[Changes in the composition of anionic membrane phospholipids influence the protein secretion and biogenesis of cell envelope in Escherichia coli].
The secretion of alkaline phosphatase (PhoA) and peculiarities of biogenesis of the cell envelope were studied in Escherichia coli strains HD30/pHD 102 and HDL11 with controlled synthesis of anionic phospholipids, phosphatidylglycerol, and cardiolipin. Inactivation of the pgsA gene encoding the synthesis of anionic phospholipids or changes in the regulation of its expression by an environmental factor caused changes in the metabolism and composition of membrane phospholipids, which resulted in a decrease in the secretion of alkaline phosphatase through the cytoplasmic membrane and an increase in PhoA secretion from the periplasm into the culture medium. A conforming increase was observed in exopolysaccharide secretion, as well as a decrease in the contents of lipopolysaccharide and lipopolyprotein of the outer membrane that determine the membrane barrier properties. The results obtained testify that anionic phospholipids play a significant role in protein secretion and are probably involved in the interrelation between the protein secretion and biogenesis of cell envelope components.


Antifungal activity of lactobacilli and its relationship with 3-phenyllactic acid production.
In this study, 13 lactic acid bacteria (LAB) strains (including 5 Lactobacillus casei, 2 Lactobacillus rhamnosus, 2 Lactobacillus fermentum, 1 Lactobacillus acidophilus, 1 Lactobacillus plantarum, 1 Lactobacillus sakei, and 1 Lactobacillus reuteri species) were assessed for both their antifungal activity against four food spoilage molds (Colletotrichum gloeosporioides, Botrytis cinerea, Penicillium expansum, and Aspergillus flavus) and their capability to produce the novel antimicrobial compound 3-phenyllactic acid (PLA). Results demonstrated that all molds were sensitive to varying degrees to the cell-free supernatants (CFS) from LAB fermentations (p<0.05), with growth inhibitions ranging from 2.65% to 66.82%. The inhibition ability of CFS was not affected by a heating treatment (121°C, 20 min); however, it declined markedly when the pH of CFS was adjusted to 6.5. With the exception of L. plantarum NRRL B-4496 and L. acidophilus ATCC-4495, all other LAB strains produced PLA ranging from 0.021 to 0.275 mM. The high minimum inhibitory concentration for commercial PLA (3.01-36.10mM) suggests that it cannot be considered the only compound related with the antifungal potential of studied LAB and that synergistic effects may exist among other metabolism products.


Knee biomechanics during walking gait following matrix-induced autologous chondrocyte implantation.
Matrix-induced autologous chondrocyte implantation is a technique for repairing articular cartilage defects in the knee. Despite reported improvements in pain, little is known about the recovery of knee biomechanics during walking gait. A randomized controlled study design was used to investigate knee biomechanics during gait in 61 patients following matrix-induced autologous chondrocyte implantation, in conjunction with either 'accelerated' or 'traditional' approaches to post-operative weight-bearing rehabilitation. Gait analysis was performed at 3, 6 and 12 months post-surgery in both patient groups, and two matched, unaffected control groups for comparison. The spatiotemporal and ground reaction force parameters were similar between patient groups and their respective control groups at all time points. When compared with controls, both patient groups demonstrated significantly reduced knee extension moments up until, and including, 12 months. The traditional group demonstrated a significantly reduced knee adduction moment at 3, 6 and 12 months, and a significantly reduced knee flexion moment at 3 months. There were no differences in these knee moments between the accelerated patient group and controls. Overall, a higher level of gait dysfunction was observed in patients who underwent traditional rehabilitation. Future research is needed to investigate the recovery of normal gait following matrix-induced autologous chondrocyte implantation, and its effect on repair tissue development.


Firearm safety counseling among caregivers of high-school age teens: Results from a National Survey.
Firearms are the leading cause of death for high-school age teens. To inform prevention efforts, we characterize the prevalence of healthcare provider (HCP) counseling of caregivers of teens around firearm safety, safety conversation elements, and caregiver receptivity towards counseling. A cross-sectional web survey (6/24/2020-7/22/2020) was conducted among caregivers (n = 2924) of teens (age:14-18). Weights were applied to generate nationally representative estimates. Bivariate analyses and multivariate regressions were examined. Among respondents, 56.0% were women, 75.1% were non-Hispanic White, and mean (SD) age was 47.4. Firearm safety was the least discussed topic among caregivers reporting their teen received HCP preventative counseling (14.9%). For caregivers receiving counseling, the most common issues discussed were household firearms screening (75.7%); storing firearms locked (66.8%); and storing firearms unloaded (53.0%). Only 24.6% of caregivers indicated firearm safety was an important issue for teen HCPs to discuss and only 21.9% trusted teen HCPs to counsel about firearm safety. Female caregivers (aOR = 1.86;95%CI = 1.25-2.78), those trusting their teen's HCP to counsel on firearm safety (aOR = 9.63;95%CI = 6.37-14.56), and those who received teen HCP firearm safety counseling (aOR = 5.14;95%CI = 3.02-8.72) were more likely to favor firearm safety counseling. Caregivers of teens with prior firearm safety training (aOR = 0.50;95%CI = 0.31-0.80) were less likely to agree that firearm safety was an important preventative health topic. In conclusion, few caregivers receive preventive counseling on firearm safety from their teen's HCP, with trust a key barrier to effective intervention delivery. Future research, in addition to understanding barriers and establishing effective strategies to increase safety practices, should focus on increasing provider counseling competency.


[Non-fatal disseminated mucormycosis in a solid organ transplant].
Mucormycosis is a rare fungal infection occurring most frequently in immunocompromised patients. The pathogens are filamentous fungi, order of Mucorales. Disseminated mucormycosis is a severe, life treating disease. Early diagnosis is a major determinant for prognosis, however, it remains difficult. The management consists in an early antifungal therapy using lipid formulation of amphotericin B associated with an extensive surgical debridement. Despite this therapeutic of choice, the mortality of disseminated mucormycosis remains high. We report the case of disseminated mucormycosis in a 25 years old woman 9 months after a pulmonary transplantation. The clinical presentation included pulmonary and thyroid localization and the pathogen was Absidia corymbifera. The patient survived thanks to a large surgical debridement, and an early antifungal bitherapy by lipid formulation of amphotericin B and posaconazole. The re-emergence and the high mortality of mucormycosis in solid organ transplant receiver show the necessity to find new therapeutic approaches. Posaconazole associated with liposomal amphotericin B could be an interesting option to treat disseminated mucormycosis and improve their outcome.


Substitutes and alternatives to platelet transfusions in thrombocytopenic patients.
Over the past decade, there have been many improvements in both the safety profile and quality of liquid-stored allogeneic platelet concentrates. However, significant problems with the clinical use of such products remain. Efforts to overcome some of these have resulted in the development of an array of novel therapeutic strategies for the manufacture of platelet products and platelet substitutes, as well as other approaches using alternatives to platelet concentrates. These various products or procedures are at various stages of clinical development. This review summarizes some recent advancements in the preparation of liquid and frozen stored platelets, as well as approaches used for the pathogen inactivation of platelets. Thus, the status of lyophilized platelets, infusible platelet membranes, red blood cells (RBCs) bearing RGD ligands, fibrinogen-coated albumin microcapsules, and liposome-based agents are discussed. Pre-clinical studies and phase 1-3 clinical trials have been encouraging for several of these; however, to date, very few have been licensed for clinical use. Potential alternatives to allogeneic platelet transfusions including correction of anemia by RBC transfusions, recombinant activated factor VII and HLA-reduced platelets are also reviewed. With the ongoing technical and scientific development of such diverse products, those properties that may be necessary for such agents to have hemostatic efficacy will become apparent. However, safety and efficacy must be demonstrable in preclinical studies and clinical trials, before novel platelet concentrates, platelet substitutes and alternatives to platelets can be used in patients with thrombocytopenia.


Concordance of sleep and pain outcomes of diverse interventions: an umbrella review.
Pain influences sleep and vice versa. We performed an umbrella review of meta-analyses on treatments for diverse conditions in order to examine whether diverse medical treatments for different conditions have similar or divergent effects on pain and sleep. We searched published systematic reviews with meta-analyses in the Cochrane Database of Systematic Reviews until October 20, 2011. We identified randomized trials (or meta-analyses thereof, when >1 trial was available) where both pain and sleep outcomes were examined. Pain outcomes were categorized as headache, musculoskeletal, abdominal, pelvic, generic or other pain. Sleep outcomes included insomnia, sleep disruption, and sleep disturbance. We estimated odds ratios for all outcomes and evaluated the concordance in the direction of effects between sleep and various types of pain and the correlation of treatment effects between sleep and pain outcomes. 151 comparisons with 385 different trials met our eligibility criteria. 96 comparisons had concordant direction of effects between each pain outcome and sleep, while in 55 the effect estimates were in opposite directions (P<0.0001). In the 20 comparisons with largest amount of evidence, the experimental drug always had worse sleep outcomes and tended to have worse pain outcomes in 17/20 cases. For headache and musculoskeletal pain, 69 comparisons showed concordant direction of effects with sleep outcomes and 36 showed discordant direction (P<0.0001). For the other 4 pain types there were overall 27 vs. 19 pairs with concordant vs. discordant direction of effects (P = 0.095). There was a weak correlation of the treatment effect sizes for sleep vs. headache/musculoskeletal pain (r = 0.17, P = 0.092). Medical interventions tend to have effects in the same direction for pain and sleep outcomes, but exceptions occur. Concordance is primarily seen for sleep and headache or musculoskeletal pain where many drugs may both disturb sleep and cause pain.


Assessing the accuracy of species distribution models to predict amphibian species richness patterns.
1. Evaluating the distribution of species richness where biodiversity is high but has been insufficiently sampled is not an easy task. Species distribution modelling has become a useful approach for predicting their ranges, based on the relationships between species records and environmental variables. Overlapping predictions of individual distributions could be a useful strategy for obtaining estimates of species richness and composition in a region, but these estimates should be evaluated using a proper validation process, which compares the predicted richness values and composition with accurate data from independent sources. 2. In this study, we propose a simple approach to estimate model performance for several distributional predictions generated simultaneously. This approach is particularly suitable when species distribution modelling techniques that require only presence data are used. 3. The individual distributions for the 370 known amphibian species of Mexico were predicted using maxent to model data on their known presence (66,113 presence-only records). Distributions were subsequently overlapped to obtain a prediction of species richness. Accuracy was assessed by comparing the overall species richness values predicted for the region with observed and predicted values from 118 well-surveyed sites, each with an area of c. 100 km(2), which were identified using species accumulation curves and nonparametric estimators. 4. The derived models revealed a remarkable heterogeneity of species richness across the country, provided information about species composition per site and allowed us to obtain a measure of the spatial distribution of prediction errors. Examining the magnitude and location of model inaccuracies, as well as separately assessing errors of both commission and omission, highlights the inaccuracy of the predictions of species distribution models and the need to provide measures of uncertainty along with the model results. 5. The combination of a species distribution modelling method like maxent and species richness estimators offers a useful tool for identifying when the overall pattern provided by all model predictions might be representing the geographical patterns of species richness and composition, regardless of the particular quality or accuracy of the predictions for each individual species.


