Cortical Map Plasticity as a Function of Vagus Nerve Stimulation Intensity.
Pairing sensory or motor events with vagus nerve stimulation (VNS) can reorganize sensory or motor cortex. Repeatedly pairing a tone with a brief period of VNS increases the proportion of primary auditory cortex (A1) responding to the frequency of the paired tone. However, the relationship between VNS intensity and cortical map plasticity is not known. The primary goal of this study was to determine the range of VNS intensities that can be used to direct cortical map plasticity. The rats were exposed to a 9 kHz tone paired with VNS at intensities of 0.4, 0.8, 1.2, or 1.6 mA. In rats that received moderate (0.4-0.8 mA) intensity VNS, 75% more cortical neurons were tuned to frequencies near the paired tone frequency. A two-fold effective range is broader than expected based on previous VNS studies. Rats that received high (1.2-1.6 mA) intensity VNS had significantly fewer neurons tuned to the same frequency range compared to the moderate intensity group. This result is consistent with previous results documenting that VNS is memory enhancing as a non-monotonic relationship of VNS intensity.


Use of Inherent Anteversion of an Intramedullary Nail to Avoid Malrotation in Comminuted Femur Fractures: A Prospective Case- Control Study.
To (1) evaluate using the inherent anteversion of a second or third generation femoral nail to set the version of the femur during locked intramedullary nailing of comminuted femoral shaft fractures (Espinosa Technique [ET]) and compare it with our traditional method (traditional group [TG]) and (2) assess the variation of anteversion because of the inherent play in the nail itself. A prospective IRB-approved study. Academic US Level 1 Trauma Center. Fifty-two consecutive patients with comminuted femur fractures all completed the study. The first 27 patients had the anteversion determined using the patellar shadow and lesser trochanter (TG), and the next 25 patients were treated by ET. Computed tomography scanogram for femoral anteversion and length in the normal versus operated femur. A >15 degree difference from native to operated legs was found in 8/27 TG (29%, 95% CI 15.3%-54.2%), with a mean difference of 11.6 ± 10.2 degrees (95% CI 8.8-16.17) verses 1/25 in the ET group (2.5%, 95% CI 0%-15.3%), with a mean difference of 4.8 ± 6.2 degrees (95% CI 1.38-8.9) (P = 0.0068). There was a 5 degree variability in our ability to center the proximal locking screw in the femoral head and 5 degrees variation in distal locking. The inherent anteversion of a second generation nail can be used to minimize malrotation of the femur after comminuted fractures during locked intramedullary nailing in patients with normal anteversion and is superior to our present fluoroscopic technique. Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.


The beneficial effects of group-based exercises on fall risk profile and physical activity persist 1 year postintervention in older women with low bone mass: follow-up after withdrawal of exercise.
To determine whether exercise-induced reductions in fall risk are maintained in older women 1 year after the cessation of three types of interventions--resistance training, agility training, and general stretching. One-year observational study. Community. Ninety-eight women aged 75 to 85 with low bone mass. Primary outcome measure was fall risk, measured using the Physiological Profile Assessment tool. Secondary outcome measures were current physical activity level, assessed using the Physical Activity Scale for the Elderly, and formal exercise participation, assessed using an interview. At the end of the follow-up, the fall risk of former participants of all three exercise programs was maintained (i.e., still reduced) from trial completion. Mean fall risk value at the end of follow-up was 43.3% lower than mean baseline value in former participants of the resistance-training group, 40.1% lower in the agility-training group, and 37.4% lower in the general stretching group. Physical activity levels were also maintained from trial completion. Specifically, there was a 3.8% increase in physical activity from baseline for the resistance-training group, a 29.2% increase for the agility-training group, and a 37.7% increase for the general stretching group. After three types of group-based exercise programs, benefits are sustained for at least 12 months without further formal exercise intervention. Thus, these 6-month exercise interventions appeared to act as a catalyst for increasing physical activity with resultant reductions in fall risk profile that were maintained for at least 18 months in older women with low bone mass.


Presence of endothelial colony-forming cells is associated with reduced microvascular obstruction limiting infarct size and left ventricular remodelling in patients with acute myocardial infarction.
Endothelial colony-forming cells (ECFCs) are known to increase after acute myocardial infarction (AMI). We examined whether the presence of ECFCs is associated with preserved microvascular integrity in the myocardium at risk by reducing microvascular obstruction (MVO). We enrolled 88 patients with a first ST elevation AMI. ECFC colonies and circulating progenitor cells were characterized at admission. MVO was evaluated at 5 days and infarct size at 5 days and at 6-month follow-up by magnetic resonance imaging. ECFC colonies were detected in 40 patients (ECFC(pos) patients). At 5 days, MVO was of greater magnitude in ECFC(neg) versus ECFC(pos) patients (7.7 ± 5.3 vs. 3.2 ± 5%, p = 0.0002). At 6 months, in ECFC(pos) patients, there was a greater reduction in infarct size (-32.4 ± 33 vs. -12.8 ± 24%; p = 0.003) and a significant improvement in left ventricular (LV) volumes and ejection fraction. Level of circulating CD34+/VEGF-R2+ cells was correlated with the number of ECFC colonies (r = 0.54, p < 0.001) and relative change in infarct size (r = 0.71, p < 0.0001). The results showed that the presence of ECFC colonies is associated with reduced MVO after AMI, leading to reduced infarct size and less LV remodelling and can be considered a marker of preserved microvascular integrity in AMI patients.


Development of a sandwich-dot enzyme linked immunosorbent assay for Streptococcus pneumoniae antigen detection in cerebrospinal fluid.
A new sandwich dot-enzyme linked immunosorbent assay (sdot-ELISA) was developed using omniserum prepared against different strains of Streptococcus pneumoniae as capture antibody and also as second or revealing antibody after its conjugation with horseradish peroxidase (HRP) for detection of pneumococcal antigen in cerebrospinal fluid (CSF). A total of 103 CSF samples of different categories were screened with newly developed dot-ELISA and results were compared with commercially available latex agglutination (LA) kit. The newly developed sdot-ELISA was more sensitive than LA test and can be used as an alternative diagnostic tool in laboratory and in field conditions. An added advantage of this ELISA system was that it did not require antibodies produced in two different animal species.


Infliximab: a novel treatment for sight-threatening thyroid associated ophthalmopathy.
We describe a patient with sight threatening thyroid associated ophthalmopathy (TAO) who was successfully treated with infliximab, an anti-tumour necrosis factor (TNF)-a antibody.


Discovery of a Kelch-like ECH-associated protein 1-inhibitory tetrapeptide and its structural characterization.
Keap1 constitutively binds to the transcription factor Nrf2 to promote its degradation, resulting in negative modulation of genes involved in cellular protection against oxidative stress. Keap1 is increasingly recognized as an attractive target for treating diseases involving oxidative stress, including cancer, atherosclerosis, diabetes, arthritis, and neurodegeneration. We used phage-display peptide screening to identify a tetrapeptide showing moderate binding affinity, which inhibits the interaction between Nrf2 and Keap1. The tetrapeptide does not include an ETGE motif, which is a commonly found consensus sequence in known peptidic inhibitors. In addition to affinity parameters, IC50, KD, and thermodynamic parameters, the crystal structure of the complex was determined to elucidate the binding conformation. The binding interactions resemble those of known small-molecule inhibitors as opposed to those of substrates and peptidic inhibitors. Although the tetrapeptide's affinity is not very high, our results may help facilitate the designing of small-molecule inhibitors during lead generation in drug discovery.


Choledochal Cysts Resected during Childhood Show No Mutations of KRAS and BRAF as Early Markers of Malignancy in Cholangiocytes.
In patients with choledochal cysts (CDC), a hyperplasia-dysplasia-carcinoma sequence can lead to biliary tract malignancy. The limited data available suggest that the risk decreases considerably after excision in childhood. We analyzed samples of resected CDC from pediatric patients histologically and performed mutational analysis of the proto-oncogenes KRAS and BRAF as early markers of malignant alteration in cholangiocytes. After institutional review board approval, patients undergoing resection for CDC in our center from 2011 to 2019 were retrospectively identified. Histopathological reports were searched for inflammation and endothelial alteration. Cases with sufficient tissue specimen were tested for KRAS codon 12/13 and BRAF codon 600 mutations by pyrosequencing. In total, 42 patients underwent resection for choledochal cyst in the study period. Median age at surgery was 2.4 years (range = 18 days-18 years). Histopathological analysis showed no malignancy, but various degrees of inflammation or fibrosis in approximately 50% of the patients and in all age groups. Sufficient tissue for mutation analysis was available for 22 cases, all of which tested negative for KRAS or BRAF mutation. In our series, chronic inflammatory changes were frequently present in CDC of infants and children. However, the lack of KRAS and BRAF mutations suggests that no malignant changes have been initiated in this group of European patients undergoing early resection.


Higher Levels of Dynamin-related Protein 1 are Associated with Reduced Radiation Sensitivity of Glioblastoma Cells.
Dynamin-related protein 1 (DRP1) is a GTPase involved in mitochondrial fission, mitochondrial protein import, and drug sensitivity, suggesting an association with cancer progression. This study was conducted to evaluate the prognostic significance of DRP1 in glioblastoma multiforme (GBM). DRP1 expression was measured by immunohistochemistry and Western blotting. Correlations between DRP1 expression and clinicopathological parameters were determined by statistical analysis. Differences in survival were compared using the log-rank test. DRP1 expression was detected in 87.2% (41/47) of the investigated patients with GBM. The patients with higher DRP1 levels had worse survival (p = 0.0398). In vitro, the silencing of DRP1 reduced cell proliferation, invasive potential, and radiation resistance. The addition of shikonin inhibited DRP1 expression and increased drug uptake. Moreover, shikonin reduced the nuclear entry of DNA repair-associated enzymes and increased radiation sensitivity, suggesting that reducing DRP1 expression could inhibit DNA repair and increase the radiation sensitivity of GBM cells. Our results indicate that DRP1 overexpression is a prospective radio-resistant phenotype in GBM. Therefore, DRP1 could be a potential target for improving the effectiveness of radiation therapy.


