Comparison of effectiveness and safety of sodium polystyrene sulfonate and sodium zirconium cyclosilicate for treatment of hyperkalemia in hospitalized patients.
Potassium binders are frequently utilized for the treatment of hyperkalemia in hospitalized patients; however, there is limited data directly comparing individual agents. The purpose of this study was to compare the effectiveness and safety of sodium polystyrene sulfonate (SPS) and sodium zirconium cyclosilicate (SZC) for hyperkalemia treatment in hospitalized patients. This retrospective cohort study evaluated adult patients who were admitted within a 7-hospital health system and received SPS or SZC for a serum potassium level greater than 5.0 mEq/L. Patients receiving dialysis prior to SPS/SZC administration, those receiving other potassium-lowering medications within 6 hours prior to blood sampling for a repeat potassium level, and those started on kidney replacement therapy prior to sampling for a repeat potassium level were excluded. Following evaluation of 3,903 patients, the mean reduction in serum potassium 4 to 24 hours after binder administration was 0.96 mEq/L with SPS and 0.78 mEq/L with SZC (P < 0.0001). The median dose of SPS was 30 g (interquartile range [IQR], 15-30 g) while the median (IQR) dose of SZC was 10 g (10-10 g). Resolution of hyperkalemia within 24 hours was achieved in a higher percentage of patients with use of SPS (74.9%) versus SZC (68.8%) (P < 0.001). One of the largest comparisons of SPS and SZC conducted to date, this study demonstrated the effectiveness and safety of both agents. While a statistically greater reduction in serum potassium was observed with use of SPS, there was significant dosing variability among agents that limited the ability to directly compare specific doses. Further investigation is needed to determine the optimal dose of each agent for acute hyperkalemia management. This data will inform clinical decisions about the choice of potassium binder for acute hyperkalemia.


Gastro-clip gastroplasty: a very long-term complication.
For most surgeons, the gastro-clip gastroplasty is an unfamiliar operation. It was performed during the mid 1980s as an alternative to more complex bariatric operations. However, the device had problems. Because of its rigid nature, it occasionally eroded into the stomach and chest. Many of these devices required removal. However, patients may occasionally present with delayed complications. We present a patient with a Gastro-clip gastroplasty, who presented years after the procedure with a functional gastric outlet obstruction.


Increased elevated plus maze open-arm time in mice during spontaneous morphine withdrawal.
Rats undergoing both naloxone-precipitated and spontaneous opioid withdrawal exhibit anxiogenic behaviors in the elevated plus maze (EPM). Recently, we observed an unexpected result, namely mice exhibited increased EPM open-arm time during naloxone-precipitated morphine withdrawal. This was surprising since this behavioral outcome is usually associated with an anxiolytic profile. This study demonstrates that mice exhibit an increase in both EPM open-arm time and % open-arm entries also during spontaneous opioid withdrawal.


The Nedd4-like family of E3 ubiquitin ligases and cancer.
Accumulating evidence suggests that E3 ubiquitin ligases play important roles in cancer development. In this article, we provide a comprehensive summary of the roles of the Nedd4-like family of E3 ubiquitin ligases in human cancer. There are nine members of the Nedd4-like E3 family, all of which share a similar structure, including a C2 domain at the N-terminus, two to four WW domains in the middle of the protein, and a homologous to E6-AP COOH terminus domain at the C-terminus. The assertion that Nedd4-like E3s play a role in cancer is supported by the overexpression of Smurf2 in esophageal squamous cell carcinoma, WWP1 in prostate and breast cancer, Nedd4 in prostate and bladder cancer, and Smurf1 in pancreatic cancer. Because Nedd4-like E3s regulate ubiquitin-mediated trafficking, lysosomal or proteasomal degradation, and nuclear translocation of multiple proteins, they modulate important signaling pathways involved in tumorigenesis like TGFbeta, EGF, IGF, VEGF, SDF-1, and TNFalpha. Additionally, several Nedd4-like E3s directly regulate various cancer-related transcription factors from the Smad, p53, KLF, RUNX, and Jun families. Interestingly, multiple Nedd4-like E3s show ligase independent function. Furthermore, Nedd4-like E3s themselves are frequently regulated by phosphorylation, ubiquitination, translocation, and transcription in cancer cells. Because the regulation and biological output of these E3s is such a complex process, study of the role of these E3s in cancer development poses some challenges. However, understanding the oncogenic potential of these E3s may facilitate the identification and development of biomarkers and drug targets in human cancer.


Building Porous Ni(Salen)-Based Catalysts from Waste Styrofoam via Autocatalytic Coupling Chemistry for Heterogeneous Oxidation with Molecular Oxygen.
The development of robust and industrially viable catalysts from plastic waste is of great significance, and the facile construction of high performance heterogeneous catalyst systems for phenol-quinone conversions remains a grand challenge. Herein, a feasible strategy is demonstrated to reclaim Styrofoam into hierarchically porous nickel-salen-loaded hypercrosslinked polystyrene (PS@Ni-salen) catalysts with high activities through an unusual autocatalytic coupling route. The salen is immobilized onto PS chain by Friedel-Crafts alkylation of benzyl chloride derivatives, and the generated hydrogen chloride coordinately promotes the simultaneous crosslinking and bridge formation between aromatic rings via a Scholl coupling route, leading to hierarchically porous networks. After the metallization with Ni, the resultant networks exhibit high catalytic activity for the oxidation of 2,3,6-trimethylphenol to 2,3,5-trimethyl-1,4-benzoquinone under mild conditions (303 K, 1 bar of O2 ). This catalyst also demonstrates attractive recycling performance without an obvious loss of catalytic efficiency over five consecutive cycles. This methodology might provide a potential sustainable alternative to construct environmentally benign and cost-effective catalysts for specific organic transformation.


Barium bis-[tetra-fluorido-bromate(III)].
Single crystals of barium bis-[tetra-fluorido-bromate(III)], Ba[BrF4]2, were obtained in the form of tiny blocks. Crystal-structure refinement of Ba[BrF4]2 from single-crystal X-ray diffraction data confirmed the previous model obtained on the basis of powder data [Ivlev et al. (2014 ▸). Eur. J. Inorg. Chem. pp. 6261-6267], but with all atoms refined with anisotropic displacement parameters. The crystal structure consists of two symmetry-independent barium cations that are each coordinated by twelve fluorine atoms, forming edge-sharing polyhedra, and an almost square-planar [BrF4]- anion. The compound crystallizes in the Ba[AuF4]2 structure type.


Pancreatic endocrine cells in sea bass (Dicentrarchus labrax L.) II. Immunocytochemical study of insulin and somatostatin peptides.
Insulin (INS)- and somatostatin (SST)-immunoreactive cells were demonstrated by light immunocytochemistry in the endocrine pancreas of sea bass (Dicentrarchus labrax). INS-immunoreactive cells were identified using bovine/porcine, bonito, and salmon (s) INS antisera; the immunostaining was abolished when each antiserum was preabsorbed with its respective peptide but not with unrelated peptides. These cells also reacted with mammal (m) SST-28 (4-14) antiserum. The immunoreaction did not change when this antiserum was preabsorbed by bovine INS. INS-immunoreactive cells were located in the central part of the endocrine areas of the principal, intermediate, and small islets. Two SST-immunoreactive cell types (D1 and D2) were revealed. D1 cells, immunoreactive to SST 14 (562) and sSST-25 antisera, were located next to the glucagon-immunoreactive cells in the peripheral part of the endocrine areas. D2 cells, immunoreactive to SST-14 (562), SST-14 (566), and mSST-28 (4-14) antisera, were found in apposition to the INS-immunoreactive cells. The specificity controls showed that D1 cells expressed sSST-25-like peptides, while D2 cells might contain SST-14 and/or mSST-28-like peptides. The close topographic association between the different SST-immunoreactive cells and both glucagon- and insulin-immunoreactive cells might indicate the existence of a specific paracrine regulation of each endocrine cell type in the sea bass endocrine pancreas.


Mutant Kras as a Biomarker Plays a Favorable Role in FL118-Induced Apoptosis, Reactive Oxygen Species (ROS) Production and Modulation of Survivin, Mcl-1 and XIAP in Human Bladder Cancer.
Tumor heterogeneity in key gene mutations in bladder cancer (BC) is a major hurdle for the development of effective treatments. Using molecular, cellular, proteomics and animal models, we demonstrated that FL118, an innovative small molecule, is highly effective at killing T24 and UMUC3 high-grade BC cells, which have Hras and Kras mutations, respectively. In contrast, HT1376 BC cells with wild-type Ras are insensitive to FL118. This concept was further demonstrated in additional BC and colorectal cancer cells with mutant Kras versus those with wild-type Kras. FL118 strongly induced PARP cleavage (apoptosis hallmark) and inhibited survivin, XIAP and/or Mcl-1 in both T24 and UMUC3 cells, but not in the HT1376 cells. Silencing mutant Kras reduced both FL118-induced PARP cleavage and downregulation of survivin, XIAP and Mcl-1 in UMUC3 cells, suggesting mutant Kras is required for FL118 to exhibit higher anticancer efficacy. FL118 increased reactive oxygen species (ROS) production in T24 and UMUC3 cells, but not in HT1376 cells. Silencing mutant Kras in UMUC3 cells reduced FL118-mediated ROS generation. Proteomics analysis revealed that a profound and opposing Kras-relevant signaling protein is changed in UMUC3 cells and not in HT1376 cells. Consistently, in vivo studies indicated that UMUC3 tumors are highly sensitive to FL118 treatment, while HT1376 tumors are highly resistant to this agent. Silencing mutant Kras in UMUC3 cell-derived tumors decreases UMUC3 tumor sensitivity to FL118 treatment. Together, our studies revealed that mutant Kras is a favorable biomarker for FL118 targeted treatment.


Clozapine attenuates mitochondrial burdens and abnormal behaviors elicited by phencyclidine in mice via inhibition of p47 phox; Possible involvements of phosphoinositide 3-kinase/Akt signaling.
Oxidative stress and mitochondrial dysfunction have been implicated in the pathophysiology of schizophrenia. We investigated whether antipsychotic clozapine modulates nicotinamide adenine dinucleotide phosphate oxidase and mitochondrial burdens induced by phencyclidine in mice. We examined the effect of clozapine on nicotinamide adenine dinucleotide phosphate oxidase activation, mitochondrial burdens (i.e. oxidative stress and mitochondrial dysfunction), and activities of enzymatic antioxidant in the prefrontal cortex, and subsequent abnormal behaviors induced by repeated treatment with phencyclidine. p47 phox Knockout mice and LY294002, a phosphoinositide 3-kinase inhibitor, were employed to elucidate the pharmacological mechanism of clozapine. Phencyclidine treatment resulted in an early increase nicotinamide adenine dinucleotide phosphate oxidase activity, membrane translocation of p47 phox, interaction between p-Akt and p47 phox, and mitochondrial burdens in wild-type mice. Although these increases returned to near control level four days post-phencyclidine, mitochondrial superoxide dismutase and glutathione peroxidase activities were decreased at that time. Clozapine, LY294002, or p47 phox knockout significantly ameliorated social withdrawal and recognition memory deficits produced by phencyclidine. Importantly, LY294002 did not significantly alter the effects of clozapine against abnormal behaviors and the interaction between p-Akt and p47 phox induced by phencyclidine. Furthermore, neither LY294002 nor clozapine exhibited any additive effects to the protection afforded by p47 phox knockout against phencyclidine insult. Our results suggest that p47 phox gene mediates phencyclidine-induced mitochondrial burdens and abnormal behaviors, and that the interactive modulation between p47 phox and phosphoinositide 3-kinase/Akt is important for the understanding on the pharmacological mechanism of clozapine.