Congenital short QT syndrome.
The Short QT Syndrome is a recently described new genetic disorder, characterized by abnormally short QT interval, paroxysmal atrial fibrillation and life threatening ventricular arrhythmias. This autosomal dominant syndrome can afflict infants, children, or young adults; often a remarkable family background of cardiac sudden death is elucidated. At electrophysiological study, short atrial and ventricular refractory periods are found, with atrial fibrillation and polymorphic ventricular tachycardia easily induced by programmed electrical stimulation. Gain of function mutations in three genes encoding K(+) channels have been identified, explaining the abbreviated repolarization seen in this condition: KCNH2 for I(kr) (SQT1), KCNQ1 for I(ks) (SQT2) and KCNJ2 for I(k1) (SQT3). The currently suggested therapeutic strategy is an ICD implantation, although many concerns exist for asymptomatic patients, especially in pediatric age. Pharmacological treatment is still under evaluation; quinidine has shown to prolong QT and reduce the inducibility of ventricular arrhythmias, but awaits additional confirmatory clinical data.


Production of transgenic and non-transgenic clones in miniature pigs by somatic cell nuclear transfer.
Miniature pigs have been recognized as valuable experimental animals in various fields such as medical and pharmaceutical research. However, the amount of information on somatic cell cloning in miniature pigs, as well as genetically modified miniature pigs, is much less than that available for common domestic pigs. The objective of the present study was to establish an efficient technique of cloning miniature pigs by somatic cell nuclear transfer. A high pregnancy rate was achieved following transfer of parthenogenetic (3/3) and cloned (5/6) embryos using female miniature pigs in the early pregnancy period as recipients after estrus synchronization with prostaglandin F2 alpha analog and gonadotrophins. The production efficiency of the cloned miniature pigs using male and female fetal fibroblasts as nucleus donors was 0.9% (2/215 and 3/331, respectively). Cloned miniature pigs were also produced efficiently (7.8%, 5/64) by transferring reconstructed embryos into the uteri of common domestic pigs. When donor cells transfected with the green fluorescent protein (GFP) gene were used in nuclear transfer, the production efficiency of the reconstructed embryos and rate of blastocyst development were comparable to those obtained by non-transfected cells. When transfected cell-derived reconstructed embryos were transferred to three common domestic pig recipients, all became pregnant, and a total of ten transgenic cloned miniature pigs were obtained (piglet production efficiency: 2.7%, 10/365). Hence, we were able to establish a practical system for producing cloned and transgenic-cloned miniature pigs with a syngeneic background.


Astrocytic mitochondrial frataxin-A promising target for ischemic brain injury.
In the ischemic brain, hypoxia leads to mitochondrial dysfunction, insufficient energy production, and astrocyte activation. Yet, most studies investigating mitochondrial dysfunction in cerebral ischemia have focused exclusively on neurons. This review will highlight the importance of the morphological, molecular, and functional heterogeneity of astrocytes in their role in brain injuries and explore how activated astrocytes exhibit calcium imbalance, reactive oxygen species overproduction, and apoptosis. In addition, special focus will be given to the role of the mitochondrial protein frataxin in activated astrocytes during ischemia and its putative role in the pharmacological management of cerebral ischemia.


Arthrogenic human synovial cysts: immunohistochemical profile of interleukin-1beta, interleukin-6, tumour necrosis factor-alpha.
Synovial cysts are currently classified as degenerative lesions affecting the joint capsule or adjacent structures. In our study we describe the results obtained in an immunohistochemical study comprising 18 patients with synovial cysts, performed to evaluate the pathophysiological role of some inflammatory cytokines such as: interleukin (IL)-1β, IL-6 and tumour necrosis factor-alpha (TNF-α). Results showed an over-expression of TNF-α, IL-1β and IL-6 which appears to be involved in the onset and progression of the disease. At the present time it is not possible to affirm that these molecules play a direct role also due to the absence of further and more specific investigations. The authors therefore hypothesize that inhibition of inflammation may have a significant role in the pathogenesis and regression of synovial cysts. Hence, these inflammatory cytokines may be considered potential therapeutic targets. The development of synthetic inhibitors of these inflammatory factors could lead to a reduction in the intensity of inflammation, thus inhibiting the onset and development of the disease.


Synchronization transitions and sensitivity to asymmetry in the bimodal Kuramoto systems with Cauchy noise.
We analyze the synchronization dynamics of the thermodynamically large systems of globally coupled phase oscillators under Cauchy noise forcings with a bimodal distribution of frequencies and asymmetry between two distribution components. The systems with the Cauchy noise admit the application of the Ott-Antonsen ansatz, which has allowed us to study analytically synchronization transitions both in the symmetric and asymmetric cases. The dynamics and the transitions between various synchronous and asynchronous regimes are shown to be very sensitive to the asymmetry degree, whereas the scenario of the symmetry breaking is universal and does not depend on the particular way to introduce asymmetry, be it the unequal populations of modes in a bimodal distribution, the phase delay of the Kuramoto-Sakaguchi model, the different values of the coupling constants, or the unequal noise levels in two modes. In particular, we found that even small asymmetry may stabilize the stationary partially synchronized state, and this may happen even for an arbitrarily large frequency difference between two distribution modes (oscillator subgroups). This effect also results in the new type of bistability between two stationary partially synchronized states: one with a large level of global synchronization and synchronization parity between two subgroups and another with lower synchronization where the one subgroup is dominant, having a higher internal (subgroup) synchronization level and enforcing its oscillation frequency on the second subgroup. For the four asymmetry types, the critical values of asymmetry parameters were found analytically above which the bistability between incoherent and partially synchronized states is no longer possible.


Making information available for quality improvement and service planning in neonatal care.
We describe a prospective two year study aimed at assessing information collected throughout a geographically defined region as a basis for clinical governance, quality improvement and service planning in neonatal intensive and special care. All 13 Northern Ireland units returned a range of socio-demographic, obstetric and neonatal data for all admissions or readmissions within 28 days of life. 8.2% of all live births required neonatal intensive or special care, with a requirement of 374 and 645 days per 1,000 births for intensive and special care respectively. In total there were 4,205 episodes of care provided for 3,946 infants (18,072 days of intensive and 31,141 days of special care). Complications arising during intensive care episodes included the following: septicaemia/bacteraemia (7.6%), necrotising enterocolitis (2.8%), pneumothorax (4.6%), patent ductus arteriosus (6.5%) and seizures (6.9%). Opportunities for quality improvement exist in a number of areas with potential for further reduction in morbidity. Comparisons with published criteria demonstrate the value of this type of information for local, regional and national quality improvement initiatives and service planning.


Living environments and older people.
The influence of care environments on patients has long been a fundamental concern for nurses. Considerations of how environments might be defined, particularly how multiple aspects of environments might impact on any individual, are complex. This article aims to unpick some of the complexities and to offer ideas on how nurses can positively influence environments, particularly in settings where older people live and are offered care.


A phosphorylation in the c-terminal auto-inhibitory domain of the plant plasma membrane H+-ATPase activates the enzyme with no requirement for regulatory 14-3-3 proteins.
The plant plasma membrane H(+)-ATPase is regulated by an auto-inhibitory C-terminal domain that can be displaced by phosphorylation of the penultimate residue, a Thr, and the subsequent binding of 14-3-3 proteins. By mass spectrometric analysis of plasma membrane H(+)-ATPase isoform 2 (PMA2) isolated from Nicotiana tabacum plants and suspension cells, we identified a new phosphorylation site, Thr-889, in a region of the C-terminal domain upstream of the 14-3-3 protein binding site. This residue was mutated into aspartate or alanine, and the mutated H(+)-ATPases expressed in the yeast Saccharomyces cerevisiae. Unlike wild-type PMA2, which could replace the yeast H(+)-ATPases, the PMA2-Thr889Ala mutant did not allow yeast growth, whereas the PMA2-Thr889Asp mutant resulted in improved growth and increased H(+)-ATPase activity despite reduced phosphorylation of the PMA2 penultimate residue and reduced 14-3-3 protein binding. To determine whether the regulation taking place at Thr-889 was independent of phosphorylation of the penultimate residue and 14-3-3 protein binding, we examined the effect of combining the PMA2-Thr889Asp mutation with mutations of other residues that impair phosphorylation of the penultimate residue and/or binding of 14-3-3 proteins. The results showed that in yeast, PMA2 Thr-889 phosphorylation could activate H(+)-ATPase if PMA2 was also phosphorylated at its penultimate residue. However, binding of 14-3-3 proteins was not required, although 14-3-3 binding resulted in further activation. These results were confirmed in N. tabacum suspension cells. These data define a new H(+)-ATPase activation mechanism that can take place without 14-3-3 proteins.


IL-17A Contributes to Lung Fibrosis in a Model of Chronic Pulmonary Graft-versus-host Disease.
Chronic pulmonary graft-versus-host disease (cpGVHD) after hematopoietic cell transplant (HCT) manifests as progressive airway and parenchymal lung fibrosis. On the basis of our prior data, mice that undergo allogeneic HCT with Tbet-knockout donors (AlloTbet) have increased lung Th17 cells and IL-17A and develop fibrosis resembling human cpGVHD. The role of IL-17A in posttransplant pulmonary fibrosis remains incompletely understood. We hypothesized that IL-17A is necessary for development of murine cpGVHD in this model. AlloTbet mice received weekly intraperitoneal anti-IL-17A or IgG (200 μg/mouse) starting 2 weeks post-HCT and were sacrificed after week 5. Histologic airway and parenchymal fibrosis were semiquantitatively graded in a blinded fashion. Lung cells and proteins were measured by flow cytometry, ELISA, and multicytokine assays. Anti-IL-17A modestly decreased airway and parenchymal lung fibrosis, along with a striking reduction in pulmonary neutrophilia, IL-6, MIP-1α, MIP-1β, CXCL1, and CXCL5 in AlloTbet mice. Additionally, anti-IL-17A decreased CCL2, inflammatory monocytes and macrophages, and Th17 cells. In the setting of murine AlloHCT with Tbet donors, IL-17A blockade decreases fibrotic features of cpGVHD. This may be mediated by the observed reduction in neutrophils or specific lung monocyte and macrophage populations or alternatively via a direct effect on fibroblasts. Collectively, our results further suggest that anti-IL-17A strategies could prove useful in preventing alloimmune-driven fibrotic lung diseases.


