Multiresidue method for pesticide residue analysis in food of animal and plant origin based on GC or LC and MS or MS/MS.
A multiresidue method based on GC or LC and MS or MS/MS for the determination of 204 pesticides in diverse food matrixes of animal and plant origin is described. The method can include different stages of cleanup according to the chemical characteristics of each sample. Samples were extracted using accelerated solvent extraction. Those with a high fat content or that contained chlorophyll required further purification by gel permeation chromatography and/or SPE (ENVI-Carb). The methodology developed here was fully validated; the LOQs for the 204 pesticides are presented. The LOQ values lie between 0.01 to 0.02 mg/kg. However, in some cases, mainly in baby food, they were as low as 0.003 mg/kg, thereby meeting European Union requirements on maximum residue levels for pesticides, as outlined in European regulation 396/2005 and the Commission Directive 2003/13/EC. The procedure has been accredited for a wide scope of pesticides and matrixes by the Spanish Accreditation Body (ENAC) following ISO/IEC 17025:2005, as outlined in ENAC technical note NT-19.


Intracellular accumulation of potassium and glutamate specifically enhances survival of Escherichia coli in seawater.
The high resistance of Escherichia coli grown in saline media to seawater was suppressed by an osmotic down-shock. The shock released several molecules into the medium, including potassium, glutamate, and glycine betaine when cells were previously grown in the presence of this osmolyte. Incubation of such sensitized cells in a solution containing K+ (80 mM) and glutamate (50 mM) at pH 7.4 restored their resistance to seawater up to a level close to that observed initially. The protective effect was partly due to the rapid accumulation of K+; a significant exponential relationship between intracellular concentration of K+ and resistance to seawater was observed. Glutamate was accumulated more slowly and progressively completed the action of K+. These data emphasize the specific influence of potassium glutamate on osmotically stressed E. coli cells. They confirm that regulation of osmotic pressure and, probably, of intracellular pH strongly enhances survival of E. coli in seawater. Osmotic fluctuations in waters carrying enteric bacteria from intestines to seawater, together with variations in their K+ and amino acid contents, could modify the ability of cells to survive in marine environments. These results demonstrate the need to strictly control conditions (K+ content, temperature) used to wash cells before their transfer to seawater microcosms. They suggest that the K+ and glutamate contents of media in which E. coli cells are transported to the sea can influence their subsequent survival in marine environments.


Carnitines increase plasma levels of adenosine and ATP in humans.
In order to help to clarify the mode of action of carnitine derivatives, plasma levels of adenosine, ATP and inosine were evaluated following the infusion of 0.75, 0.50 and 0.25 mg/kg/min propionyl-L-carnitine (PLC) for 30 min in patients affected with peripheral arterial disease. Moreover, the effects of 0.75 mg/kg/min acetyl-L-carnitine (ALC) and L-carnitine (LC) were studied in the same conditions. Finally, the activity of 7.5 mg/kg/min PLC administered for 3 min was also evaluated. PLC and ALC produced a significant increase in plasma levels of adenosine and ATP, whereas LC induced less relevant changes. The administration of the compounds did not affect the adenosine/inosine ratio. Peak plasma levels of adenosine preceded in any case those of ATP. The possibility can be suggested that the pharmacological activity of PLC, ALC, and LC may be mediated, at least in part, by an interference with the endogenous purine system. Since these effects may be related to physiological mechanisms of tissue protection, new pharmacological perspectives for the compounds may arise.


[Vascular endoprostheses in the treatment of intracranial aneurysms: a systematic review].
To evaluate the effectiveness and safety of endovascular prostheses (stents) in the treatment of intracranial aneurysms. We performed a systematic review of the literature using the databases Medline, Embase, HTA, and the Cochrane Library. Relevant articles were selected by reading the abstracts found in the search and applying a series of inclusion and exclusion criteria. Afterwards, the entire text was read critically and the results were extracted and analyzed. Only ten series fulfilled the inclusion criteria established, and different methodological limitations were observed. A total of 287 lesions were treated; 76 of these were wide-neck aneurysms, and total or nearly total occlusion was achieved in approximately 77% of cases. Among the 281 patients included, 14 deaths (4.9%) and 48 complications (17.1%) occurred; 55% of the complications were of thromboembolic origin. Moreover, in 71 cases (24.7%) there were difficulties in placing the stent, stent displacement, or other technical problems. Despite the data reported in this review, the lack of methodologically sound studies with long-term follow-up as well as the methodological limitations and heterogeneity found in the observational studies included in this review make it impossible to reach definitive, categorical conclusions regarding the efficacy and safety of this technique. Therefore, it would be recommendable to initiate randomized clinical trials to compare this technique with other treatment options, using appropriate and homogeneous criteria for the selection of both patients and centers together with strict follow-up, registering, and evaluation of the results obtained.


Chemical composition of potato tubers: the effect of cultivars and growth conditions.
The aim of the study involved evaluating the chemical composition of tubers of five potato cultivars that were grown under the same cultural practices in soils with low, medium, and high availability of phosphorus. The experimental designs corresponded to a randomized block with four replicates. Tuber samples were analyzed in terms of moisture, ash, protein, lipid, total sugar, fiber, starch, and phosphorus contents. The results suggested that increased availability of phosphorus in soil allowed the production of tubers with higher dry matter content, lower total sugar content, and a higher percentage of starch and protein. Hence, the aforementioned parameters constitute important factors corresponding to the nutritional and industrial quality of potatoes. Increased phosphorus availability in soil can promote significant changes in the composition of potato tubers, and thereby in potential uses of tubers.


Properties of the antiferromagnetic selenite MnSeO3 and its non-magnetic analogue ZnSnO3 from first principles calculations.
We report the properties of the antiferromagnetic selenite MnSeO3 and the non-magnetic analogue ZnSeO3, based on first principles calculations. These compounds are rare examples of ABO3 perovskites with a tetravalent A-site and a divalent B-site. The electronic structure is discussed in the context of the bonding and crystal structure. There is cross-gap hybridization between the O p states that form the valence bands of these compounds and the unoccupied p states of Se, reflecting the lone pair physics that leads to the strong off-centering of Se from the perovskite A-site. The G-type antiferromagnetism of MnSeO3 is a local moment in nature arising from high spin [Formula: see text] with short range interactions. Additionally, there is an interesting spin-dependent hybridization of Mn d and O p states analogous to that in colossal magnetoresistance manganites.


Foundry air contaminants from green sand molds.
The major gases evolved from foundry molds have been determined in the laboratory. The principal gases evolved during pouring and shakeout of castings include hydrogen, carbon monoxide, carbon dioxide, methane and other low molecular weight hydrocarbons with smaller amounts of ammonia, hydrogen cyanide, and sulfur dioxide.


Antioxidants as therapeutics in the intensive care unit: Have we ticked the redox boxes?
Critically ill patients are under oxidative stress and antioxidant administration reasonably emerged as a promising approach to combat the aberrant redox homeostasis in this patient cohort. However, the results of the antioxidant treatments in the intensive care unit are conflicting and inconclusive. The main objective of the present review is to highlight some inherent, yet widely overlooked redox-related issues about the equivocal effectiveness of antioxidants in the intensive care unit, beyond methodological considerations. In particular, the discrepancy in the literature partially stems from: (1) the largely unspecified role of reactive species in disease onset and progression, (2) our fragmentary understanding on the interplay between inflammation and oxidative stress, (3) the complex spatiotemporal specificity of in vivo redox biology, (4) the pleiotropic effects of antioxidants and (5) the divergent effects of antioxidants according to the temporal administration pattern. In addition, two novel and sophisticated practices with promising pre-clinical results are presented: (1) the selective neutralization of reactive species in key organelles after they are formed (i.e., in mitochondria) and (2) the targeted complete inhibition of dominant reactive species sources (i.e., NADPH oxidases). Finally, the reductive potential of NADPH as a key pharmacological target for redox therapies is rationalized. In light of the above, the recontextualization of knowledge from basic redox biology to translational medicine seems imperative to perform more realistic in vivo studies in the fast-growing field of critical care pharmacology.


Severe hypoglycaemia is a major predictor of incident diabetic retinopathy in Japanese patients with type 2 diabetes.
Hypoglycaemia is a common complication in diabetes patients. However, its relationship with retinopathy has not been well documented in patients with type 2 diabetes (T2D). This study aimed to investigate the associations between hypoglycaemia and the incidence and progression of diabetic retinopathy (DR). In this longitudinal cohort study, which was part of the Japan Diabetes Complications Study (JDCS), adult patients with T2D were recruited at 59 diabetes clinics across Japan. Their history of hypoglycaemia was assessed by standardized self-reported questionnaires. Severe hypoglycaemia was defined as having at least one episode with coma requiring an outpatients visit or hospitalization. Adjusted hazard ratios (HRs) for incidence and progression of DR over 8 years of follow-up were determined. Of 1221 patients without DR, 127 (10.4%) had experienced non-severe hypoglycaemia within the previous year, whereas 10 (0.8%) reported severe hypoglycaemia episodes. During the 8-year follow-up involving 8492 person-years, 329 patients developed DR. In 410 patients with prevalent DR, the adjusted HRs for incident DR were 4.35 (95% CI: 1.98-9.56; P<0.01) and, for progression of DR, 2.29 (95% CI: 0.45-11.78; P=0.32) with severe hypoglycaemia. Having a history of severe hypoglycaemia was one of the strongest predictors of incident DR in patients with T2D, with a fourfold increased risk. Identifying patients with greater risks of DR based on their history of hypoglycaemia may help to personalize risk evaluation in patients with diabetes.


Dynamics of enhanced tracer diffusion in suspensions of swimming eukaryotic microorganisms.
In contexts such as suspension feeding in marine ecologies there is an interplay between brownian motion of nonmotile particles and their advection by flows from swimming microorganisms. As a laboratory realization, we study passive tracers in suspensions of eukaryotic swimmers, the alga Chlamydomonas reinhardtii. While the cells behave ballistically over short intervals, the tracers behave diffusively, with a time-dependent but self-similar probability distribution function of displacements consisting of a gaussian core and robust exponential tails. We emphasize the role of flagellar beating in creating oscillatory flows that exceed brownian motion far from each swimmer.