Impact of the category of early tumor recurrence on tumor progression in bladder tumors treated by transurethral resection.
Forty-six newly diagnosed patients with T1 and T2 bladder tumors were treated with transurethral resection. During a 6-months period more than 50% of the tumors recurred. Subsequent progression of tumors was seen within 24 months in 35 and 28% of the patients with T1 and T2 tumors, respectively. Prognosis with regard to progression was significantly better in patients with Ta recurrence at first control than in patients with invasive recurrent tumors, irrespective of category of tumor at a later recurrence. It is concluded that the continued transurethral treatment of patients with early recurrent invasive tumors may have to be reconsidered.


[Pre-exposure prophylaxis of new COVID-19 coronavirus infection with tixagevimab/cilgavimab in adult Moscow patients with primary immunodeficiencies].
Primary immunodeficiencies (PIDs), now known as inborn errors of immunity, are a group of inherited diseases caused by defects in the genes that control the immune response. Patients with PIDs have risks of developing a severe course and/or death in COVID-19. Passive immunization with long-acting monoclonal antibodies (MABs) to SARS-CoV-2 should be considered as pre-exposure prophylaxis in patients with PIDs. Tixagevimab/cilgavimab is a combination of MABs that bind to the SARS-CoV-2 spike protein. To evaluate the efficacy and safety of pre-exposure prophylaxis of new SARS-CoV-2 infection in PIDs with the combination of tixagevimab/cilgavimab. Forty eight patients diagnosed with PIDs were included in the study. Median follow-up after drug administration was 174 days. The total number of confirmed coronavirus infections in patients with PIDs as well as 6 months before and after administration of MAT were assessed. In the analyzed cohort, the overall incidence of COVID-19 from pandemic onset to MABs administration was 75% (36/48), with 31% (11/36) of over-infected patients having had the infection more than once. The incidence of COVID-19 immediately 6 months before the introduction of tixagevimab/cilgavimab was 40%. All patients who had COVID-19 after pre-exposure prophylaxis had a mild infection. The incidence of COVID-19 6 months after tixagevimab/cilgavimab administration significantly decreased compared to the incidence 6 months before administration (7 and 40%, respectively; p<0.001). The use of tixagevimab/cilgavimab in patients with PIDs is effective as pre-exposure prophylaxis and reduces the risk of severe COVID-19.


Bone Marrow derived Cell Therapy in Critical Limb Ischemia: A Meta-analysis of Randomized Placebo Controlled Trials.
Critical limb ischemia (CLI) is the most advanced stage of peripheral artery disease (PAD), and many patients with CLI are not eligible for conventional revascularization. In the last decade, cell based therapies have been explored as an alternative treatment option for CLI. A meta-analysis was conducted of randomized placebo controlled trials investigating bone marrow (BM) derived cell therapy in patients with CLI. The MEDLINE, Embase, and the Cochrane Controlled Trials Register databases were systematically searched, and all included studies were critically appraised by two independent reviewers. The meta-analysis was performed using a random effects model. Ten studies, totaling 499 patients, were included in this meta-analysis. No significant differences were observed in major amputation rates (relative risk [RR] 0.91; 95% confidence interval [CI] 0.65-1.27), survival (RR 1.00; 95% CI 0.95-1.06), and amputation free survival (RR 1.03; 95% CI 0.86-1.23) between the cell treated and placebo treated patients. The ankle brachial index (mean difference 0.11; 95% CI 0.07-0.16), transcutaneous oxygen measurements (mean difference 11.88; 95% CI 2.73-21.02), and pain score (mean difference -0.72; 95% CI -1.37 to -0.07) were significantly better in the treatment group than in the placebo group. This meta-analysis of placebo controlled trials showed no advantage of stem cell therapy on the primary outcome measures of amputation, survival, and amputation free survival in patients with CLI. The potential benefit of more sophisticated cell based strategies should be explored in future randomized placebo controlled trials.


Angiotensin-converting enzyme gene polymorphism, carotid intima-media thickness, and left ventricular mass index in adolescent hypertension.
The aim of this study was to determine whether a positive correlation exists between the DD genotype of angiotensin-converting enzyme (ACE) and the carotid intima-media thickness (IMT) or left ventricular mass index (LVMI) in adolescents with hypertension. We studied 120 hypertensive and 58 normotensive (control) adolescents. ACE gene polymorphism was determined by a standardized method. The IMT was measured in the common carotid arteries, and the LVMI was calculated on transthoracic echocardiography. The severity of hypertension was graded according to the results of ambulatory blood pressure monitoring as white coat, borderline, or proven hypertension. The association between ACE gene polymorphism and the obtained parameters was analyzed using analysis of variance and chi-square testing. Both the IMT and LVMI were higher in hypertensive than in control adolescents. In hypertensive subjects, no relationship was found between the different ACE genotypes and the IMT: the mean (+/- standard deviation) IMT in patients with the DD genotype was 0.57 +/- 0.11 mm; in those with the DI genotype, 0.53 +/- 0.01 mm; and in those with the II genotype, 0.55 +/- 0.01 mm. The LVMI was also similar in all 3 ACE genotypes: DD, 106.7 +/- 32.3 g/m(2); DI, 102.2 +/- 38.1 g/m(2); and II, 103.2 +/- 26.3 g/m(2). The severity of hypertension as assessed by ambulatory blood pressure monitoring was independent of the ACE genotype. Target-organ damage (left ventricular hypertrophy and carotid atherosclerosis) is detectable in adolescents with hypertension and, in those subjects, ACE genotype polymorphism is not correlated with the severity of target-organ damage as measured by IMT and LVMI.


Design of potent, non-toxic anticancer peptides based on the structure of the antimicrobial peptide, temporin-1CEa.
Recent advances in the search for novel anticancer agents have indicated that the positively charged antimicrobial peptides have emerged as promising agents offering several advantages over the conventional anticancer drugs. As a naturally occurring, cationic, α-helical antimicrobial peptide, temproin-1CEa has been proved to exhibit a potent anticancer effect and a moderate hemolytic activity. In order to reduce the hemolytic activity of temporin-1CEa and improve its anticancer potency towards a range of human breast cancer cells, in the present study, six analogs of temporin-1CEa were rationally designed and synthesized. The amphipathicity levels and α-helical structural patterns of peptides were reserved, while their cationic property and hydrophobicity were changed. The results of MTT and hemolysis assay indicated that the analog peptides displayed an improved anticancer activity and showed an overall optimized therapeutic index. The hydrophobicity of peptides was positively correlated with their hemolytic and antitumor activities. Moreover, the data suggest a strategy of increasing the cationicity while maintaining the moderate hydrophobicity of naturally occurring amphipathic α-helical peptides to generate analogs with improved cytotoxicity against tumor cells but decreased activity against non-neoplastic cells such as human erythrocytes. This work highlights the potential for rational design and synthesis of improved antimicrobial peptides that have the capability to be used therapeutically for treatment of cancers.


The risk of falls among the aging population: A systematic review and meta-analysis.
This study aims to clarify the risk factors for falls to prevent severe consequences in older adults. We searched the PubMed, Web of Science, Embase, and Google Scholar databases using the terms "risk factors" OR "predicting factors" OR "predictor" AND "fall" OR "drop" to identify all relevant studies and compare their results. The study participants were divided into two groups, the "fall group" and the "control group", and differences in demographic characteristics, lifestyles, and comorbidities were compared. We included 34 articles in the analysis and analyzed 22 factors. Older age, lower education level, polypharmacy, malnutrition, living alone, living in an urban area, smoking, and alcohol consumption increased the risk of falls in the aging population. Additionally, comorbidities such as cardiac disease, hypertension, diabetes, stroke, frailty, previous history of falls, depression, Parkinson's disease, and pain increased the risk of falls. Demographic characteristics, comorbidities, and lifestyle factors can influence the risk of falls and should be taken into consideration.


Characteristics of individuals who fell while receiving home health services.
Many patients receiving home health services are at risk for falling, but fall risk factors have not been previously investigated in this population. A retrospective record review was used to describe individuals who fell while being served by a home health agency. The 98 individuals who fell while receiving home health services were compared with a random sample of 98 subjects served by the home health agency during the same period who did not report falling. Subjects were compared by age, sex, days of receiving home health services, number of falls prior to admission to the home health agency, diagnosis, medication category, home health services received, and type of health care coverage. In the group with falls, causes of falls and interventions were described. The group with falls had comorbidities of neurological and cardiovascular impairment, took more medications associated with increased risk of falling, and had almost 3 times the number of falls prior to admission than the group without falls. Home care providers should consider medical history, medication usage, and fall history as risk factors for falls in the home environment.


Bu-2470, a new peptide antibiotic complex. II. Structure determination of Bu-2470 A, B1, B2a and B2b.
The structures of Bu-2470 A, B1, B2a, and B2b have been determined. Bu-2470 A is a simple octapeptide having no fatty acid moiety, while Bu-2470 B1, B2a and B2b are octapeptides that have been acylated with a beta-hydroxy C11 or C10 fatty acid. The octapeptide structure of Bu-2470 components was found identical with that of octapeptin C1, hence generic names of octapeptin C0, C2, C3 and C4 are proposed for Bu-2470 A, B1, B2a and B2b, respectively.


A child with partial trisomy of chromosome 17 and partial monosomy of chromosome 3: 46,XY,der(3),t(3;17)(p25;q23).
A male infant with multiple congenital abnormalities and global retardation was found to have a translocation resulting in partial trisomy for the distal end of the long arm of chromosome 3. The phenotypically normal father carried a balanced reciprocal translocation between chromosomes 3 and 17.