Simultaneous bilateral elbow dislocation with bilateral medial epicondyle fractures in a 13-year-old female gymnast with hyperlaxity.
Bilateral simultaneous elbow dislocations are extremely rare and have only been described in 12 cases. In the paediatric population unilateral elbow dislocations are rare with 3-6% of all elbow injuries and there are only few studies describing this injury exclusively in children. There is only one case report of a paediatric patient who sustained a simultaneous bilateral elbow dislocation with medial epicondyle fractures. We present a second paediatric case of simultaneous bilateral elbow dislocation with associated displaced bilateral medial epicondyle fractures in a gymnast with joint hyperlaxity (3 of 5 Wynne-Davies criteria) treated with closed reduction and short-term immobilisation (3 weeks). The patient returned to full trampoline gymnastics between 4 and 5 months postinjury and made an uneventful recovery.


Design of Peptide Substrate for Sensitively and Specifically Detecting Two Aβ-Degrading Enzymes: Neprilysin and Angiotensin-Converting Enzyme.
Upregulation of neprilysin (NEP) to reduce Aβ accumulation in the brain is a promising strategy for the prevention of Alzheimer's disease (AD). This report describes the design and synthesis of a quenched fluorogenic peptide substrate qf-Aβ(12-16)AAC (with the sequence VHHQKAAC), which has a fluorophore, Alexa-350, linked to the side-chain of its C-terminal cysteine and a quencher, Dabcyl, linked to its N-terminus. This peptide emitted strong fluorescence upon cleavage. Our results showed that qf-Aβ(12-16)AAC is more sensitive to NEP than the previously reported peptide substrates, so that concentrations of NEP as low as 0.03 nM could be detected at peptide concentration of 2 μM. Moreover, qf-Aβ(12-16)AAC had superior enzymatic specificity for both NEP and angiotensin-converting enzyme (ACE), but was inert with other Aβ-degrading enzymes. This peptide, used in conjunction with a previously reported peptide substrate qf-Aβ(1-7)C [which is sensitive to NEP and insulin-degrading enzyme (IDE)], could be used for high-throughput screening of compounds that only upregulate NEP. The experimental results of cell-based activity assays using both qf-Aβ(1-7)C and qf-Aβ(12-16)AAC as the substrates confirm that somatostatin treatment most likely upregulates IDE, but not NEP, in neuroblastoma cells.


Distributed Consensus Optimization in Multiagent Networks With Time-Varying Directed Topologies and Quantized Communication.
This paper considers solving a class of optimization problems which are modeled as the sum of all agents' convex cost functions and each agent is only accessible to its individual function. Communication between agents in multiagent networks is assumed to be limited: each agent can only interact information with its neighbors by using time-varying communication channels with limited capacities. A technique which overcomes the limitation is to implement a quantization process to the interacted information. The quantized information is first encoded as a binary sequence at the side of each agent before sending. After the binary sequence is received by the neighboring agent, corresponding decoding scheme is utilized to resume the original information with a certain degree of error which is caused by the quantization process. With the availability of each agent's encoding states (associated with its out-channels) and decoding states (associated with its in-channels), we devise a set of distributed optimization algorithms that generate two iterative sequences, one of which converges to the optimal solution and the other of which reaches to the optimal value. We prove that if the parameters satisfy some mild conditions, the quantization errors are bounded and the consensus optimization can be achieved. How to minimize the number of quantization level of each connected communication channel in fixed networks is also explored thoroughly. It is found that, by properly choosing system parameters, one bit information exchange suffices to ensure consensus optimization. Finally, we present two numerical simulation experiments to illustrate the efficacy of the algorithms as well as to validate the theoretical findings.


Recessive mutations in SPTBN2 implicate β-III spectrin in both cognitive and motor development.
β-III spectrin is present in the brain and is known to be important in the function of the cerebellum. Heterozygous mutations in SPTBN2, the gene encoding β-III spectrin, cause Spinocerebellar Ataxia Type 5 (SCA5), an adult-onset, slowly progressive, autosomal-dominant pure cerebellar ataxia. SCA5 is sometimes known as "Lincoln ataxia," because the largest known family is descended from relatives of the United States President Abraham Lincoln. Using targeted capture and next-generation sequencing, we identified a homozygous stop codon in SPTBN2 in a consanguineous family in which childhood developmental ataxia co-segregates with cognitive impairment. The cognitive impairment could result from mutations in a second gene, but further analysis using whole-genome sequencing combined with SNP array analysis did not reveal any evidence of other mutations. We also examined a mouse knockout of β-III spectrin in which ataxia and progressive degeneration of cerebellar Purkinje cells has been previously reported and found morphological abnormalities in neurons from prefrontal cortex and deficits in object recognition tasks, consistent with the human cognitive phenotype. These data provide the first evidence that β-III spectrin plays an important role in cortical brain development and cognition, in addition to its function in the cerebellum; and we conclude that cognitive impairment is an integral part of this novel recessive ataxic syndrome, Spectrin-associated Autosomal Recessive Cerebellar Ataxia type 1 (SPARCA1). In addition, the identification of SPARCA1 and normal heterozygous carriers of the stop codon in SPTBN2 provides insights into the mechanism of molecular dominance in SCA5 and demonstrates that the cell-specific repertoire of spectrin subunits underlies a novel group of disorders, the neuronal spectrinopathies, which includes SCA5, SPARCA1, and a form of West syndrome.


Effects of 3-month dapagliflozin on left atrial function in treatment-naïve patients with type 2 diabetes mellitus: assessment using 4-dimensional echocardiography.
The sodium-glucose transporter-2 (SGLT-2) inhibitor dapagliflozin can improve left ventricular (LV) performance in patients with type 2 diabetes mellitus (T2DM). However, the effects on left atrial (LA) function in treatment-naïve T2DM patients remain unclear. The aim of our study was 1) to investigate the effects of 3-month treatment with dapagliflozin on LA function in treatment-naïve patients with T2DM using 4-dimensional automated LA quantification (4D Auto LAQ) and 2) to explore linked covariation patterns of changes in clinical and LA echocardiographic variables. 4D Auto LAQ was used to evaluate LA volumes, longitudinal and circumferential strains in treatment-naïve T2DM patients at baseline, at follow-up, and in healthy control (HC). Sparse canonical correlation analysis (sCCA) was performed to capture the linked covariation patterns between changes in clinical and LA echocardiographic variables within the treatment-naïve T2DM patient group. This study finally included 61 treatment-naïve patients with T2DM without cardiovascular disease and 39 healthy controls (HC). Treatment-naïve T2DM patients showed reduced LA reservoir and conduit function at baseline compared to HC, independent of age, sex, BMI and blood pressure (LASr: 21.11 ± 5.39 vs. 27.08 ± 5.31 %, padjusted = 0.017; LAScd: -11.51 ± 4.48 vs. -16.74 ± 4.51 %, padjusted = 0.013). After 3-month treatment with dapagliflozin, T2DM patients had significant improvements in LA reservoir and conduit function independent of BMI and blood pressure changes (LASr: 21.11 ± 5.39 vs. 23.84 ± 5.74 %, padjusted < 0.001; LAScd: -11.51 ± 4.48 vs. -12.75 ± 4.70 %, padjusted < 0.001). The clinical and LA echocardiographic parameters showed significant covariation (r = 0.562, p = 0.039). In the clinical dataset, changes in heart rate, insulin, and BMI were most associated with the LA echocardiographic variate. In the LA echocardiographic dataset, changes in LAScd, LASr, and LASr_c were most associated with the clinical variate. Compared with HC, treatment-naïve patients with T2DM had lower LA function, and these patients benefited from dapagliflozin administration, particularly in LA function.


Genetic analysis of size-scaling patterns in the mouse mandible.
The relationship between multidimensional form of the adult mouse mandible and body size is examined from an ontogenetic perspective. The origin and ontogeny of phenotypic correlations are described in terms of genetic and environmental covariance patterns between adult skeletal morphology and growth in body weight. Different ontogenetic patterns are observed in the genetic correlations, and these can be related to the developmental as well as the functional aspects of mandibular form. The quantitative genetic aspects of craniomandibular growth and morphogenesis are explored, together with an examination of the impact of ontogenetic changes in the genetic variance-covariance structure on morphogenetic integration and evolution by selection.


Molecular and cellular mechanisms of leukocyte chemotaxis.
The application of modern scientific methods to the study of leukocyte function has begun to reveal the molecular and cytostructural bases of the chemotactic responses of these cells. Leukocyte chemotaxis is initiated by the binding of chemoattractants to distinct plasma membrane receptors; this finding alters transmembrane potential and activates ionic fluxes. The subsequent sequence of metabolic processes leads to a rearrangement of cytoskeletal elements that is manifested by orientation and migration of the cells toward the source of the chemotactic gradient.


Fatty acid ethyl esters and ethanol-induced pancreatitis.
Conjugation of xenobiotic alcohols with endogenous fatty acids is considered one of the mechanisms of their retention in the target organs. A number of fatty acid esters of alcohol's detected in the human tissues were found to be toxic in vivo and in vitro. Non-oxidative metabolism of ethanol resulting in the formation of fatty acid ethyl esters (FAEEs) appears to be one of the major pathways of ethanol disposition in the pancreas during chronic alcohol abuse, and could be associated with pancreatitis. In most cases, pancreatic damage occurs in alcoholics preceding the onset of clinical pancreatitis. Early markers of ethanol-induced pancreatitis could be important for early prevention of such injury. Although FAEEs have been implicated in the ethanol-induced pancreatitis, mechanism(s) of such injury is not well understood. Studies by others and by our own group have shown that plasma levels of FAEEs correlate well with plasma/blood alcohol concentration. FAEE synthase is known to catalyze the formation of FAEEs. The activity of FAEE synthase was found highest in the pancreas. Excessive synthesis of FAEEs during chronic alcohol abuse in the pancreas may be associated with pancreatic injury as supported by in vivo and cell culture studies. Human studies correlating plasma FAEE levels with that of markers of pancreatic injury could be important in developing markers of ethanol-induced toxicity. Although toxicity of exogenously administered FAEEs is shown in vivo and in vitro, the toxicity associated with endogenously formed FAEEs has not been studied. Therefore, studies regarding the role of endogenously formed FAEEs could be important in understanding the mechanism of ethanol-induced pancreatitis.