Chemotherapy response is an important predictor of local recurrence in Ewing sarcoma.
Local recurrence in Ewing sarcoma is associated with a poor prognosis. The purpose of the study was to determine the factors that predict local recurrence after surgical treatment of the primary tumor. Between 1990 and 2001, 64 patients underwent surgical resection of Ewing sarcoma. Surgical margins were assessed histologically and radiologically. Response to preoperative chemotherapy was determined by detailed specimen mapping. Local recurrence-free survival (LRFS) was calculated by Kaplan-Meier analysis. Multivariate analysis was performed with the Cox proportional hazards model. A number of factors were found to be associated with local recurrence on univariate analysis. Patients with a good response to chemotherapy (> or = 90% tumor necrosis), had superior LRFS at 5 years (86% vs 51%, P = .015). Central site of disease was associated with an increased rate of recurrence. The LRFS at 5 years was 50% for the chest wall, 74% for pelvic/scapular, and 86% for extremity tumors (P = .083). Positive surgical margin was not a strong predictor of recurrence (P = .72). A critical analysis of minimal surgical margin based on preoperative magnetic resonance imaging (MRI) and computed tomography (CT) scans also failed to reveal an association between margin and local recurrence. In multivariate analysis, the 2 independent predictors of local recurrence were histological response to chemotherapy and central site of disease. Local recurrence after surgical resection is a complex phenomenon. An important predictive factor is the response to chemotherapy. In the current study, this seems to have the largest impact. Central site of disease may be a second independent predictive factor.


Oral glucocorticoid therapy and all-cause and cause-specific mortality in patients with rheumatoid arthritis: a retrospective cohort study.
Previous studies of glucocorticoid (GC) therapy and mortality have had inconsistent results and have not considered possible perimortal bias-a type of protopathic bias where illness in the latter stages of life influences GC exposure, and might affect the observed relationship between GC use and death. This study aimed to investigate all-cause and cause-specific mortality in association with GC therapy in patients with rheumatoid arthritis (RA), and explore possible perimortal bias. A retrospective cohort study using the primary care electronic medical records. Oral GC exposure was identified from prescriptions. Mortality data were obtained from the UK Office for National Statistics. Multivariable Cox proportional hazards regression models assessed the association between GC use models and death. Several methods to explore perimortal bias were examined. The cohort included 16,762 patients. For ever GC use there was an adjusted hazard ratio for all-cause mortality of 1.97 (95 % CI 1.81-2.15). Current GC dose of below 5 mg per day (prednisolone equivalent dose) was not associated with an increased risk of death, but a dose-response association was seen for higher dose categories. The association between ever GC use and all-cause mortality was partly explained by perimortal bias. GC therapy was associated with an increased risk of mortality for all specific causes considered, albeit to a lesser extent for cardiovascular causes. GC use was associated with an increased risk of death in RA, at least partially explained by perimortal bias. Importantly, GC doses below 5 mg were not associated with an increased risk of death.


Primary Angioplasty for the Treatment of Acute ST Elevated Myocardial Infarction: Single Centre Experience.
Worldwide primary angioplasty is a recommended strategy of reperfusion in patient with acute myocardial infarction as because it ensures reperfusion of the infarct-related vessels more than 90% whereas, with thrombolytics it is only 60-70%. This retrospective observational study includes all patients treated with primary angioplasty at United Hospital from Between March 2007 to January 2011. Total 114 consecutive patients with acute myocardial infarction were treated with primary angioplasty included. Those presented beyond 12 hours of onset of chest pain, in cardiogenic shock, resuscitate and intubated before the procedure were excluded from the study. Majority (89%) of the patient were male, age was minimum 30 years and maximum 90 years, 41.5% were diabetics, 58.4% were hypertensive, 43.5% were dyslipidaemic, 17% were smoker, 29.3% with positive family history. Fifty seven percent patients presented with anterior MI , 42 % with inferior MI and 1% with lateral MI. Left anterior descending (LAD) is the most common vessel involved (57%), followed by Right coronary artery (RCA) 31%, Left circumflex artery (LCX) 8 %, Ramus 1.3% and Graft vessel 2.7%. Our door to balloon time was minimum 23 min, maximum 184 min. We used drug eluting stents for most of the patients, GP IIb- IIIa receptor blockers used in 50% cases and thrombus suction device were used when indicated. We faced complications like arrhythmias in 24%, hypotension in18%, no flow or slow flow in 45%, cardiac arrest in 3% and coronary perforation in 1%. Our overall survival was 97.9%. Primary angioplasty is an emerging area in context of our country. Many of the new centers start this novel strategy which helps to save many lives Primary angioplasty is feasible and safe method of reperfusion in patient with acute myocardial infarction in our center. With the help of our initial experience we can perform PAMI with confidence to those who can afford and who need most.


Cognitive Impact of Deep Brain Stimulation on Parkinson's Disease Patients.
Subthalamic nucleus (STN) or globus pallidus interna (GPi) deep brain stimulation (DBS) is considered a robust therapeutic tool in the treatment of Parkinson's disease (PD) patients, although it has been reported to potentially cause cognitive decline in some cases. We here provide an in-depth and critical review of the current literature regarding cognition after DBS in PD, summarizing the available data on the impact of STN and GPi DBS as monotherapies and also comparative data across these two therapies on 7 cognitive domains. We provide evidence that, in appropriately screened PD patients, worsening of one or more cognitive functions is rare and subtle after DBS, without negative impact on quality of life, and that there is very little data supporting that STN DBS has a worse cognitive outcome than GPi DBS.


Inspiratory muscle training may increase peak inspiratory flow in chronic obstructive pulmonary disease.
When choosing a specific inhalation device for a chronic obstructive pulmonary disease (COPD) patient, the internal airflow resistance and the ability of the patient to overcome it and to create an optimal inspiratory flow are essential. The purpose of the present study was to investigate: (1) the peak inspiratory flow (PIF) that a patient with COPD can generate while breathing through two dry powder inhalers and (2) whether in patients with low PIF specific inspiratory muscle training (SIMT) will increase the PIF and exceed the minimal PIF that is considered necessary to guarantee optimal lung deposition of the drug. Inspiratory muscle strength and PIFs were measured in 60 patients with COPD. Then 28 patients with severe COPD and low PIF were randomized to receive SIMT or to a control group. With the Turbuhaler, 12 patients (20%) could not generate the optimal flow of 60 l/min. PIF correlated very well with maximal inspiratory mouth pressure (PI(max)) for the Diskus and the Turbuhaler, as well as for both males and females (p < 0.001). Following the training period, there was a statistically significant increase in the PI(max) in the training group. This increase was associated with a significant increase in the PIF. All patients overcame the minimal threshold PIF following the training. Some patients with severe COPD are not able to generate adequate flow to secure optimal lung deposition of the inhalation with the Turbuhaler. SIMT improves inspiratory muscle strength as well as PIF. Following 8 weeks of training, the optimal PIF enabling adequate lung deposition of the drug was attained in all the trained patients.


Perceived and Objective Measures of Neighborhood Environment for Physical Activity Among Mexican Adults, 2011.
Environmental supports for physical activity may help residents to be physically active. However, such supports might not help if residents' perceptions of the built environment do not correspond with objective measures. We assessed the associations between objective and perceived measures of the built environment among adults in Cuernavaca, Mexico, and examined whether certain variables modified this relationship. We conducted a population-based (n = 645) study in 2011 that used objective (based on geographic information systems) and perceived (by questionnaire) measures of the following features of the built environment: residential density, mixed-land use, intersection density, and proximity to parks and transit stops. We used linear regression to assess the adjusted associations between these measures and to identify variables modifying these relationships. Adjusted associations were significant for all features (P < .05) except intersection density and proximity to transit stops. Significantly stronger associations between perceived and objective measures were observed among participants with low socioeconomic status, participants who did not own a motor vehicle or did not meet physical activity recommendations, and participants perceiving parks as safe. Perceived measures of residential density, mixed-land use, and proximity to parks are associated with objective environmental measures related to physical activity. However, in Mexico, it should not be assumed that perceived measures of intersection density and proximity to transit stops are the same as objective measures. Our results are consistent with those from high-income countries in that associations between perceived and objective measures are modified by individual sociodemographic and psychosocial factors.


Ruling out nosocomial transmission of Cryptosporidium in a renal transplantation unit: case report.
Cryptosporidium spp. is a ubiquitous parasite affecting humans as well as domestic and wild vertebrates, causing diarrhea in both immunocompetent and immunocompromised hosts worldwide. Its transmission occurs primarily by the fecal-oral route. In humans, C. parvum and C. hominis are the most prevalent species, whereas immunocompetent and immunocompromised individuals can also be infected by other zoonotic species. Renal transplant patients are prone to develop cryptosporidiosis, which can induce severe and life-threatening diarrhea. We report here a series of nearly concomitant cases of acute symptomatic cryptosporidiosis in three renal transplant patients attending the Strasbourg University Hospital Nephrology Unit. The clinical presentation was persistent diarrhea and acute renal failure. The diagnosis was confirmed by microscopic stool examination using a modified Ziehl-Neelsen staining method and species identification by molecular tools. All patients were treated with nitazoxanide and recovered from diarrhea after 14 days of therapy. Genotypic species identification was not consistent with an epidemic context, thus underlining the need for genotyping to monitor at risk patients.


Calcium phosphate/octadecyl-quatemized carboxymethyl chitosan nanoparticles: an efficient and promising carrier for gene transfection.
Calcium phosphate (CaP) has been widely used as the vector for gene transfection in the past three decades. However, clinical application is still not popular due to the poor-controlling of DNA/CaP complexes preparation, cytotoxicity and its low transfection efficiency. In this study, a novel amphipathic octadecyl-quatemized carboxymethyl chitosan (OQCMC) derivative from chitosan was combined with calcium phosphate to synthesize CaP/OQCMC nanoparticles (CaP/OQCMC NPs). The nanoparticles were 122-177 nm in diameter exhibited neutral zeta potential (from -0.115 mV to 0.216 mV), and they were applied as DNA vectors for DNA loading and in vitro transfection. The results showed that CaP/OQCMC NPs displayed high DNA loading capacity and enhanced transfection efficiency with extremely low cytotoxicity. In addition, both CaP and OQCMC are biocompatible and biodegradable, thus the as-prepared CaP/OQCMC NPs are promising in gene delivery.


Total knee arthroplasty with modular rotating-platform hinge.
Third-generation modular rotating hinged knee systems are now widely available. The S-ROM rotating hinge features slotted and splined stems for torsional stability, and metaphyseal filling and loading sleeves for the bony defects encountered in revision total knee arthroplasty (TKA). Primary indications for a hinge include medial or lateral collateral loss, massive bone loss, and metaphysis and cortical shell, which includes collateral origins or insertions, and severe flexion gap imbalance requiring a link system for stability. Indications for a hinge in primary TKA include patients with neuromuscular deficits such as polio or flail knee, who require the hyperextension stop. Reported midterm results are excellent with no mechanical failures and positive bone remodeling in 65 patients.


