De novo variants in CACNA1E found in patients with intellectual disability, developmental regression and social cognition deficit but no seizures.
De novo variants in the voltage-gated calcium channel subunit α1 E gene (CACNA1E) have been described as causative of epileptic encephalopathy with contractures, macrocephaly and dyskinesias. Following the observation of an index patient with developmental delay and autism spectrum disorder (ASD) without seizures who had a de novo deleterious CACNA1E variant, we screened GeneMatcher for other individuals with CACNA1E variants and neurodevelopmental phenotypes without epilepsy. The spectrum of pathogenic CACNA1E variants was compared to the mutational landscape of variants in the gnomAD control population database. We identified seven unrelated individuals with intellectual disability, developmental regression and ASD-like behavioral profile, and notably without epilepsy, who had de novo heterozygous putatively pathogenic variants in CACNA1E. Age of onset of clinical manifestation, presence or absence of regression and degree of severity were variable, and no clear-cut genotype-phenotype association could be recognized. The analysis of disease-associated variants and their comparison to benign variants from the control population allowed for the identification of regions in the CACNA1E protein that seem to be intolerant to substitutions and thus more likely to harbor pathogenic variants. As in a few reported cases with CACNA1E variants and epilepsy, one patient showed a positive clinical behavioral response to topiramate, a specific calcium channel modulator. The significance of our study is limited by the absence of functional experiments of the effect of identified variants, the small sample size and the lack of systematic ASD assessment in all participants. Moreover, topiramate was given to one patient only and for a short period of time. Our results indicate that CACNA1E variants may result in neurodevelopmental disorders without epilepsy and expand the mutational and phenotypic spectrum of this gene. CACNA1E deserves to be included in gene panels for non-specific developmental disorders, including ASD, and not limited to patients with seizures, to improve diagnostic recognition and explore the possible efficacy of topiramate.


Novel and simple method for isolating autologous mesothelial cells from the tunica vaginalis.
To report the development of a new method of isolating autologous mesothelial cells from the tunica vaginalis that are easily obtained and generally free from the effects of abdominal cancer, and to investigate whether transplanting these mesothelial cells is effective in preventing postoperative adhesions. The tunica vaginalis was resected from male Lewis rats, and mesothelial cells were collected by enzymatic disaggregation. To investigate the efficacy of mesothelial cells in preventing adhesion, harvested cells were transplanted into a rat intestinal hernia adhesion model. Cells isolated from the tunica vaginalis were homogenous, polygonal when confluent, expressed cytokeratin and vimentin, and the cell surface was covered with microvilli, which is the characteristic appearance of endogenous mesothelial cells. The transplantation of autologous mesothelial cell sheets reduced peritoneal adhesion. We developed a new method of obtaining autologous mesothelial cells from the tunica vaginalis. These cells may provide a valuable option for treating patients at risk of postoperative adhesions.


Effects of Metabolic Surgery on Diabetic Kidney Disease and Diabetic Retinopathy Among Obese Asian Indians with Type 2 Diabetes.
To evaluate the effect of metabolic surgery on microvascular changes associated with diabetic retinopathy (DR) and diabetic kidney disease (DKD) in obese Asian Indians with type 2 diabetes (T2DM), one year after metabolic surgery. This is a follow up study in 21 obese Asian Indians with T2DM who underwent metabolic surgery (MS). Diabetic microvascular complications were assessed before and one-year post surgery using urinary albumin, protein creatinine ratio, eGFR, retinal colour photography and Optical coherence tomography (OCT). Microalbuminuria (54±26 vs 28±16 vs 21±6 µg/mg, p<0.001) and protein creatinine ratio (0.4±0.1 vs 0.2±0.03 vs 0.1±0.02, p<0.05) reduced significantly 6 months and one year after Metabolic surgery (MS) respectively compared to baseline values. Estimated Glomerular Filtration (eGFR) rate and creatinine was stable and there was no decline in renal function one year after MS. DR was present in eight individuals at baseline. After metabolic surgery, 12 % of individuals achieved regression of DR and 12% individuals showed a one step regression from severe to moderate non proliferative DR while 12 % individuals progressed from moderate to severe non proliferative DR. Of the 14 (53.8%) individuals who had micro or macroalbuminuria at baseline, 43% individuals reverted back to normoalbuminuria. There was also a reduction in the usage of anti- hypertensive medications after MS. In obese Asian Indians with T2DM, metabolic surgery reduced urinary microalbuminuria and protein creatinine ratios at one-year post MS. MS resulted in stable D. Retionpathy status one-year post surgery. MS may help to improve in stabilisation of the microvascular complications in obese patients with T2DM.