Effect of carbon source conditions on response of nitrifying sludge to 3,5-dichlorophenol.
Nutritional conditions of activated sludge had a significant influence on nitrification inhibition response. This study comprehensively investigated the inhibition of 3,5-dichlorophenol (3,5-DCP) on nitrification of activated sludge with different C/N ratios and carbon source types. The corresponding extracellular polymeric substances (EPS), microbial communities and functional genes were analysed. The results indicated that the addition of carbon source would reduce the nitrification activity and nitrification sensitivity to 3,5-DCP, and the order of the EC50 was sequenced as sodium acetate > methanol > glucose. The response mechanisms of activated sludge under diverse carbon source conditions to 3,5-DCP were summarised as follows. When the 3,5-DCP content was increased from 0.4 mg/L to 0.8 mg/L, the protein content increased from 73.2 ± 2.6 mg/g SS ∼122.4 ± 4 mg/g SS to 92.2 ± 11.2 mg/g SS ∼130.8 ± 9.6 mg/g SS in the tightly bound EPS (TB-EPS). The increase of protein content was attributed to cellular self-protection mechanisms. Furthermore, fluorescence characteristic analysis revealed that tyrosine and tryptophan in loosely bound EPS (LB-EPS) might account for higher EC50 in activated sludge fed with methanol and sodium acetate. In addition, the redundancy analyses (RDA) showed activated sludge with organics enriched the resistant species, such as Proteobacteria and Patescibacteria, while activated sludge without organics enriched the sensitive species, such as Ferruginibacter. Finally, the nitrification genes were found to be consistent with nitrification activity. Thus, the findings provide new insights into nitrification inhibition mechanism under different carbon source conditions.


Pre-school development and behavior screening with a consecutive support programs for 5-year-olds reduces the rate of school refusal.
The efficacy of pre-school health consultation in improving developmental and behavioral problems at 5-years of age with follow-up consecutive educational support before and after entrance into regular elementary school for 8 years in a rural city, Taketa, Oita prefecture, was evaluated. This program involved a survey with a three-step method as follows. Step 1: interviews and checklists conducted by public health nurses and nursery/kindergarten teachers for all children. Step 2: medical screening for all children performed by a local/home-school doctor. Step 3: diagnosis in selected children carried out by child neurologists, special support education teachers and clinical/school psychologists. Subsequently, for 1-2 years until entrance into elementary school, these children and their parents were given speech, behavioral and mental support as well as group play therapy in nursery/kindergarten. During the 8-years study period, 56 children (5.4%) were diagnosed with developmental disorders and six children were diagnosed with maltreatment by their parents among 1165 eligible children. Of these subjects, 40 children received support consecutively after entrance into school, 38 of whom entered regular elementary school and 32 attended regular classes for 1-6 years. A total of 39 of 40 children have attended school without refusal. Moreover, the total number of students refusing to attend school in elementary school decreased for 3 years from 8 of 3246 children (0.25%) in 2006-2008 and 13 of 2889 children (0.45%) in 2009-2011 to only 1 of 2646 children (0.04%) in 2012-2014. Pre-school developmental-behavioral screening and consecutive support programs in a rural city reduced the number of students refusing to attend school.


Safety profiles of leading nonsteroidal anti-inflammatory drugs.
Recently introduced nonsteroidal anti-inflammatory drugs (NSAIDs) have capitalized on new formulations or unique physical and pharmacologic properties in an attempt to provide a greater margin of gastrointestinal (GI) safety. The use of enteric coatings and nonoral or pro-drug formulations have not necessarily provided the expected safety, but other properties have been identified that appear to be more promising. However, as demonstrated by oxaprozin, considered to be one of the least safe NSAIDs but one of the leading drugs on the US market, success may not be dependent on safety. In contrast, the improved tolerability of 2 other new NSAIDs, nabumetone and etodolac, has been established in clinical trials and limited postmarketing surveillance. This improved tolerability is probably associated with several pharmacologic properties that have been suggested to contribute to GI safety: (1) nonacidic pro-drug formulation; (2) lack of enterohepatic recirculation; (3) a short plasma half-life; and (4) preferential inhibition of cyclo-oxygenase-2 (COX-2). Although these factors may not improve efficacy, their incorporation into the design of drugs suggests that safer NSAIDs may be a clinical reality. However, the safety and clinical value of any new drug for the general population will be validated only through extensive postmarketing surveillance.


Environmental risk factors of incident distal sensorimotor polyneuropathy: Results from the prospective population-based KORA F4/FF4 study.
Distal sensorimotor polyneuropathy (DSPN) is a common condition in older populations with high prevalence of obesity and type 2 diabetes. We hypothesised that the risk of DSPN is increased by multiple ubiquitous environmental risk factors, particularly in people with obesity. This study was based on 423 individuals aged 62-81 years without DSPN who participated in the population-based Cooperative Health Research in the Region of Augsburg (KORA) F4 survey (2006-2008) in Southern Germany. During 6.5 years of follow-up, 188 participants developed clinical DSPN as assessed by the Michigan Neuropathy Screening Instrument. Environmental exposures, including air temperature, surrounding greenness (assessed with the normalized difference vegetation index [NDVI]), long-term road traffic noise and air pollution, were assessed at participants' residences. The cumulative risk index (CRI) evaluated the joint effects of co-occurring exposures on DSPN risk based on effect estimates from multi-exposure Poisson regression models. The models were adjusted for age, sex, height, waist circumference, smoking, alcohol consumption, physical activity, education and neighbourhood socioeconomic status. In the entire cohort, the co-occurrence of an interquartile range (IQR) decrease in temperature of the warm season and NDVI in a 100-m buffer and of an IQR increase in night-time average traffic noise and in annual average particle number concentration (PNC) was positively associated with incident DSPN (CRI [95 % CI] 1.39 [1.02, 1.91]). Effect estimates for exposure combinations were generally higher in individuals with obesity (CRI 1.34-2.01) than in those without obesity (CRI 0.90-1.33). The four-exposure model showed a twofold increased risk of DSPN among obese (CRI [95 % CI] 2.01 [1.10, 3.67]), but not among non-obese individuals (CRI [95 % CI] 1.18 [0.83, 1.67]). Thus, ubiquitous environmental exposures jointly augment the risk of DSPN in the older population. Lower air temperature in the warm season, less greenness, and higher noise levels and ultrafine particle concentrations identified people with obesity as a particularly vulnerable subgroup.


Parvalbumin isoforms for enhancing cardiac diastolic function.
Diastolic heart failure (DHF), characterized by depressed myocardial relaxation performance and poor ventricular filling, is a distinct form of heart failure accounting for nearly half of the heart failure patients with otherwise normal systolic performance. Defective intracellular calcium (Ca2+) cycling is an important mechanism underlying impaired relaxation in DHF. Recently, genetic manipulation of Ca2+ handling proteins in cardiac myocytes has been explored for its potential therapeutic application in DHF. Specifically, ectopic expression of the skeletal muscle Ca2+ binding protein parvalbumin (Parv) has been shown to accelerate myocardial relaxation in vitro and in vivo. Parv acts as a unique "delayed" Ca2+ buffer during diastole by promoting Ca2+ transient decay and sequestration and corrects diastolic dysfunction in an energy-independent manner. This brief review summarizes the rationale and development of Parv gene transfer approaches for DHF, and in particular, discusses the divergent effects of Parv isoforms on cardiac myocyte Ca2+ handling and contractile function with the long-range goal of alleviating diastolic dysfunction in DHF.


The production of Cyprideis torosa Jones 1850 (Crustacea, Ostracoda).
The ostracod Cyprideis torosa Jones, 1850 is a dominant species in the meiofauna of brackish water habitats. Its production in the field over a five-year period has been calculated using two production models. The first model uses the age-distribution of shells preserved in the sediment to assess the stage-specific mortality rates and the stage durations. The second model is the size-frequency model, modified for use with developmental stages instead of size-classes. Productions calculated with both methods agree very well. Their values are 9.7 and 9.2 g dwt·m-2·y-1 respectively. The yearly P/B-ratio is 2.7 or 2.6 y-1, production efficiency P/A is 0.38 or 0.37.The production efficiency of Cyprideis torosa nearly equals the mean efficiency of non-insect invertebrate detritivores. The species' conservative strategy and long generation time enables it to maintain a relatively high biomass with a fixed amount of food. These characteristics make it a superior competitor.


[Estimation of pharmacokinetic constants in irregular repeated drug administration (author's transl)].
Least squares estimations for the fraction of the dose absorbed, volume of distribution, absorption and elimination rate based on drug measurements in blood and urine after aperiodical administration are described for a one-compartment model with first-order absorption. The non-linear regression analysis is carried out by means of a modified Gauss-Newton iteration procedure by Hartley. BASIC and FORTRAN functions are developed and applied in an example. The advantages of unbiased and consistent least-squares estimations in pharmacokinetics are pointed out.


On-chip enzymatic assay for chloramphenicol acetyltransferase using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.
Herein, we report a chloramphenicol (CAP) acetyltransferase (CAT) activity assay based on self-assembled monolayers on gold as an alternative to conventional CAT reporter gene assay systems, which sometimes require toxic materials and complicated steps that limit their use. A CAP derivative presented on a monolayer was converted to the acetylated CAP by CAT in the presence of acetyl-CoA. The conversion was directly monitored by observing the molecular weight changes in CAP using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. CAT activity was determined under various reaction conditions by changing reaction times, CAT and acetyl-CoA concentrations. As a practical application, we identified gene expression in bacteria that were transformed with pCAT plasmid DNA. Our strategy can provide a simple and rapid assay that eliminates some commonly used but potentially detrimental steps in enzymatic assays, such as radioactive labeling and complicated separation and purification of analytes prior to detection.


Lipopolysaccharide Structural Differences between Western and Asian Helicobacter pylori Strains.
Recent structural analysis of the lipopolysaccharide (LPS) isolated from Helicobacter pylori G27 wild-type and O-antigen ligase mutant resulted in the redefinition of the core-oligosaccharide and O-antigen domains. The short core-oligosaccharide (Glc⁻Gal⁻Hep-III⁻Hep-II⁻Hep-I⁻KDO) and its attached trisaccharide (Trio, GlcNAc⁻Fuc⁻Hep) appear to be highly conserved structures among H. pylori strains. The G27 LPS contains a linear glucan⁻heptan linker between the core-Trio and distal Lewis antigens. This linker domain was commonly identified in Western strains. In contrast, out of 12 partial LPS structures of Asian strains, none displayed the heptan moiety, despite the presence of Lewis antigens. This raises the question of how Lewis antigens are attached to the Trio, and whether the LPS structure of Asian strains contain another linker. Of note, a riban was identified as a linker in LPS of the mouse-adapted SS1 strain, suggesting that alternative linker structures can occur. In summary, additional full structural analyses of LPS in Asian strains are required to assess the presence or absence of an alternative linker in these strains. It will also be interesting to study the glucan-heptan linker moieties in pathogenesis as H. pylori infections in Asia are usually more symptomatic than the ones presented in the Western world.