Transfer of genes to chondrocytic cells of the lumbar spine. Proposal for a treatment strategy of spinal disorders by local gene therapy.
In the current study, chondrocytic cells from bovine intervertebral end plates were cultivated in vitro and modified genetically. The authors intended to perform isolation and cultivation of cells from bovine end plates of the spine. They also intended to show, in principle, the feasibility of introducing exogenous genes into chondrocytic cells from bovine intervertebral end plates by way of retroviral vectors. The involvement of cytokines in the destruction of articular cartilage is established. It appears possible that similar mechanisms may play a role in intervertebral disc degeneration and other spinal disorders. Conventional medication and surgery of intervertebral disc degeneration addresses neither the pathophysiology nor the chronicity of the disease. Therapeutic proteins carry great potential as locally produced drugs after transfer of their cognate genes to the sites of interest. Vertebral end plate tissue was obtained from bovine os coccygis. Chondrocytic cells were isolated and cultured in vitro. The bacterial beta-galactosidase (LacZ) gene and, alternatively, the complementary DNA (DNA copy of the mRNA) of the human interleukin-1 receptor antagonist were introduced into the isolated cells by retrovirus mediated gene transfer. beta-galactosidase activity was determined by staining, and interleukin-1 receptor antagonist protein was quantitated by enzyme-linked immunosorbent assay. Isolation and cultivation of chondrocytic end plate cells is possible. Native cells continue to grow in culture for more than 2 months. Transfer of the beta-galactosidase gene to cultured cells resulted in approximately 1% beta-galactosidase positive cells. Transfer of the interleukin-1 receptor antagonist complementary DNA resulted in the production of 24 ng/ml/10(6) cells interleukin-1 receptor antagonist protein in 48 hours. The introduction of exogenous therapeutic genes into cells from the intervertebral end plate opens the possibility for a local gene-based treatment of intervertebral disc degeneration. This approach avoids some of the shortcomings of conventional drug- and surgery-based treatments and has the potential to be specific, effective, and appropriate to the chronicity of the disease.


Origin of Photovoltage Enhancement via Interfacial Modification with Silver Nanoparticles Embedded in an a-SiC:H p-Type Layer in a-Si:H Solar Cells.
We used silver nanoparticles (Ag-NPs) embedded in the p-type semiconductor layer of hydrogenated amorphous silicon (a-Si:H) solar cells in the Schottky barrier contact design to modify the interface between aluminum-doped ZnO (ZnO:Al, AZO) and p-type hydrogenated amorphous silicon carbide (p-a-SiC:H) without plasmonic absorption. The high work function of the Ag-NPs provided a good channel for the transport of photogenerated holes. A p-type nanocrystalline SiC:H layer was used to compensate for the real surface defects and voids on the surface of Ag-NPs to reduce recombination at the AZO/p-type layer interface, which then enhanced the photovoltage of single-junction a-Si:H solar cells to values as high as 1.01 V. The Ag-NPs were around 10 nm in diameter and thermally stable in the p-type a-SiC:H film at the solar-cell process temperature. We will also show that a wide range of photovoltages between 1.01 and 2.89 V could be obtained with single-, double-, and triple-junction solar cells based on the single-junction a-Si:H solar cells with tunable high photovoltage. These solar cells are suitable photocathodes for solar water-splitting applications.


[Construction and culture conditions of dextransucrase-secreting engineered strain].
Dextransucrase was a glucosyltransferases catalyzing the transfer of D-glucopyranosyl units from sucrose to synthesize alpha-glucans or oligosaccharides. dexYG gene (GenBank Accession No. DQ345760), encoding the dextransucrase from Leuconstoc mesenteriodes 0326, was subcloned into expression plasmid pET28a(+). The recombinant plasmid was then transformed into E. coli BL21 (DE3). Kanamycin resistant transformants were selected and verified by restriction endonuclease assay. Dextransucrase could be efficiently expressed in engineered strain BL21 (DE3)/pET28-dexYG by Isopropyl beta-D-thiogalactopyranoside (IPTG) induction, although the growth of E. coli host was inhibited during induction. Recombinant enzyme producing conditions such as induction time, IPTG concentration, incubation temperature, cell density (OD(600)) and pH value were studied. The optimum conditions for producing dextransucrase were as follows: incubation at 25 degrees C, 0.5 mmol/L Isopropyl beta-D-thiogalactopyranoside (IPTG) induction at cell density (OD(600)) of 1.0 for 5h, pH 6.0. Under these conditions, the recombinant dextransucrase activity was increased from 5.39U/mL to 35.62 U/mL. The highest activity under the optimal culture conditions after 5h induction in medium with pH 6.0 was 3.5 times as that of in Luria-Bertani medium without pH-adjustment. Moreover, the pH value was one of the main reasons that caused the degradation of enzyme in the later stage of induction. These results showed that dextransucrase could be efficiently heterologous expressed in E. coli and a strong dextransucrase activity had been detected.


Autophagy, apoptosis, vitamin D, and vitamin D receptor in hepatocellular carcinoma associated with hepatitis C virus.
The aims of this study were to investigate the interplay between autophagy and apoptosis and to investigate the association between both of autophagy and apoptosis and vitamin D and its receptor in hepatitis C virus (HCV) viral infection and its implication in the progression into hepatocellular carcinoma (HCC).A cross-sectional study where serum levels of microtubule-associated protein 1A/1B-light chain 3 (LC3); marker of autophagy, caspase-3; marker of apoptosis, vitamin D3 and vitamin D receptor (VDR) were measured in healthy subjects as well as HCV and HCV-HCC patients using enzyme-linked immunosorbent assay technique.Collectively, the liver profile revealed hepatic dysfunctions in HCV patients with or without HCC. A significant reduction in the serum concentration levels LC3 and caspase-3 were observed referring to the down regulation of autophagy and host-mediated apoptosis in HCV patients with or without HCC. Deficiency of vitamin D and decreased levels of its receptor were observed in HCV and HCV-HCC patients.The perturbation in vitamin D/VDR axis, which modulates both of autophagy and apoptosis in HCV infection, may point out to its involvement and implication in the pathogenesis of HCV infection and the development of HCV-related HCC. Therefore, supplementation with vitamin D may not be the only solution to restore the vital biological functions of vitamin D but VDR-targeted therapy may be of great importance in this respect.


Giant hydatid cyst in the posterior fossa of a child.
The hydatid cyst (HC) is endemic in Mediterranean region including Syria. The central nervous system is involved in 2-3% of cases. HC in cerebellum is very rare. We report a case that presented as an emergency for high intracranial pressure and deteriorating Glascow coma scale. Close monitoring and precise surgical management using Dowling's technique resulted in very good outcome with full recovery. We highlight the need for very careful surgical treatment because cyst rupture and secondary hydatidosis due to spillage of the cyst contents can dramatically worsen the outcome. HC should be taken into consideration in countries where hydatid infestation is endemic.


Role of alpha 2-macroglobulin in phagocytosis of group A and C streptococci.
Binding of alpha 2-macroglobulin (alpha 2M) to streptococci and its effects on phagocytosis were investigated. Two types of streptococcal binding sites for alpha 2M were observed: Streptococcus pyogenes from human infections interacted only with native alpha 2M whereas S. dysgalactiae from bovine and S. equi from equine infections bound only a complex of alpha 2M with trypsin (alpha 2M-T). Preincubation of S. pyogenes with native alpha 2M substantially enhanced their phagocytosis by human polymorphonuclear neutrophils (PMN) whereas preincubation with alpha 2M-T was without any effect. On the other hand, incubation of S. dysgalactiae and S. equi with alpha 2M-T markedly reduced their phagocytosis by PMN from the respective host species. Native alpha 2M did not affect the phagocytosis of these streptococci. Digestion of the streptococcal binding sites for alpha 2M and alpha 2M-T pronase abolished the enhancement of phagocytosis of S. pyogenes by native alpha 2M as well as the inhibition of phagocytosis of S. dysgalactiae and S. equi by alpha 2M-T. Thus, binding of alpha 2M or its complexes appeared to play a role in streptococcal pathogenicity.


Role for phospholipid acyl chains and cholesterol in pulmonary infections and inflammation.
Bacterial and viral respiratory tract infections result in millions of deaths worldwide and are currently the leading cause of death from infection. Acute inflammation is an essential element of host defense against infection, but can be damaging to the host when left unchecked. Effective host defense requires multiple lipid mediators, which collectively have proinflammatory and/or proresolving effects on the lung. During pulmonary infections, phospholipid acyl chains and cholesterol can be chemically and enzymatically oxidized, as well as truncated and modified, producing complex mixtures of bioactive lipids. We review recent evidence that phospholipids and cholesterol and their derivatives regulate pulmonary innate and adaptive immunity during infection. We first highlight data that oxidized phospholipids generated in the lung during infection stimulate pattern recognition receptors, such as TLRs and scavenger receptors, thereby amplifying the pulmonary inflammatory response. Next, we discuss evidence that oxidation of endogenous pools of cholesterol during pulmonary infections produces oxysterols that also modify the function of both innate and adaptive immune cells. Last, we conclude with data that n-3 polyunsaturated fatty acids, both in the form of phospholipid acyl chains and through enzymatic processing into endogenous proresolving lipid mediators, aid in the resolution of lung inflammation through distinct mechanisms. Unraveling the complex mechanisms of induction and function of distinct classes of bioactive lipids, both native and modified, may hold promise for developing new therapeutic strategies for improving pulmonary outcomes in response to infection.


Glucose-6-phosphate dehydrogenase deficiency in internationally adopted children.
There are conflicting guidelines about screening of internationally adopted children for glucose-6-phosphate dehydrogenase (G6PD) deficiency, a common genetic disorder. In a multi-ethnic population of 2,169 internationally adopted children, we found that the prevalence of G6PD deficiency was 1.6% overall and 2.2% in males. Prevalence differed by country or region of origin, ranging from 0 to 13% overall and 0 to 22% in males. The prevalence in females was 1%. A diagnosis of G6PD deficiency informs the treatment of malaria and enables education and counseling to prevent morbidity and mortality from G6PD deficiency. Screening for G6PD deficiency should be strongly considered for internationally adopted children.