Radioproteomics in Breast Cancer: Prediction of Ki-67 Expression With MRI-based Radiomic Models.
We aimed to investigate the value of magnetic resonance image (MRI)-based radiomics in predicting Ki-67 expression of breast cancer. In this retrospective study, 159 lesions from 154 patients were included. Radiomic features were extracted from contrast-enhanced T1-weighted MRI (C+MRI) and apparent diffusion coefficient (ADC) maps, with open-source software. Dimension reduction was done with reliability analysis, collinearity analysis, and feature selection. Two different Ki-67 expression cut-off values (14% vs 20%) were studied as reference standard for the classifications. Input for the models were radiomic features from individual MRI sequences or their combination. Classifications were performed using a generalized linear model. Considering Ki-67 cut-off value of 14%, training and testing AUC values were 0.785 (standard deviation [SD], 0.193) and 0.849 for ADC; 0.696 (SD, 0.150) and 0.695 for C+MRI; 0.755 (SD, 0.171) and 0.635 for the combination of both sequences, respectively. Regarding Ki-67 cut-off value of 20%, training and testing AUC values were 0.744 (SD, 0.197) and 0.617 for ADC; 0.629 (SD, 0.251) and 0.741 for C+MRI; 0.761 (SD, 0.207) and 0.618 for the combination of both sequences, respectively. ADC map-based selected radiomic features coupled with generalized linear modeling might be a promising non-invasive method to determine the Ki-67 expression level of breast cancer.


Thrombospondin-5 and fluvastatin promote angiogenesis and are protective against endothelial cell apoptosis.
The thrombospondins (TSPs), multifunctional matricellular proteins, are known mediators of endothelial cell (EC) angiogenesis and apoptosis. TSP-1, an antiangiogenic molecule, is important in the progression of vascular disease, in part by inducing EC apoptosis. TSP-2, although less studied, also induces EC apoptosis and inhibits angiogenesis. The effects of TSP-5 are largely unexplored in ECs, but TSP-5 is believed to be protective against arterial disease. Statin drugs have been shown to have beneficial pleiotropic effects, including decreasing EC apoptosis, increasing angiogenesis, and blocking TSP signaling. We hypothesized TSP-5 will be proangiogenic and antiapoptotic, and statin pretreatment would reverse the proapoptotic and antiangiogenic phenotype of TSP-1 and TSP-2. ECs were exposed to serum-free medium, TSP-1, TSP-2, or TSP-5 with or without fluvastatin pretreatment. Quantitative real-time polymerase chain reaction was performed on 96 apoptosis and 96 angiogenesis-related genes using microfluidic card assays. Angiogenesis was measured using Matrigel assays, while apoptosis was measured by fluorescent caspase assay. TSP-5 suppressed apoptotic genes and had a mixed effect on the angiogenic genes; however, TSP-5 did not alter apoptois but was proangiogenic. Pretreatment with fluvastatin downregulated proapoptotic genes and apoptosis and upregulated proangiogenic genes and angiogenesis. Findings indicate TSP-5 and fluvastatin have a protective effect on ECs, being proangiogenic and reversing the antiangiogenic effects of TSP-1 and TSP-2. In conclusion, TSP-5 and fluvastatin may be beneficial for inducing angiogenesis in the setting of ischemia.


Identification and differential expression of microRNAs in Madin-Darby canine kidney cells with high and low tumorigenicities.
Madin-Darby canine kidney (MDCK) cells are widely used for vaccine production, however, the safety of MDCK cells needs to be considered seriously because of high tumorigenicity. Micro RNAs (miRNAs) that are involved in the tumorigenicity of MDCK cells have been never been reported. To reveal the role of miRNA in the tumorigenic phenotype of MDCK cell line. The miRNA expression profiles of two monoclonal MDCK cells (M09CL and M35CL) with low tumorigenicity and one MDCK cell line (M73P) with high tumorigenicity were characterized and investigated by using small RNA-seq technology. A total of 5 known miRNAs and 5 novel miRNAs were highly expressed in M73P. In addition, 4 known miRNAs and 4 novel miRNAs were highly expressed in M09CL and M35CL. The target genes of the differentially expressed miRNAs were significantly enriched in several biological processes, and the majority of these genes were involved in pathways in cancer and the MAPK signaling pathway. Through interaction analysis, 4 up-regulated miRNAs (cfa-miR-452, cfa-miR-8826, cfa-miR-224, and cfa-miR-2387) and their crucial target genes related to the tumor regulation network were identified. Results indicated these 4 miRNAs might play crucial roles in the tumorigenesis of MDCK cells. Our findings, which were based on the functional prediction of miRNAs and target genes, suggested that miRNAs might influence the tumorigenicity of MDCK cells by regulating target genes. Moreover, the results provided important data for understanding the miRNA-mediated regulatory networks that control the tumorigenicities of MDCK cells.


Monitoring hemodynamics in the critically ill.
Intelligent, safe patient management based on hemodynamic monitoring requires that the right measurements be made, that the data so generated be accurate, and that the clinician's judgment and understanding of their use be appropriate. This article discusses the catheterization of systemic and pulmonary arteries, with an emphasis on the purposes to be served by monitoring rather than on specific measurements, techniques, or devices.