Multimodality imaging of hydrogel scleral buckles.
Hydrogel scleral buckles were used for treating retinal detachment in the 1980s and early 1990 s. However, these devices have a propensity to degrade over time and cause several long-term complications, including hydration and overexpansion, fragmentation, extrusion, intrusion, and intraocular erosion, and the potential to mimic mass lesions. The imaging features of hydrogel scleral buckles and their complications are reviewed in this article. Radiographic imaging plays an important role in managing patients with complications of hydrogel buckles. Hydrated buckles display attenuation intermediate between fluid and soft tissue on computed tomography, demonstrate approximately fluid signal on magnetic resonance imaging, and are anechoic on ultrasonography. Linear margins and peripheral dystrophic calcification are characteristic. The constellation of imaging features helps distinguish expanded hydrogel buckles from other orbital diseases. Imaging also serves to precisely localize hydrogel scleral buckle components requiring removal.


Gynecologic manifestations of hereditary nonpolyposis colorectal cancer. From inherited to sporadic disease.
Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominant cancer susceptibility syndrome associated with inherited defects in the DNA mismatch repair system. HNPCC family members are at high risk for developing colorectal, endometrial, and ovarian cancers. Studies of HNPCC families have helped define the important role that mismatch repair genes play in the molecular pathogenesis of endometrial and ovarian cancers. This review will describe some of the important clinical and molecular features of HNPCC-related endometrial and ovarian cancer and describe how genetic susceptibility can be identified in patients with sporadic endometrial and ovarian cancers. It is important to identify patients with HNPCC, as families of mutation carriers may benefit from genetic counseling, testing, and intensified cancer surveillance.


C4 leaf development and evolution.
C4 photosynthesis is more efficient than C3 photosynthesis for two reasons. First, C4 plants have evolved efficient C4 enzymes to suppress wasteful photorespiration and enhance CO2 fixation. Second, C4 leaves have Kranz anatomy in which the veins are surrounded by one layer of bundle sheath (BS) cells and one layer of mesophyll (M) cells. The BS and M cells are functionally well differentiated and also well coordinated for rapid assimilation of atmospheric CO2 and transport of photo-assimilates between the two types of cells. Recent comparative transcriptomics of developing M and BS cells in young maize embryonic leaves revealed not only potential regulators of BS and M cell differentiation but also rapid early BS cell differentiation whereas slower, more prolonged M cell differentiation, contrary to the traditional view of a far simpler process of M cell development. Moreover, new upstream regulators of Kranz anatomy development have been identified and a number of gene co-expression modules for early vascular development have been inferred. Also, a candidate gene regulatory network associated with Kranz anatomy and vascular development has been constructed. Additionally, how whole genome duplication (WGD) may facilitate C4 evolution has been studied and the reasons for why the same WGD event led to successful C4 evolution in Gynandropsis gynandra but not in the sister species Tarenaya hassleriana have been proposed. Finally, new future research directions are suggested.


Stiff auxetics: Hierarchy as a route to stiff, strong lattice based auxetic meta-materials.
Using a combination of analytic and computational methods, we examine the effect of adding hierarchical substructure to an auxetic lattice. Our novel methodology, involving a coarse grain approach, allows for the analysis of hierarchically sub-structured lattices where direct computation would prove intractable. We show that through hierarchy one can create ultra-lightweight auxetic meta-materials of high strength and stiffness. Through scaling law arguments, we show that the benefits of hierarchical design can also be obtained in the general class of bending-dominated lattices. Furthermore, we show that the hierarchical structures presented show a wide range of tailorability in their mechanical properties, and exhibit increased strength when optimised for buckling resistance. Auxetic materials have a broad range of potential applications, and thus the creation of ultra-light auxetic meta-materials with enhanced stiffness and strength is undoubtedly of practical importance.


Prevention of early postoperative deep vein thrombosis by intermittent compression of the leg during surgery.
A clinical trial is described in which the effect of intermittent compression of the lower limb during surgery on the incidence of early postoperative deep vein thrombosis was assessed. Deep vein thromboses were diagnosed by the (125)I-fibrinogen uptake test. Peroperative intermittent compression was achieved by means of an inflatable plastic splint coupled to a pneumatic controller. By compressing only one leg of each patient, each patient acted as his own control.With a sequential statistical analysis, 39 patients were required to pass the 5% level of significance. Eleven thrombi were detected in the control (uncompressed) legs and two occurred in the compressed legs; one of the latter was bilateral. The investigation shows that increasing the pulsatility of the venous flow in the leg is a potent prophylactic against postoperative deep vein thrombosis.


Surgical decision making. The reproducibility of clinical judgement.
A considerable portion of negative surgical second opinions may represent nothing more than reasonable interobserver variation (reliability) among clinicians. In a previous study, four fictional cases were developed for each of seven different disease processes. The appropriate case histories were mailed to a random sample of board-certified surgeons. They were asked to render a decision on the need for elective operative intervention. This report presents a two-year follow-up, in which all surgeons who responded to the original questionnaire were asked to reevaluate the same vignettes. By comparing an individual surgeon's set of responses, the presence of intraobserver variation (reproducibility) was noted. The results of this follow-up showed that a surgeon's judgment with regard to the same hypothetical elective clinical situation seems to differ over time. If both the reproducibility and reliability of clinical surgical judgment are as variable as these studies indicate, then the theoretical premise on which second-opinion programs are based would seem to be in need of reexamination.


Use of home pulse oximetry with daily short message service messages for monitoring outpatients with COVID-19: The patient's experience.
Studies have shown COVID-19 patients may have a low oxygen saturation (SpO2) independent of visible respiratory distress, a phenomenon termed "silent hypoxia." Silent hypoxia creates uncertainty in the outpatient setting for clinicians and patients alike. In this study, we examined the potential for pulse oximeters in identifying early signs of clinical deterioration. We report descriptive results on COVID-positive patients' experiences with a comprehensive home monitoring tool comprised of home SpO2 measurements with a novel symptom-tracking short message service/text messaging application. Of patients who required hospitalization, 83% sought care as a result of low pulse oximeter readings. Nearly all patients who did not require hospitalization reported that having a pulse oximeter provided them with the confidence to stay at home. Essentially all patients found a home pulse oximeter useful. Keeping COVID-19-positive patients at home reduces the potential for disease spread and prevents unnecessary costs and strain on the healthcare system.


Textured Image Demoiréing via Signal Decomposition and Guided Filtering.
Moiré artifacts are generally caused by the interference between the overlap of the sensor's sampling grid and high-frequency (nearly) periodic textures, and heavily affect the image quality. However, it is difficult to effectively remove moiré artifacts from textured images as the structure of moiré patterns is similar to that of textures in some sense. In this paper, we propose a novel textured image demoiréing method by signal decomposition and guided filtering. Given a textured image with moiré artifacts, we first remove moiré artifacts in the green (G) channel using the proposed low-rank and sparse matrix decomposition model. This model regularizes the texture layer by the low-rank prior in spatial domain and the moiré layer by sparse representation in frequency domain. An alternating direction method under the augmented Lagrangian multiplier framework is used to solve the matrix decomposition model. Then, since the red (R) and blue (B) channels are more heavily polluted by moiré artifacts than the G channel, we propose to remove moiré artifacts in its R and B channels via guided filtering by the obtained texture layer of the G channel. Experimental results demonstrate that our method outperforms the state-of-the-art methods for both synthetic and real images.


Burden of paediatric Rotavirus Gastroenteritis (RVGE) and potential benefits of a universal Rotavirus vaccination programme with a pentavalent vaccine in Spain.
Rotavirus is the most common cause of gastroenteritis in young children worldwide. The aim of the study was to assess the health outcomes and the economic impact of a universal rotavirus vaccination programme with RotaTeq, the pentavalent rotavirus vaccine, versus no vaccination programme in Spain. A birth cohort was followed up to the age of 5 using a cohort model. Epidemiological parameters were taken from the REVEAL study (a prospective epidemiological study conducted in Spain, 2004-2005) and from the literature. Direct and indirect costs were assessed from the national healthcare payer and societal perspectives by combining health care resource utilisation collected in REVEAL study and unit costs from official sources. RotaTeq per protocol efficacy data was taken from a large worldwide rotavirus clinical trial (70,000 children). Health outcomes included home care cases, General Practioner (GP)/Paediatrician, emergency department visits, hospitalisations and nosocomial infections. The model estimates that the introduction of a universal rotavirus vaccination programme with RotaTeq (90% coverage rate) would reduce the rotavirus gastroenteritis (RVGE) burden by 75% in Spain; 53,692 home care cases, 35,187 GP/Paediatrician visits, 34,287 emergency department visits, 10,987 hospitalisations and 2,053 nosocomial infections would be avoided. The introduction of RotaTeq would avoid about 76% of RVGE-related costs from both perspectives: euro22 million from the national health system perspective and euro38 million from the societal perspective. A rotavirus vaccination programme with RotaTeq would reduce significantly the important medical and economic burden of RVGE in Spain.