Multihit mode direct-detection laser radar system using a Geiger-mode avalanche photodiode.
In this paper, a direct-detection laser radar system that uses a Geiger-mode avalanche photodiode (GAPD) of relatively short dead time (45 ns) is described. A passively Q-switched microchip laser is used as a laser source and a compact peripheral component interconnect system, which includes a time-to-digital converter (TDC), is set up for fast signal processing. With both the GAPD and the TDC functioning multistop acquisition, the system operates in a multihit mode. The software for the three-dimensional visualization and an algorithm for the removal of noise are developed. It is shown that the single-shot precision of the system is approximately 10 cm (sigma) and the precision is improved by increasing the number of laser pulses to be averaged so that the precision of approximately 1 cm (sigma) was acquired with more than 150 laser pulses scattered from the target. The accuracy of the system is measured to be 12 cm when the energy of the emitted laser pulse varies with a factor of 7.


Retro-MoRFs: identifying protein binding sites by normal and reverse alignment and intrinsic disorder prediction.
Many cell functions in all living organisms rely on protein-based molecular recognition involving disorder-to-order transitions upon binding by molecular recognition features (MoRFs). A well accepted computational tool for identifying likely protein-protein interactions is sequence alignment. In this paper, we propose the combination of sequence alignment and disorder prediction as a tool to improve the confidence of identifying MoRF-based protein-protein interactions. The method of reverse sequence alignment is also rationalized here as a novel approach for finding additional interaction regions, leading to the concept of a retro-MoRF, which has the reversed sequence of an identified MoRF. The set of retro-MoRF binding partners likely overlap the partner-sets of the originally identified MoRFs. The high abundance of MoRF-containing intrinsically disordered proteins in nature suggests the possibility that the number of retro-MoRFs could likewise be very high. This hypothesis provides new grounds for exploring the mysteries of protein-protein interaction networks at the genome level.


Cardiac failure after liver transplantation requiring a biventricular assist device.
Increased hepatic iron load in extrahepatic organs of cirrhotic patients with and without hereditary hemochromatosis portends a poorer long term prognosis after liver transplant. Hepatic as well as nonhepatic iron overload is associated with increased infectious and postoperative complications, including cardiac dysfunction. In this case report, we describe a cirrhotic patient with alpha 1 antitrypsin deficiency and nonhereditary hemochromatosis (non-HFE) that developed cardiogenic shock requiring mechanical circulatory support for twenty days after liver transplant. Upon further investigation, she was found to have significant iron deposition in both the liver and heart biopsies. Her heart regained complete and sustained recovery following ten days of mechanical biventricular support. This case highlights the importance of preoperatively recognizing extrahepatic iron deposition in patients referred for liver transplantation irrespective of etiology of liver disease as this may prevent postoperative complications.


Antidiuretic effect of bremazocine and U-50,488 in rats after alpha 2-adrenoceptor blockade.
The role of alpha 2-adrenoceptors and kappa-opioid receptors in urination was studied in rats. In water-loaded rats (40 mL kg-1 p.o.) the kappa-opioid agonist bremazocine (0.05 0.2 mg kg-1 i.p.) induced a dose-related diuretic response in the second hour after administration, but had no effect in the first hour. When rats were pretreated with the alpha 2-adrenoceptor antagonist idazoxan (1 mg kg-1 s.c.), bremazocine induced a dose-related antidiuretic response in the first hour; thereafter the rats showed an increase of urination similar to that with bremazocine alone. The antidiuretic effect of bremazocine was dependent on the dose of idazoxan with maximal response after 1-3 mg kg-1. Similar results were obtained with bremazocine in the presence of yohimbine (1 mg kg-1 s.c.). The antidiuretic profile of bremazocine after idazoxan was shared by U-50,488 (2.5-10 mg kg-1 i.p.), although this compound alone at the high dose reduces urine output in the first hour. The antidiuresis induced by bremazocine in the presence of idazoxan in water-loaded rats was completely antagonized by 10 but not 2 mg kg-1 i.p. of the opioid antagonist naloxone. Thus, kappa-opioid agonists, in addition to their diuretic effect, also produce an antidiuretic response which may be mediated by alpha 2-adrenoceptors.


Evaluation of reference genes for reverse transcription quantitative PCR analyses of fish-pathogenic Francisella strains exposed to different growth conditions.
Reverse transcription quantitative PCR has become a powerful technique to monitor mRNA transcription in response to different environmental conditions in many bacterial species. However, correct evaluation of data requires accurate and reliable use of reference genes whose transcription does not change during the course of the experiment. In the present study exposure to different growth conditions was used to validate the transcription stability of eight reference gene candidates in three strains from two subspecies of Francisella noatunensis, a pathogen causing disease in both warm and cold water fish species. Relative transcription levels for genes encoding DNA gyrase (gyrA), RNA polymerase beta subunit (rpoB), DNA polymerase I (polA), cell division protein (ftsZ), outer membrane protein (fopA), riboflavin biosynthesis protein (ribC), 16S ribosomal RNA (16S rRNA) and DNA helicases (uvrD) were quantified under exponential, stationary and iron-restricted growth conditions. The suitability of selected reference genes for reliable interpretation of gene expression data was tested using the virulence-associated intracellular growth locus subunit C (iglC) gene. Although the transcription stability of the reference genes was slightly different in the three strains studied, fopA, ftsZ and polA proved to be the most stable and suitable for normalization of gene transcription in Francisella noatunensis ssp.


Genome-Wide Identification of Effector Candidates With Conserved Motifs From the Wheat Leaf Rust Fungus Puccinia triticina.
Rust fungi secrete various specialized effectors into host cells to manipulate the plant defense response. Conserved motifs, including RXLR, LFLAK-HVLVxxP (CRN), Y/F/WxC, CFEM, LysM, EAR, [SG]-P-C-[KR]-P, DPBB_1 (PNPi), and ToxA, have been identified in various oomycete and fungal effectors and are reported to be crucial for effector translocation or function. However, little is known about potential effectors containing any of these conserved motifs in the wheat leaf rust fungus (Puccinia triticina, Pt). In this study, sequencing was performed on RNA samples collected from the germ tubes (GT) of uredospores of an epidemic Pt pathotype PHTT(P) and Pt-infected leaves of a susceptible wheat cultivar "Chinese Spring" at 4, 6, and 8 days post-inoculation (dpi). The assembled transcriptome data were compared to the reference genome of "Pt 1-1 BBBD Race 1." A total of 17,976 genes, including 2,284 "novel" transcripts, were annotated. Among all these genes, we identified 3,149 upregulated genes upon Pt infection at all time points compared to GT, whereas 1,613 genes were more highly expressed in GT. A total of 464 secreted proteins were encoded by those upregulated genes, with 79 of them also predicted as possible effectors by EffectorP. Using hmmsearch and Regex, we identified 719 RXLR-like, 19 PNPi-like, 19 CRN-like, 138 Y/F/WxC, and 9 CFEM effector candidates from the deduced protein database including data based on the "Pt 1-1 BBBD Race 1" genome and the transcriptome data collected here. Four of the PNPi-like effector candidates with DPBB_1 conserved domain showed physical interactions with wheat NPR1 protein in yeast two-hybrid assay. Nine Y/F/WxC and seven CFEM effector candidates were transiently expressed in Nicotiana benthamiana. None of these effector candidates showed induction or suppression of cell death triggered by BAX protein, but the expression of one CFEM effector candidate, PTTG_08198, accelerated the progress of cell death and promoted the accumulation of reactive oxygen species (ROS). In conclusion, we profiled genes associated with the infection process of the Pt pathotype PHTT(P). The identified effector candidates with conserved motifs will help guide the investigation of virulent mechanisms of leaf rust fungus.


Interactions of the vaccinia virus A19 protein.
The A19 protein of vaccinia virus (VACV) is conserved among chordopoxviruses, expressed late in infection, packaged in the virus core, and required for a late step in morphogenesis. Multiple-sequence alignments of A19 homologs indicated conservation of a series of lysines and arginines, which could represent a nuclear localization or nucleic acid binding motif, and a pair of CXXC motifs that suggested a zinc finger or redox active sites. The importance of the CXXC motif was confirmed by cysteine-to-serine substitutions, which rendered the altered protein unable to trans-complement infectivity of a null mutant. Nevertheless, the cysteines were not required for function of the poxvirus-specific redox pathway. Epitope-tagged A19 proteins were detected in the nucleus and cytoplasm in both infected and uninfected cells, but this distribution was unaffected by alanine substitutions of the arginine residues, which only partially reduced the ability of the mutated protein to trans-complement infectivity. Viral proteins specifically associated with affinity-purified A19 were identified by mass spectrometry as components of the transcription complex, including RNA polymerase subunits, RAP94 (RNA polymerase-associated protein 94), early transcription factors, capping enzyme, and nucleoside triphosphate phosphohydrolase I, and two core proteins required for morphogenesis. Further studies suggested that the interaction of A19 with the RNA polymerase did not require RAP94 or other intermediate or late viral proteins but was reduced by mutation of cysteines in the putative zinc finger domain. Although A19 was not required for incorporation of the transcription complex in virus particles, the transcriptional activity of A19-deficient virus particles was severely reduced.


Hypersensitivity Pneumonitis: An Updated Diagnostic Guide for Internists.
This summary highlights updated definitions, terminology, and classification systems proposed in the diagnosis of hypersensitivity pneumonitis. Clinical presentation, epidemiology, and pathophysiology are reviewed from the most recent data. Radiographic and histopathologic diagnostic criteria are presented in a manner relevant to the practice of general medicine internists, including new guideline recommendations. The role of adjunctive tests, such as serum IgG testing, bronchoalveolar lavage lymphocyte analysis, and pulmonary function testing is discussed in the context of supporting diagnostic confidence for hypersensitivity pneumonitis diagnosis. Finally, new diagnostic algorithms are synthesized and applied to the general internal medicine setting.


Safety and efficacy of tamsulosin, alfuzosin or silodosin as monotherapy for LUTS in BPH - a double-blind randomized trial.
Currently alpha1-adrenoceptor blockers (AB) are widely used as first-line therapy to improve lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH). We compared the efficacy and safety profile of tamsulosin, alfuzosin and silodosin in LUTS due to BPH. Consecutive consenting male patients (N = 269) undergoing medical management of BPH with AB from February 2012 to October 2015 were enrolled. Patients were randomized to a 0.4 mg tamsulosin (group T), 10 mg alfuzosin (group A) or a 8 mg silodosin (group S) by double-blind randomization. All patients were assessed for improvements and post-void residual urine (PVR) and for adverse drug events (ADE). IPSS showed significant improvement in Group S at the first week (11.7 ±4.18, p = 0.027) and at 3 months (7.97 ±3.84, p = 0.020). QOL showed significant improvement at 1 (2.2 ±0.76, p = 0.020), 4 (1.47 ±0.63, p <0.001) and 12 (1.2 ±0.66, p <0.001) weeks in Group S. The mean Qmax improvement was the maximum (13.76 ±2.44, p = 0.028) in Group S at 1 week. Reduction in PVR was the maximum in Group S, but it was not statistically significant. Adverse drug events (ADE) were observed in 20.07% (54/269) patients and distribution was similar in the three groups with decreasing incidence with progression of time. Silodosin is the most efficacious AB with rapid onset of action. Silodosin also improves the quality of life in patients with LUTS due to BPH and objectively improves maximum flow rate. However, silodosin has more adverse events when compared to tamsulosin and alfuzosin.