Higher Extrusion Temperature Induces Greater Formation of Less Digestible Type V and Retrograded Starch in Iron-Fortified Rice Grains But Does Not Affect Iron Bioavailability: Stable Isotope Studies in Young Women.
Hot extrusion is widely used to produce iron-fortified rice, but heating may increase resistant starch and thereby decrease iron bioavailability. Cold-extruded iron-fortified rice may have higher bioavailability but has higher iron losses during cooking. Thus, warm extrusion could have nutritional benefits, but this has not been tested. Whether the addition of citric acid (CA) and trisodium citrate (TSC) counteracts any detrimental effect of high-extrusion temperature on iron bioavailability is unclear. Our aim was to assess the effects of varying processing temperatures on the starch microstructure of extruded iron-fortified rice and resulting iron solubility and iron bioavailability. We produced extruded iron-fortified rice grains at cold, warm, and hot temperatures (40°C, 70°C, and 90°C), with and without CA/TSC at a molar ratio of iron to CA/TSC of 1:0.3:5.5. We characterized starch microstructure using small- and wide-angle X-ray scattering and differential scanning calorimetry, assessed color over 6 mo, and measured in vitro iron solubility. In standardized rice and vegetable test meals consumed by young women (n = 22; mean age: 23 y; geometric mean plasma ferritin: 29.3 μg/L), we measured iron absorption from the fortified rice grains intrinsically labeled with 57ferric pyrophosphate (57FePP), compared with ferrous sulfate (58FeSO4) solution added extrinsically to the meals. Warm and hot extrusion altered starch morphology from native type A to type V and increased retrograded starch. However, extrusion temperature did not significantly affect iron solubility or iron bioavailability. The geometric mean fractional iron absorption of iron from fortified rice extruded with CA/TSC (8.2%; 95% CI: 7.9%, 11.0%) was more than twice that from extruded rice without CA/TSC (3.0%; 95% CI: 2.7%, 3.4%; P < 0.001). Higher extrusion temperatures did not affect iron bioavailability from extruded rice in young women, but co-extrusion of CA/TSC with FePP sharply increased iron absorption independently from extrusion temperature. This trial is registered at www.clinicaltrials.gov as NCT03703726.


The effects of brainstem peribrachial stimulation on neurons of the lateral geniculate nucleus.
The intracellular effects of brainstem peribrachial stimulation on lateral geniculate neurons were investigated in the cat. Experiments were performed in cats under barbiturate or urethane anaesthesia and in non-anaesthetized deafferented animals. Most animals were pretreated with reserpine and were acutely deprived of their retinal and visual cortical inputs. Short trains of stimuli triggered a transient depolarization in most relay neurons (latency: 20-30 ms; duration: 200-300 ms). This depolarization could be interrupted by a short-duration unitary inhibitory postsynaptic potential. The depolarization increased with membrane hyperpolarization and was associated with an increase in membrane conductance. The inhibitory postsynaptic potential had an intrathalamic origin and likely resulted from parallel activation of intrageniculate interneurons. The above responses were largely enhanced in reserpinized cats and were completely abolished by small doses of barbiturates. Iontophoretic applications of the nicotinic blocker, hexamethonium, eliminated peribrachial-evoked discharges in these cells, while similar applications of the muscarinic antagonist, scopolamine, were devoid of any effect. The conclusion is reached that the depolarization of lateral geniculate relay neurons by peribrachial afferents represents a direct postsynaptic effect and does not result from a global disinhibitory mechanism involving inhibition of perigeniculate cells and intrageniculate interneurons. This peribrachial-evoked transient excitation of relay neurons results from a nicotinic mechanism.


Distinct nuclear gene expression profiles in cells with mtDNA depletion and homoplasmic A3243G mutation.
The pathobiochemical pathways determining the wide variability in phenotypic expression of mitochondrial DNA (mtDNA) mutations are not well understood. Most pathogenic mtDNA mutations induce a general defect in mitochondrial respiration and thereby ATP synthesis. Yet phenotypic expression of the different mtDNA mutations shows large variations that are difficult to reconcile with ATP depletion as sole pathogenic factor, implying that additional mechanisms contribute to the phenotype. Here, we use DNA microarrays to identify changes in nuclear gene expression resulting from the presence of the A3243G diabetogenic mutation and from a depletion of mtDNA (rho0 cells). We find that cells respond mildly to these mitochondrial states with both general and specific changes in nuclear gene expression. This observation indicates that cells can sense the status of mtDNA. A number of genes show divergence in expression in rho0 cells compared to cells with the A3243G mutation, such as genes involved in oxidative phosphorylation. As a common response in A3243G and rho0 cells, mRNA levels for extracellular matrix genes are up-regulated, while the mRNA levels of genes involved in ubiquitin-mediated protein degradation and in ribosomal protein synthesis is down-regulated. This reduced expression is reflected at the level of cytosolic protein synthesis in both A3243G and rho0 cells. Our finding that mitochondrial dysfunction caused by different mutations affects nuclear gene expression in partially distinct ways suggests that multiple pathways link mitochondrial function to nuclear gene expression and contribute to the development of the different phenotypes in mitochondrial disease.


The impact of a diagnosis of personality disorder on service usage in an adult Community Mental Health Team.
Patients with a diagnosis of personality disorder (PD) have multiple and diverse needs. It has been noted that individuals with personality disorder are high users of health care resources, especially psychiatric services, ambulance services and emergency departments. In addition PD has been shown to be a significant predictor of disability and mental health consultations independent of Axis I disorders and physical conditions. This study aimed to compare the patterns of service usage, clinical ratings of symptoms and functioning, as well as demographic and clinically relevant historical variables between a group of patients with PD and a random sample of all other patients registered with a South London Community Mental Health Team. A case–control design was used to examine service usage patterns over a one-year period for 73 cases and 96 controls. Diagnoses were established by clinician discussion. Clinical outcomes were measured with Health of the Nation Outcome Scales and Global Assessment of Functioning, while service use was recorded using ten variables obtained from case note review. People with a diagnosis of PD were more often white and had a history of abuse, particularly childhood emotional abuse. They were higher users of some aspects of the service as compared to controls, and had significantly higher severity of symptoms and poorer functioning on clinician-rated measures. This study confirms previous findings that people with PD have more severe symptomatology and greater degrees of functional impairment when compared to those without. Community clinicians should routinely screen attenders to predict likely difficulties that might arise and to make provision for these difficulties in the treatment and management of clients.


A new visual illusion of aspect-ratio context.
Perception of local properties of the visual field is influenced by aftereffects of adaptation. The tilt aftereffect describes repulsion of the perceived orientation of a line from the orientation of an adapting line. Analogous effects of spatial context are often called illusions. Repulsion of the perceived orientation of a grating from the orientation of a surrounding grating is referred to as the tilt illusion. In the same manner, the size aftereffect and Ebbinghaus illusion form a complementary pair of temporal and spatial context effects of size. Here we report psychophysical evidence for a previously unknown aspect-ratio illusion which causes the perceived aspect-ratio of a rectangle to be repelled from the aspect-ratio of rectangles surrounding it. This illusion provides a spatial analogue to the aspect-ratio aftereffect.


The development of real-time digital PCR technology using an improved data classification method.
For digital polymerase chain reaction (PCR), data classification is always a crucial task. The dynamic real-time amplification process information of each partition is always ignored in typical digital PCR analysis, which can easily lead to inaccurate outcomes. In this work, an integrated device that offers real-time chip-based digital PCR analysis was established. In addition, an enhanced process-based classification model (PAM) was built and trained. And then the device and the analytical model were employed in classification tasks for different concentrations of Epstein-Barr Virus (EBV) plasmid quantification assays. The results indicated that the real-time analysis device achieved a linearity of 0.97, the classification method was able to distinguish the false-positive curves, and the recognition error of positive wells was decreased by 64.4% compared with typical static analysis techniques when low concentrations of samples were tested. With these advantages, it is supposed that the real-time digital PCR analysis apparatus and the improved classification method can be employed to enhance the performance of digital PCR technology.


Clinical implementation of 3D in vivo dosimetry for abdominal and pelvic stereotactic treatments.
To analyze results from three years of in vivo transit EPID dosimetry of abdominal and pelvic stereotactic radiotherapy and to establish tolerance levels for routine clinical use. 80 stereotactic VMAT treatments (152 fractions) targeting the abdomen or pelvis were analyzed. In vivo 3D doses were reconstructed with an EPID commercial algorithm. Gamma Agreement Index (GAI) and DVH differences in Planning Target Volume (PTV) and Clinical Target Volume (CTV) were evaluated. Initial tolerance level was set to GAI > 85% in PTV. Fractions Over Tolerance Level (OTL) were deemed to be due to set-up errors, incorrect use of immobilization devices, 4D errors, transit EPID algorithm errors and unknown/unidentified errors. Statistical Process Control (SPC) was applied to determine local tolerance levels. Average GAI were (82.7 ± 20.9) % in PTV and (72.9 ± 29.7) % in CTV. 37.8% of fractions resulted OTL and were classified as: set-up errors (3.3%), incorrect use of immobilization devices (2.1%), 4D errors (2.1%), EPID transit algorithm errors (17.1%). OTL causes for the remaining 13.2% of fractions were not identified. The differences between PTV and CTV measured in vivo and calculated mean dose (average difference ± standard deviation) were (-3.3% ± 3.2%) and (-2.3% ± 3.0%). When tolerance levels based on SPC to PTV mean dose differences were applied, the percentage of OTL decreased to 7% and no EPID algorithm error occurred. One error was not identified. The application of local tolerance levels to EPID in vivo dosimetry proved to be useful for detecting extra-lung SBRT treatment errors.


Quality assurance device for four-dimensional IMRT or SBRT and respiratory gating using patient-specific intrafraction motion kernels.
Emerging technologies such as four-dimensional computed tomography (4D CT) and implanted beacons are expected to allow clinicians to accurately model intrafraction motion and to quantitatively estimate internal target volumes (ITVs) for radiation therapy involving moving targets. In the case of intensity-modulated (IMRT) and stereotactic body radiation therapy (SBRT) delivery, clinicians must consider the interplay between the temporal nature of the modulation and the target motion within the ITV. A need exists for a 4D IMRT/SBRT quality assurance (QA) device that can incorporate and analyze customized intrafraction motion as it relates to dose delivery and respiratory gating. We built a 4D IMRT/SBRT prototype device and entered (X, Y, Z)(T) coordinates representing a motion kernel into a software application that 1. transformed the kernel into beam-specific two-dimensional (2D) motion "projections," 2. previewed the motion in real time, and 3. drove a recision X-Y motorized device that had, atop it, a mounted planar IMRT QA measurement device. The detectors that intersected the target in the beam's-eye-view of any single phase of the breathing cycle (a small subset of all the detectors) were defined as "target detectors" to be analyzed for dose uniformity between multiple fractions. Data regarding the use of this device to quantify dose variation fraction-to-fraction resulting from target motion (for several delivery modalities and with and without gating) have been recently published. A combined software and hardware solution for patient-customized 4D IMRT/SBRT QA is an effective tool for assessing IMRT delivery under conditions of intrafraction motion. The 4D IMRT QA device accurately reproduced the projected motion kernels for all beam's-eye-view motion kernels. This device has been proved to, effectively quantify the degradation in dose uniformity resulting from a moving target within a static planning target volume, and, integrate with a commercial respiratory gating system to ensure that the system is working effectively. Such a device is discussed as a potential tool to optimize the gating duty cycle to maximize delivery efficiency while minimizing dose variability.