Regression of experimental iris neovascularization with systemic alpha-interferon.
Intraocular neovascularization leads to visual loss in many eye diseases, including diabetic retinopathy, age-related macular degeneration, and neovascular glaucoma. Current treatment relies on laser photocoagulation, involving the destruction of functional retinal tissue. A pharmacologic treatment directed at the newly growing vessels would represent a major advance. The authors investigated the effect of systemic alpha-interferon in an experimental model of iris neovascularization in cynomolgus monkeys. Alpha-interferon was administered systemically to animals with angiographically documented iris neovascularization. Animals in the treatment group showed regression of neovascularization angiographically and histologically in eight of eight eyes. Control animals with documented iris neovascularization, followed without drug treatment, showed progression of the neovascularization in three of three eyes. Systemic alpha-interferon led to inhibition of neovascularization and regression of new vessels in an experimental model of iris neovascularization. This represents the first successful, controlled treatment of experimental neovascularization in the eye using a systemic drug directed specifically at the neovascular tissue.


Rebamipide reduces recurrence of experimental gastric ulcers: role of free radicals and neutrophils.
Mucosal inflammation is a crucial factor for the recurrence of peptic ulcer. In this study, we examined the effect of rebamipide on neutrophils infiltration, lipid peroxidation, and antioxidative enzyme activities in the recurrence of experimental gastric ulcer. Ulcer recurrence was examined at 60, 100, and 140 days after production of acetic acid-induced gastric ulcers in rats. Gastric neutrophil infiltration, lipid peroxidation, and antioxidative enzyme activities were determined by analyses of myeloperoxidase (MPO) activity, thiobarbituric acid reactive substance (TBARS) levels, and glutathione peroxidase (GSHpx) and superoxide dismutase (SOD) activities in the ulcer region, respectively. The effect of rebamipide, an antigastric-ulcer agent, on ulcer recurrence was assessed following oral administration at 60 mg/kg/day from day 20. In the control and rebamipide groups, gastric ulcer indices were reduced on day 100 compared with day 60; however, increases were observed on day 140, indicating ulcer recurrence. In the rebamipide group, the ulcer index was smaller than in the control group at each time point and the effect was significant on day 140. Although marked elevation of MPO activities was observed in the control group during the experiment, no significant elevations were seen in the rebamipide group on days 100 and 140. TBARS levels were significantly elevated in the control group on day 140, but not in the rebamipide group. Rebamipide suppressed the decrease in GSHpx activity on day 60. These results suggest that lipid peroxidation of gastric tissue mediated by free radicals from neutrophils is responsible for the recurrence of acetic acid-induced gastric ulcers in rats, and that the elimination of free radicals by rebamipide may contribute to the reduction of severity in ulcer recurrence.


Determination of gamma-hydroxybutyric acid in clinical samples using capillary electrophoresis with contactless conductivity detection.
A method for the determination of gamma-hydroxybutyric acid (GHB) in urine and serum samples with capillary electrophoresis using capacitively coupled contactless conductivity detection (CE-C(4)D) was developed. The optimized separation buffer consisting of 20 mM of arginine, 10 mM of maleic acid and 30 microM of cetyltrimethylammonium bromide (CTAB) contained 5 mM vancomycin to facilitate the separation of gamma-hydroxybutyric acid from beta-hydroxybutyric acid (BHB), which is also present in clinical samples. The detection limits in the clinical samples were found to be about 2 microg/ml, which is well below the required sensitivity for the recognition of overdosage and adequate for the determination of endogenous concentrations in urine. The determination of GHB in both types of samples was carried out directly after a fourfold dilution without requiring any derivatization or extraction procedures.


Establishment of Next-Generation Neurosurgery Research and Training Laboratory with Integrated Human Performance Monitoring.
Quality of neurosurgical care and patient outcomes are inextricably linked to surgical and technical proficiency and a thorough working knowledge of microsurgical anatomy. Neurosurgical laboratory-based cadaveric training is essential for the development and refinement of technical skills before their use on a living patient. Recent biotechnological advances including 3-dimensional (3D) microscopy and endoscopy, 3D printing, virtual reality, surgical simulation, surgical robotics, and advanced neuroimaging have proved to reduce the learning curve, improve conceptual understanding of complex anatomy, and enhance visuospatial skills in neurosurgical training. Until recently, few means have allowed surgeons to obtain integrated surgical and technological training in an operating room setting. We report on a new model, currently in use at our institution, for technologically integrated surgical training and innovation using a next-generation microneurosurgery skull base laboratory designed to recreate the setting of a working operating room. Each workstation is equipped with a 3D surgical microscope, 3D endoscope, surgical drills, operating table with a Mayfield head holder, and a complete set of microsurgical tools. The laboratory also houses a neuronavigation system, a surgical robotic, a surgical planning system, 3D visualization, virtual reality, and computerized simulation for training of surgical procedures and visuospatial skills. In addition, the laboratory is equipped with neurophysiological monitoring equipment in order to conduct research into human factors in surgery and the respective roles of workload and fatigue on surgeons' performance.


Evolution analysis of research on disaster-causing mechanism and prevention technology of mine goaf disaster.
The goaf is an important factor that induces major accidents. Based on the quantitative analysis of the existing research results, summarize and sort out the research and prevention technology of the goaf disaster with the experience of experts. Temporally, the research on goaf disasters was divided into two stages: the embryonic stage and the rapid development stage. Spatially, a collaborative network with the United States, China, Germany, France, Turkey, and the United Kingdom as the core, including India, Japan, Belgium, Italy, South Korea, and Canada, was analyzed. By constructing a co-occurrence and clustering network of keywords and co-cited literature to explore the focus and hotspots of goaf disaster research, the hotspots of goaf disaster research are summarized into four main aspects, such as goaf detection technology, goaf disaster analysis, goaf risk assessment and goaf treatment technology, which grasp the content of goaf research from a macro perspective. The burst detection analysis of keywords and co-cited literature was conducted to obtain the research frontiers of goaf disaster research in different periods. At the current stage, the microstructural characteristics of surrounding rocks in the context of deep mining and complex goaf group effect and the mining technology of the integration of excavation, anchoring and supporting are the current frontier research directions. This combined qualitative and quantitative method is more helpful to grasp the development context of goaf disaster research and provides a new reference perspective for sorting out the process of goaf disaster research.


Evaluation of Longitudinal Lymphatic Function Changes upon Injury in the Mouse Tail with Photodynamic Therapy.
The lymphatic system is an essential but often understudied component of the circulatory system in comparison with its cardiovascular counterpart. Such disparity could often be explained by the difficulty in imaging lymphatics and the specialized microsurgical skills that are often required for lymphatic injury models. Recently, it has been shown that verteporfin, a photosensitive drug used for photodynamic therapy (PDT) to ablate the blood vessels, provides a similar effect on lymphatic vessels. Here, we seek to administer verteporfin and perform a modified form of PDT on collecting lymphatics in the mouse tail, a commonly used location for the study of lymphatic disorders, and examine lymphatic remodeling, contractility, and transport in response to the procedure. Mice collecting lymphatics in the tail were injured by PDT through an intradermal injection of verteporfin in the distal tip of the tail followed by light activation on the proximal portion of the tail downstream of the injection site. Lymphatic function was evaluated using a near-infrared (NIR) imaging system weekly for up to 28 days after injury. PDT resulted in a loss in lymphatic function contractile frequency that persisted for up to 7 days after injury. Packet transport and packet amplitude, measurements reflective of the strength of contraction, were significantly reduced 14 days after injury. The lymphatics showed a delayed increase in lymphatic leakage at 7 days that persisted until the study endpoint on day 28. This technique provides an easy-to-use method for injuring lymphatics to understand their remodeling response to injury by PDT as well as potentially for screening therapeutics that seek to normalize lymphatic permeability or contractile function after injury.


Activity changes in jaw motor neurons induced by egg-laying hormone contribute to the feeding suppression during egg-laying behavior in Aplysia kurodai.
Egg-laying behavior in Aplysia is accompanied by behavioral changes such as feeding suppression. We investigated the effects of the egg-laying hormone (ELH) on food intake, the activity patterns of jaw muscles, and the activity of buccal neurons (multi-action neuron [MA1] and jaw-closing motor neuron [JC2]), which are elements of the feeding neural circuits controlling jaw movements in Aplysia kurodai. Injection of ELH into the body cavity inhibited the intake of seaweed. After ELH application, the rhythmic activity of jaw muscles that was induced by preferred taste stimulation elicited fewer ingestion-like responses and increased the number of rejection-like responses. ELH applied to the buccal ganglia increased the firing activity of JC2 during spontaneous rhythmic responses and during the rhythmic feeding-like responses that were evoked by electrical stimulation of the esophageal nerves. In the 2 types of rhythmic responses, the Dn (normalized value of the delay time of JC2 firing onset) decreased after ELH application as compared with the control. Furthermore, ELH decreased the size of MA1-induced inhibitory postsynaptic currents in JC2. These results suggest that ELH changes the buccal motor program from ingestion to rejection on the basis of our previous results, and may contribute to a decrease in food intake during egg laying.


[Social characteristics of a HIV-positive patient group].
To discover the social, economic and cultural characteristics of the HIV+ population within our health area and any consequent implications for the spread of the disease. A descriptive study by means of a direct questionnaire. The Macarena area in Sevilla. 110 HIV+ patients. A questionnaire, which included items concerning work situation, cultural and economic status, drug habits, sexual behaviour and social situation, was administered to 110 people. The determinant social profile of those patients studied was: male, PVDU, between 25 and 34, heterosexual, with multiple sexual partners, resident in the urban area, economically dependent on their parents with whom they live, and having a low education level. Homosexual patients had a higher education level. 1. The social conditions of marginal groups must be changed, in order to lessen drug consumption and so cut the epidemiological transmission chain. 2. High-risk behaviour, rather than high-risk groups, should be referred to, given that (albeit to a lesser degree) this infection can affect people at any social level, who engage in high-risk activities.