Congenital maxillary double lip: review of the literature and report of a case.
A double lip is an anomaly that may be either congenital or acquired. It occurs most often in the upper lip, although both upper and lower lips are occasionally involved. Surgical intervention (simple excision) produces good functional and cosmetic results. In this report, we describe a case of congenital double upper lip, present a review of the literature and discuss the differential diagnosis. Double lip is of special interest in dentistry because the general practitioner is often the first professional to detect and establish the diagnosis of this uncommon condition.


Geospatial Variation of Real-World Tailpipe Emission Rates for Light-Duty Gasoline Vehicles.
Spatial variability in real-world on-road tailpipe light-duty gasoline vehicle nitrogen oxides, hydrocarbon, carbon monoxide, and carbon dioxide emission rates, the locations of emissions hotspots, and factors that explain spatial variability are quantified. A sample of 205 vehicles were measured on four predefined round-trip study routes using Portable Emission Measurement Systems. The trips on each route were divided into segments, averaging 1/4 mile in length. Segment-average emission rates were estimated based on measured 1 Hz emission rates. Emission hotspots are defined as segments with ≥90th percentile of segment-average emission rates. The hotspots have average emission rates 2-4 times greater, depending on the pollutant, than other segments. Hotspots are of heterogeneous characteristics including road attributes and vehicle activity metrics. For example, some hotspots were on arterial roads with an upstream signalized intersection and positive road grade, whereas some hotspots were on interstates with positive grade. Vehicle activity metrics, including average vehicle specific power and relative positive acceleration, help identify the hotspots. To reliably identify a fleet-average hotspot, data are needed for at least 36-130 vehicles, depending on the pollutant.


Production of transgenic mice by random recombination of targeted genes in female germline stem cells.
Oocyte production in most mammalian species is believed to cease before birth. However, this idea has been challenged with the finding that postnatal mouse ovaries possess mitotically active germ cells. A recent study showed that female germline stem cells (FGSCs) from adult mice were isolated, cultured long term and produced oocytes and progeny after transplantation into infertile mice. Here, we demonstrate the successful generation of transgenic or gene knock-down mice using FGSCs. The FGSCs from ovaries of 5-day-old and adult mice were isolated and either infected with recombinant viruses carrying green fluorescent protein, Oocyte-G1 or the mouse dynein axonemal intermediate chain 2 gene, or transfected with the Oocyte-G1 specific shRNA expression vector (pRS shOocyte-G1 vector), and then transplanted into infertile mice. Transplanted cells in the ovaries underwent oogenesis and produced heterozygous offspring after mating with wild-type male mice. The offspring were genetically characterized and the biological functions of the transferred or knock-down genes were investigated. Efficiency of gene-transfer or gene knock-down was 29%-37% and it took 2 months to produce transgenic offspring. Gene manipulation of FGSCs is a rapid and efficient method of animal transgenesis and may serve as a powerful tool for biomedical science and biotechnology.


The role of katanin p60 in breast cancer bone metastasis.
p60 is a subunit of katanin involved in microtubule-severing. Previous studies of p60 were primarily focused on microtubule regulation and cell cycle regulation. More recent research has demonstrated that katanin p60 possesses a function in prostate cancer bone metastasis; however, its role in breast cancer bone metastasis remains unclear. In the present study, immunohistochemistry was used to analyze the expression of katanin p60 in primary and bone metastatic breast cancer. The role of up- and downregulated katanin p60 was investigated using cell proliferation, and migration experiments. Overall, katanin p60 was highly expressed in breast cancer bone metastatic tissue compared with primary tumor tissue. In breast cancer cells, overexpression of katanin p60 inhibited cell proliferation, but promoted cell migration, whereas silencing katanin p60 expression promoted cell proliferation but inhibited cell migration. Overall, the present study indicated that katanin p60 serves a role in cell proliferation and migration, and thus may be a novel therapeutic target for prevention of breast cancer metastasis.


L3MBTL1 polycomb protein, a candidate tumor suppressor in del(20q12) myeloid disorders, is essential for genome stability.
The l3mbtl1 gene is located on the long arm of chromosome 20 (q12), within a region commonly deleted in several myeloid malignancies. L3MBTL1 is a human homolog of the Drosophila polycomb L(3)MBT tumor suppressor protein and thus a candidate tumor suppressor in del(20q12) myeloid disorders. We used the loss-of-function approach to explore the possible tumor suppressive mechanism of L3MBTL1 and found that depletion of L3MBTL1 from human cells causes replicative stress, DNA breaks, activation of the DNA damage response, and genomic instability. L3MBTL1 interacts with Cdc45, MCM2-7 and PCNA, components of the DNA replication machinery, and is required for normal replication fork progression, suggesting that L3MBTL1 causes DNA damage, at least in part, by perturbing DNA replication. An activated DNA damage response and genomic instability are common features in tumorigenesis and a consequence of overexpression of many oncogenes. We propose that the loss of L3MBTL1 contributes to the development of 20q(-) hematopoietic malignancies by inducing replicative stress, DNA damage, and genomic instability.


Differences in emotional responses in living and deceased donor kidney transplant patients.
The psychological functioning of living donor (LD) and deceased donor (DD) recipients are important factors for emotional adjustment to transplantation. This study investigated differences in medical, sociodemographic and emotional factors between these two groups. A total of 241 kidney transplant recipients (68 LD, 173 DD) completed questionnaires on emotional and behavioural responses to transplantation, including quality of life, anxiety and depression, social support and experience with immunosuppressive medication. Overall, LD recipients were younger, better educated, more often employed and had a shorter duration of dialysis prior to transplantation. Findings indicate that LD recipients expressed more guilt towards the donor than DD recipients. In addition, more LD recipients experienced clinically significant levels of anxiety. Both groups experienced high levels of negative effects of immunosuppressant medication. No differences between LD and DD recipients were found for gender, relationship status, time since transplantation or transplant rejection treatment during the last 12 months. In addition, perceived social support and quality of life were comparable between the two groups. Feelings of guilt and anxiety may be an important focus for interventions to improve emotional adjustment to transplantation, especially in LD recipients.


The DIAP1 RING finger mediates ubiquitination of Dronc and is indispensable for regulating apoptosis.
Members of the Inhibitor of Apoptosis Protein (IAP) family block activation of the intrinsic cell death machinery by binding to and neutralizing the activity of pro-apoptotic caspases. In Drosophila melanogaster, the pro-apoptotic proteins Reaper (Rpr), Grim and Hid (head involution defective) all induce cell death by antagonizing the anti-apoptotic activity of Drosophila IAP1 (DIAP1), thereby liberating caspases. Here, we show that in vivo, the RING finger of DIAP1 is essential for the regulation of apoptosis induced by Rpr, Hid and Dronc. Furthermore, we show that the RING finger of DIAP1 promotes the ubiquitination of both itself and of Dronc. Disruption of the DIAP1 RING finger does not inhibit its binding to Rpr, Hid or Dronc, but completely abrogates ubiquitination of Dronc. Our data suggest that IAPs suppress apoptosis by binding to and targeting caspases for ubiquitination.


Statistical substantiation of the van der Waals theory of inhomogeneous fluids.
Computer experiments on simulation of thermodynamic properties and structural characteristics of a Lennard-Jones fluid in one- and two-phase models have been performed for the purpose of checking the base concepts of the van der Waals theory. Calculations have been performed by the method of molecular dynamics at cutoff radii of the intermolecular potential r(c,1)=2.6sigma and r(c,2)=6.78sigma. The phase equilibrium parameters, surface tension, and density distribution have been determined in a two-phase model with a flat liquid-vapor interface. The strong dependence of these properties on the value of r(c) is shown. The p,rho,T properties and correlation functions have been calculated in a homogeneous model for a stable and a metastable fluid. An equation of state for a Lennard-Jones fluid describing stable, metastable, and labile regions has been built. It is shown that at T > or =1.1 the properties of a flat interface within the computer experimental error can be described by the van der Waals square-gradient theory with an influence parameter kappa independent of the density. Taking into account the density dependence of kappa through the second moment of the direct correlation function will deteriorate the agreement of the theory with data of computer simulation. The contribution of terms of a higher order than (nablarho)(2) to the Helmholtz free energy of an inhomogeneous system has been considered. It is shown that taking into account terms proportional to (nablarho)(4) leaves no way of obtaining agreement between the theory and simulation data, while taking into consideration of terms proportional to (nablarho)(6) makes it possible to describe with adequate accuracy all the properties of a flat interface in the temperature range from the triple to the critical point.


Localization of an anatomic substrate for the anticonvulsant activity induced by D-cycloserine.
D-Cycloserine is a partial agonist of the strychnine-insensitive glycine site that inhibits the tonic hindlimb extension (THE) component of maximal electroshock seizures (MES). This study determined the effect of focal D-clycoserine microinfusion into nucleus reticularis pontis oralis (RPO) on the THE component of MES in rats. Bilateral microinfusion of D-cycloserine (50 nmol per side) into the RPO region 5.4 and 5.6 mm posterior to bregma inhibited THE in 80% of rats tested. Unilateral D-cycloserine (50 nmol) RPO microinfusions were ineffective. Likewise, RPO microinfusion of vehicle, L-cycloserine (50 nmol per side), or the strychnine-insensitive glycine site antagonist 7-chlorokynurenic acid (10 and 50 nmol per side) did not alter THE incidence. However, coinfusion of 7-chlorokynurenic acid (50 nmol per side) with D-cycloserine (50 nmol per side) completely antagonized the anticonvulsant activity induced by D-cycloserine (8 of 8 rats with THE). These data indicate that the anticonvulsant activity of D-cycloserine is mediated by RPO. Because the anticonvulsant effect is stereospecific and is reversible by 7-chlorokynurenic acid, these results also indicate that D-cycloserine acts through the strychnine-insensitive glycine site to inhibit THE.