Toxoplasma gondii ROP38 protein: Bioinformatics analysis for vaccine design improvement against toxoplasmosis.
Rhoptry proteins (ROPs) play a significant role in various stages of Toxoplasma gondii (T. gondii) life cycle, being critical for both invasion and intracellular survival. ROP38 is a key manipulator of host gene expression and has a function in tachyzoite to bradyzoite conversion. In this study, we've employed various bioinformatics online tools for immunogenicity prediction of ROP38 protein, comprising physico-chemical, antigenic and allergenic profiles, transmembrane domain, subcellular localization, post-translational modification (PTM) sites, secondary and 3D structure, B-cell, MHC-binding and cytotoxic T-lymphocyte (CTL) epitopes. The findings showed 54 PTM sites without a transmembrane domain. Also, ROP38 was proved a non-allergenic and antigenic protein. The protein had Sec signal peptide (Sec/SPI) with 0.8762 likelihood. The secondary structure included 52.68% random coil, 29.57% alpha helix and 17.74% extended strand. Based on Ramachandran plot output for refined model, 95.3%, 3.4%, and 1.4% of amino acid residues were incorporated in the favored, allowed, and outlier regions, respectively. B-cell epitopes TFPGDDIQTSS (67-72) and KAKNKWGRTRYTLQG (207-221) as well as T-cell epitope LSPVGFFTAL (6-15) possessed the highest antigenic index in the protein sequence. This paper is a premise for further researches, and provides insights for the development of a suitable vaccine against toxoplasmosis. More empirical studies are required using the ROP38 alone or in combination with other antigens/epitopes in the future.


[Distribution pattern of histocompatibility antigens (HLA) in nasopharyngeal tumors].
HLA typing in 20 patients with tumors of the nasopharynx showed no significantly increased frequency of HLA A2, BW46 (Sin2), and B5 as demonstrated by other authors. In our investigations, we found no particular HLA antigen as a genetic marker for nasopharyngeal tumors in the population of middle and northern Europe.


Efficacy of inotuzumab ozogamicin in patients with Philadelphia chromosome-positive relapsed/refractory acute lymphoblastic leukemia.
Patients with relapsed/refractory (R/R) Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) have a poor prognosis and limited treatment options. The efficacy of inotuzumab ozogamicin (InO), a humanized anti-CD22 monoclonal antibody conjugated to the cytotoxic antibiotic calicheamicin, was evaluated in R/R ALL patients in the phase 1/2 study 1010 (NCT01363297) and open-label, randomized, phase 3 study 1022 (INO-VATE; NCT01564784). This analysis focused specifically on Ph+ R/R ALL patients. In study 1022, Ph+ patients were randomly assigned 1:1 to InO (n = 22) or standard intensive chemotherapy (SC) (n = 27) and 16 Ph+ patients in study 1010 received InO. In study 1022, rates of complete remission/complete remission with incomplete hematologic recovery (CR/CRi) and minimal residual disease (MRD) negativity (patients achieving CR/CRi) were higher with InO (CR/CRi = 73%; MRD = 81%) versus SC (CR/CRi = 56%; MRD = 33%). The corresponding rates in study 1010 were 56% (CR/CRi) and 100% (MRD). The hematopoietic stem cell transplantation (HSCT) rate in study 1022 was 41% versus 19% for InO versus SC; however, there was no benefit in overall survival (median OS: 8.7 vs 8.4 months; hazard ratio, 1.17 [95% CI, 0.64-2.14]). The probability of being event-free (progression-free survival) at 12 months was greater with InO versus SC (20.1% vs 4.8%). Given the substantial improvement in responses and rates of HSCT, InO is an important treatment option for patients with R/R Ph+ ALL. Future studies need to consider better characterization of disease characteristics, more sensitive MRD measurements, MRD-directed therapy before HSCT, and potentially combination therapies, including tyrosine kinase inhibitors.


Acclimation of nitrogen uptake capacity of rice to elevated atmospheric CO2 concentration.
Nitrogen (N) is a major factor affecting yield gain of crops under elevated atmospheric carbon dioxide concentrations [CO(2)]. It is well established that elevated [CO(2)] increases root mass, but there are inconsistent reports on the effects on N uptake capacity per root mass. In the present study, it was hypothesized that the responses of N uptake capacity would change with the duration of exposure to elevated [CO(2)]. The hypothesis was tested by measuring N uptake capacity in rice plants exposed to long-term and short-term [CO(2)] treatments at different growth stages in plants grown under non-limiting N conditions in hydroponic culture. Seasonal changes in photosynthesis rate and transpiration rate were also measured. In the long-term [CO(2)] study, leaf photosynthetic responses to intercellular CO(2) concentration (Ci) were not affected by elevated [CO(2)] before the heading stage, but the initial slope in this response was decreased by elevated [CO(2)] at the grain-filling stage. Nitrate and ammonium uptake capacities per root dry weight were not affected by elevated [CO(2)] at panicle initiation, but thereafter they were reduced by elevated [CO(2)] by 31-41 % at the full heading and mid-ripening growth stages. In the short-term study (24 h exposures), elevated [CO(2)] enhanced nitrate and ammonium uptake capacities at the early vegetative growth stage, but elevated [CO(2)] decreased the uptake capacities at the mid-reproductive stage. This study showed that N uptake capacity was downregulated under long-term exposure to elevated [CO(2)] and its response to elevated [CO(2)] varied greatly with growth stage.


Development of a sustained release dosage form for alpha-lipoic acid. I. Design and in vitro evaluation.
The purpose of this study was the design and evaluation of a sustained release dosage form for the oral administration of alpha-lipoic acid. The cationic polymer chitosan was used in order to provide a controlled drug release based on ionic interactions with the anionic drug. The effect of such ionic interactions on the release of alpha-lipoic acid could be verified by diffusion studies. In vitro release studies with tablets (diameter: 10.0 mm; thickness: approximately 4 mm) containing 80% alpha-lipoic acid and 20% chitosan acetate showed a controlled drug release over a time period of 24 h. Raising the ratio of chitosan acetate in such delivery systems led to an even stronger retardation of drug release. In addition, permeation studies carried out in Ussing-type chambers with freshly excised intestinal mucosa from guinea pigs demonstrated no significant (p < 0.05) influence of the degree of drug ionization on its absorption behavior. The apparent permeability coefficient (Papp) for alpha-lipoic acid was determined to be 1.39 +/- 0.28 x 10(-5) cm/sec at pH 6.4 (means +/- SD). The use of a sustained delivery system for alpha-lipoic acid, which is based on ionic interactions, should therefore have no influence on the absorption behavior of the drug. The sustained release dosage forms described here might provide a constant plasma level of the drug being highly beneficial for various therapeutic reasons.


Work-family balance after childbirth: the association between employer-offered leave characteristics and maternity leave duration.
Early return to work after childbirth has been increasing among working mothers in the US. We assessed the relationship between access to employer-offered maternity leave (EOML) (both paid and unpaid) and uptake and duration of maternity leave following childbirth in a socio-economically diverse sample of full-time working women. We focus on California, a state that has long provided more generous maternity leave benefits than those offered by federal maternity leave policies through the State Disability Insurance program. The sample included 691 mothers who gave birth in Southern California in 2002-2003. Using weighted logistic regression, we examined the EOML-maternity leave duration relationship, controlling for whether the leave was paid, as well as other occupational, personality and health-related covariates. Compared with mothers who were offered more than 12 weeks of maternity leave, mothers with <6 weeks of EOML and those offered 6-12 weeks had five times higher odds of returning to work within 12 weeks; those offered no leave had six times higher odds of an early return. These relationships were similar after controlling for whether the leave was paid and after controlling for other occupational and health characteristics. Access to and duration of employer-offered maternity leave significantly determine timing of return to work following childbirth, potentially affecting work-family balance. Policy makers should recognize the pivotal role of employers in offering job security during and after maternity leave and consider widening the eligibility criteria of the Family and Medical Leave Act.


[Research on the analgesic effect and mechanism of bornyl acetate in volatile oil from amomum villosum].
To study the analgesic effect and mechanism of bornyl acetate, the main ingredient of Amomum Villosum Volatile oil. The analgesic effects were tested by pressing tail method. The I, and II phase pain were observed with the pain model caused by formalin test. Influence of naloxone antagonism test on analgesic effect of bornyl acetate. Bornyl acetate produced obvious analgesic effects on pain models induced by pressing tail. Bornyl acetate had inhibitory effect on I and II phase pain in formalin inducing pain model animals. Analgesic effect induced by Bornyl acetate wasn't significantly reduced by naloxone. Bornyl acetate shows analgesic effects. The analgesic site may locate in both central and peripheral nervous system. Its analgesic action way not be related to the opioid receptor.


[Risk groups in travel to tropical countries within the frame of mass tourism].
More than 10,000 tourists returning from tropical countries have been asked about health problems during their stay abroad. Preliminary results from the first 5,550 questionnaires indicate that 74,8% had complaints of any kind concerning their health and 13,6% can be considered as having been ill. The frequency of complaints and illness in relation to different variables is shown and the possibility of definition of high risk groups is being discussed.


Patient, radiological, and operative factors associated with surgical difficulty in the extraction of third molars: a systematic review.
The aim of this systematic review was to determine the patient, radiological, and operative variables associated with surgical difficulty in the extraction of third molars, according to a visual analogue scale completed by the surgeon, operative time, or surgical technique. Searches of the PubMed (MEDLINE), Scopus, and Cochrane Library databases were conducted by two independent reviewers. Randomized and non-randomized clinical trials and prospective cohort studies evaluating surgical difficulty in the extraction of impacted mandibular or maxillary third molars according to patient, radiological, and operative variables were included. The full texts of 21 of the 859 articles initially retrieved were analysed, and 15 articles were included in the final systematic review. All 15 reported prospective cohort studies. The following variables were found to be on the spectrum of highly difficult or complex cases: older patient age and being overweight (patient variables), surgeons with little experience and the use of complex surgical techniques requiring tooth sectioning linked to hard tissue impaction (operative variables), and adverse radiological factors such as deep impaction, unfavourable angulation and root morphology, and a close relationship with the second molar, maxillary sinus, or the inferior alveolar nerve canal (radiological variables).