The potential of piR-823 as a diagnostic biomarker in oncology: A systematic review.
Emerging evidence has demonstrated that PIWI-interacting RNAs (piRNAs) play important roles in various physiological processes and contribute to cancer progression. Moreover, piRNAs and PIWI protein levels are associated with the prognosis and chemoresistance of various cancers. The limitations of biomarkers challenge early detection and monitoring of chemoresistance and cancer relapse. To evaluate the potential of piRNA as a diagnostic biomarker in oncology, we systematically reviewed previous studies on the subject. PubMed, Embase, and Cochrane databases were searched to evaluate the diagnostic relevance of piRNAs in cancer. Eighteen studies (2,352 patients) were included. The quality of each study was evaluated with AMSTAR and QUADAS-2 tool. The area under the curve (AUC) values of 26 piRNAs in patients with cancer ranged from 0.624 to 0.978, with piR-9491 showing the highest value (0.978). The sensitivity of the total of 21 piRNAs in cancer patients was between 42.86 and 100, with piR-9491 showing the highest sensitivity (100). The specificity of these 21 piRNAs ranged from 60.10 to 96.67 (with piR-018569 showing the highest specificity (96.67)). Their odds ratios were between 1.61 and 44.67, and piR-12488 showed the highest odds ratio (44.67). Generally, the piRNAs in this review showed better sensitivity and AUC values than current clinical diagnostic biomarkers, although current biomarkers appear to be more specific. Reviewed piRNAs showed better diagnostic performance than currently used clinical biomarkers. Notably, piR-823 showed a significant diagnostic performance in four types of cancer (colorectal, esophageal, gastric, and renal cell cancer). However, all 18 studies included in this review were a case-control study. So, further prospective studies are required for their validation.


Update on Chronic Prurigo.
Chronic prurigo is itself a common condition, but it can also occur secondary to a large number of diseases. Management is challenging as historically chronic prurigo has been poorly defined and very few treatments are available. Clinically, it presents as excoriated, hyperkeratotic lesions. When chronic prurigo is suspected, a comprehensive differential diagnosis is essential. New diagnostic criteria have appeared in recent years and new drugs have been developed. Although no truly effective treatment is yet available, patients will benefit from a greater understanding of this condition.


Recurrent carotid stenosis. Results and complications of 57 operations.
Among 1992 patients undergoing carotid endarterectomy from January 1972 through December 1984, 57 operations were performed in 51 patients for recurrent carotid stenosis. Thirty-four of these cases had undergone initial surgery at this institution while 23 had endarterectomy elsewhere. Fifty-two of the 57 operations were for symptomatic disease while five were for evidence of a progressing lesion. All operative procedures were monitored with intracerebral blood flow measurements and continuous electroencephalograms. Twenty-three patients required intraoperative shunting. There were no complications related to shunt usage or to the period of temporary occlusion in patients who did not require shunting. Recurrent stenosis was related to intimal hyperplasia in 14 cases, recurrent atherosclerosis with interluminal thrombi or degenerated plaque in 27, unexplained soft thrombus in eight, proximal scarring in six, and to aneurysms in two. Intimal hyperplasia was the most common cause for restenosis within 2 years from the date of surgery and developed earlier in patients with a primary closure than in patients closed with a patch graft. The operative complication rate was 10.5% or 4 times the risk of surgery for primary atherosclerosis at this institution. Complications were attributed primarily to intraoperative and postoperative thromboembolic events related to apparent increased thrombogenicity of these vessels. The highest complication rate occurred in the group of patients undergoing surgery for thrombotic material in the internal carotid artery, either primary or with underlying atherosclerosis. There were no neurological complications in the group with myointimal hyperplasia. The authors' experience suggests that on-lay patch grafting without endarterectomy should be used in patients with myointimal hyperplasia. Patients with complicated recurrent atherosclerosis can be treated with endarterectomy and patch grafting, but interposition vein grafts should be considered in cases in which the vessels are extensively damaged by the recurrent plaque or with an unexplained thrombus at the site of previous endarterectomy.


[Effect of dalarginum on the level of nitric oxide stable metabolites in rat kidneys during apoptosis activation].
The influence of dalarginum on the level of nitric oxide stable metabolites in the rat kidneys was investigated at various models of apoptosis activation (formed by two methods of acute renal failure). Dalarginum (synthetic leu-enkephaline) was entered in a dose of 100 micrograms/kg a day. Detection of apoptosis was carried out by determination of DNA fragmentation. Administration of dalarginum resulted in the significant decrease of NO--nitrite- and nitrate anions stable metabolites content, the latter is capable to be one of the mechanisms of the preparation antiapoptotic effect.


Downregulation of FIP200 induces apoptosis of glioblastoma cells and microvascular endothelial cells by enhancing Pyk2 activity.
The expression of focal adhesion kinase family interacting protein of 200-kDa (FIP200) in normal brain is limited to some neurons and glial cells. On immunohistochemical analysis of biopsies of glioblastoma tumors, we detected FIP200 in the tumor cells, tumor-associated endothelial cells, and occasional glial cells. Human glioblastoma tumor cell lines and immortalized human astrocytes cultured in complete media also expressed FIP200 as did primary human brain microvessel endothelial cells (MvEC), which proliferate in culture and resemble reactive endothelial cells. Downregulation of endogenous expression of FIP200 using small interfering RNA resulted in induction of apoptosis in the human glioblastoma tumor cells, immortalized human astrocytes, and primary human brain MvEC. It has been shown by other investigators using cells from other tissues that FIP200 can interact directly with, and inhibit, proline-rich tyrosine kinase 2 (Pyk2) and focal adhesion kinase (FAK). In the human glioblastoma tumor cells, immortalized human astrocytes, and primary human brain MvEC, we found that downregulation of FIP200 increased the activity of Pyk2 without increasing its expression, but did not affect the activity or expression of FAK. Coimmunoprecipitation and colocalization studies indicated that the endogenous FIP200 was largely associated with Pyk2, rather than FAK, in the glioblastoma tumor cells and brain MvEC. Moreover, the pro-apoptotic effect of FIP200 downregulation was inhibited significantly by a TAT-Pyk2-fusion protein containing the Pyk2 autophosphorylation site in these cells. In summary, downregulation of endogenous FIP200 protein in glioblastoma tumor cells, astrocytes, and brain MvECs promotes apoptosis, most likely due to the removal of a direct interaction of FIP200 with Pyk2 that inhibits Pyk2 activation, suggesting that FIP200 expression may be required for the survival of all three cell types found in glioblastoma tumors.


Ser235 phosphorylation of hepatitis C virus NS5A is required for NS5A dimerization and drug resistance.
Hepatitis C virus (HCV) infection is recognized as a major causative agent of chronic hepatitis, cirrhosis, and hepatocellular carcinoma. HCV non-structural protein 5A (NS5A) is a dimeric phosphoprotein with a hyperphosphorylated form to act as a switch that regulates HCV replication and assembly. NS5A inhibitors have been utilized as the scaffold for combination therapy of direct-acting antiviral agents (DAA). However, the mode of action of NS5A inhibitors is still unclear due to the lack of mechanistic detail regarding NS5A phosphorylation and dimerization in the HCV life cycle. It has been demonstrated that phosphorylation of NS5A at Ser235 is essential for RNA replication of the JFH1 strain. In this report, we found that NS5A phosphomimetic Ser235 substitution (Ser-to-Asp mutation) formed a dimer that was resistant to disruption by NS5A inhibitors as was the NS5A resistance-associated substitution Y93H. Phosphorylation of NS5A at Ser235 residue was required for the interaction of two NS5A-WT molecules in JFH1-based cell culture system but not absolutely required for dimerization of the NS5A-Y93H mutant. Interestingly, HCV nonstructural proteins from the subgenomic replicon NS3-5A was required for NS5A-WT dimerization but not required for NS5A-Y93H dimerization. Our data suggest that spontaneous Ser235 phosphorylation of NS5A and ensuing dimerization account for resistance of the JFH1/NS5A-Y93H mutant to NS5A inhibitors.


Perilymph total protein levels associated with cerebellopontine angle lesions.
The total protein levels in the perilymph of patients with acoustic neuromas, meningiomas, and Meniere's disease are contrasted. All specimens were obtained from the lateral semicircular canal during removal of the bony labyrinth. Any specimens with significant contamination by hemoglobin or serum proteins, as judged by the presence of hemoglobin/haptoglobin complexes, were discarded from this study. The findings of greatly increased perilymph protein levels in the tumor groups confirmed the reports of other workers. The levels in the Meniere's disease group compared favorably with the normal protein levels in perilymph. A very significant (p Less Than 0.05) difference between the acoustic neuroma group and the meningioma group is noted. This difference is probably tumor related, because in all cases of both groups, tumor entered and filled the internal auditory meatus.


Treatment approaches and antibiotic use for emergency dental treatment in Turkey.
The purpose of this study was to gather information about Turkish general dental practitioners' treatment approaches towards endodontic emergencies, antibiotic-prescribing habits, and their participation in lifelong learning programs. Questionnaires were given to dentists who attended the 16th National Congress organized by the Turkish Dental Association. From 1,400 questionnaires distributed, 589 (43%) were deemed usable in this study. This survey dealt with questions that were subdivided into two main topics: dental emergency treatment approaches, and antibiotic prescription and information on lifelong learning program participation. The statistical analysis was conducted with a χ (2) test at a significance level of P<0.05. For irreversible pulpitis cases in vital teeth, most of the dental practitioners (65.3%) preferred single-visit root canal treatments. For teeth presenting a periapical lesion, the preferred treatment approach was root canal treatment (91.5%). The rate of prescription of analgesics and antibiotics was 21.7% in untreated acute apical periodontitis cases and 41% in acute apical abscess cases. Frequently prescribed antibiotics were amoxicillin-clavulanate (61.8%) and amoxicillin (46.5%). There was a tendency for practitioners to attend congresses as their years of professional practice increased (P<0.0001). There have been discrepancies between taught and observed practice. Educational initiatives are needed to prevent inappropriate prescription of antibiotics.


A genetic variation in the PGC-1 gene could confer insulin resistance and susceptibility to Type II diabetes.
Peroxisome proliferator activated receptor gamma coactivator-1 (PGC-1), a transcriptional coactivator of the nuclear receptor PPARgamma, plays a role in adaptive thermogenesis and insulin sensitivity. Plasma fasting insulin has been linked to the chromosomal region where the PGC-1 gene is located. Thus, PGC-1 can be viewed as a functional and positional candidate for the susceptibility gene for Type II (non-insulin-dependent) diabetes mellitus. After screening the PGC-1 gene for single nucleotide polymorphisms (SNPs), we performed an association study using the newly detected SNPs in 537 Type II diabetic patients and 417 non-diabetic subjects. We found three relatively frequent SNPs in the PGC-1 gene (IVS4-11T > C, Thr394Thr and Gly482Ser). There were significant differences in fasting insulin (Gly/Gly; 37.7 +/- 1.43, Gly/Ser; 40.2 +/- 1.21, Ser/Ser; 44.3 +/- 1.82 pmol/l, p = 0.018) and insulin resistance index (Gly/Gly; 1.48 +/- 0.06, Gly/Ser; 1.56 +/- 0.05, Ser/Ser; 1.75 +/- 0.08, p = 0.027) according to the genotype of the Gly482Ser polymorphism. The Thr394Thr - Gly482Ser haplotype was associated with Type II diabetes (p = 0.00003). CONCLUSION/INTERPRETATION. The results of this study suggested that the PGC-1 gene might be implicated in the pathogenesis of Type II diabetes.