[The role of transcutaneous fine-needle aspiration biopsy of the regional lymph nodes in the management of cancer of the penis].
Knowledge of the status of the regional lymph-nodes is essential for establishing the stage and the optimal treatment of carcinoma of the penis. Lymphadenectomy cannot be performed routinely because of its morbidity (30-50%) and mortality. Various noninvasive procedures such as lymphography, T.A.C. and echography have been proposed but are of limited diagnostic value because of the unacceptable frequency of the false positive and false negative findings. The transcutaneous fine-needle aspiration biopsy of the draining nodes visualized by lymphography is an innocuous, non invasive, excellent procedure, alternative to staging surgery in determining or excluding the presence of the nodal metastases. The positive cytology is conclusive of stage III and implies early, sometime, curative lymphadenectom. If the aspirate is abundant and largely representative the negative findings may also be considered to indicate the reactive nature of the lymphadenopathy.


Can We Predict Long-Duration Running Power Output? Validity of the Critical Power, Power Law, and Logarithmic Models.
Ruiz-Alias, SA, Ñancupil-Andrade, AA, Pérez-Castilla, A, and García-Pinillos, F. Can we predict long-duration running power output? Validity of the critical power, power law, and logarithmic models. J Strength Cond Res XX(X): 000-000, 2023-Predicting long-distance running performance has always been a challenge for athletes and practitioners. To ease this task, different empirical models have been proposed to model the drop of the running work rate with the increase of time. Therefore, this study aims to determine the validity of different models (i.e., CP, power law, and Peronnet) to predict long-duration running power output (i.e., 30 and 60 minutes). In a 4-week training period, 15 highly trained athletes performed 7-time trials (i.e., 3, 4, 5, 10, 20, 30, and 60 minutes) in a randomized order. Then, their power-duration curves (PDCs) were defined through the work-time critical power model (CPwork), power-1/time (CP1/time), 2-parameter hyperbolic (CP2hyp), 3-parameter hyperbolic (CP3hyp), the undisclosed Stryd (CPstryd), and Golden Cheetah (CPcheetah) proprietary models, and the power law and Peronnet models using the 3 to 20 minutes time trials. These ones were extrapolated to the 30- and 60-minute power output and compared with the actual performance. The CP2hyp, CP3hyp, CPstryd, and CPcheetah provided valid 30- and 60-minute power output estimations (≤2.6%). The CPwork and CP1/time presented a large predicting error for 30 minutes (≥4.4%), which increased for 60 minutes (≥8.1%). The power law and Peronnet models progressively increased their predicting error at the longest duration (30 minutes: ≤-1.6%; 60 minutes: ≤-6.6%), which was conditioned by the endurance capability of the athletes. Therefore, athletes and practitioners are encouraged to applicate the aforementioned valid models to their PDC to estimate the 30-minute and 60-minute power output.


Lipopolysaccharides from various Capnocytophaga strains possess potent Limulus amoebocyte lysate clotting activity.
Lipopolysaccharides (LPSs) were extracted by the hot phenol-water method from three ATCC strains (C. sputigena ATCC 33612, C. ochracea ATCC 33596, and C. gingivalis ATCC 33624) and three clinical isolates (C. sputigena TE-1, C. ochracea ONO-26, and C. gingivalis M-12). Endospecy was used to determine the Limulus amoebocyte lysate clotting activities. The activities of LPSs from Capnocytophaga strains were stronger than those of Escherichia coli, with the exception of the LPS from C. gingivalis M-12. Except for the LPS from C. sputigena TE-1, the SDS-PAGE analyses of these preparations showed slow-migrating and repeating ladder bands similar to the LPSs of E. coli and Salmonella typhimurium (wild type) and included both the core-lipid A region and various lengths of O-antigen. The LPS from C. sputigena TE-1 possessed fast-migrating bands and did not have an O-side chain.


Regulatory Effect of Bacillus subtilis on Cytokines of Dendritic Cells in Grass Carp (Ctenopharyngodon Idella).
Bacillus subtilis is a common group of probiotics that have been widely used in the feed industry as they can increase host resistance to pathogens and balance the immune response. However, the regulatory mechanism of Bacillus subtilis on the host immune system remains unclear in teleosts. In this study, we isolated and enriched dendritic cells from white blood cells (WBCs), and then stimulated them with Bacillus subtilis. Morphological features, specific biological functions, and authorized functional molecular markers were used in the identification of dendritic cells. Subsequently, we collected stimulated cells at 0, 4, and 18 h, and then constructed and sequenced the transcriptomic libraries. A transcriptome analysis showed that 2557 genes were up-regulated and 1708 were down-regulated at 4 h compared with the control group (|Fold Change| ≥ 4), and 1131 genes were up-regulated and 1769 were down-regulated between the cells collected at 18 h and 4 h (|Fold Change| ≥ 4). Gene Ontology (GO) annotations suggested many differentially expressed genes (DEGs) (p < 0.05 and |Fold Change| ≥ 4) were involved in immune-related biological functions including immune system progress, cytokine receptor binding, and cytokine binding. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that the cytokine⁻cytokine receptor interaction pathways were significantly enriched at both time points (p < 0.05), which may play a key role in the response to stimulation. Furthermore, mRNA expression level examination of several pro-inflammatory cytokines and anti-inflammatory cytokines genes by quantitative real-time polymerase chain reaction (qRT-PCR) indicated that their expressions can be significantly increased in Bacillus subtili, which suggest that Bacillus subtilis can balance immune response and tolerance. This study provides dendritic cell (DC)-specific transcriptome data in grass carp by Bacillus subtilis stimulation, allowing us to illustrate the molecular mechanism of the DC-mediated immune response triggered by probiotics in grass carp.


An alternative approach to treating lateral epicondylitis. A randomized, placebo-controlled, double-blinded study.
To investigate the effect of noxious level electrical stimulation on pain, grip strength and functional abilities in subjects with chronic lateral epicondylitis. Randomized, placebo-control, double-blinded study. Physical Therapy Department, North Georgia College and State University. Eighteen subjects with chronic lateral epicondylitis between the ages of 24 and 72 years participated in this study. Subjects were randomly assigned into treatment or placebo groups. Subjects received six sessions of low-frequency electrical stimulation over the palpated tender points. The intensity of electrical stimulation was set at 0 in the placebo group. Grip strength, functional status, pain intensity and limited activity due to pain were assessed before and after treatment. Six-month follow-up data were collected in treatment group only. Both clinically and statistically significant improvements in average grip strength were found (treatment group: 28% increase; placebo group: 2.5% decrease; P=0.04), functional activity (treatment group: 110% increase; placebo group: 22% increase; P= 0.003), pain intensity (treatment group: 3.1 point decrease; placebo group: 0.2 point increase; P=0.01) and activity limitation due to pain (treatment group: 4.1 points increase; placebo group: 1.9 point decrease; P= 0.003) between the treatment and placebo groups. Follow-up data showed that 100% of subjects maintained the improved function, and 83% remained pain-free for at least six months post treatment. The results of this study indicated that symptoms of chronic lateral epicondylitis could be effectively treated by noxious level low-frequency electrical stimulation.


Evaluation of a community-based automated blood pressure measuring device.
Automated devices are widely available in the community for people to measure their blood pressure. We assessed the accuracy and reproducibility of a brand of community-based automated device against the standard mercury sphygmomanometer. Same-arm pairs of blood pressure readings were obtained with the Vita-Stat 90550 automated device, a sphygmomanometer and the Omron HEM-705CP automated device in random order on volunteers in 3 community pharmacies using a modified protocol for evaluating blood pressure devices. Comparison of readings between the Omron device and the sphygmomanometer served as a positive control of how well a laboratory-validated automated device could perform in the community. Both the Association for the Advancement of Medical Instrumentation (AAMI) and British Hypertension Society (BHS) criteria were used to assess the accuracy and reproducibility of readings. The mean blood pressure reading and standard error (SE) of the mean for the 108 volunteers (66 women and 42 men) was 133/77 (SE 2/1) mm Hg with the Vita-Stat device, 131/77 (SE 2/1) mm Hg with the Omron device and 129/76 (SE 2/1) mm Hg with the sphygmomanometer. The mean difference in readings was 4.4/1.0 (standard deviation [SD] 9.4/6.2) mm Hg between the Vita-Stat device and the sphygmomanometer and 1.6/0.6 (SD 9.3/6.4) mm Hg between the Omron device and the sphygmomanometer. Neither automated device met the AAMI accuracy criteria for the systolic readings. The BHS grades were C/A (systolic unacceptable/diastolic acceptable) for each automated device. According to the BHS analytical criterion, all devices achieved acceptable reproducibility grades. Neither automated device met the AAMI or BHS criteria for accuracy while in use in the community, and neither performed as well in the community as in the laboratory.


Endophytic Fungi Piriformospora indica Mediated Protection of Host from Arsenic Toxicity.
Complex intercellular interaction is a common theme in plant-pathogen/symbiont relationship. Cellular physiology of both the partners is affected by abiotic stress. However, little is known about the degree of protection each offers to the other from different types of environmental stress. Our current study focused on the changes in response to toxic arsenic in the presence of an endophytic fungus Piriformospora indica that colonizes the paddy roots. The primary impact of arsenic was observed in the form of hyper-colonization of fungus in the host root and resulted in the recovery of its overall biomass, root damage, and chlorophyll due to arsenic toxicity. Further, fungal colonization leads to balance the redox status of the cell by adjusting the antioxidative enzyme system which in turn protects photosynthetic machinery of the plant from arsenic stress. We observed that fungus has ability to immobilize soluble arsenic and interestingly, it was also observed that fungal colonization restricts most of arsenic in the colonized root while a small fraction of it translocated to shoot of colonized plants. Our study suggests that P. indica protects the paddy (Oryza sativa) from arsenic toxicity by three different mechanisms viz. reducing the availability of free arsenic in the plant environment, bio-transformation of the toxic arsenic salts into insoluble particulate matter and modulating the antioxidative system of the host cell.


Multidrug resistant bacteria are sensitive to Euphorbia prostrata and six others Cameroonian medicinal plants extracts.
Multidrug resistant (MDR) bacteria are responsible for therapeutic failure and there is an urgent need for novels compounds efficient on them. Eleven methanol extracts from seven Cameroonian medicinal plants were tested for their antibacterial activity using broth micro-dilution method against 36 MDR bacterial strains including Escherichia coli, Enterobacter aerogenes, Enterobacter cloacae, Klebsiella pneumoniae, Providencia stuartii, Pseudomonas aeruginosa and Staphylococcus aureus. Euphorbia prostrata extract was found active against all the 36 tested bacteria including Gram-negative phenotypes over-expressing efflux pumps such as P. aeruginosa PA124, E. aerogenes CM64 and E. coli AG102. E. prostrata had minimal inhibitory concentrations values between 128 and 256 µg/mL on 55.55% of the studied microorganisms. Other plants extract displayed selective antibacterial activity. Results obtained in this study highlight the antibacterial potential of the tested plants and the possible use of E. prostrata to combat bacterial infections including MDR phenotypes.