Evaluating the Health-Related Quality of Life of the Rare Disease Population in Hong Kong Using EQ-5D 3-Level.
This study aimed to establish a normative profile of health-related quality of life (HRQOL) of the rare disease (RD) population in Hong Kong (HK) and identify potential predictors. Between March 2020 and October 2020, patients with RD and caregivers were recruited through Rare Disease Hong Kong, the largest RD patient group alliance in HK. HRQOL was derived using the EQ-5D 3-Level with reference to the established HK value set. Utility scores were stratified according to demographics and disease-related information. Multiple linear regression was performed to explore the associations between patient characteristics and HRQOL. A total of 286 patients, covering 107 unique RDs, reported a mean utility score of 0.53 (SD 0.36). Thirty patients (10.5%) reported negative utility scores, indicating worse-than-death health states. More problems were recorded in the "usual activities" and "self-care" dimensions. Univariate analyses revealed that neurologic diseases, high out-of-pocket expenditure, home modification, and living in public housing or subdivided flats/units were significantly associated with lower HRQOL. A total of 99 caregivers reported a mean utility score of 0.78 (SD 0.17), which was significantly associated with the utility score of patients they took care of (r = 0.32; P = .001). The normative profile of the RD population was established, which revealed lower HRQOL in the RD population than other chronic disease groups and general population in HK. Findings were corroborated by evidence from other cohorts using EQ-5D, combined as part of a meta-analysis. Identifying predictors highlight areas that should be prioritized to improve HRQOL of RD population through clinical and psychosocial dimensions.


Outcomes of Concomitant Coronary Artery Bypass Grafting in Patients With Infective Endocarditis: A Systematic Review and Meta-Analysis.
It is current practice to perform concomitant coronary artery bypass grafting (CABG) in patients with infective endocarditis who have relevant coronary artery disease. However, CABG may add complexity to the operation. We performed a systematic review and a meta-analysis of studies that presented outcomes from patients who underwent valve surgery because of infective endocarditis with or without concomitant CABG. Three databases were assessed. Perioperative mortality was the primary outcome. Long-term mortality and postoperative stroke were the secondary outcomes. Inverse variance method and random model were performed. Five studies with a total of 5,408 patients were included. Mean follow-up was 8.2 years. Just 1 study addressed exclusively patients with documented coronary artery disease. Perioperative mortality did not differ between patients with or without concomitant CABG (odds ratio 1.53, 95% confidence interval 0.52 to 4.48, p = 0.44). Long-term mortality did not differ between patients who received and those who did not receive concomitant CABG (odds ratio 1.79, confidence interval 0.88 to 3.65, p = 0.11). Only 1 study from a multicenter registry reported data on the occurrence of postoperative stroke, which demonstrated that its incidence after adjustment was 26% in patients with concomitant CABG versus 21% in patients without concomitant CABG (p = 0.003). The results suggest that in endocarditis patients, adding CABG to valve surgery does not affect perioperative or long-term mortality. Data available on the impact of concomitant CABG on neurologic outcomes are limited to a retrospective multicenter registry and suggest that concomitant CABG may be associated with higher postoperative stroke.


Entrustable professional activities in nursing: A concept analysis.
Entrustable professional activities (EPAs) is a newly emerging concept. This paper aims at analyzing the concept of "EPAs" to clarify the meaning and to identify its components for optimum understanding of the concept for use in nursing education and future research. Three databases - ProQuest, Ovid, and PubMed- were retrieved, and Walker and Avant's concept analysis approach was used to analyze the concept of EPAs. Based on the analysis, three attributes of EPAs were defined, namely 1) EPAs should be restricted to a limited number of tasks; 2)reflect the experience curve; and 3) include acceptance of responsibility and accountability. The antecedent of EPAs is a holistic and integrated assessment approach. This will eventually lead to anticipated consequences such as a mastery of core competencies and an increase in the level of autonomy. The study may contribute to a reduction in the ambiguity of this concept to better apply it in nursing practice.


Brain oxytocin receptors mediate ejaculation elicited by 7-hydroxy-2-(di-N-propylamino) tetralin (7-OH-DPAT) in anaesthetized rats.
The involvement of the neuropeptide oxytocin in the control of male sexual responses is documented although its exact mechanisms of action, and especially the site(s) of action, are not fully delineated. In order to clarify this issue, we tested the effects of a peptide oxytocin antagonist delivered through different routes on sexual responses elicited, in anaesthetized male rats, by i.c.v. 7-hydroxy-2-(di-N-propylamino) tetralin (7-OH-DPAT), a dopamine agonist, preferentially active on D3 receptors. Seminal vesicle pressure (SVP) and bulbospongiosus muscle (BS) electromyograms were recorded as physiological markers of emission and expulsion phases of ejaculation respectively and intracavernosal pressure (ICP) was monitored as a physiological marker of erection. When injected i.v., the oxytocin antagonist did not impair 7-OH-DPAT-induced SVP and ICP responses while BS burst frequency was diminished. When delivered i.c.v., the oxytocin antagonist dose-dependently inhibited occurrence of 7-OH-DPAT-induced sexual responses. When delivered intrathecally (i.t.) at the level of the 6th lumbar (L6) segment, but not the 13th thoracic (T13) segment, the oxytocin antagonist reduced the duration of BS responses and the occurrence of ejaculation without impairing ICP responses. Brain oxytocin receptors mediate male sexual responses elicited by i.c.v. 7-OH-DPAT in anaesthetized rats whereas L6 spinal oxytocin receptors only impair the occurrence of ejaculation. Peripheral oxytocin receptors are marginally involved in 7-OH-DPAT-induced sexual responses. These findings should be considered for the development of potential pharmacological treatment of premature ejaculation in man.


Association between family members of dialysis patients and chronic kidney disease: a multicenter study in China.
Family members of patients with end stage renal disease were reported to have an increased prevalence of chronic kidney disease (CKD). However, studies differentiated genetic and non-genetic family members are limited. We sought to investigate the prevalence of CKD among fist-degree relatives and spouses of dialysis patients in China. Seventeen dialysis facilities from 4 cities of China including 1062 first-degree relatives and 450 spouses of dialysis patients were enrolled. Sex- and age- matched controls were randomly selected from a representative sample of general population in Beijing. CKD was defined as decreased estimated glomerular (eGFR<60 mL/min/1.73 m2) or albuminuria. The prevalence of eGFR less than 60 mL/min/1.73 m2, albuminuria and the overall prevalence of CKD in dialysis spouses were compared with their counterpart controls, which was 3.8% vs. 7.8% (P<0.01), 16.8% vs. 14.6% (P=0.29) and 18.4% vs. 19.8% (P=0.61), respectively. The prevalence of eGFR less than 60 mL/min/1.73 m2, albuminuria and the overall prevalence of CKD in dialysis relatives were also compared with their counterpart controls, which was 1.5% vs. 2.4% (P=0.12), 14.4% vs. 8.4% (P<0.01) and 14.6% vs. 10.5% (P<0.01), respectively. Multivariable Logistic regression analysis indicated that being spouses of dialysis patients is negatively associated with presence of low eGFR, and being relatives of dialysis patients is positively associated with presence of albuminuria. The association between being family members of dialysis patients and presence of CKD is different between first-degree relatives and spouses. The underlying mechanisms deserve further investigation.


Distribution of endosulfan in plasma and brain after repeated oral administration to rats.
Rats were fed endosulfan (5 or 10 mg/kg) containing alpha- and beta-isomers in the ratio of 2:1, daily for 15 days. The distribution pattern of endosulfan, its isomers and metabolite, endosulfan sulfate, was estimated in the plasma and brain of the rats. On day 16, the alpha-isomer in rats receiving 5 mg/kg was highest in the cerebrum (3.76 microgram/g) followed by the remaining part of the brain (2.66 microgram/g), and the cerebellum (2.04 microgram/g). The concentration of the beta-isomer was 0.06 microgram/g in the cerebrum and 0.02 microgram/g in the cerebellum; no beta-isomer was detected in the remaining part of the brain. The plasma concentration of alpha- and beta-isomers was 2.26 and 0.46 microgram/ml, respectively. No metabolite other than endosulfan sulfate was detected in plasma. No significant changes in brain tissue were observed in any of the groups under treatment. On day 30 (15 days after the last treatment), the concentration in plasma declined more rapidly than that in the brain tissue. At a higher dose (10 mg/kg), the distribution pattern of isomers and its metabolite, endosulfan sulfate, followed almost the same trend except that the concentration was higher than in rats receiving lower doses.


Effects of pH on inactivation of maize phosphoenolpyruvate carboxylase.
Maize leaf phosphoenolpyruvate carboxylase (PEPC) is inactivated by incubation at pH's above neutrality. Both the amount and the rapidity of inactivation increase as the pH rises. The presence of phosphoenolpyruvate (PEP), malate, glucose 6-phosphate and dithiothreitol in the incubation medium give protection to the enzyme. While the presence of PEP during incubation at pH 8 prevents inactivation, the level of PEP in the assay after incubation has no effect on the relative inactivation. When the enzyme is incubated at pH 7 with 5 mM malate (a treatment known to cause dimerization) subsequent assay at saturating levels of MgPEP completely restores activity while assay at less than Km MgPEP produces greater than 99% inhibition of the same sample, showing that high PEP concentration has reconverted the PEPC to the malate-resistant tetramer. Thus the protective effect of PEP against inactivation at high pH probably is not related to its effect on the aggregation state of the enzyme but rather is due to the presence of PEP at the active site. Protection of PEPC at pH 8 by EDTA and its inactivation by low concentrations of Cu2- indicates that the loss of activity at high pH probably is in a sense an artifact resulting from the binding to a deprotinated cysteine of heavy metal ions contaminating the enzyme preparation or present in reagents. This suggests that caution should be used in the interpretation of experiments involving PEPC activity at alkaline pH's.


Mapping multiple visual areas in the human brain with a short fMRI sequence.
It is a fundamental insight of neuroscience that the cerebral cortex is divided into spatially separated and functionally distinct areas. In this study, we tried to map a large number of visual areas in individual subjects passively viewing a simple stimulus sequence during functional magnetic resonance imaging (fMRI) at 1.5 T. The blocked stimulus sequence contrasted static object photographs with video takes of movement through natural indoor and outdoor scenes, alternated with a control fixation task. Two runs of the 5-min sequence sufficed to invoke 29 distinguishable activations, 16 (13 bilateral) of which were observed in all 10 participants. At the ventral side, object responsive activations were organized along the lateral occipital-temporal surface and near the collateral and occipital-temporal sulci. The latter activations, corresponding to the lateral occipital complex, showed a different activation profile from those near the collateral sulcus, most likely corresponding to the color constancy areas V4/V8-V4alpha. A potentially new fusiform object area was seen in 6 subjects, even more anterior than the parahippocampal place area. At the dorsal side, consistent activations were mainly related to motion stimuli and included the well-known areas V3a, VIPS, POIPS, hV5+, STS and the cingulate sulcus. There was consistent activation in the parietal-occipital sulcus, containing the areas V6a and V6. In addition, all subjects showed activation in the superior-anterior precuneus. Thus, the short stimulus sequence robustly invoked multiple visual areas and can be used to map the organization of the visual system in normal and brain-damaged individuals.


