a finite sampling interval for the Bloch oscillation in a semiconductor superlattice, a misplacement of the time origin was indeed detected with an accuracy limited by the worse of the MEM inherent uncertainty and the sampling interval.


The nonsense mutation MSH2 c.2152C>T shows a founder effect in Portuguese Lynch syndrome families.
The mutational spectrum of the MMR genes is highly heterogeneous, but specific mutations are observed at high frequencies in well-defined populations or ethnic groups, due to founder effects. The MSH2 mutation c.2152C>T, p.(Gln718*), has occasionally been described in Lynch families worldwide, including in Portuguese Lynch syndrome families. During genetic testing for Lynch syndrome at the Portuguese Oncology Institutes of Porto and Lisbon, this mutation was identified in 28 seemingly unrelated families. In order to evaluate if this alteration is a founder mutation, haplotype analysis using microsatellite and SNP markers flanking the MSH2 gene was performed in the 28 probands and 87 family members. Additionally, the geographic origin of these families was evaluated and the age of the mutation estimated. Twelve different haplotypes were phased for 13 out of the 28 families and shared a conserved region of ∼3.6 Mb. Based on the mutation and recombination events observed in the microsatellite haplotypes and assuming a generation time of 25 years, the age estimate for the MSH2 mutation was 273 ± 64 years. The geographic origins of these families were mostly from the Northern region of Portugal. Concluding, these results suggest that the MSH2 c.2152C>T alteration is a founder mutation in Portugal with a relatively recent origin. Furthermore, its high proportion indicates that screening for this mutation as a first step, together with the previously reported Portuguese founder mutations, may be cost-effective in genetic testing of Lynch syndrome suspects of Portuguese ancestry.


Genetic factors for idiopathic choroidal neovascularization.
Objective: The aim of this study was to investigate genetic factors associated with idiopathic choroidal neovascularization (ICNV). Methods: We conducted a case-control study including 69 cases with ICNV and 114 controls who underwent cataract surgery. Single nucleotide polymorphisms (SNPs) from genes reported to be related to AMD, CNV and uveitis were selected for this study. Results: In an univariate analysis, the rs669676 SNP located in the COL8A1 gene was associated with the proportion of people who has idiopathic CNV ( X2 = 9.3453, corrected p-value = 0.1). For the rs669676 SNP, minor allele homozygotes, in the dominant model of genotype analysis (GG versus AA-GA), it showed significant differences in the ICNV group vs controls (p = .01, OR = 1.219 (95%CI: 1.04-1.429)). Conclusions: The rs669676 SNP located in the COL8A1 gene may contribute to a genetic susceptibility for ICNV.


An Organogold(III) Difluoride with a trans Arrangement.
The trans isomer of the organogold(III) difluoride complex [PPh4 ][(CF3 )2 AuF2 ] has been obtained in a stereoselective way and in excellent yield by reaction of [PPh4 ][CF3 AuCF3 ] with XeF2 under mild conditions. The compound is both thermally stable and reactive. Thus, the fluoride ligands are stereospecifically replaced by any heavier halide or by cyanide, the cyanide affording [PPh4 ][trans-(CF3 )2 Au(CN)2 ]. The organogold fluoride complexes [CF3 AuFx ]- (x=1, 2, 3) have been experimentally detected to arise upon collision-induced dissociation of the [trans-(CF3 )2 AuF2 ]- anion in the gas phase. Their structures have been calculated by DFT methods. In the isomeric forms identified for the open-shell species [CF3 AuF2 ]- , the spin density residing on the metal center is found to strongly depend on the precise stereochemistry. Based on crystallographic evidence, it is concluded that Auiii and Agiii have similar covalent radii, at least in their most common square-planar geometry.


Jet injection--local anesthesia for fitting and removal of IUDs.
Women with small uterine cavities and narrow cervical canals in particular suffer from symptoms such as discomfort, pain, cramps, bradycardia, syncope, and epileptoid convulsions during IUD insertions. These problems can be avoided by paracervical block (PCB) with syringe and needle, which may, in rare cases, entail hazardous side effects. These can be eliminated by the use of Jet Injection PCB. The Jet Injector deposits a 2% or 3% anesthetic solution paracervically submucously under high carbon dioxide pressure. The patient's fear of injection with a needle is avoided. The method can be applied by paramedics since intravascular application of anesthetic solution is impossible. The use of a more concentrated anesthetic solution allows dose reduction and the method of dispersion of the micro-drops ensures a more rapid onset. Premedication is not required and disposable material is economized on. This study is based on the application of Jet Injection PCB before insertion of medicated IUDs in 447 women; 60% nulligravidae, 14% nulliparous with abortion(s), 13% primiparae, and 13% multiparous. Age ranged from 15-47 years.


alpha(2A)-adrenergic receptor derived peptide adsorbates: a G-protein interaction study.
The affinity of alpha(2A)-adrenergic receptor (alpha(2A)-AR) derived peptide adsorbates for the functional bovine brain G-protein is studied in the search for the minimum sequence recognition. Three short peptides (GPR-i2c, GPR-i3n, and GPR-i3c) are designed to mimic the second and third intracellular loops of the receptor. X-ray photoelectron spectroscopy is used to study the chemical composition of the peptides and the binding strength to the surfaces. Chemisorption of the peptides to the gold substrates is observed. Infrared spectroscopy is used to study the characteristic absorption bands of the peptides. The presence of peptides on the surfaces is verified by prominent amide I and amide II bands. The interaction between the peptides and the G-protein is studied with surface plasmon resonance. It is shown that GPR-i3n has the highest affinity for the G-protein. Equilibrium analysis of the binding shows that the G-protein keeps its native conformation when interacting with GPR-i3c, but during the interaction with GPR-i2c and GPR-i3n the conformation of G-protein is changed, leading to the formation of aggregates and/or multilayers.