Kisspeptins and GPR54--the new biology of the mammalian GnRH axis.
Recent genetic evidence in humans and from mouse knockouts has linked kisspeptin-driven GPR54 signaling to the regulation of GnRH release from the hypothalamus. These molecules appear to represent a previously unsuspected control point for GnRH secretion, with important implications for the biology and pathology of the sex steroid axis.


Grignard-mediated synthesis and preliminary biological evaluation of novel 3-substituted farnesyl diphosphate analogues.
A series of substituents was installed at the 3 position of farnesyl diphosphate through a copper-cyanide mediated coupling of a vinyl triflate with various Grignard reagents. These novel FPP mimetics were then evaluated as inhibitors of or substrates for mammalian protein farnesyl transferase. The IC50 values for these compounds range from 18 to 10,100 nm, with the 3-isopropenyl analogue being one of the most potent FPP-mimetic mFTase inhibitors yet synthesized.


Tumor physiology and drug resistance.
Clinical resistance is usually assumed to be due to the initial presence or selection of drug-resistant cells in tumors. While important, it is suggested in this review that genetically-determined causes of cellular resistance represent but one cause (and possibly not the major cause) of effective clinical resistance of solid tumors. Factors that depend on tumor physiology, and on the microenvironment and three-dimensional structure of solid tumors, may have a profound influence on their sensitivity to anti-cancer drugs. Particular emphasis is placed on the limited penetration of some drugs from tumor blood vessels and on the repopulation of tumor cells between courses of chemotherapy as causes of clinical resistance. Both of these mechanisms are amenable to modulation to improve therapeutic index. Failure to recognize that clinical drug resistance cannot be explained entirely by mechanisms operative at the level of the single cell may lead to disappointing results in clinical trials such as, for example, clinical failure of the strategy of reversal of multidrug resistance.


Characterization and properties of steroid binding protein in Bufo arenarum serum.
Serum steroid binding properties of mature Bufo arenarum females were studied. Binding data obtained using charcoal adsorption assay and equilibrium dialysis methods indicates a single protein, named Bufo arenarum sex binding protein (Ba SBP), which binds 5 alpha-dihydrotestosterone (DHT), testosterone (T), and estradiol-17 beta (E2) with high affinity (10(-7) M-1 - 10(8) M-1) and fair capacity (10(-6) M). Scatchard plot analysis demonstrated the coexistence of two binding sites. Ba SBP has a sedimentation coefficient of 5.2 S in sucrose gradient centrifugation in low salt and under steady-state conditions. The specificity of this protein, determined by competitive binding experiments, is comparable to human SBP. DHT and T bind with higher affinity than E2. Estriol and estrone competed poorly, while diethylstilbestrol and C21 steroids did not compete. The binding capacity of this protein is under estrogenic control.


LGBTQ+ Perspective in Hand Surgery: Surgeon and Patient.
Lesbian, gay, bisexual, transgender, queer, and other sexual and gender minority (LGBTQ+) individuals and patients face high levels of discrimination both in the workplace and in the clinic setting, with more than 25% of LGBTQ+ people experiencing discrimination in the workplace due to their sexual orientation. Hand Surgery stands to continue to advance by encouraging the brightest students into the field no matter their background. LGBTQ+ patients also have specific needs within the field of Hand Surgery, where we are uniquely positioned to treat them or guide them by being well versed in the needs of the community.


Relationship of serum leptin with some biochemical, anthropometric parameters and abdominal fat volumes as measured by magnetic resonance imaging.
To measure the level of leptin in volunteers and correlate it with several anthropometric, biochemical variables and abdominal fat volumes. The level of leptin was investigated in 167 disease-free volunteers. Serum levels of IL-6, adiponectin, and resistin, blood lipid profile (cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triglyceride (TG) were determined. Waist circumference (WC) was measured using tape and magnetic resonance imaging (MRI) images. All measured anthropometric (BMI, WC measured by tape and MRI) and biochemical variables (adiponectin, resistin, cholesterol, HDL, LDL and TG); and abdominal fats showed a significant (p<0.05) difference between participants with abnormal serum leptin levels and those with normal leptin levels. A higher percentage of participants with abnormal serum leptin were obese males while participants with normal leptin levels were either overweight or normal weight females. A significant (p <0.05) positive correlation was detected between serum leptin concentration and WC, BMI, subcutaneous fat, visceral fat, total abdominal fat, and resistin. A moderate association was found between serum leptin concentration and the inflammatory cytokine IL-6. Abnormal serum leptin, was detected in obese male individuals which may be considered as an important indicator for the development of cardiovascular diseases and type 2 diabetes.


Evaluation of medicinal plants from Mali for their in vitro and in vivo trypanocidal activity.
Water, methanol and dichloromethane extracts prepared from various parts of 40 medicinal plant species from Mali were investigated for their trypanocidal activity against Trypanosoma brucei brucei. Of a total of 165 extracts tested in vitro in the Low Inoculation Long Incubation Test (LILIT), 24 extracts showed a high trypanocidal activity. Using the Long-Term Viability Assay (LtVA) for corroboration of the results of the 24 extracts, it was found that 15 samples had minimum inhibitory concentration (MIC) values > 10 microg/ml, eight MIC values of 100 microg/ml and one MIC values of 50-100 microg/ml. So far, four extracts with MIC values < or = 100 microg/ml were tested for antitrypanosomal activity in mice, experimentally infected with Trypanosoma brucei brucei. Only, the aqueous extracts of the leaves of Terminalia avicennioides Guill. and Perr. (Combretaceae) and the stem bark of Ceiba pentandra (L.) Gaertn. (Bombacaceae) were able to reduce the parasitaemia in animals treated at the dose of 100 mg/kg b.w. (intraperitoneally, two times daily for 3 days) and of 150 mg/kg b.w. (per os, two times daily for 3 days), respectively. The reduction of parasitaemia was, however, statistically significant (p=0.002) only in case of treatment with Terminalia avicennioides.


Aging affects spatial reconstruction more than spatial pattern separation performance even after extended practice.
Although the hippocampus experiences age-related anatomical and functional deterioration, the effects of aging vary across hippocampal-dependent cognitive processes. In particular, whether or not the hippocampus is known to be required for a spatial memory process is not an accurate predictor on its own of whether aging will affect performance. Therefore, the primary objective of this study was to compare the effects of healthy aging on a test of spatial pattern separation and a test of spatial relational processing, which are two aspects of spatial memory that uniquely emphasize the use of multiple hippocampal-dependent processes. Spatial pattern separation supports spatial memory by preserving unique representations for distinct locations. Spatial relational processing forms relational representations of objects to locations or between objects and other objects in space. To test our primary objective, 30 young (18-30 years; 21F) and 30 older participants (60-80 years; 21F) all completed a spatial pattern separation task and a task designed to require spatial relational processing through spatial reconstruction. To ensure aging effects were not due to inadequate time to develop optimal strategies or become comfortable with the testing devices, a subset of participants had extended practice across three sessions on each task. Results showed that older adults performed more poorly than young on the spatial reconstruction task that emphasized the use of spatial relational processing, and that age effects persisted even after controlling for pattern separation performance. Further, older adults performed more poorly on spatial reconstruction than young adults even after three testing sessions each separated by 7-10 days, suggesting effects of aging are resistant to extended practice and likely reflect genuine decline in hippocampal memory abilities.


Correlations between population-levels of prescription opioid dispensing and related deaths in Ontario (Canada), 2005-2016.
Canada is experiencing an ongoing opioid-related public health crisis, including persistently rising opioid (e.g., poisoning) mortality. Previous research has documented marked correlations between population-levels of opioid dispensing and deaths. We examined possible correlations between annual population-level dispensing of specific opioid formulations and related poisoning deaths in Ontario (Canada), for the period 2005-2016. Annual coroner statistics-based numbers of poisoning deaths associated with six main opioid formulations (codeine, fentanyl, hydromorphone, methadone, morphine, and oxycodone) for Ontario were converted into annual death rates (per 100,000 population). Annual dispensing data for the opioid formulations under study were based on commercial retail-sales data from a representative, stratified sample of community pharmacies (IMSQuintiles/IQVIA CompuScript), converted into Defined Daily Doses (DDD/1,000 population/day). Possible relationships between the annual death and dispensing rates were assessed by Pearson's correlation coefficient analyses. Death rates increased for almost all, while dispensing rates increased for half of the opioid categories. A significant positive correlation between death and dispensing rates was found for hydromorphone (r = 0.97, 95% CI: 0.88-0.99) and oxycodone (r = 0.90, 95% CI: 0.68-0.97) formulations; a significant negative correlation was found for codeine (r = -0.78, 95% CI: -0.93 to -0.37). No significant correlations were detected for fentanyl, methadone, and morphine related deaths. Strong correlations between levels of dispensing and deaths for select opioid formulations were found. For select others, extrinsic factors - e.g., increasing involvement of non-medical opioid products (e.g., fentanyl) in overdose deaths - likely confounded underlying correlation effects. Opioid dispensing levels continue to influence population-level mortality levels, and need to be addressed by prevention strategies.


Organic carbon source tracing and the BCP effect in the Yangtze River and the Yellow River: Insights from hydrochemistry, carbon isotope, and lipid biomarker analyses.
Autochthonous organic carbon (AOC) formed by biological carbon pump (BCP) in surface waters may serve as a significant carbon sink. The locations, magnitudes, variations and mechanisms responsible for the terrestrial missing carbon sink by BCP are uncertain, especially in large river systems. In this study, hydrochemical characteristics, carbon isotope compositions of dissolved inorganic carbon (DIC) and organic carbon (OC), n-alkane homologues and C/N ratios of organic matter along the Yangtze River and the Yellow River were investigated to constrain the OC source and the significance of BCP effect. It was found that (1) DIC concentrations in the Yellow River were much higher than those in the Yangtze River, which was controlled primarily by the temperature effect; (2) AOC in the both rivers was characterized by lower C/N ratios and δ13CPOC values. Based on calculation of n-alkanes compounds, the AOC proportions ranged from 29 to 88% (49% on average, with a higher proportion (55%) in the rainy season than in the dry season (46%)) and 19-68% (41% on average; with a lower proportion in the rainy season (31%) than in the dry season (51%)) in the Yangtze River and the Yellow River, respectively, indicating intense aquatic production. Low dissolved CO2 concentration (6.17 μmol/L on average) of the Yangtze River limited the aquatic production and decreased the BCP effect in the dry season, indicated by lower AOC proportion. However, the BCP effect increased in the Yellow River in the dry season mainly due to the increased light penetration; (3) even in high turbidity riverine systems such as the Yellow River, the aquatic photosynthetic uptake of DIC could produce considerable AOC. These findings clearly show the formation of AOC by BCP in both the clear and high turbidity riverine systems, suggesting a potential direction for finding the terrestrial missing carbon sink.