Urinary excretion of orally ingested gastrografin on CT.
Renal excretion of orally ingested gastrografin has rarely been reported on computed tomography (CT). We studied the unenhanced scans of 82 patients with bowel disorders or perforation to assess the prevalence of urinary contrast material (CM) in various bowel diseases. We also assessed the clinical significance of this sign. In addition, we reviewed the unenhanced CT scans of 100 randomly selected patients without bowel diseases as a control group. Twenty-nine of the 58 patients with bowel diseases, six of nine with free perforation, and one of 15 with covered perforation had CM in the urinary tract. None of the 100 without bowel disease showed urinary CM. Statistical analysis was done by using the Fisher's exact test. The prevalence of urinary CM was highest in inflammatory bowel disease, radiation enteritis, and free perforation (p < 0. 0001). This study shows that the CT finding of orally ingested gastrografin in the urinary tract differentiates patients with bowel disease from those without.


Slit-lamp measurement of anterior chamber depth and its agreement with anterior segment optical coherence tomography and Lenstar LS 900 in pseudoexfoliation and normal eyes.
There is a considerable lack of awareness of slit-lamp measurement of anterior chamber depth (ACD) by the Redmond Smith method (SACD) in present day-to-day clinical practice, which may provide rapid assessment in pseudoexfoliation (PXF) when assessing for angle closure and planning for cataract surgery. This assumes importance not only in outreach clinics but also in the ongoing pandemic caused by the highly contagious novel coronavirus, where social distancing is advocated to contain the spread. We aimed to compare the axial ACD in PXF and normal patients by SACD, and its agreement with the anterior segment optical coherence tomography (ASOCT) and LenstarLS-900. A prospective comparative observational study was done at a tertiary eye care hospital. A PXF group and a normal group of controls were recruited. All eyes were phakic with normal cornea. Any eye with previous intraocular/refractive surgery and cause of other secondary or uncontrolled glaucoma was excluded. SACD was measured clinically via slit-lamp method and also via ASOCT and Lenstar; agreement between the methodologies was plotted. Fifty patients were recruited in each group. Mean age was 66.82 ± 4.88 years in PXF patients and 65 ± 5.46 years in controls (P = 0.2). ACD was found to be greater in controls compared with the PXF patients; this difference was statistically significant (P < 0.001) across all methodologies. A good agreement with narrow 95% limits of agreement was found between these methodologies. Redmond Smith slit-lamp methodology of estimating the axial ACD is recommended as a rapid, quantifiable, noncontact screening technique during routine examination, especially in primary outreach centers, and is also advantageous during the ongoing pandemic by reducing expendable investigations.


Chest X-Ray Not Routinely Indicated Prior to the YEARS Algorithm in the Diagnostic Management of Suspected Pulmonary Embolism.
Background The YEARS algorithm was designed to simplify the diagnostic process of suspected pulmonary embolism (PE) and to reduce the number of required computed tomography pulmonary angiography (CTPA) scans. Chest X-ray (CXR) is often used as initial imaging test in patients suspected for PE. Aim To determine if CXR results differ between patients with confirmed PE and with PE ruled out, and to investigate whether CXR provides incremental diagnostic value to the YEARS criteria that is used for selecting patients with CTPA indication. Methods This post-hoc analysis concerned 1,473 consecutive patients with suspected PE who were managed according to YEARS and were subjected to CXR as part of routine care. The prevalence and likelihood ratios of seven main CXR findings for a final diagnosis of PE were calculated. Results A total of 214 patients were diagnosed with PE at baseline (15%). Abnormal CXR occurred more often in patients with confirmed PE (36%, 77/214) than in patients without PE (26%; 327/1,259), for an odds ratio of 1.60 (95% confidence interval: 1.18-2.18). Only the unexpected finding of a (rib)fracture or pneumothorax, present in as few as six patients (0.4%), significantly lowered the post-test probability of PE to an extent that CTPA could have been avoided. Conclusion The incremental diagnostic value of CXR to the YEARS algorithm to rule out PE was limited. CXR was more frequently abnormal in patients with PE than in those in whom PE was ruled out. These data do not support to perform CXR routinely in all patients with suspected PE, prior to CTPA imaging.


Thiabendazole, a well-known antifungal drug, exhibits anti-metastatic melanoma B16F10 activity via inhibiting VEGF expression and inducing apoptosis.
Thiabendazole, an orally available antifungal drug, has been used in clinical practice for 40 years. Previous studies indicated its potential in inhibiting angiogenesis in both animal models and in human cells. Malignant melanoma is associated with angiogenesis and it is unknown whether thiabendazole is effective for malignant melanoma or not. In our research, the effects of thiabendazole on the proliferation of the murine metastatic melanoma cell line B16F10 in vitro and in vivo and the molecular mechanism were investigated. Assay of cell viability, chick embryo chorioallantoic membrane assay, quantitative real-time PCR, Western blot, wound healing assay, annexin V/propidium iodide (AV/PI) assay and B16F10-xenograft model were applied to elucidate the mechanism of thiabendazole on B16F10 cells. Thiabendazole inhibited B16F10 proliferation in vitro in a dose- and time-dependent manner with an IC50 of 532.4 +/- 32.6, 322.9 +/- 28.9, 238.5 +/- 19.8 microM at 24, 48, and 72 h, respectively. Moreover, thiabendazole inhibited the angiogenesis and the migration of B16F10 cells in vitro. Furthermore, thiabendazole restrained transcription and translation of the VEGF gene in B16F10 in vitro, and the apoptotic percentage of B16F10 cells was increased after exposure to thiabendazole. Finally, in the B16F10-bearing mice model, thiabendazole significantly suppressed tumor growth with inhibitory rates of 16.5%, 35.4% and 48.7% at the treatment of thiabendazole 20, 40 and 80 mg/kg, respectively. These results further indicated that thiabendazole may be a potential candidate for the treatment of malignant melanoma.


Enhancement of the responsiveness of vas deferens and ileum smooth muscle in sensitized guinea pigs: in vitro study.
Changes in the reactivity of the ileum (to histamine and barium chloride) and vas deferens (to acetylcholine and barium chloride), isolated from actively egg albumen-sensitized guinea pigs, have been investigated. The study was performed on 2 guinea pig strains: the Dunkin-Hartley strain, usually used as an airway allergic model, and the BFA strain. In actively sensitized guinea pigs of both strains, concentration-response curves exhibited a significant dose-dependent upward shift compared to those obtained in control guinea pigs. The maximal contraction strength calculated from these curves was significantly enhanced in both sensitized guinea pig strains, without a change in EC50 values. This study showed that the active antigen sensitization procedure involved several smooth muscle functions, and not exclusively the trachea.


Transfusion indications for patients with cancer.
During the last few years, considerable focus has been given to the management of anemia and coagulopathies. This article provides current concepts of red blood cell (RBC) and plasma coagulation factor replacements. The literature was reviewed for clinical studies relevant to RBC transfusion indications and outcomes as well as for the uses of coagulation factor replacement products for coagulopathies most likely encountered in patients with cancer. Most patients without complications can be treated with a hemoglobin level of 7 g/dL as an indication for RBC transfusion. However, the effects of disease among patients with cancer may cause fatigue, so transfusions at higher hemoglobin levels may be clinically helpful. Leukoreduced RBCs are recommended as standard therapy for all patients with cancer, most of whom do not develop coagulopathy. Transfusions to correct mild abnormalities are not indicated in this patient population. Data are inconclusive regarding the value of coagulation factor replacement for invasive procedures when the international normalized ratio is below 2. Indications for RBC transfusion have become more conservative as data and experience have shown that patients can be safely and effectively maintained at lower hemoglobin levels. Coagulation factor replacement is unnecessary for most modest coagulopathies.


Surface deposition and phase behavior of oppositely charged polyion/surfactant ion complexes. 1. Cationic guar versus cationic hydroxyethylcellulose in mixtures with anionic surfactants.
Mixtures of cationic guar (cat-guar) or cationic hydroxyethylcellulose (cat-HEC) with the anionic surfactants sodium dodecyl sulfate or sodium lauryl ether-3 sulfate have been investigated by a wide range of complementary techniques (phase studies, turbidity measurements, dynamic light scattering, gel-swelling experiments, and in situ null ellipsometry), with the following objectives in mind: (1) to establish the relationship between the bulk phase behavior (precipitation and redissolution) of the polyion/surfactant ion complexes and formation/deposition of such complexes at silica surfaces and (2) to obtain molecular interpretations of the large, previously unresolved, quantitative differences between the various investigated mixtures. There were clear similarities, for each studied system, between the bulk phase behavior, gel swelling, and surface deposition on increasing surfactant concentration. This is because all phenomena reflect the polyion/surfactant ion binding isotherm: an initial binding step at a low critical association concentration (cac) of the surfactant and a second more-or-less cooperative binding step beginning at a second cac, the cac(2). The details of the interactions are system-specific, however, and cat-guar/surfactant mixtures generally had larger precipitation regions and gave rise to larger adsorbed amounts on silica compared to mixtures with cat-HEC of a similar charge density. The observed quantitative differences are attributed to a difference in the hydrophobicity of the polyions. For cat-guar, the comparatively weak hydrophobic polyion/surfactant attraction is seen as a very gradual binding commencing at the cac(2) and continuing past the bulk critical micelle concentration of the surfactant, resulting in an unusually large phase-separation region. For cat-HEC, the dissolution of the precipitate takes place at lower surfactant concentrations because of a stronger hydrophobic interaction between the surfactant and the polyion. The results have implications for the successful design of oppositely charged polyelectrolyte/surfactant formulations for surface deposition applications.