Relative binding affinity of norgestimate and other progestins for human sex hormone-binding globulin.
The relative binding affinity of norgestimate for human sex hormone-binding globulin was compared with that of its metabolites and other progestins by measuring their abilities to displace [3H]testosterone from this carrier protein in vitro. Norgestimate and its 17-deacetylated and 3-keto metabolites did not significantly displace [3H]testosterone from sex hormone-binding globulin at concentrations up to 10,000 nM, whereas gestodene, levonorgestrel, and 3-keto desogestrel displaced [3H]testosterone from sex hormone-binding globulin with IC50 concentrations of 23.1, 53.4, and 91.0 nM, respectively. Since it is believed that a progestin may exert androgenic effects by displacing testosterone from sex hormone-binding globulin, thereby increasing circulating levels of free, active testosterone, these data are consistent with the results of preclinical and clinical studies demonstrating the selective progestational activity of norgestimate.


Biochemical Effects of Heavy Metals and Organochlorine Compounds Accumulated in Different Tissues of Yellow-Legged Gulls (Larus Michahellis).
In the present study, livers, kidneys and adipose tissue of Yellow-legged Gull (Larus michahellis) were collected. Samples were used to determine relationships between heavy metals/metalloids in liver and kidneys (Hg, Cd, Pb, Se and As) or persistent organic pollutants in adipose tissue (7 PCBs and 11 organochlorine pesticides) with biomarkers of oxidative stress (CAT, GPx, GR, GSH, GST, MDA) analysed in both internal organs. Three possible influencing variables have been studied: age, sex and sampling area. As a result, statistically significant differences (P < 0.05, P < 0.01) were only found according to the sampling area, with differences among the three studied areas found in both organs. Significant positive correlations (P < 0.01) were found in liver (Hg vs. GST; Se vs. MDA) and in kidney (As vs. GR; As vs. GPx; PCB52 vs. CAT; PCB138 vs. CAT). The scarcity in correlations suggests that the levels of pollutants found in animals were not high enough to trigger an effect at the oxidative level.


The current state of research and potential applications of insects for resource recovery and aquaculture feed.
Concerns about fishmeal use and its ecological footprints must be addressed for the aquaculture industry to move on as a sustainable food production sector. Through recent research outcomes, the insect-based meals in fish diets have promise and harnessed promises for commercial applications. In this midst, the efficiency of the selected insects in valorizing biological waste, as well as the nutritional profile of the harvested insects for use in fish diets, will be the driving forces behind such an approach. More extensive research has been published on the suitability of the waste substrate, the nutritional profiling of the meals, the level of substitution, the effects on growth, the immune physiology, and the flesh quality of the animals. Previously, there are only a few reviews available in insect protein applications in aqua feed that focused particularly on the nutritional quality and substitution levels. Considering the dearth of available work, the goal of this review is to provide a more comprehensive account of the resource recovery potential of insects and its derivatives, with a special emphasis on quality as determined by substrate used and processing techniques. Suggestions and policy implications for a sustainable approach to achieving a circular bio-economy of insect farming and its application in aquaculture are discussed for progression and advancement of the existing state of the art.


Effects of Different Loading Types on the Validity and Magnitude of Force-Velocity Relationship Parameters.
Force-velocity (F-V) relationship models gained popularity as a tool for muscle mechanical assessment. However, it is not clear whether the validity of the F-V relationship parameters (maximal theoretical force [F0], velocity [V0] and power [Pmax]) is affected using different load types: gravitational (W, rubber bands pulling the barbell downward), inertial (I, rubber bands pulling the barbell, which is equalized to the weight of the added plates upward), and combined (W + I, weight of the plates). Load type would affect both the magnitude and validity of F-V relationship parameters. The highest magnitude and validity was expected for F0 using a W, for V0 using an I, and for Pmax using a W + I load. Cross-sectional. Level 3. A total of 13 resistance-trained men (body mass, 87.7 ± 11.2 kg and body height, 183.9 ± 6.4 cm) performed bench press (BP) throws (BPTs) using 3 types of loads against 30 to 80 kg. The validity of F-V relationship parameters was explored with respect to the tests used traditionally for force (maximal voluntary contraction and 1-repetition maximum [1RM]), velocity (maximal velocity achieved during almost unloaded tasks), and power (BPT against the 50%1RM and medicine ball throws) assessment. The W + I loading promoted the highest values of F0 and Pmax, while the highest magnitude of V0 was promoted by the I loading. The validity was acceptable for F0 obtained using the 3 loading conditions with respect to the BP 1RM (r range, 0.30-0.83), and V0 obtained using the I loading with respect to the stick throw (r = 0.54). The magnitude of the F-V relationship parameters is affected by load type, but their validity with respect to standardized tests is comparable, with the exception of the higher validity of V0 when obtained using the I loading. Any load type can be used for assessing F0, while I load should be selected when assessing V0.


Prognostic value of mild-to-moderate pulmonary hypertension in patients with severe aortic valve stenosis undergoing aortic valve replacement.
Optimal timing of elective aortic valve replacement (AVR) for severe aortic stenosis (AS) is challenging. Hence, a sensitive marker in AS patients indicating increasing risk after AVR would be of great clinical value. In the present study, we hypothesized that mild-to-moderate pulmonary hypertension (PH) assessed prior to AVR is a sensitive marker for adverse events in patients after successful AVR. We enrolled 200 consecutive patients with severe AS undergoing AVR. Among them, 176 patients (88%) were symptomatic. Patients were divided according to systolic pulmonary artery pressure (PAP(sys)) into three groups: no PH (PAP(sys) <30 mmHg), mild-to-moderate PH (PAP(sys) ≥30 and PAP(sys) <60 mmHg) and severe PH (≥60 mmHg). Multivariable analyses were adjusted for age and gender and included PH, left ventricular ejection fraction ≤35%, renal insufficiency and logistic EuroSCORE ≥20%. Primary endpoint was death of any cause within 5 years after AVR. During follow-up, 23 patients died (cumulative 5-year mortality rate 14.6%). Patients without (n = 78), mild-to-moderate (n = 99) and severe PH (n = 23) had 5-year mortality rates of 2.6, 15.2 and 26.1% (p = 0.001). PAPsys ≥30 mmHg yielded an excellent level of sensitivity of 92.8%. On multivariable analysis, mild-to-moderate PH was the only independent risk factor (hazard ratio 4.9, 95% confidence interval 1.1-21.8). In patients with severe AS undergoing AVR, mild-to-moderate PH is a strong and independent predictor of late mortality. Conversely, patients with normal PAP(sys) have an extremely good prognosis.


The effect of dietary nicotine on the allocation of assimilated food to energy metabolism and growth in fourth-instar larvae of the southern armyworm, Spodoptera eridania (Lepidoptera: Noctuidae).
Dietary nicotine (0.5%), which is a substrate of the PSMO (polysubstrate monooxygenase) detoxification system in the southern armyworm Spodoptera eridania, has significant negative effects on the weight of food ingested, weight gained, relative growth rate (RGR), and efficiency of conversion of digested food (ECD) by fourthinstar S. eridania larvae on a nutrient-rich artificial diet. It has a significant positive effect on the weight of food respired by the larvae. Thus, the detoxification of nicotine by the PSMO system exacts a fitness cost and imposes a metabolic cost on S. eridania larvae. In contrast, dietary α-(+)-pinene, an inducer of the PSMO system, neither exacts a fitness cost nor imposes a metabolic cost on the larvae. We believe this to be the first study to demonstrate unequivocally that the negative effect of a dietary toxin on net growth efficiency (ECD) in an insect herbivore is due to an increase in the allocation of assimilated food to energy metabolism and not to a decrease in the amount of food assimilated. This study, therefore, supports the hypothesis that detoxification can impose a significant metabolic load on an insect herbivore. Implications of a corroboration of the metabolic load hypothesis are discussed.


Short- and mid-term effects of sleeve gastrectomy on left ventricular function with two-dimensional speckle tracking echocardiography in obese patients.
This study aimed to investigate left ventricular functions of obese patients with no known heart disease who underwent laparoscopic sleeve gastrectomy by speckle tracking echocardiography in their early and medium-term postoperative follow-up. Thirty-seven obese patients (10 M, 27 F) without coronary artery disease or heart failure who had undergone LSG were included in the study. Apical four-, three-, and two-chamber images were analyzed longitudinally by conventional methods and speckle tracking echocardiography (STE) for left ventricle functions preoperatively, at the postoperative Month 1 and at the postoperative Month 6 (QLAB 6.0), using current software. No difference was found between standard echocardiography and Doppler parameters in terms of the 1-month versus 6-month follow-up values compared to baseline. Left ventricular STE longitudinal measurements demonstrated significantly higher longitudinal strain and strain velocity parameters in the follow-up values at Month 6 compared to the values at Month 1 and at baseline. Global longitudinal strain (GLS) was -17.48 ± 1.09% in 6-month follow-up, -16.16 ± 1.26% in 1-month follow-up, and -16.06 ± 1.25% at baseline (P < .001). A significant correlation was found between delta GLS, which represents patients' GLS change in 6 months, and delta weight, which represents patients' body weight change in 6 months. Obese patients who had undergone LSG were observed to have improved left ventricular function in the mid-term.


The use of band-selectable digital filtering in magnetic resonance image enhancement.
Manipulation of the data describing two-dimensional magnetic resonance (MR) images can be used to zoom an image, decrease image noise and artifacts by modeling, or emphasize object edges in the field of view. In this paper, a two-dimensional band-selectable digital filtering (2D-BSDF) technique is detailed. This can be used to decrease the computational burden and increase algorithm stability associated with such data manipulation. Many display devices have the ability of expanding an image by pixel or linear interpolation. Application of the efficient zooming fast Fourier transformation algorithms provides a superior quality sinc-function interpolated image. In 2D-BSDF, the ideal rectangular windows used in sinc-function interpolation are replaced by windows with a more gradual roll-off. This gradual roll-off results in a slight degradation of the image edges but substantially reduces the computation time. Modeling of MRI data has been attempted to remove noise and artifacts from the image. These algorithms are computationally expensive and frequently unstable because of the high model orders required. The 2D-BSDF can be used to prepare a reduced data set, without loss of information. A lower order model may be applied to the subset and computation times approaching that required for normal fast Fourier transform algorithms result. The absence of noise and signal from objects outside the region of interest can considerably enhance the stability of the modeling algorithms. The use of BSDF is equally applicable when used in association with the modeling of 2D NMR spectroscopy data or with edge enhancement or any other data manipulation of magnetic resonance imaging images. In this paper an explanation of 1D-BSDF is provided and an algorithm for 2D-BSDF is developed. A comparison of filter designs and computational times is given when applying the technique to zooming and modeling of MR images. Images from medical MRI data are provided.