A clinical method to assess the effect of visual loss on the ability to perform activities of daily living.
To develop a clinically applicable, performance-based measure of the ability to perform visually related activities. 99 patients with glaucoma and 21 subjects with a normal ocular examination completed a nine-item performance-based test (the Assessment of Ability Related to Vision (AARV)), received a standard ophthalmic clinical examination and answered the questions on the National Eye Institute's Visual Functioning Questionnaire (NEI-VFQ-25). All combinations of two, three or four items of the full nine-item AARV test were analysed, and their scores were compared with the full AARV scores and with clinical measures. The correlation of four items (detecting motion, reading signs, finding objects and navigating an obstacle course) reduced test time from 60±5 min to 14±4 min and yielded results highly related to the nine-item test, including maintaining the relationship with clinical measures and with the NEI-VFQ-25. A compressed AARV correlates highly with the full test, with a method of evaluating quality of life, and with clinical measures, yet takes on average 14 min to perform. As such, it may provide a clinically useful method of evaluating the worsening effects of illness and the benefits of treatments that affect visual loss on the ability to perform visually related activities.


HIV Infection and Risk of Cardiovascular Diseases Beyond Coronary Artery Disease.
Cardiovascular disease (CVD) increasingly afflicts people living with HIV (PLWH) in the contemporary era of antiretroviral therapy (ART). Coronary artery disease (CAD) is the most widely studied cardiovascular problem in PLWH; however, less is known about other clinically relevant subtypes of CVD such as heart failure (HF), cerebrovascular disease, sudden cardiac death, pericardial diseases, and pulmonary hypertension. This paper reviews evidence of other subtypes of CVD as emerging issues in the post-ART era. Recent studies have shown that PLWH have higher risk of HF as well as subclinical impairment of left ventricular (LV) mechanics (systolic and diastolic dysfunction) and myocardial abnormalities (fibrosis and steatosis). The underlying mechanisms, however, are not well-understood. A few studies have also shown higher rates of atrial fibrillation and sudden cardiac death in PLWH. Ischemic stroke is the most common stroke type in the post-ART era, with underlying mechanisms like those identified in CAD: chronic inflammation and associated vasculopathy. Studies of great vessels (carotid artery and aorta) and peripheral arterial disease show heterogeneous results. Small subclinical pericardial effusions are common in PLWH in post-ART era. Pulmonary hypertension continues to be an underdiagnosed and potentially fatal complication of HIV infection. PLWH remain at higher risk for all types of CVD including heart failure, stroke, and arrhythmias in the post-ART era. Chronic inflammation may play an important role in this increased risk. More studies are needed to further elucidate the extent of non-coronary CVD in PLWH and the underlying mechanisms for them.


Cardiovascular effects of leukotriene D4 in SHR and WKY rats.
Leukotriene D4 (LTD4, 0.8-4 micrograms/kg i.a.) increased blood pressure and heart rate of conscious SHR and WKY rats. LTD4, 20 micrograms/kg (i.a.), caused a short lasting increase in blood pressure and heart rate in WKY. In SHR, LTD4, 20 micrograms/kg (i.a.) caused a triphasic effect: hypotension and bradycardia (0.5-1 min), hypertension and tachycardia (2-5 min) and prolonged hypotension and bradycardia (5-180 min). Leukopenia was observed after LTD4, 20 micrograms/kg in both groups of rats but platelets count was unaffected. These results show that SHR are mor sensitive than WKY to the hypotension-bradycardia effect of LTD4.


Recovery of a catalase-negative Staphylococcus epidermidis strain in blood and urine cultures from a patient with pyelonephritis.
This report describes a 60-year-old patient with bilateral nephrolithiasis. A catalase-negative Staphylococcus epidermidis strain was recovered from both urine and blood cultures. Although rare, isolates of catalase-negative Staphylococcus spp., including Staphylococcus aureus, have been reported. Here, we describe the first report of a catalase-negative S. epidermidis strain.


Methods for investigating intestinal absorption of amino acids in chicken intestine in vitro.
Certain techniques for measuring amino acid absorption are considered, their specific roles are defined and both theoretical and practical considerations are used to evaluate each system. Some methodological considerations are presented.


Prospective Fellows' Appraisal of Hand Surgery Fellowships.
The nature and focus of hand surgery fellowships has been shown to vary. Compounding this issue is a paucity of information regarding the educational goals and desires of prospective fellows. The purpose of this study was to understand applicant motivation for pursuing a fellowship and the most important components of these fellowships. We performed an anonymous survey of all the candidates who applied for a hand surgery fellowship during the 2019-2020 academic year to establish general demographic information, preferences regarding fellowship size, and the importance of various educational and logistical components. We also recorded self-reported comfort level in treating pathologies encountered during a hand-focused subspecialty practice. The most important motivation cited for pursuing a fellowship in hand surgery was the "complexity and variety of cases" (n = 55, 90%). The 5 most important desired components of a fellowship were the exposure to "bread and butter" hand surgery (n = 35, 57%), ability to take level 1 hand call (n = 26, 43%), exposure to complex wrist reconstruction (n = 26, 43%) or peripheral nerve surgery/transfers (n = 23, 38%), and soft tissue coverage including free flaps (n = 19, 31%). Further analysis revealed that the orthopedic surgery residents frequently rated exposure to level 1 call (n = 20, 45%) as 1 of their 3 most important characteristics, whereas the plastic/general surgery residents frequently ranked exposure to complex wrist reconstruction (n = 16, 38%) as 1 of their 3 most important characteristics. The components of a fellowship that received the fewest selections into an applicant's top 3 components were exposure to shoulder surgery (n = 1, 1.64%), education regarding practice building/billing (n = 2, 3.2%), and the ability to conduct research (n = 4, 6.5%). Most applicants pursue a subspecialty training in hand surgery because of the field's variety and breadth of cases. The applicants prioritize exposure to "bread and butter" cases in conjunction with both complex soft tissue and microsurgical reconstruction. Assisting hand fellowships in understanding what is most important to prospective fellows will allow for appropriate recruitment and development of the field of hand surgery in general.


Self-contained, biomolecular motor-driven protein sorting and concentrating in an ultrasensitive microfluidic chip.
We developed a molecular sorter that operates without external power or control by integrating the microtubule-based, biological motor kinesin into a microfluidic channel network to sort, transport, and concentrate molecules. In our devices, functionalized microtubules that capture analyte molecules are steered along kinesin-coated microchannel tracks toward a collector structure, concentrated, and trapped. Using fluorescent analyte molecules and nanoliter sample volumes, we demonstrated 14 fM sensitivity, even in the presence of high concentrations of other proteins.


Evaluation of anaerobic degradation, biogas and digestate production of cereal silages using nylon-bags.
In this study, the degradation efficiency and the biogas and digestate production during anaerobic digestion were evaluated for the cereal silages most used to feed biogas plants. To this purpose, silages of: maize from the whole plant, maize from the ear, triticale and wheat were digested, inside of nylon bags, in laboratory scale digesters, for 75days. Overall, the test involved 288 nylon bags. After 75days of digestion, the maize ear silage shows the highest degradation efficiency (about 98%) while wheat silage the lowest (about 83%). The biogas production ranges from 438 to 852Nm(3)/t of dry matter for wheat and ear maize silage, respectively. For all the cereal silages, the degradation as well as the biogas production are faster at the beginning of the digestion time. Digestate mass, expressed as percentage of the fresh matter, ranges from 38% to 84% for wheat and maize ear silage, respectively.


Developmental aspects of blood-brain barrier (BBB) and rat brain endothelial (RBE4) cells as in vitro model for studies on chlorpyrifos transport.
The mammalian central nervous system (CNS) is characterized by the blood-brain barrier (BBB), a restrictive barrier endowed with the maintenance of homeostatic control of an optimal milieu within the brain. Whereas in tissues other than the CNS, concentrations of various metabolites (amino acids, K+) can undergo frequent fluctuations, the CNS must keep rigorous control over the extracellular cerebral fluid composition, preventing the mirroring of transient fluctuations in blood, because abrupt changes in these metabolites can translate to aberrant CNS function. The BBB is a specialized structure accomplished by individual endothelial cells that are continuously linked by tight junctions. This brief review will address pertinent issues to development of the BBB. Particular emphasis will be directed at the role of astrocytes in the induction and maintenance of the restrictive properties of this barrier, and the utility of in vitro culture models in surveying transport kinetics, exemplified by recent studies with the pesticide, chlorpyrifos.


Can severe aortic stenosis be identified by emergency physicians when interpreting a simplified two-view echocardiogram obtained by trained echocardiographers?
Aortic stenosis (AS) is a common valve problem that causes significant morbidity and mortality. The goal of this study was to determine whether an emergency physician (EP) could determine severe AS by reviewing only two B-mode echocardiographic views (parasternal long axis (PSLA) and parasternal short axis (PSSA)) obtained by trained echocardiographers. A convenience sample of 60 patients with no AS, mild/moderate AS or severe AS was selected for health record and echocardiogram review. The echocardiograms were performed in an accredited echocardiography laboratory. An EP blinded to the cardiologist's final report reviewed the PSLA and PSSA views after the cases were randomly sorted. Severe AS was defined as no cusp movement seen by the EP reviewers. A second EP independently reviewed 25% of randomly selected patients for inter-rater reliability. Collected data included patient demographics, EP interpretation and details of each echo view (quality, the number of cusps visualized, presence of calcification) and compared to final cardiology reports. Analyses included descriptive statistics, test characteristics for severe AS and kappa for agreement. The mean age was 75.3 years (range 18 to 90) with 36.7% females. The cardiologist's diagnosis was as follows: 38.3% severe AS, 28.3% mild/moderate AS and 33.3% no AS. The PSSA view was poorer in quality compared with the PSLA (33.3% vs. 13.3%, p = 0.02), but the PSSA view was better than PSLA to visualize all three cusps (83.3% vs. 0%, p = 0.001). There was no difference in the presence of calcification between the mild/moderate and severe AS groups (94.1% vs. 100.0%, p = 0.46). The sensitivity and specificity for EP diagnosis of severe AS was 75.0% (95% CI 56.7% to 85.4%) and 92.5% (83.3% to 97.7%). The kappa for severe AS was 0.69 (0.41 to 0.85), and there was no significant difference between observers in the quality of the view, presence of aortic calcification and the number of cusps visible. PSLA and PSSA views obtained by trained echocardiographers can be interpreted by an EP with appropriate training to identify severe AS with good specificity. Further larger prospective studies are required before widespread use by EPs.