Characterizing ultrathin and thick organic layers by surface plasmon resonance three-wavelength and waveguide mode analysis.
A three-wavelength angular-scanning surface plasmon resonance based analysis has been utilized for characterizing optical properties of organic nanometer-thick layers with a wide range of thicknesses. The thickness and refractive index were determined for sample layers with thicknesses ranging from subnanometer to hundreds of nanometers. The analysis approach allows for simultaneous determination of both the refractive index and thickness without prior knowledge of either the refractive index or the thickness of the sample layers and without the help of other instruments, as opposed to current methods and approaches for characterizing optical properties of organic nanometer-thick layers. The applicability of the three-wavelength angular-scanning surface plasmon resonance approach for characterizing thin and thick organic layers was demonstrated by ex situ deposited mono- and multilayers of stearic acid and hydrogenated soy phosphatidylcholine and in situ layer-by-layer deposition of two different polyelectrolyte multilayer systems. In addition to the three-wavelength angular-scanning surface plasmon resonance approach, another surface plasmon resonance optical phenomenon, i.e., the surface plasmon resonance waveguide mode, was utilized to characterize organic sample layers whose thicknesses border the micrometer scale. This was demonstrated by characterizing both in situ layer-by-layer deposited polyelectrolyte multilayer systems and an ex situ deposited spin-coated polymer layer.


Free palmaris longus graft tenodesis effectively treats swan neck adduction collapse secondary to thumb basilar joint arthritis.
Compensatory thumb metacarpophalangeal joint hyperextension may occur with basilar joint arthritis and subluxation. Instability at the metacarpophalangeal joint must be corrected when the basilar joint is operated on. The authors use a simple surgical procedure that provides correction of thumb metacarpophalangeal joint hyperextension by a free palmaris longus graft to provide volar tenodesis across the metacarpophalangeal joint. Twelve patients (14 extremities) were evaluated at a minimum of 11 months postoperatively. Outcome analysis was performed using the Disability of the Arm, Shoulder, and Hand Questionnaire, the McGill Pain Questionnaire, and a patient satisfaction survey. Clinical assessments evaluated thumb appearance, range of flexion and extension at the metacarpophalangeal joint, opposition, span, and cylindrical grip strength and pinch strength. Special attention was devoted to stability of the metacarpophalangeal joint while maintaining range of motion and strength. The average score on the Disability of the Arm, Shoulder, and Hand Questionnaire was 13.0 (good return of function), and the McGill Pain Questionnaire revealed mild to no postoperative pain. Overall postoperative patient satisfaction was high. There was good range of motion at the metacarpophalangeal joint (mean flexion, 44 degrees), and assessment of thumb strength revealed a mean tip pinch strength of 6.8 pounds and a mean key pinch strength of 8.7 pounds. Firm thumb stability was demonstrated during these strength measurements. Thumb metacarpophalangeal joint tenodesis can be an alternative to arthrodesis in patients who have swan neck deformity of the thumb secondary to basilar joint arthritis. It has the advantage of retaining useful motion. The procedure provides high patient satisfaction and good thumb function, strength, and range of motion. It is easily performed simultaneously with trapezial resection arthroplasty without complications.


Adverse clinical events in patients treated with sirolimus-eluting stents: the impact of Type D personality.
Little is known about the impact of psychological risk factors on cardiac prognosis in the drug-eluting stent era. We examined whether the distressed personality (Type D) moderates the effect of percutaneous coronary intervention with sirolimus-eluting stent implantation on adverse clinical events at 2-year follow-up. Type D is an emerging risk factor in patients with cardiovascular disease. Prospective follow-up study. Three hundred and fifty-eight patients with ischemic heart disease, who consecutively underwent percutaneous coronary intervention with sirolimus-eluting stent as part of the Rapamycin-Eluting Stent Evaluated At Rotterdam Cardiology Hospital registry, completed the Type D Scale (DS14) post-percutaneous coronary intervention (PCI). The end-point was a composite of death and non-fatal myocardial infarction 2 years after PCI. At follow-up, there were 22 events (12 deaths and 11 myocardial infarctions). Type D patients had a greater than two-fold risk of an event at follow-up compared with non-Type D patients (10.4 vs. 4.4%, P=0.031). In multivariable analysis, Type D remained an independent predictor of adverse outcome (hazard ratio: 2.61; 95% confidence interval: 1.12-6.09; P=0.027) adjusting for sex, age, and history of coronary artery disease, multivessel disease, diabetes, hypercholesterolemia, hypertension, renal impairment and smoking. Previous cardiac history was also an independent predictor of death or myocardial infarction (hazard ratio: 2.83; 95% confidence interval: 1.00-7.96; P=0.049). Type D personality moderated the effect of percutaneous coronary intervention on hard clinical events despite treatment with the latest innovation in interventional cardiology. The inclusion of psychological risk factors in general and personality factors in particular may optimize risk stratification in the drug-eluting stent era.


Measurement properties of the neck disability index: a systematic review.
Systematic review of clinical measurement. To find and synthesize evidence on the psychometric properties and usefulness of the neck disability index (NDI). The NDI is the most commonly used outcome measure for neck pain, and a synthesis of knowledge should provide a deeper understanding of its use and limitations. Using a standard search strategy (1966 to September 2008) and 4 databases (Medline, CINAHL, Embase, and PsychInfo), a structured search was conducted and supplemented by web and hand searching. In total, 37 published primary studies, 3 reviews, and 1 in-press paper were analyzed. Pairs of raters conducted data extraction and critical appraisal using structured tools. Ranking of quality and descriptive synthesis were performed. Horizon estimation suggested the potential for 1 missed paper. The agreement between raters on quality assessments was high(kappa = 0.82). Half of the studies reached a quality level greater than 70%. Failures to report clear psychometric objectives/hypotheses or to rationalize the sample size were the most common design flaws. Studies often focused on less clinically applicable properties, like construct validity or group reliability, than transferable data, like known group differences or absolute reliability (standard error of measurement [SEM] or minimum detectable change [MDC]). Most studies suggest that the NDI has acceptable reliability, although intraclass correlation coefficients (ICCs) range from 0.50 to 0.98. Longer test intervals and the definition of stable can influence reliability estimates. A number of high-quality published (Korean, Dutch, Spanish, French, Brazilian Portuguese) and commercially supported translations are available. The NDI is considered a 1-dimensional measure that can be interpreted as an interval scale. Some studies question these assumptions. The MDC is around 5/50 for uncomplicated neck pain and up to 10/50 for cervical radiculopathy. The reported clinically important difference (CID) is inconsistent across different studies ranging from 5/50 to 19/50. The NDI is strongly correlated (>0.70) to a number of similar indices and moderately related to both physical and mental aspects of general health. The NDI has sufficient support and usefulness to retain its current status as the most commonly used self-report measure for neck pain. More studies of CID in different clinical populations and the relationship to subjective/work/function categories are required.


Pyrethroid activity-based probes for profiling cytochrome P450 activities associated with insecticide interactions.
Pyrethroid insecticides are used to control diseases spread by arthropods. We have developed a suite of pyrethroid mimetic activity-based probes (PyABPs) to selectively label and identify P450s associated with pyrethroid metabolism. The probes were screened against pyrethroid-metabolizing and nonmetabolizing mosquito P450s, as well as rodent microsomes, to measure labeling specificity, plus cytochrome P450 oxidoreductase and b5 knockout mouse livers to validate P450 activation and establish the role for b5 in probe activation. Using PyABPs, we were able to profile active enzymes in rat liver microsomes and identify pyrethroid-metabolizing enzymes in the target tissue. These included P450s as well as related detoxification enzymes, notably UDP-glucuronosyltransferases, suggesting a network of associated pyrethroid-metabolizing enzymes, or "pyrethrome." Considering the central role P450s play in metabolizing insecticides, we anticipate that PyABPs will aid in the identification and profiling of P450s associated with insecticide pharmacology in a wide range of species, improving understanding of P450-insecticide interactions and aiding the development of unique tools for disease control.


Community-level determinants of contraceptive use in the Philippines: a structural analysis.
We use household and community data from the Philippines to estimate a multilevel model of contraceptive use. We go beyond previous efforts in this field by developing a structural model that recognizes joint endogeneity and the temporal ordering of variables. by considering a wider range of community influences on fertility behavior, and by employing an econometric procedure allowing for a multilevel error structure. The results suggest that there are significant effects on fertility behavior of community-level family planning services, labor-conditions, and infrastructure development. These results provide insights regarding the structural determinants of contraceptive use and fertility that are useful for drawing policy implications.


Detailed analysis of antibody responses to SARS-CoV-2 vaccination and infection in macaques.
Macaques are a commonly used model for studying immunity to human viruses, including for studies of SARS-CoV-2 infection and vaccination. However, it is unknown whether macaque antibody responses resemble the response in humans. To answer this question, we employed a phage-based deep mutational scanning approach (Phage-DMS) to compare which linear epitopes are targeted on the SARS-CoV-2 Spike protein in convalescent humans, convalescent (re-infected) rhesus macaques, mRNA-vaccinated humans, and repRNA-vaccinated pigtail macaques. We also used Phage-DMS to determine antibody escape pathways within each epitope, enabling a granular comparison of antibody binding specificities at the locus level. Overall, we identified some common epitope targets in both macaques and humans, including in the fusion peptide (FP) and stem helix-heptad repeat 2 (SH-H) regions. Differences between groups included a response to epitopes in the N-terminal domain (NTD) and C-terminal domain (CTD) in vaccinated humans but not vaccinated macaques, as well as recognition of a CTD epitope and epitopes flanking the FP in convalescent macaques but not convalescent humans. There was also considerable variability in the escape pathways among individuals within each group. Sera from convalescent macaques showed the least variability in escape overall and converged on a common response with vaccinated humans in the SH-H epitope region, suggesting highly similar antibodies were elicited. Collectively, these findings suggest that the antibody response to SARS-CoV-2 in macaques shares many features with humans, but with substantial differences in the recognition of certain epitopes and considerable individual variability in antibody escape profiles, suggesting a diverse repertoire of antibodies that can respond to major epitopes in both humans and macaques. Differences in macaque species and exposure type may also contribute to these findings.