Co-occurrence of Campylobacter Species in Children From Eastern Ethiopia, and Their Association With Environmental Enteric Dysfunction, Diarrhea, and Host Microbiome.
High Campylobacter prevalence during early childhood has been associated with stunting and environmental enteric dysfunction (EED), especially in low resource settings. This study assessed the prevalence, diversity, abundance, and co-occurrence of Campylobacter spp. in stools from children in a rural area of eastern Ethiopia and their association with microbiome, diarrhea, and EED in children. Stool samples (n = 100) were collected from randomly selected children (age range: 360-498 days) in five kebeles in Haramaya District, Ethiopia. Diarrhea, compromised gut permeability, and gut inflammation were observed in 48, 45, and 57% of children, respectively. Campylobacter prevalence and species diversity were assessed using PCR and meta-total RNA sequencing (MeTRS). The prevalence of Campylobacter spp. in the children's stools was 50% (41-60%) by PCR and 88% (80-93.6%) by MeTRS (P < 0.01). Further, seven Campylobacter species (Campylobacter jejuni, Campylobacter upsaliensis, Campylobacter hyointestinalis, Campylobacter coli, Campylobacter sp. RM6137, uncultured Campylobacter sp., and Campylobacter sp. RM12175) were detected by MeTRS in at least 40% of children stools in high abundance (>1.76-log read per million per positive stool sample). Four clusters of Campylobacter species (5-12 species per cluster) co-occurred in the stool samples, suggesting that Campylobacter colonization of children may have occurred through multiple reservoirs or from a reservoir in which several Campylobacter species may co-inhabit. No associations between Campylobacter spp., EED, and diarrhea were detected in this cross-sectional study; however, characteristic microbiome profiles were identified based on the prevalence of Campylobacter spp., EED severity, and diarrhea. Forty-seven bacterial species were correlated with Campylobacter, and 13 of them also correlated with gut permeability, gut inflammation and/or EED severity. Forty-nine species not correlated with Campylobacter were correlated with gut permeability, gut inflammation, EED severity and/or diarrhea. This study demonstrated that (1) in addition to C. jejuni and C. coli, multiple non-thermophilic Campylobacter spp. (i.e., Campylobacter hyointestinalis, Campylobacter fetus, and Campylobacter concisus) were frequently detected in the children's stools and (2) the Campylobacter, gut permeability, gut inflammation, EED severity, and diarrhea were associated with characteristic microbiome composition. Additional spatial and longitudinal studies are needed to identify environmental reservoirs and sources of infection of children with disparate Campylobacter species and to better define their associations with EED in low-income countries.


The risk of hospitalization for ischemic stroke among older adults.
The purpose of this study was to identify risk factors for stroke and to estimate their relative importance in a large, nationally representative sample of very old men and women. The study was designed as a secondary analysis of the Longitudinal Study on Aging. Baseline (1984) in-person interview data were linked to Medicare hospitalization records for 1984 to 1991. Participants were 6,071 noninstitutionalized adults 70 years old or older at baseline. Hospitalization for ischemic stroke was defined as having one or more episodes with a primary discharge diagnosis containing ICD-9-CM codes of 433.0-434.9, 436, and 437.0-437.1. Multivariable proportional hazards regression was used to estimate the risks associated with previously identified epidemiologic factors. Five hundred and three persons (8.3%) had at least one primary discharge diagnosis of ischemic stroke. In descending order of importance-based on the partial r statistics associated with their adjusted hazards ratios (AHRs), the salient risk factors were having a previous history of stroke (AHR = 2.86), age (AHR = 1.04 per year), diabetes (AHR = 1.78), male gender (AHR = 1.42), lower body limitations (AHR = 1.09 per limitation), arthritis (AHR = 0.74), hypertension (AHR = 1.29), and poverty (AHR = 1.33). Patients presenting with the high risk factors identified in this study should be considered for further evaluation and monitoring. Current protocols for the therapeutic management of these higher risk patients should be considered, and compliance should be encouraged.


CFTR Modulator Therapy and Its Impact on Lung Transplantation in Cystic Fibrosis.
Cystic fibrosis (CF) is the most common autosomal recessive disorder in Caucasian people and is caused by mutations in the gene encoding for the CF transmembrane conductance regulator (CFTR) protein. It is a multisystem disorder; however, CF lung disease causes most of its morbidity and mortality. Although survival for CF has improved over time due to a multifaceted symptomatic management approach, CF remains a life-limiting disease. For individuals with progressive advanced CF lung disease (ACFLD), lung transplantation is considered the ultimate treatment option if compatible with goals of care. Since 2012, newer drugs, called CFTR modulators, have gradually become available, revolutionizing CF care, as these small-molecule drugs target the underlying defect in CF that causes decreased CFTR protein synthesis, function, or stability. Because of their extremely high efficacy and overall respectable tolerability, CFTR modulator drugs have already proven to have a substantial positive impact on the lives of individuals with CF. Individuals with ACFLD have generally been excluded from initial clinical trials. Now, however, these drugs are being used in clinical practice in selected individuals with ACFLD, showing promising results, although randomized controlled trial data for CFTR modulators in this subgroup of patients are lacking. Such data need to be gathered, ideally in randomized controlled trials including patients with ACFLD. Furthermore, the efficacy and tolerability of the newer modulator therapies in individuals with ACFLD need to be monitored, and their impact on lung disease progression and the need for lung transplantation as the ultimate therapy call for an objective evaluation in larger patient cohorts. As of today, guidelines for referral and listing of lung transplant candidates with CF have not incorporated the status of the new CFTR modulator therapies in the referral and listing process. The purpose of this review article, therefore, is threefold: first, to describe the effects of new therapies, with a focus on the subgroup of individuals with ACFLD; second, to provide an update on the recent outcomes after lung transplantation for individuals with CF; and third, to discuss the referral, evaluation, and timing for lung transplantation as the ultimate therapeutic option in view of the new treatments available in CF.


The stratifying role of job level for sickness absence and the moderating role of gender and occupational gender composition.
The study investigates whether sickness absence is stratified by job level - understood as the authority and autonomy a worker holds - beyond the association with education, income, and occupation. A second objective is to establish the moderating role of gender and occupational gender composition on this stratification of sickness absence. Four competing hypotheses are developed that predict different patterns of moderation. Associations between job level and sickness absence are estimated for men and women in three groups of differing occupational gender composition, using data from the German Socio-Economic Panel Study (SOEP). For the purpose of moderation analysis, this study employs a new method based on Bayesian statistics, which enables the testing of complex moderation hypotheses. The data support the hypothesis that the stratification of sickness absence by job level is strongest for occupational minorities, meaning men in female-dominated and women in male-dominated occupations.


Inhibition of lymphocyte proliferation by factor(s) produced by Schistosoma mansoni.
Normal spleen cells of CBA mice or Fischer rats were cultured with mitogens or allogeneic cells, together with various substances of Schistosoma mansoni origin, and thymidine uptake was measured. The proliferation (DNA synthesis) of normal lymphocytes was inhibited by the incubation product of the parasite as well as by cell-free supernatant of schistosome culture. Inhibition was obtained only when active materials were added at the beginning of the culture. Both T and B cell proliferation were inhibited. The inhibitory activity found in cell-free supernatant suggested the release by the parasite of some factor(s) interfering with lymphocyte proliferation. Moreover, serum from rats infected by S. mansoni inhibited lymphocyte proliferation also. The inhibitor(s) appeared heat resistant, dialyzable and of low molecular weight (500-1000). Incubation of normal spleen cells with S. mansoni inhibitor(s) did not enhance the release of nonspecific suppressor cell factor. The inhibition of product(s) released by the parasite could explain part of the immunosuppression status found in schistosomiasis.


Expression of intercellular adhesion molecule-1 (ICAM-1) in the skin of patients with systemic scleroderma.
The expression and tissue distribution of intercellular adhesion molecule-1 (ICAM-1) in skin biopsies from 12 patients with systemic (SSc) and localized (LS) scleroderma was studied and compared to the biopsies from patients with lupus erythematosus (LE) and normal individuals. In normal human skin ICAM-1 expression was restricted to the vascular endothelium, infiltrating mononuclear cells (MNC), and to few individual keratinocytes. In the inflammatory stage of SSc, however, the expression of ICAM-1 was dramatically increased at the site of MNC infiltrates and could also be detected on fibroblast-like cells lying well apart from these infiltrates in the deep dermis. In contrast, in LS ICAM-1 was expressed mainly at the sites of MNC infiltrates. In LE ICAM-1 expression was confined to the keratinocytes, endothelial cells, and mononuclear cells in the upper parts of the dermis. Analysis of serial tissue sections from patients with SSc demonstrated also colocalization of staining of ICAM-1 around blood vessels with LFA-1-positive lymphocytes. Increased expression of ICAM-1 in the dermis of patients with SSc may represent an important mechanism by which MNC become localized and retained at a site of connective tissue inflammation, leading to the activation of fibroblasts.


Necrobiotic palisading suture granulomas involving bone and joint: report of two cases.
Biomaterial used in surgery is relatively inert and non-toxic; however, adverse reactions may follow implantation of such foreign material. We describe the first two cases of bone and joint destruction by necrobiotic palisading suture granulomas. The hypersensitivity reaction occurred years after shoulder repair using silk sutures. One patient received chemotherapy for a mistaken diagnosis of tuberculous arthritis. Although very rare, foreign material should be included in the differential diagnosis of necrotizing granulomas. A history of surgery and microscopic examination with polarized light should allow recognition of this entity.


Synthesis of enantiomerically pure, highly functionalized, medium-sized carbocycles from carbohydrates: formal total synthesis of (+)-calystegine b(2).
The free radical cyclization (FR) and the ring-closing metathesis (RCM) reaction have been analyzed in order to develop new and original synthetic protocols for the synthesis of enantiomerically pure, highly functionalized, medium-sized carbocycles from carbohydrates. As a result, we report here for the first time examples of the 7-exo FR cyclization of acyclic radical precursors derived from sugars. This process appears to be extremely sensitive to the conformational mobility of the radical species in the transition state. The use of two isopropylidene groups blocking four of the total present hydroxyl groups and a good radical acceptor (as an alpha,beta-unsaturated ester) are mandatory conditions for a successful ring closure protocol. The RCM reaction by using Grubbs' catalyst on selected carbohydrate-derived precursors has afforded variable yields of the expected unsaturated cycloheptane or cycloctane derivatives. The synthesis of the cycloheptitols has been carried out in good yields, regardless of the absolute configuration at the different stereocenters and the nature of the O-functional groups bound in allylic positions to one of the double bonds implicated in the metathesis reaction. Conversely, in the cyclooctane synthesis, we have observed that the success of the reaction depends not only on the absolute configuration at the different stereocenters close to the double bonds but also on the nature of the O-protecting groups on these stereocenters. Finally, the RCM strategy has been used in an attempt to prepare natural (+)-calystegine B(2) from D-glucose. The synthesis of compound 92 from D-glucose constitutes a formal total synthesis of (+)-calystegine B(2), showing the importance of the steric hindrance in allylic positions for a successful RCM reaction.