Trimming tusks in the Yucatan minipig.
The Yucatan minipig boar's tusks grow continuously throughout its life. Although these animals tend to be gentle in disposition, boars used in biomedical research should have their tusks trimmed to avoid injury to personnel as well as discomfort to the animal. The authors describe in detail a tusk-trimming procedure.


Increasing gender and ethnic diversity in the health care workforce: The case of Arab male nurses in Israel.
Despite recent attempts at increasing health care workforce diversity, a measure that was found to reduce health disparities, men remain a minority in the traditionally female occupation of nursing. One exception to this observation is the Arab ethnic minority in Israel that includes numerous male nurses. Determining the percentage of Arab male nurses in the Israeli health care system and understanding how they perceive and negotiate their masculinity. We used both quantitative and qualitative methodologies. Quantitative statistics were obtained from the 2011 to 2013 Labor Force Survey conducted by the Israel Central Bureau of Statistics and qualitative data derived from 13 semi-structured, in-depth interviews with Arab nurses working in Israeli public hospitals, conducted during 2014. Nursing constitutes a prominent employment path for Arab men in Israel and is more prominent as an employment path for Arab men than that for Jewish men. A total of 38.6% of all Arab nurses were men and only 7.5% of Jews and others. Quantitative data thus reveal that men do not constitute a minority among Arab nurses. Similarly, qualitative findings show that Arab male nurses do not manifest marginal masculinity but rather demonstrate many elements of hegemonic masculinity. Arab male nurses distinguish themselves and differentiate their roles from those of female nurses, expressing their motives for choosing the nursing profession in terms of hegemonic gender roles for men in Arab society in Israel. Although nursing is a traditionally female occupation, it offers an opportunity for Arab men to demonstrate their masculinity. Arab male nurses choose nursing as a means rather than an end, however, meaning that many of them might not remain in the profession. This observation is significant because of the importance of retaining men from ethnic minorities in nursing, especially in multicultural societies.


The medical-student spouse syndrome: grief reactions to the clinical years.
Medical students beginning the clinical years experience a change in routine that results in their spouses suffering the partial loss of a loved one. The author describes the way in which the spouses react to this loss as a grieving process with three stages--protest, despair, and detachment.


One-pot sequential Ti-/Cu-catalysis for tandem amidation/Ullmann-type cyclization: synthesis of model benzodiazepine(di)ones promoted by microwave irradiation.
The application of sequential Ti-/Cu-catalysis in the model one-pot synthesis of benzodiazepine(di)ones promoted by microwave irradiation demonstrates the expediency of dual catalysis in coupling-cyclization methods useful for diversity-oriented synthesis.


Induction of mixed function oxidases on oral administration of dieldrin.
The administration of dieldrin (30 mg/kg body weight) caused an increase in the liver weight of rats. The metabolism of aflatoxins B1 and G1 by the microsomes obtained from the liver of dieldrin-treated animals was enhanced significantly as compared to the controls showing that dieldrin increased the activity of mixed function hydroxylases. Dieldrin caused an increase in the activity of liver microsomal NADPH oxidase and a decrease in the lipid peroxidation. Dieldrin brought about an increase in the phosphatidylcholine content of rat liver.


Skin Test-Guided Strategy to Select Alternative Iodinated Contrast Media in Patients With Immediate Hypersensitivity Reaction: A Prospective Confirmative Study.
Iodinated contrast media (ICM) are a common cause of drug-induced immediate hypersensitivity reaction (IHR). Repeated use of ICM is often necessary; therefore, a standardized protocol to prevent recurrence of IHR is required. We aimed to propose an intradermal skin test (IDT)-guided strategy for previous reactors to prevent recurrence of IHR. We conducted a prospective multicenter study from May 2018 to December 2020 and recruited patients who had experienced IHR to ICM. Once enrolled, the participants underwent IDT with a causative ICM. The alternatives for reexposure were selected using the following protocol: (1) if the IDT with the culprit ICM was positive, further skin tests with other available ICM were conducted to choose IDT-negative agents as alternatives, and (2) if the IDT with the culprit ICM was negative, a randomly changed ICM was used without additional skin tests. The recurrence and severity of hypersensitivity were assessed in subsequent computed tomography examinations. Premedication was administered according to the severity of the index event in all cases. A total of 496 participants were enrolled, and 299 were reexposed to ICM. Among 269 participants who followed the protocol, 228 (84.8%) completed computed tomography examinations without adverse reactions, and IHR recurred in 16 of 30 participants (53.3%) who did not follow the protocol (P < .001). In addition, application of the protocol reduced the severity of IHR in recurred cases (P = 0.003). Our IDT-guided strategy not only reduced recurrence of IHR to ICM but also mitigated the severity in recurred cases. This provides evidence for recommending an IDT to diagnose ICM allergy and find safe alternatives.


A surface-fluorinated-TiO2-KMnO4 photocatalytic system for determination of chemical oxygen demand.
A new method for chemical oxygen demand (COD) determination has been developed, based on photocatalytic oxidative degradation by using a fluorinated-TiO2-KMnO4 system. In such a system, a linear correlation is observed between the amount of oxidizable dissolved organic matter and the amount of MnO4- consumed by the coupled reduction process. Thus, the COD determination is transformed to a simple and direct determination of the deletion of MnO4-. The surface fluorination of TiO2 nanoparticles can enhance the rate of photocatalytic oxidation of organic matter and the rate of coupled photocatalytic reduction of MnO4-. This makes the method be rapid, environment friendly and easy for operation. Under optimized conditions, this method can respond linearly to COD of potassium hydrogen phthalate (KHP) in the range of 0.1-280 mg L(-1), with a detection limit of 0.02 mg L(-1) COD. The COD in samples of tap water, lake water and paper industry sewage has been determined satisfactorily by using this method.


Hospitals Known for Nursing Excellence Associated with Better Hospital Experience for Patients.
To examine the relationship between Magnet recognition, an indicator of nursing excellence, and patients' experience with their hospitalization reported in the Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) survey. This secondary analysis includes cross-sectional data from the 2010 HCAHPS survey, the American Hospital Association, and the American Nurses Credentialing Center. We conducted a retrospective observational study. Using common hospital identifiers, we created a matched set of 212 Magnet hospitals and 212 non-Magnet hospitals. Patients in Magnet hospitals gave their hospitals higher overall ratings, were more likely to recommend their hospital, and reported more positive care experiences with nurse communication. Magnet recognition is associated with better patient care experiences, which may positively enhance reimbursement for hospitals.


Beach morphodynamics modulate the effects of multidirectional habitat loss on population density and size structure of the Atlantic ghost crab Ocypode quadrata.
Sandy beaches are land-sea transitional habitats experiencing 'multidirectional' habitat loss due to coastal developments (e.g. armoring and/or conversion of natural vegetation into manmade structures) and beach erosion. This 'coastal squeeze' is a chronic and progressive process; however, its impacts on beach biodiversity across morphodynamic gradients are still to be unveiled. We hypothesized that the effects of multidirectional habitat loss would be more severe on dissipative than on reflective beaches, due to the higher elevation, amount of built up sediment, and width of the backshore compartment of the latter. We, thus, examined the effects of coastal developments and erosion on density and size structure of the Atlantic ghost crab, Ocypode quadrata, on beaches with different morphodynamics. Given that the living area of ghost crabs spans all cross-shore compartments and the whole dissipative-to-reflective morphodynamic gradient, they are appropriate organisms to access the synergic effects of coastal developments and beach erosion under different morphodynamic regimes. On dissipative beaches, density and mean crab size increased with moderate erosion, attributed to the effects of space loss, which might increase territorial competition, favoring the remaining larger individuals. However, mean size and density decreased with high erosion given the more intense reduction in the abundance of large-sized crabs living in up-shore habitats. Mean crab size also decreased in the presence of coastal development while crab density did not vary with loss of backshore habitats occupied by larger individuals. On reflective beaches, both density and crab size decreased with coastal development; the crab size decrease recorded under moderate erosion was more evident in the presence of coastal development. Under high erosion, mean crab sizes declined, reflecting those under low erosion conditions. Overall, populations on reflective beaches appeared more resilient to extreme erosion. Notwithstanding, coastal developments affected population structure across all beach types, and especially in areas subjected to high erosion, exhibiting a synergic effect. We predict that, in combination, these stressors may lead to functionally extinct populations where conditions necessary for individuals to reach sexual maturity (i.e. occurrence of only small-sized and immature individuals) are not met. Thus, the connectivity between water, beach compartments and dunes/coastal plain, on both local and regional scales, may be essential to maintain viable and connected populations of ghost crabs. Further, our results strongly suggest that both size and density (complemented with crab abundance) must be considered equally important and in combination in future efforts to assess anthropogenic stressors on ghost crab populations and when guiding conservation strategies and policies to prevent their local and regional extinctions.


Prevalence of deep venous thrombosis in the lower limbs and the pelvis and pulmonary embolism in patients with positive antiphospholipid antibodies.
Antiphospholipid antibodies (AA) are immunoglobulins that cross-react with phospholipid on cell membrane, and are therefore associated with a hypercoagulable state manifested by arterial/venous thromboses. We aimed to determine the prevalence of deep venous thrombosis in the lower limbs and the pelvic region (DVT) and pulmonary embolism (PE) in patients with positive AA. Sixty-six patients (48 female, 18 male) with positive lupus anticoagulant (LA) and/or positive anticardiolipin antibody (aCL) underwent radionuclide (RN) venography with 370 MBq of 99mTc-MAA. Pulmonary perfusion scintigraphy was performed in 58 patients. Fifteen patients had positive LA and positive aCL (LA+/aCL+), 33 patients had positive LA only (LA+/ aCL-) and 18 patients had positive aCL only (LA-/aCL+). 43 patients were diagnosed with primary antiphospholipid syndrome (APS) and 19 were diagnosed with APS associated with SLE. DVT was detected in 21 of 66 patients (32%). Patients with LA+/aCL+ showed higher prevalence of DVT (53%) as compared to LA+/aCL- (27%) and LA-/aCL+ (22%). PE was found in 13 of 58 patients (22%). The prevalence of PE was higher in patients with positive aCL (33% in LA+/aCL+; 36% in LA-/aCL+) than in patients with negative aCL (10%). Because of the high prevalence of DVT and PE in patients with AA, RN scintigraphy must be recommended in screening for these clinical troubles. These results indicate that the prevalence of DVT and PE may vary in subgroups of AA.