Enrollment of minority women and their main sexual partners in an HIV/STI prevention trial.
There is a paucity of empirical reports that quantitatively assess the success of recruitment strategies in randomized clinical trials (RCTs) using sampling units other than the individual. As innovations in HIV and sexually transmitted infection (STI) preventive intervention protocols and targets of change evolve, there is a need to examine the efficacy of attendant adaptations to recruitment protocols and strategies in the enrollment of study participants. This article examines factors related to enrollment of women and their main, male sexual partners in an RCT of a relationship-based HIV/STI preventive intervention conducted from 1997 to 2001. Among eligible participants (N = 388), findings indicate that race/ethnicity, employment status, marital status, and language preference were significantly associated with enrollment among eligible, potential participants. Additionally, being HIV-positive and having a past or current STI were significantly associated with enrollment. These findings underscore the need to ensure sufficient representation of all risk groups in RCTs, especially those testing innovative HIV/STI preventive intervention approaches or using novel enrollment strategies.


Strain-specific response to beta 3-adrenergic receptor agonist treatment of diet-induced obesity in mice.
Fat intake has long been associated with the development of obesity. The studies described herein show that fat adversely affects adipocyte adrenergic receptor (AR) expression and function. As beta 3AR agonists have been shown to acutely reduce adipose tissue mass and improve thermogenesis in genetically obese rodents, we examined whether chronic supplementation of a high fat diet with a highly selective beta 3AR agonist, CL316,243 could prevent diet-induced obesity, and whether the effect could be sustained over prolonged treatment. C57BL/6J and A/J mice were weaned onto one of three diets: low fat (10.5% calories from fat), high fat (58% calories from fat), or high fat supplemented with 0.001% CL316,243. B/6J mice gained more weight on the high fat diet than A/J mice (at 16 weeks: B/6J, 36.6 +/- 1.4 g; A/J, 32.9 +/- 0.8 g; P < 0.002; n = 10), whereas weights on the low fat diets were similar (B/6J, 29.5 +/- 0.5 g; A/J, 28.8 +/- 0.6 g; P > 0.05; n = 10). CL316,243 prevented the development of diet-induced obesity in A/J animals, but not in B/6J animals. A/J mice weighed 26.0 +/- 0.5 g at 16 weeks, whereas B/6J animals on the same diet weighed 34.1 +/- 0.8 g (P < 0.00001; n = 10), but food intake was not different between the strains throughout the study. beta-Adrenergic stimulation of adenylyl cyclase in obese B/6J mice was decreased by more than 75% in white adipose tissue and by more than 90% in brown adipose tissue (BAT). In contrast, in fat-fed A/J mice, beta-agonist-stimulated adenylyl cyclase was decreased in white adipose tissue by about 10%, whereas the activity in interscapular BAT was decreased by 50%, indicating significant retention of beta AR-stimulated activity in A/J mice compared to B/6J mice. High fat feeding was associated with decreased expression of beta 3AR and beta 1AR in white adipose tissue of both strains. However, chronic CL316,243 treatment prevented both the obesity and the decline in beta 3AR and beta 1AR messenger RNA levels in all adipose depots from A/J mice, but not B/6J mice. As CL316,243-treated A/J mice, but not B/6J mice, also showed marked uncoupling protein expression in white adipose depots, the ability of chronic CL316,243 treatment to prevent diet-induced obesity is dependent upon the elaboration of functional BAT in these regions.


The Swedish ICRP Project--a presentation.
This project was financed by subsidiaries to the Swedish nuclear industry and performed in collaboration with national authorities and others. It was aimed at analysing general radiological protection principles and their consequences in view of the discussion opened up by the ICRP; 'road testing' some case studies was one important component. The main conclusions are: that radiological protection decisions will probably remain much the same under modified ICRP recommendations following ideas currently floated by the ICRP, that there are possibilities in those ideas, but also that a number of issues need to be addressed and their implementation will require time.


Development of a fluorescence detection system using optical parametric oscillator (OPO) laser excitation for in vivo diagnosis.
In this work, the development and applications of a fluorescence detection system using optical parametric oscillator (OPO) laser excitation for in vivo disease diagnosis including oral carcinoma are described. The optical diagnosis system was based on an OPO laser for multi-wavelength excitation and time-resolved detection. The pulsed Nd-YAG-pumped OPO laser system (6 ns, 20 Hz) is compact and has a rapid, broad, and uniform tuning range. Time-gated detection of intensified charge-coupled device (ICCD) making use of external triggering was used to effectively eliminate the laser scattering and contribute to the highly sensitive in vivo measurements. Artificial tissue-simulating phantoms consisting of polystyrene microspheres and tissue fluorophores were tested to optimize the gating parameters. 51-ns gate width and 39-ns gate delays were determined to be the optimal parameters for sensitive detection. In vivo measurements with the optical diagnosis system were applied to esophagus, stomach, and small intestine using an endoscope in canine animal studies. The rapid tuning capability of the optical diagnosis system contributed greatly to the optimization of wavelength for the observation of porphyrin in the small intestine. When the small intestine was thoroughly washed with water, the emission band which corresponds to porphyrin disappeared. Based on this observation, it was concluded that the detected signal was yielded by porphyrin-containing bile secretion. Also, multispectral analyses using multiple excitations from 415 to 480 nm at 5 nm intervals confirmed the porphyrin detection in the small intestine. The optical diagnosis system was also applied to the detection of human xenograft of oral carcinoma in mice using 5-aminolevulinic acid (5-ALA) which is a photodynamic therapy (PDT) drug. Significant differences in protoporphyrin IX fluorescence intensity between normal and tumor tissue could be obtained 2 hours after the injection of 5-ALA into mice due to the preferential accumulation of 5-ALA in tumors. Results reported herein demonstrate potential capabilities of the LIF-OPO system for in vivo disease diagnosis.


Instability of the Salmonella RcsCDB signalling system in the absence of the attenuator IgaA.
IgaA is a Salmonella enterica membrane protein that attenuates the response of the RcsCDB signalling system to envelope stress. This protein is essential unless the RcsCDB system is inactivated, suggesting that IgaA may constantly adjust the magnitude of the response. Such a functional link is also supported by the concurrence of the igaA and rcsD-rcsB-rcsC loci in genomes of enteric bacteria and the selection of spontaneous mutations in the RcsCDB system following IgaA deprivation. However, the exact nature of the spontaneous mutations rendering IgaA dispensable remains undefined. In this work, we examined how the transduction of an igaA null allele affects the status of the RcsCDB system. Loss of RcsCDB response was registered in approximately 90 % of the IgaA-defective clones, which failed to produce the capsule material positively regulated by this system. About half of these non-mucoid clones suppressed the loss of IgaA with large deletions encompassing variable regions of the rcsD-rcsB-rcsC locus. Unexpectedly, mucoid transductants were also reproducibly obtained and indicated the capacity of S. enterica to retain a functional RcsCDB system in the absence of IgaA. Decreased levels of either RcsC or RcsD were shown in 'mucoid' clones lacking IgaA and displaying low responsiveness to stimuli. Taken together, these data demonstrate that the stability and responsiveness of the RcsCDB system relies on its attenuator IgaA. The type of suppressions found also support a model with IgaA controlling the level of signal flowing through RcsC and RcsD.


Simple preparation of microstructure by using an organic-inorganic raspberry-like hybrid as a building block.
A single-step strategy has been developed for synthesizing a micrometer-sized structure by using the raspberry-like hybrid as a building block comprising a repeated sequence of a three-dimensional gold nanoparticle (AuNP)-aniline oligomer-AuNP arrangement. The hybrid holds a high density of highly dispersible AuNPs without any contact with each other, and therefore the microstructure has many nanometer-sized gaps between the adjacent AuNPs for both electrical and optical sensing. We have discussed how the formation mechanism of the microstructure is based on using the hybrid.


Criteria for the interpretation of cocaine levels in human biological samples and their relation to the cause of death.
The determination that cocaine is directly responsible for the immediate cause of death should be considered only when there is a reasonably complete understanding of the circumstances or facts surrounding the death. Another, more obvious and immediate cause of death must be absent, or, at least cocaine must be shown to be a significant contributing factor in the chain of medical findings that lead directly to the immediate cause of death. Not all death investigation requires the sequential steps described in this paper, but these steps must be considered early on in the investigation whenever there is scene, investigational, medical or a historical basis to believe that cocaine is directly related to the cause of death. A relatively high profile death when cocaine is known to be involved, or a death involving unusual behavior on the part of the deceased with police involvement are examples where these considerations may well apply. Information needs to be obtained as soon as possible to have the highest chance of successfully documenting the toxicologic basis for the diagnosis. These facts would include, but would not necessarily be limited to, a scene investigation (whenever possible), a careful review of the investigative reports from all involved agencies, the initial core temperature of the body as well as that of the environment at the time of the collapse or death, the past medical history of the individual, and the results of a complete forensic autopsy and toxicologic studies. Knowledge of and an understanding of the current relevant forensic literature on this subject should be available to the reviewer prior to any interpretation of the significance of cocaine upon a specific death.


Capsaicin-sensitive afferent fibers contribute to gastric mucosal blood flow response to electrical vagal stimulation.
Electrical stimulation of the peripheral vagus produces a noncholinergic increase in gastric mucosal blood flow (GMBF) via unknown mechanisms. The purpose of this study was 1) to investigate whether a portion of the increase in GMBF during prolonged electrical vagal stimulation involves a mechanism separate from augmented acid secretion and 2) to determine whether antidromic activation of afferent fibers contributes to the vascular or secretory responses to electrical vagal stimulation. Electrical vagal stimulation (40 V, 6 Hz, 2 ms) applied for 30 min to the distal cut end of the subdiaphragmatic ventral vagus significantly increased gastric acid secretion and GMBF measured by hydrogen gas clearance. Atropine (0.15 mg/kg iv) or omeprazole (10 mumol/kg iv) completely abolished the secretory response to electrical vagal stimulation, while a significant increase in GMBF remained. Pretreatment with perineural application of the sensory neurotoxin capsaicin to both cervical vagi significantly reduced by 48% the increase in GMBF but not gastric acid secretion; atropine completely abolished the remaining vascular response in capsaicin-treated rats. These results suggest that prolonged electrical vagal stimulation induces a sustained increase in GMBF partially independent of augmented acid secretion and that the noncholinergic portion of the vascular response is mediated by capsaicin-sensitive vagal afferent fibers.