Efficacy and Safety of Dose Escalation to Adalimumab 80 mg Every Other Week in Japanese Patients with Crohn's Disease Who Lost Response to Maintenance Therapy.
Dose escalation is often recommended for loss of response in anti-TNFα-treated patients with Crohn's disease (CD). This 52-week phase 3, multicenter study investigated the efficacy and safety of escalation to adalimumab 80 mg every other week (EOW) in Japanese patients with CD who lost response to maintenance adalimumab 40 mg EOW. Twenty-eight patients aged ≥15 years with moderately to severely active CD who had previously attained and subsequently lost clinical response to maintenance ada limumab received open-label adalimumab 80 mg EOW during weeks 0-50. Loss of response was defined as CD activity index (CDAI) ≥200, increases in CDAI ≥50 from minimum observed value, and C-reactive protein (CRP) ≥1 mg/dL at screening. The primary endpoint was the proportion of patients achieving a CDAI decrease ≥50 (CR-50) from baseline at week 8. At weeks 8 and 52, 75.0 and 57.1$ of patients achieved CR-50 and 25.0 and 35.7$ achieved clinical remission (CDAI < 150), respectively; median CRP changes from baseline were -0.39 and -0.77 mg/dL, respectively. Most treatment-emergent adverse events were mild to moderate. Adalimumab dose escalation to 80 mg EOW improved CD activity in patients who had lost response to maintenance adalimumab, with no new safety signals. (ClinicalTrials.gov Identifier: NCT01958827.).


Rebound hypertension after sudden discontinuation of methyldopa therapy.
A case of "rebound hypertension" resulting from the sudden cessation of methyldopa (Aldomet) therapy is described. The importance of educating patients about the possible outcome of abruptly withdrawing antihypertensive medication is emphasized.


Perspectives, practices, and challenges of online teaching during COVID-19 pandemic: A multinational survey.
The result of the movement restrictions during the COVID-19 pandemic was an impromptu and abrupt switch from in-person to online teaching. Most focus has been on the perception and experience of students during the process. The aim of this international survey is to assess staffs' perspectives and challenges of online teaching during the COVID-19 lockdown. Cross-sectional research using a validated online survey was carried out in seven countries (Brazil, Saudi Arabia, Jordan, Indonesia, India, the United Kingdom, and Egypt) between the months of December 2021 and August 2022, to explore the status of online teaching among faculty members during the COVID-19 pandemic. Variables and response are presented as percentages while logistic regression was used to assess the factors that predict levels of satisfaction and the challenges associated with online instruction. A total of 721 response were received from mainly male (53%) staffs. Most respondents are from Brazil (59%), hold a Doctorate degree (70%) and have over 10 years of working experience (62%). Although, 67% and 79% have relevant tools and received training for online teaching respectively, 44% report that online teaching required more preparation time than face-to-face. Although 41% of respondents were uncertain about the outcome of online teaching, 49% were satisfied with the process. Also, poor internet bandwidth (51%), inability to track students' engagement (18%) and Lack of technical skills (11.5%) were the three main observed limitations. Having little or no prior experience of online teaching before the COVID-19 pandemic [OR, 1.58 (95% CI, 1.35-1.85)], and not supporting the move to online teaching mode [OR, 0.56 (95% CI,0.48-0.64)] were two main factors independently linked with dissatisfaction with online teaching. While staffs who support the move to online teaching were twice likely to report no barriers [OR, 2.15 (95% CI, 1.61-2.86)]. Although, relevant tools and training were provided to support the move to online teaching during COVID-19 lockdown, barriers such as poor internet bandwidth, inability to track students' engagement and lack of technical skills were main limitations observed internationally by teaching staffs. Addressing these barriers should be the focus of higher education institution in preparation for future disruptions to traditional teaching modes.


Anti-C-reactive protein antibodies in chronic hepatitis C infection: correlation with severity and autoimmunity.
The aim of this work was to detect circulating anti-C-reactive protein (CRP) antibodies in serum samples of patients with chronic hepatitis C virus (HCV) and to investigate a possible association with other autoimmune manifestations. A total of 94 patients with chronic HCV infections and 108 healthy controls were enrolled. All patients underwent a baseline evaluation: immunological assessment of cryoglobulin,antinuclear antibodies (ANA), rheumatoid factor (RF), anticardiolipin (aCLA), and anti-CRP antibodies. Patients with HCV underwent a liver biopsy scored according to the modified Knodell score. Anti-CRP antibodies were detected in 17% of HCV patients compared with 6.4% of the healthy controls (p < 0.025). When HCV patients positive for anti-CRP antibodies were compared with patients who were negative for anti-CRP antibodies, the prevalence of positive RF was significantly higher, 50% versus 17.9% (p < or = 0.05). Cryoglobulinemia was also significantly more frequent in patients who were positive for anti-CRP antibodies, 75% versus 32%, p < or = 0.01. ANA and aCLA did not differ significantly between the two groups. The presence of anti-CRP antibodies was associated with greater liver disease severity (histology activity index, 9 +/- 3.3 versus 6 +/- 2.9, p = 0.01). An increased prevalence of anti-CRP antibodies was manifested in HCV-infected patients. The presence of anti-CRP antibodies correlated with the presence RF, cryoglobulinemia, and severity of liver disease.


Detection of circulating tumor cells and tumor stem cells in patients with breast cancer by using flow cytometry: a valuable tool for diagnosis and prognosis evaluation.
Circulating tumor stem cells (CTSC), a subpopulation of circulating tumor cells (CTC), may lead to recurrent diseases. The aim of this study was to detect CTC (CD45(-)EpCAM(+)) and CTSC (CD45(-)EpCAM(+)CD44(+)CD24(-)) of breast cancer (BC) patients, as well as to explore their clinical relevance. CTC and CTSC in peripheral blood (PB) of 45 female BC patients were detected by using flow cytometry (FCM). SKBR-3 cells were mixed with MNC of four healthy volunteers at different ratios in order to evaluate the sensitivity of FCM. Real-time quantitative polymerase chain reaction (QRT-PCR) was conducted and compared with FCM. The expression of EPCAM between CTC < 50 and CTC ≥ 50 groups (19.98 ± 23.93 versus 29.46 ± 29.27 × 10(-5)), and the expression of CD44 between CTSC negative and positive groups (0.85 ± 0.91 versus 0.81 ± 0.75) were statistically the same. FCM had higher specificity than QRT-PCR. Statistical differences were obtained between CTC < 50 and CTC ≥ 50 groups among different TNM stages, histology stages, estrogen receptor (ER) status and progesterone receptor (PR) status (P < 0.05). Statistical differences between CTSC negative and positive groups within different TNM stages and regional lymph node metastasis (RLNM) status (P < 0.05) were also obtained. Moreover, the percentage of CTC on CD45 negative cells (CD45(-)C) among different clinical pathology was statistically different, P = 0.000. Additionally, the percentage of CTSC on CD45(-)C with TNM stage was rising (0: 0.00 ± 0.00‰, I: 0.03 ± 0.05‰, II: 0.06 ± 0.14‰, III: 0.10 ± 0.09‰, IV: 0.29 ± 0.35‰, P = 0.034). Statistical difference in the percentage of CTSC on CD45(-)C among different RLNM status (P = 0.001) was also obtained. FCM to detect CTC and CTSC may be used to diagnose disease at early stage, to guide clinical therapy or to predict prognosis.


Effectiveness of ultrasound screening in right upper quadrant pain: A comparative study in a basic emergency service.
The use of ultrasound screening is primarily facilitated by point-of-care ultrasound (POCUS) and its integration into healthcare systems is a result of the versatility of this imaging technique. This study intends to compare the accuracy and pertinence of sonographic findings obtained by a sonographer in a Basic Emergency Service (BES) with that of radiologists at referral hospital (RH) in Portugal. Twenty patients with right upper quadrant (RUQ) pain and suspected cholecystitis or biliary pathology underwent sonography screening using POCUS in the BES. They were then forwarded to the RH where a radiologist performed a conventional ultrasound exam on the same patients. The results of both exams were compared to determine if the findings obtained in the BES were confirmed by the radiologist in the RH. In our sample, 60% of cases were related to biliary pathology, 20% were liver-related, 10% had hepatopancreatic biliary etiology, and 10% had unknown etiology. A strong association between the sonographic findings in the BES and the RH was found in the variables "Sonographic Murphy sign" (V = 0.859; p = 0.001), "Cholelithiasis/Gallbladder sludge" (V = 0.840; p = 0.001), and "Intrahepatic biliary tract dilatation" (V = 0.717; p = 0.006). Adequate measures of agreement between the findings of the radiographer and radiologist were obtained for the "Sonographic Murphy sign" (k = 0.664; p = 0.001) and the presence of "Cholelithiasis/Gallbladder sludge" (k = 0.712; p = 0.000). Major biliary abnormalities were detected in patients with RUQ pain in BES using sonography. The correlation between the sonographic findings obtained by the sonographers at BES and those obtained by radiologists at the RH in Portugal was strong, showing that POCUS screening could be extended to other similar settings; however, more studies are needed.


Prognostic Significance of Sleep Apnea Syndrome on False Lumen Aortic Expansion in Post-Acute Aortic Syndrome.
Obstructive sleep apnea syndrome (OSAS) is a risk factor for resistant arterial hypertension and aortic dilatation. We assessed the value of systematic screening for OSAS in patients soon after the onset of acute aortic syndrome (AAS). Between January 2010 and June 2014, patients were prospectively screened for post AAS OSAS. The severity of OSAS was defined by the Apnea-Hypopnea Index (AHI) and the Oxygen Desaturation Index (ODI). Blood pressure control was assessed with 24-h ambulatory monitoring. The study population comprised 71 patients (males: 64.7%; median age [interquartile range]: 57 [49 to 64] years; type A AAS: 49.3%; type B AAS: 50.7%). According to the AHI, 58 patients (81.7%) had OSAS and 31 (43.6%) had severe OSAS. A prognostic analysis revealed that the descending thoracic false lumen dilatation rate rose significantly with the severity of OSAS (p = 0.0008 for the AHI and p = 0.0284 for the ODI). The median rate of increase was 7.5 (5 to 10) mm/year in the AHI greater than 30 events/h group and 5.0 (0 to 8) mm/year in the ODI greater than 30 events/h group. With regard to blood pressure control, the diastolic blood pressure varied as function of the ODI category (p = 0.0074). Our results suggest that systematic screening for post-ASS OSAS is of value. The false lumen dilatation rate appears to be related to the severity of OSAS. It remains to be seen whether treatment of OSAS would modify the false lumen dilatation rate.