Prevalence of premenstrual dysphoric disorder among school-going adolescent girls.
Premenstrual dysphoric disorder (PMDD) is a severe form of premenstrual syndrome which has a significant negative impact on the various domains of life of adolescent girls. The aim of this study was to estimate the prevalence of PMDD in adolescent girls studying in classes 7th-10th and ascertain the level of stress, anxiety, and depression among them. A cross-sectional study was conducted in three all-girls schools in Chandigarh (two - government and one - private) after taking necessary permissions. Participants were evaluated on a self-rated questionnaire which included the PMDD scale, Perceived Stress Scale, Generalized Anxiety Disorder-7 (GAD-7) questionnaire, and Patient Health Questionnaire-9. A total of 397 girls participated in the study. The mean age of respondents was 14.34 (standard deviation [SD]: 1.17; range: 11-20) years, with most (44%) studying in class 10th. The mean age of attaining menarche was 12.54 (SD: 0.92; range: 10-15) years. The prevalence of PMDD was found to be 4.8% (n = 19). Majority of the respondents reported moderate levels of perceived stress (62%). A positive correlation was seen between the severity of PMDD, age, levels of perceived stress, severity of depression, and anxiety in the respondents. Nearly 5% of adolescent girls suffer from PMDD, with higher prevalence among those with depression, GAD, and higher perceived stress. Thus, there is a need to screen adolescent females for PMDD at the earliest and institute intervention to minimize its negative impact.


Molecular analysis of a de novo mutation for spinocerebellar ataxia type 6 and (CAG)n repeat units in normal elder controls.
Spinocerebellar ataxia type 6 (SCA6) is an autosomal dominant spinocerebellar degenerative disease caused by CAG repeat expansions in the human alpha1A voltage-dependent calcium channel subunit gene (CACNL1A4). We analyzed 15 SCA6 patients in 14 unrelated Japanese families and 52 healthy Japanese aged over 74 years. Sequence analysis was performed to determine the correct number of CAG repeats. The expanded CAG repeat number was 23.6+/-2.1 (mean+/-S.D., n=15) with a range of 20-29, and the shortest expanded allele was 20 repeats. Moreover, the analysis of normal subjects revealed that the CAG repeat number of normal alleles was 12.3+/-1.9 (n=104) with a range of 7-18. We concluded that the normal range of CAG repeats in the CACNL1A4 gene is 18 or less, and that the disease range is 20 or more. Of 15 SCA6 patients, three sporadic cases were observed. In one male patient with 26 CAG repeats, the CAG repeat numbers of his parents were within normal range. His expanded allele was considered to be caused by an expansion of a normal allele from his mother (14 or 17 repeats). This is the first SCA6 case which was genetically proven to occur due to a de novo mechanism, suggesting that larger CAG repeats of normal alleles in the CACNL1A4 gene may be unstable and result in full expansion.


Effects of different agronomic practices on the selective soil properties and nitrogen leaching of black soil in Northeast China.
Considering the large amount and high frequency application of concentrated fertilizer nitrogen in the Black Soil Region of Northeast China, the current laboratory/field simulation study aimed to explore the pollution risk of added nitrogen in black soil to groundwater and identify effective measures to prevent and control soil nitrogen leaching with an undisturbed soil column. The results showed that the saturated nitrogen adsorption capacities increased by 1.7%, 7.7% and 18.5% in ploughing, impervious agent (starch grafted polyacrylic acid) addition, and corn straw returning treatments, respectively, relative to the control (no-till). When the collection volume of the leaching solution reached the experimental maximum (4,000 mL), the total amount of nitrogen leaching from the control soil column (i.e., the no-tillage treatment) accounted for more than 50% of the added nitrogen, indicating a great risk of nitrogen pollution in groundwater. Compared with the no-tillage treatment, the amount of nitrogen leaching from the ploughing treatment increased insignificantly, and the amount of nitrogen leaching in the following spring in the corn straw returning treatment increased by 11.2%. The amount of nitrogen leaching decreased by 12.5% in the soil sampled in autumn of the second year. The total amount of nitrogen leaching in the soil with impervious agents decreased by 40.1%. Therefore, the permeability-reducing agent could significantly reduce underground water pollution risk posed by nitrogen leaching.


Transcriptomic profiling and characterization of microRNAs in Macrobrachium rosenbergii potentially involved in immune response to Enterobacter cloacae infection.
Enterobacter cloacae is a member of the Enterobacter family, which could prevent Macrobrachium rosenbergii from growing and cause mass mortality. However, no research has focused on microRNA immunity in M. rosenbergii infected with E. cloacae. To clarify the immune response mechanisms, transcriptomic analysis was performed on the miRNAs of M. rosenbergii infected with E. cloacae YZ3 strain. Following quality screening, 10,616,712 clean reads were obtained from the control group and 12,726,421 from the infected group. Among 899 known miRNAs, 446 differentially expressed miRNAs (DEMs) were identified. Meanwhile, 59 novel miRNAs were predicted, along with 39 DEMs. Target genes of DEMs have been predicted in order to gain a deeper understanding of the immune-related functions. GO and KEGG pathway analysis revealed the biological functions and signaling pathways of target genes. The results indicated that E. cloacae significantly affected the NOD-like receptor, RIG-I-like receptor and Toll-like receptor pathways. Ten DEMs were randomly selected, and their expression level was verified by Quantitative Real-time PCR technology. Overall, this study highlights the influential role of miRNAs in the innate immune system of M. rosenbergii, which has important implications for developing new strategies to prevent and treat related diseases in the future.


Introduction of Chlamydia trachomatis screening for young women in Germany.
Screening for genital Chlamydia trachomatis infections for young sexually active women was incorporated into routine medical care of German statutory health insured patients starting in January 2008. The primary goal of this new preventive measure is the reduction of severe sequelae for women such as tubal infertility and ectopic pregnancies. The course of the deliberations leading to the Federal Joint Committee's decision is summarized in this review.


Biomechanical model of the human shoulder--I. Elements.
In a first step of a biomechanical modelling of the human shoulder the points of application of muscle forces to the bones were determined in a dissection study on four human shoulder specimens. A kinematic description of the shoulder was presented employing bone fixed coordinate systems. Actions of the shoulder muscles were modelled as a system of forces acting along ideal strings. The shoulder complex was treated as a three rigid body twelve degrees of freedom system.


Benign Schwannoma of the Thumb; a diagnostic challenge.
Benign Schwannomas are one of the less frequently encountered soft tissue tumours of the hand. We report an interesting case of an 80-year-old gentleman with a painful soft tissue swelling on the radial aspect of his thumb. Ultrasound revealed a well-defined lesion separate from bone and tendon, with mixed echogenicity and moderate internal vascularity. Magnetic resonance imaging demonstrated a 15 × 10 × 23mm lesion with low signal on T1 and high signal on T2. Following surgical excision, histology confirmed benign schwannoma.


Expression profiling and functional annotation of noncoding genes across 11 distinct organs in rat development.
Accumulating evidence suggests that noncoding RNAs (ncRNAs) have important regulatory functions. However, lacking of functional annotations for ncRNAs hampered us from carrying out the subsequent functional or predictive research. Here we dissected the expression profiles of 3,458 rat noncoding genes using rat bodymap RNA-sequencing data consisting of 11 solid organs over four developmental stages (juvenile, adolescent, adult and aged) from both sexes, and conducted a comprehensive analysis of differentially expressed noncoding genes (DEnGs) between various conditions. We then constructed a co-expression network between protein-coding and noncoding genes to infer biological functions of noncoding genes. Modules of interest were linked to online databases including DAVID for functional annotation and pathway analysis. Our results indicated that noncoding genes are functionally enriched through pathways similar to those of protein-coding genes. Terms about development of the immune system were enriched with genes from age-related modules, whereas terms about sexual reproduction were enriched with genes in sex-related modules. We also built connection networks on some significant modules to visualize the interactions and regulatory relationship between protein-coding and noncoding genes. Our study could improve our understanding and facilitate a deeper investigation on organ/age/sex-related regulatory events of noncoding genes, which may lead to a superior preclinical model for drug development and translational medicine.


Do extraversion and neuroticism moderate the association between bullying victimization and internalizing symptoms? A three-wave longitudinal study.
The current study examined the moderating roles of neuroticism and extraversion in victims of bullying. According to a stress-diathesis model, we hypothesized that adolescents with high levels of neuroticism and low levels of extraversion would react to victimization with increased symptoms of depression and social anxiety. A sample of 1440 adolescents (648 girls and 792 boys; ages between 13- and 17-years-old) completed measures of extraversion and neuroticism at time 1, as well as measures of bullying victimization, depressive symptoms and social anxiety symptoms at time 1, time 2, and time 3 (in intervals of six months). The results of multilevel analyses for longitudinal data indicated that there was a weak association between bullying victimization and social anxiety symptoms for the adolescents who scored high on extraversion. In addition, the adolescents with high levels of extraversion presented a greater reduction in depressive symptoms over time than adolescents with low levels. Although neuroticism predicted both depression and social anxiety, no significant interactions were evident between neuroticism and bullying victimization. Regarding gender differences, the association between bullying victimization and social anxiety was stronger for boys than for girls, whereas the association between neuroticism and depression was stronger for girls.