A nude mouse model of human osteosarcoma lung metastases for evaluating new therapeutic strategies.
The purpose of these studies was to develop a metastatic osteosarcoma nude mouse model to evaluate the in vivo efficacy of new therapeutic compounds. Human SAOS-2 osteosarcoma cells (10(6) cells) were injected i.v. into nude mice. Cells isolated from a rare pulmonary metastases 6 months later were established (SAOS-LM1) in culture and re-injected. This procedure was repeated 5 additional times to produce the SAOS-LM6 cell line. Visible pulmonary nodules were present 8 weeks following i.v. injection of 10(6) SAOS-LM6 cells as compared to 17 weeks using SAOS-LM2 cells. Microscopic SAOS-LM6 pulmonary metastases were demonstrated at 6 weeks. Administration of adriamycin on week 9 resulted in regression of macroscopic SAOS-LM6 lung tumors. The ability of the model to be used to evaluate the effectiveness of a biologic agent against microscopic disease was also verified. It was concluded that this model can assess therapeutic efficacy and therefore, may have a role in investigating the potential of novel approaches aimed at eliminating pulmonary metastatic osteosarcoma.


Combining pyramidal tract mapping, microscopic-based neuronavigation, and intraoperative magnetic resonance imaging improves outcome of epilepsy foci resection in the sensorimotor cortex.
To explore the clinical value of combining pyramidal tract mapping, microscopic-based neuronavigation, and intraoperative magnetic resonance imaging (iMRI) in the surgical treatment of epileptic foci involving sensorimotor cortex. We retrospectively analyzed 69 patients with focal epilepsy involving motor and sensory cortex. The surgical operations in Group I (n=38) were performed under the guidance of conventional neuronavigation, and the operations of Group II (n=31) were aided by combining pyramidal tract mapping, microscopic-based neuronavigation and the iMRI technique. Chi square test was used to compare seizure outcome and neurological deficits across groups. 7 patients (18.4%) in Group I, and 3 patients (9.7%) in Group II didn't recover to the level of preoperative strength within one year post-operation. The 2-year follow-up survey showed that more patients in Group II compared to Group I (71% vs. 55.3%, p=0.181) had a good outcome (Engel class I ~ II). The techniques of combining pyramidal tract mapping, microscopic-based neuronavigation and iMRI aid in precise mapping and hence resection of epileptic foci in sensorimotor cortex, which lead to improvement of surgical efficacy and significant reduction of postoperative loss of function.


Isolation and characterization of myeloperoxidase from leukocytes of rat peritoneal fluid.
Myeloperoxidase (MPO) was isolated from rat peritoneal leukocytes with a yield of 51% and A430/A280 = 0.75 - 0.80, and its physicochemical properties were studied. The molecular weight of the MPO is about 150 kD. The MPO was assayed for amino acid content. We used substrate mixture containing phenol, 4-aminoantipyrine, and H2O2 to detect 10(-10) M of the enzyme. The MPO was localized in rat blood neutrophils using polyclonal anti-MPO antibodies and secondary fluorescein isothiocyanate-labeled antibodies. Immunofluorimetric assay (IFMA) was developed for quantitative measurement of the MPO. The MPO and leukocytes can iodinate BSA using NaI or thyroxine as the source of iodine.


[Severe visual loss caused by autoimmune retinopathy].
Autoimmune retinopathy (AIR) is a rare disorder which may present as a paraneoplastic syndrome. AIR is associated with the presence of anti-retinal antibodies. These antibodies are assumed to cause damage to the retina, resulting in progressive vision loss. A 74-year-old man visited the ophthalmologist with a serious, progressive loss of vision, without any noteworthy abnormalities at routine ophthalmological examination. The electroretinogram was characteristic of loss of photoreceptor function. Anti-retinal antibodies against recoverin were detected in serum. After referral to an internist on account of a suspected diagnosis of paraneoplastic AIR, the patient was diagnosed with a lung carcinoma, confirming the diagnosis of cancer-associated paraneoplastic AIR. An unexplained loss of vision is highly suggestive of paraneoplastic AIR, even in patients without a known malignancy. Laboratory techniques for the detection of the anti-retinal antibody against recoverin have recently been implemented in the Netherlands, facilitating the diagnosis of AIR.


Screwworm eradication in the Americas.
The screwworm fly, Cochliomyia hominivorax (Coquerel), is a parasite that attacks all warm-blooded animals including humans. This parasite has caused significant losses to the livestock industries of the Americas. Since the screwworm eradication program was initiated in the Southeastern United States in 1957, the eradication program has successfully progressed to its current location in Panama. A variety of technologies and tools have been used in the eradication programs. The cooperative agreement has been a significant tool in the success of the program. In the United States, the State-Federal Cooperative programs provided the mechanism for carrying out screwworm eradication. Once screwworms were eradicated from the United States, the need to expand the program internationally, in order to protect the United States, became evident. A cooperative agreement created the Mexico-United States Commission for the Eradication of Screwworms (Commission). Commission-Guatemala and Commission-Belize Cooperative Agreements were used to eradicate screwworms from these countries. Followup programs in El Salvador, Honduras, Nicaragua, Costa Rica, and Panama were implemented by cooperative agreements between the United States Department of Agriculture and the individual countries. The positive and negative aspects, as well as the necessary elements of successful cooperative agreements, are discussed.


Quality improvement in hospitals in the Russian Federation, 2000-2016: a systematic review.
We reviewed published evidence on quality improvement in hospitals in the Russian Federation since 2000. We used three data sources: MEDLINE, 'Rossiiskaia Meditsina' (Central Scientific Medical Library), and elibrary.ru using specific search terms. No language or study design restrictions were imposed. In total, 1717 articles were identified; 51 met the inclusion criteria and were thematically analysed. Russian legislation, government acts and grey literature were sourced to contextualise identified themes. Since 2010, the Federal Ministry of Health has increasingly sought to improve quality of care, providing additional resources and new initiatives across the health system. These include clinical practice guidelines, pay for performance schemes, electronic medical records, more specialist care, paraclinical care, and quality control systems. Quality of care, increasingly a concern of the Russian government, is said to be improving. Yet most initiatives have rarely been evaluated. This reflects the limited capacity for health services research in Russia. It seems likely that the full potential for improvements in quality of care in Russia is still to be realised.


[Mechanism of cardiac hypertrophy via diacylglycerol-sensitive TRPC channels].
Activation of Ca(2+) signaling in cardiomyocytes induced by receptor stimulation or mechanical stress has been implicated in the development of cardiac hypertrophy. However, it is still unclear how intracellular Ca(2+) targets specifically decode the alteration of intracellular Ca(2+) concentration ([Ca(2+)](i)) on the background of the rhythmic Ca(2+) increases required for muscle contraction. In excitable cardiomyocytes, changes in the frequency or amplitude of Ca(2+) transients evoked by Ca(2+) influx-induced Ca(2+) release have been suggested to encode signals for induction of hypertrophy, and a partial depolarization of plasma membrane by receptor stimulation will increase the frequency of Ca(2+) oscillations. We found that activation of diacylglycerol (DAG)-responsive canonical transient receptor potential (TRPC) subfamily channels (TRPC3 and TRPC6) mediate membrane depolarization induced by G(q) protein-coupled receptor stimulation. DAG-mediated membrane depolarization through activation of TRPC3/TRPC6 channels increases the frequency of Ca(2+) spikes, leading to activation of calcineurin-dependent signaling pathways. Inhibition of either TRPC3 or TRPC6 completely suppressed agonist-induced hypertrophic responses, suggesting that TRPC3 and TRPC6 form heterotetramer channels. Furthermore, we found that hypertrophic agonists increase the expression of TRPC6 proteins through activation of G(12) family proteins, leading to amplification of DAG-mediated hypertrophic signaling in cardiomyocytes. As heart failure proceeds through cardiac hypertrophy, TRPC3/TRPC6 channels may be a new therapeutic target for heart failure.


Variation in salinity tolerance, gill Na+/K+-ATPase, Na+/K+/2Cl- cotransporter and mitochondria-rich cell distribution in three salmonids Salvelinus namaycush, Salvelinus fontinalis and Salmo salar.
We compared seawater tolerance, gill Na(+)/K(+)-ATPase and Na(+)/K(+)/2Cl(-) cotransporter (NKCC) abundance, and mitochondria-rich cell (MRC) morphology of three salmonids, lake trout Salvelinus namaycush, brook trout Salvelinus fontinalis and Atlantic salmon Salmo salar. They were transferred directly from 0 p.p.t. (parts per thousand; freshwater) to 30 p.p.t. seawater, or transferred gradually from 0 to 10, 20 and 30 p.p.t. at 1-week intervals and kept in 30 p.p.t. for 3 weeks. The survival rates of lake trout, brook trout and Atlantic salmon were 80%, 50% and 100% following direct transfer, and 80%, 100% and 100% during gradual transfer, respectively. Plasma Na(+), K(+) and Cl(-) concentrations in surviving lake trout increased rapidly and remained at high levels in 30 p.p.t. of both direct and gradual transfer, whereas those in brook trout showed a transient increase following direct transfer but did not change significantly during gradual transfer. Only minor changes in plasma ions were observed in Atlantic salmon smolts in both direct and gradual transfer. These results suggest that lake trout retains some degree of euryhalinity and that brook trout possesses intermediate euryhalinity between lake trout and Atlantic salmon smolts. Gill Na(+)/K(+)-ATPase activity of lake trout and brook trout increased in seawater, whereas that of Atlantic salmon smolts was already upregulated in freshwater and remained high after seawater exposure. NKCC abundance was upregulated in parallel with gill Na(+)/K(+)-ATPase activity in each species. Immunocytochemistry with anti-Na(+)/K(+)-ATPase alpha-subunit and anti-NKCC revealed that the two ion transporters were colocalized on the basolateral membrane of gill MRCs. Immunopositive MRCs were distributed on both primary filaments and secondary lamellae in all three species kept in freshwater; following transfer to seawater this pattern did not change in lake trout and brook trout but lamellar MRCs disappeared in Atlantic salmon. Previous studies on several teleost species have suggested that filament and lamellar MRCs would be involved in seawater and freshwater acclimation, respectively. However, our results in lake trout and brook trout suggest that lamellar MRCs could be also functional during seawater acclimation.