A survey of ixodid ticks feeding on cattle and prevalence of tick-borne pathogens in the Black Sea region of Turkey.
The study reports the frequency of infestation and the prevalence of tick-borne pathogens in feeding adult ticks detached from cattle in two climatic zones of the Black Sea region of Turkey. A total of 2160 adult ticks were collected during 2007-2008. Of these, 1062 were randomly selected, divided into 224 pools, and tested for the presence of bovine Theileria, Babesia, and Anaplasma species. Eleven tick species were recognized on cattle in the study. Hyalomma marginatum was widely disrubuted in the semi-arid bioclimatic zone, but few specimens were collected in the humid bioclimatic zone. The most prevalent tick species in the humid climatic zone was Ixodes ricinus. Infection rates were calculated as the maximum likelihood estimation with 95% confidence intervals (CI). Overall, 4% (CI 2.87-5.44) of 224 tick pools were found to be positive for the pathoges by Reverse line blot. Maximum likelihood estimation of the infection rate varied among tick species, ranging from 2.68% (CI 0.16-12.68) in Haemaphysalis sulcata to 10.49% (CI 4.07-23.66) in Rhipicephalus bursa. The most prevalent tick-borne pathogen was Anaplasma phagocytophilum at 6.78% (CI 3.41-12.18) followed by A. centrale (6.56%, CI 0.42-31.47), Anaplasma/Ehrlichia spp. (3.61%, CI 1.99-6.06), Babesia spp. (3.33%, CI 1.65-6.03), and T. buffeli/orientalis (2.71%, CI 0.73-7.18). Sequencing results indicated that Babesia spp. shared 99% to 100% similarity with the unnamed Babesia sp. Kashi 1 and 2, Babesia sp. Kayseri 1 and Babesia sp.CS58. Anaplasma/Ehrlichia spp. were 98% and 100% identical to Ehrlichia canis and Ehrlichia sp. Omatjenne strain, respectively.


Global longitudinal strain as an Indicator of cardiac Iron overload in thalassemia patients.
Cardiac involvement due to iron overload is the most common cause of morbidity and mortality in patients with thalassemia, and many patients remain asymptomatic until the late stages. Therefore, early detection of heart problems in such patients at subclinical stages can improve the prognosis of these patients. We investigated the role of speckled tracking (SI) and tissue Doppler echocardiography (TDI) in early detection of iron overload in these patients. 52 thalassemic patients who were receiving regular blood transfusion with normal global LV function were examined by two- and three-dimensional echocardiography. Cardiac MRI was done and T2* images were considered as the non-invasive gold standard for evaluating cardiac iron deposition. Serum ferritin level was assessed and the relationships between serum ferritin levels and echo finding with cardiac MRI T2* was investigated. No significant relationship was seen between serum ferritin levels and cardiac MRI T2*. Among the echocardiographic findings, septal systolic myocardial velocity (P = 0.002 and r = 0.43) and global strain (GLS) (P = 0.000 and r = 0.60) were significantly associated with T2*. A GLS < 19.5 could predict a T2* level below 20 by 82.14% sensitivity and 86.36% specificity (area under the curve = 0.87; p < 0.0001). While serum ferritin level and ejection fraction are not useful candidates, GLS may be used as a valuable marker to screen thalassemia patients for myocardial iron deposition, using a cut off value below - 19.5. This approach may facilitate the cardiac follow up, reduce the costs, and contribute to preventing deterioration of cardiac function in countries with limited availability of cardiac MRI.


An attentional limbo: Saccades become momentarily non-selective in between saliency-driven and relevance-driven selection.
Human vision involves selectively directing the eyes to potential objects of interest. According to most prominent theories, selection is the quantal outcome of an ongoing competition between saliency-driven signals on the one hand, and relevance-driven signals on the other, with both types of signals continuously and concurrently projecting onto a common priority map. Here, we challenge this view. We asked participants to make a speeded eye movement towards a target orientation, which was presented together with a non-target of opposing tilt. In addition to the difference in relevance, the target and non-target also differed in saliency, with the target being either more or less salient than the non-target. We demonstrate that saliency- and relevance-driven eye movements have highly idiosyncratic temporal profiles, with saliency-driven eye movements occurring rapidly after display onset while relevance-driven eye movements occur only later. Remarkably, these types of eye movements can be fully separated in time: We find that around 250 ms after display onset, eye movements are no longer driven by saliency differences between potential targets, but also not yet driven by relevance information, resulting in a period of non-selectivity, which we refer to as the attentional limbo. Binomial modeling further confirmed that visual selection is not necessarily the outcome of a direct battle between saliency- and relevance-driven signals. Instead, selection reflects the dynamic changes in the underlying saliency- and relevance-driven processes themselves, and the time at which an action is initiated then determines which of the two will emerge as the driving force of behavior.


Effect of honey and propolis, compared to acyclovir, against Herpes Simplex Virus (HSV)-induced lesions: A systematic review and meta-analysis.
Apitherapy is a branch of traditional medicine that uses bee products to manage numerous diseases. In this context, the antiherpetic effect of these bee products has been demonstrated in some studies with some controversial results. Thus, we conducted a systematic review and meta-analysis to compare the effectiveness of honey and propolis with acyclovir, the reference drug, in the treatment of cold sores and genital herpes. The selection of eligible studies was conducted through the search in Pubmed/MEDLINE, Scopus, Cochrane Library, LILACS, and Electronic Scientific Library. The search yielded 147 articles, of which nine were considered eligible for analysis. The analysis of these studies showed that the healing property of propolis is superior to that obtained for acyclovir (95% CI: 2.70 to 8.25; p = 0.0001). Furthermore, honey also presented a better healing effect than acyclovir against Herpes simplex virus-induced wounds (95% CI: 3.58 to -0.19; p = 0.03), inducing complete re-epithelization of herpetic lesions after 8 days, while for acyclovir, the healing time average was 9 days. It also provoked a similar reduction of pain caused by herpetic compared to acyclovir (95% CI: 2.27 to -0.42; p = 0.18). Overall, these results confirm the use of honey and propolis as potent antiherpetic agents.


Induction of muscle cramps by nociceptive stimulation of latent myofascial trigger points.
The aim of this present study is to test the hypothesis that nociceptive stimulation of latent myofascial trigger points (MTrPs) increases the occurrence of local muscle cramps. Nociceptive muscle stimulation was obtained by a bolus injection of glutamate (0.1 ml, 0.5 M) into a latent MTrP and a control point (a non-MTrP) located in the right or left gastrocnemius medialis muscles in 14 healthy subjects. A bolus of isotonic saline (0.9%, 0.1 ml) injection served as a control. The injections were guided by intramuscular electromyography (EMG) showing resting spontaneous electrical activity at a latent MTrP and no such activity at a non-MTrP. Intramuscular and surface EMG activities in the gastrocnemius medialis muscle were recorded pre-, during-, and post-injection for a period of 8 min to monitor the occurrence of muscle cramps, which are characterized by a brief episodic burst of high levels of EMG activity. The results showed that glutamate and isotonic saline injections into the latent MTrPs induced higher peak pain intensity than into the non-MTrPs (both P < 0.05). Glutamate injection induced higher peak pain intensity than isotonic saline injection into either latent MTrPs or non-MTrPs (both P < 0.05). Muscle camps were observed in 92.86% of the subjects following glutamate injection into the latent MTrPs, but not into the non-MTrPs (P < 0.001). No muscle cramps were recorded following isotonic saline injection into either the latent MTrPs or the non-MTrPs. These results suggest that latent MTrPs could be involved in the genesis of muscle cramps. Focal increase in nociceptive sensitivity at MTrPs constitutes one of the mechanisms underlying muscle cramps.


Drancourtella massiliensis gen. nov., sp. nov. isolated from fresh healthy human faecal sample from South France.
Strain GD1(T) gen. nov., sp. nov., is the type strain of the newly proposed genus and species Drancourtella massiliensis, belonging to the Clostridiales order. This strain, isolated from the stool of a healthy person, is a Gram-positive rod, oxygen intolerant and nonmotile, with spore-forming activity. The features of this organism and its genome sequence are described. The draft genome is 3 057 334 bp long with 45.24% G + C content; it contains 2861 protein-coding genes and 64 RNA genes.


Effects of a single session of transcranial direct current stimulation on static balance in a patient with hemiparesis: a case study.
[Purpose] Cerebrovascular accident (stroke) is characterized by an abrupt onset of focal or global neurological signs and symptoms. Asymmetry of the limbs is common following a stroke due to hemiplegia or hemiparesis. [Subject and Methods] A male patient having suffered an ischemic stroke was initially evaluated using the Timed Up-and-Go Test and the Six-Minute Walk Test. Static balance was evaluated using a force plate (Kistler model 9286BA) for the stabilometry analysis of center of pressure (COP) sway. The data were interpreted using the SWAY software program (BTS Engineering) synchronized with the SMART-D 140(®) system. Anodal transcranial direct current stimulation (tDCS; 2 mA) was applied over the primary motor cortex for 20 minutes during gait training on a treadmill. [Results] Under the condition of eyes open, reductions were found in anteroposterior sway (6.18%), trace length (3.3%) and sway velocity (3.3%) immediately following tDCS. [Conclusion] A single session of anodal tDCS combined with treadmill training had a positive effect on the static balance of a subject with chronic hemiparesis stemming from a stroke.


Immunologic evaluation of shrimp-allergic individuals.
Thirty-three individuals with a history of immediate hypersensitivity reactions after shrimp ingestion and 29 nonshrimp-sensitive control subjects were evaluated for evidence of crustacea-specific immunity by skin prick test titration end point, RAST, and ELISA, with extracts of shrimp, crab, crayfish, and lobster. Individuals were categorized as either atopic or nonatopic on the basis of history and skin test reactivity to common inhalant allergens. Most (28/33) shrimp-sensitive subjects had positive skin prick tests to shrimp extract, whereas skin tests were negative in 27/29 control subjects. Eighty-one percent of atopic and 41% of nonatopic shrimp-sensitive subjects had elevated shrimp-RAST ratios. The RAST ratios of atopic individuals were significantly higher than ratios of nonatopic individuals, and there was a significant correlation between shrimp-RAST ratios and historical clinical symptom scores. RAST determinations of all control subjects were negative. Shrimp-sensitive subjects also had significantly elevated serum levels of shrimp-specific IgG and IgA as compared to control individuals. Both IgG and IgA shrimp-specific reactivity demonstrated a significant positive correlation with shrimp-RAST ratios. These studies indicate that IgE-mediated, type I mechanisms, detected by positive shrimp skin tests and RASTs, appear to be operative in crustacea-sensitive individuals, particularly those with concurrent respiratory allergy. Although the role of shrimp-specific IgG and IgA antibodies in the immunopathogenesis of crustacea allergy remains unclear, such antibodies appear to represent increased immunologic recognition of shrimp allergens/antigens in shrimp-sensitive subjects.