Lead removal in fixed-bed columns by zeolite and sepiolite.
The removal efficiency of zeolite (clinoptilolite) and sepiolite from lead containing aqueous solutions was investigated. A series of experiments were conducted in batch-wise and fixed-bed columns. Synthetic wastewaters containing lead (50 mg l (-1)) and acetic acid (0.001 N) along with untreated and regenerated clinoptilolites and sepiolites were used in the adsorption studies. Batch tests were mainly conducted to isolate the magnitude of lead precipitation from real adsorption. Adsorption isotherms for both abstraction and adsorption were constructed. The removal of lead is found to be a sum of adsorption induced by ion exchange and precipitation of lead hydroxide. The breakthrough curves were obtained under different conditions by plotting the normalized effluent lead concentration (C/C0) versus bed volume (BV). The ion exchange capacity of sepiolite and clinoptilolite for lead removal showed good performance up to approximately 100 and 120 BV where the C/C0 remained below 0.1, respectively. The lead removal capacity of clinoptilolite bed from wastewater containing only lead yielded 45% higher performance compared to that of acetic acid partly due to a decrease in the effluent pH and consequently in precipitation. Also, the presence of acetic acid in the sepiolite column decreased the bed volumes treated by about 40%. Removal efficiency of lead-acetic system both in untreated clinoptilolite and sepiolite columns was found higher than that in regenerated columns.


Learning from Primary Health Care Centers in Nepal: reflective writings on experiential learning of third year Nepalese medical students.
Medical education can play important role in cultivating the willingness among the medical students to work in underprivileged areas after their graduation. Experiential learning through early exposure to primary health care centers could help students better understand the opportunities and challenges of such settings. However, the information on the real experiences and reflections of medical students on the rural primary health care settings from low-income countries like Nepal are still limited. The aim of this study is to demonstrate the learning process of the medical students through their reflective writings based on Kolb's theory of experiential learning. The students wrote their experiences, observations and reflections on the experiential learning from the primary health care centers on individual logbook as part of their community posting assignments. We analyzed the data of 50 logbooks through content analysis using Kolb's experiential learning cycle as a theoretical framework. The students' reflections are structured around the four main learning stages of Kolb's experiential learning theory. Each learning stage consisted of different categories. The first stage consisted of concrete experiences on rural health and learning by doing. The second stage included their reflective observations on primary versus tertiary care, application of theoretical knowledge and role of supervisors. In the third stage, the students developed and refined their concepts on self-development, understanding reality, compassion and sense of responsibility. The final stage, active experimentation, included their immediate future plans, suggestions to improve curriculum, plans after becoming a doctor and suggestions to improve policies. This study provided important insights on different stages of experiential learning of medical students on primary health care in low resource rural settings. Reflective writing of experiential learning could be an important step to address the gaps in medical education for resource constraint settings like that of Nepal and other low-income countries.


Identifying risk factors for chronic kidney disease stage 3 in adults with acquired solitary kidney from unilateral nephrectomy: a retrospective cohort study.
We aimed to examine the risk factors for chronic kidney disease (CKD) stage 3 among adults with ASK from unilateral nephrectomy. We retrospectively collected data from adult patients with ASK between January, 2009 and January, 2019, identified from a tertiary hospital in China. The clinical data were compared between patients who developed CKD stage 3 and those who did not develop CKD stage 3 during follow-up. In total, 172 patients with ASK (110 men; median 58.0 years) were enrolled, with a median follow-up duration of 5.0 years. During follow-up, 91 (52.9%) and 24 (14.0%) patients developed CKD stage 3 and end-stage renal disease, respectively. Multiple regression analyses showed that age (odds ratio [OR] 1.076, 95% confidence interval [CI] 1.039-1.115, p < 0.001), diabetes (OR 4.401, 95% CI 1.693-11.44, p = 0.002), hyperuricemia (OR 2.733, 95% CI 1.104-6.764, p = 0.03), a history of cardiovascular disease (CVD) (OR 5.583, 95% CI 1.884-18.068, p = 0.002), and ASK due to renal tuberculosis (OR 8.816, 95% CI 2.92-26.62, p < 0.001) were independent risk factors for developing CKD stage 3 among patients with ASK. Regular follow-up of renal function is needed among adult patients with ASK. Optimal management of diabetes, hyperuricemia, and CVD may reduce their risk of CKD stage 3, especially among those that undergo unilateral nephrectomy for renal tuberculosis.


Phylogenetic Classification, Biofilm-Forming Capacity, Virulence Factors, and Antimicrobial Resistance in Uropathogenic Escherichia coli (UPEC).
Uropathogenic Escherichia coli (UPEC) is the main cause of urinary tract infections; in recent years, its importance as a pathogen has increased due to the emergence of hypervirulent and multiresistant strains. In this study, 190 urinary isolates of E. coli were assigned into the seven phylogenetic groups A (11.1%), B1 (4.7%), B2 (46.8%), C (5.8%) D (25.3%) F (2.6%), and Clade I (2.1%), and various virulence genes were examined with polymerase chain reaction methods. All isolates had at least one virulence factor of the 9 analyzed fyuA (81.1%), fimH (96.8%), iutA (74.7%), ompT (66.8%), kpsMTII (66.8%), traT (58.9%), PAI (43.6%), PapAH (26.3%), and usp (3.2%). The results showed a direct relationship between the virulence factors and phylogenetic group A and B2. Further, virulence genetic profiles fimH, fyuA, ompT, traT, and kpsMTII correlated with the production of strong biofilm, multidrug resistance, and the production of moderate hemolysin. These results suggest that these strains may become reservoirs of genes that encode virulence factors, which could be transferred horizontally enhancing their genomic background and high possibility of acquiring new genetic information for possible dissemination. This study provides the first description of phylogroups in UPEC in the Colombian Caribbean and the association with virulence factor profile, antimicrobial susceptibility, and their possible role in the epidemiology in Colombia.


Physiopathology of natural auto-antibodies: the case for regulation.
The cause of autoimmune diseases remains unknown and, as a consequence, disease prediction and prophylaxis are not part of current clinical practice. Many autoimmune syndromes are accompanied by serological evidence of autoimmunity in the form of circulating auto-antibodies (AAb). As normal individuals produce large amounts of AAb, exploring the main differences between such physiologic AAb and those classified as pathogenic may provide the clues needed for new clinical approaches to this group of disorders. Reviewing the differential characteristics of normal and disease-associated autoantibodies, we conclude that the problem will be best tackled if we understand how the organism normally ensures that autoantigen-driven B cell activation does not lead to high titers of autoantibodies and severe autoimmunity. As natural activation of autoreactive B cells occur by both T cell dependent and T cell independent mechanisms, we argue that absence of clonal expansion in normal autoreactive B cells upon activation does not result from lack of appropriate stimulation but, rather, from the presence of negative regulation and suppressive mechanisms.


Discrepant levels of vascular endothelial growth factor in psoriasis patients treated with PUVA, Re-PUVA and narrow-band UVB.
Previous reports showed that serum levels of vascular endothelial growth factor (VEGF) are increased in patients with psoriasis. However, to our knowledge, no studies have evaluated the effects of PUVA, Re-PUVA and narrow-band UVB (NB-UVB) treatments on serum levels of VEGF in patients with psoriasis. The aim of the study was to evaluate the influence of PUVA, Re-PUVA and NB-UVB treatments on angiogenic activities in patients with psoriasis by comparing serum levels of VEGF. Forty-six patients with psoriasis and 20 healthy subjects were included in the study. Peripheral blood samples were collected before, during and after the therapies. The efficacy of PUVA, Re-PUVA and NB-UVB was delineated by the psoriasis area and severity index. A repeated measure of ANOVA, Mann-Whitney U-test, chi(2) and Pearson's correlation coefficient were used for statistical analysis. The VEGF levels were significantly decreased in the PUVA group at the end of the follow-up period (P<0.001). However, the levels were significantly increased in the groups of NB-UVB and Re-PUVA (P<0.001). We found that there was a discrepancy during the PUVA, Re-PUVA and NB-UVB treatments. We believe that VEGF plasma levels could not be a useful monitor of psoriasis activity and/or treatment response.


Reproductive patterns among Swedish women born 1936-1960.
An analysis was made of a cross-sectional survey of 4,299 women born in Sweden in the period 1936-1960, regarding their reproductive performance. Fecundability was only 12% lower for women in the 30-39 year age interval than for women up to 29 years of age. Cumulative pregnancy rates for individual years fell in the range 93-96%. No difference in fecundability could be discerned between women born in 1936-45 vis-à-vis 1946-60. Primary and secondary infertility were noted for 6.6% and 11.0% respectively of the entire population surveyed. Primary infertility, more prevalent among those born in 1946-60, was found to be related to a higher level of education, an urban life style and low age at first coitus. The risk of suffering a spontaneous abortion increased with advancing maternal age.


Evolutionary impacts of the goldenrod ball gallmaker on Solidago altissima clones.
Three ramet clones of Solidago altissima were grown under greenhouse conditions to determine the effects of varying levels of attack by the goldenrod ball gallmaker (Eurosta solidaginis) on biomass allocation, leaf senescence rate and rhizome connections among ramets. The results, examined at both the individual ramet level and the clone level, showed that galled ramets became isolated from their clone through deterioration of rhizome connections. Gall effects were only observed at the ramet level although rhizome connection effects were detected at both the ramet and clone levels. The goldenrod ball gallmaker may therefore have little evolutionary impact on large clones but could appreciably affect newly established clones.


Triclosan-containing toothpastes reduce plaque and gingivitis.
Sources of studies were the Cochrane Controlled Trials Register, Medline and Embase. Personal files and the reference lists of all articles were checked for further studies. Trials were selected if they met the following criteria: there had been random allocation of participants; participants were adults with plaque and gingivitis; there was unsupervised use of dentifrices for at least 6 months; and primary outcomes were plaque and gingivitis after 6 months. Data were extracted by two reviewers independently. For each plaque and gingivitis index, the mean differences for each study were pooled as weighted mean differences (WMD) with the appropriate 95% confidence intervals (CI) using the random effects model. Sixteen trials provided data for the meta-analysis. The triclosan/copolymer dentifrice significantly improved plaque control compared with a fluoride dentifrice, with a WMD of -0.48 (95% CI, -0.64 to -0.32) for the Quigley-Hein index and WMD of-0.15 (95% CI,-0.20 to -0.09) for the plaque severity index. When compared with a fluoride dentifrice, the triclosan/copolymer dentifrice significantly reduced gingivitis with WMD of -0.26 (95% CI, -0.34 to -0.18) and -0.12 (95% CI, -0.17 to -0.08) for the Loe and Silness index and for gingivitis. This systematic review indicates that a dentifrice that contains triclosan/copolymer provides a more effective level of plaque control and periodontal health than a conventional fluoride dentifrice.