Rapid detection of Rosa laevigata polysaccharide content by near-infrared spectroscopy.
A method of rapid detecting Rosa laevigata polysaccharide content on the basis of near infrared spectroscopy (NIRS) was established to achieve the purpose of controlling quality of R. laevigata. A total of 129 batches of R. laevigata samples were randomly divided into calibration set and prediction set, number of which were 65 and 64 respectively. The polysaccharide content was measured according to the method provided by Chinese pharmacopoeia, and was 26.05±5.44(%). The Near-infrared diffuse reflectance spectra of R. laevigata were preprocessed by first-order derivative and autoscaling, and was built model with PLS. When 6 Latent variables (LVs) were used in model, the smallest root mean square error of cross validation (RMSECV) was 1.18%, and root mean square error of prediction (RMSEP) was 1.21%. The uninformative variables in spectrum were eliminated by UVE-PLS, and 383 variables were obtained. The prediction accuracy was improved, and RMSECV and RMSEP were 0.90% and 0.99% respectively. Then, 383 variables were further optimized by genetic algorithm (UVE-GA-PLS), and 179 variables were obtained; under this condition, the RMSECV and RMSEP were 0.93% and 1.07% respectively. In this work, result of UVE-PLS was the best. Analyzing variables VIP score in PLS, variable selected by UVE-PLS and UVE-GA-PLS, spectrum region from 7200 cm(-1) to 6700 cm(-1) of the combinations of first and second overtone of C-H and from 5300 cm(-1) to 5000 cm(-1) related to the first overtone of O-H could play an important role in the detection R. laevigata polysaccharide by NIR. Therefore, it was feasible of rapid detection of R. laevigata polysaccharide content by NIRS.


The characteristics and local-regional contributions of atmospheric black carbon over urban and suburban locations in Shanghai, China.
Black carbon (BC), produced from the incomplete combustion of carbonaceous fuels, has emerged as a major contributor to global climate change with adverse health effects. Based on one-year (2016.06.01-2017.06.30) equivalent black carbon (eBC) measurements, this study analyzed the characteristics of eBC concentrations and the local-regional contributions at an urban site (Pudong, PD) and a suburban site (Qingpu, QP) in Shanghai, China. The results showed that the annual average eBC concentrations were 1.17 ± 0.61 μg m-3 and 2.09 ± 0.97 μg m-3 at PD and QP, respectively. The high eBC concentrations occurred in winter and at weekends both for PD and QP. There were significant negative correlation coefficients between the daily eBC, the daily wind speed (WS) and the daily boundary layer height (BLH) at PD (rws: 0.45, rblh = -0.35, p < 0.01) and QP (rws: 0.49, rblh = -0.32, p < 0.01). And the relative higher eBC concentrations coincided with southerly, southwesterly and westerly winds although these winds had lower frequencies. This could be related to the agricultural fire in these directions during summer harvesttime. The significant partial correlation coefficients of eBC-CO (ru:0.37-0.64, rs:0.18-0.44, p < 0.01) and eBC-NO2 (ru:0.49-0.74, rs:0.38-0.75, p < 0.01) could suggest that eBC mainly come from vehicular exhaust emissions in Shanghai. Besides, the higher eBC/PM2.5 (5.29% ± 1.94%) and eBC/CO(0.30% ± 0.14%) at QP indicated the more combustion activities and diesel-powered vehicle emissions in suburban areas. The concentration weighted trajectory (CWT) analysis indicated that the surrounding areas at the junction of Shanghai, Jiangsu, and Zhejiang provinces seemed to be relatively the most important sources outside of Shanghai.


BDNF: a key regulator for protein synthesis-dependent LTP and long-term memory?
It is generally believed that late-phase long-term potentiation (L-LTP) and long-term memory (LTM) require new protein synthesis. Although the full complement of proteins mediating the long-lasting changes in synaptic efficacy have yet to be identified, several lines of evidence point to a crucial role for activity-induced brain-derived neurotrophic factor (BDNF) expression in generating sustained structural and functional changes at hippocampal synapses thought to underlie some forms of LTM. In particular, BDNF is sufficient to induce the transformation of early to late-phase LTP in the presence of protein synthesis inhibitors, and inhibition of BDNF signaling impairs LTM. Despite solid evidence for a critical role of BDNF in L-LTP and LTM, many issues are not resolved. Given that BDNF needs to be processed in Golgi outposts localized at the branch point of one or few dendrites, a conceptually challenging problem is how locally synthesized BDNF in dendrites could ensure synapse-specific modulation of L-LTP. An interesting alternative is that BDNF-TrkB signaling is involved in synaptic tagging, a prominent hypothesis that explains how soma-derived protein could selectively modulate the tetanized (tagged) synapse. Finally, specific roles of BDNF in the acquisition, retention or extinction of LTM remain to be established.


Effect of pH and NaCl on growth from spores of non-proteolytic Clostridium botulinum at chill temperature.
The effect of combinations of temperature (2 degrees, 3 degrees, 4 degrees, 5 degrees, 8 degrees and 10 degrees C), pH (5.0-7.2) and NaCl (0.1-5.0% w/w) on growth from spores of non-proteolytic Clostridium botulinum types B, E and F was determined using a strictly anaerobic medium. Inoculated media were observed weekly for turbidity, and tests were made for the presence of toxin in conditions that approached the limits of growth. Growth and toxin production were detected at 3 degrees C in 5 weeks, at 4 degrees C in 3/4 weeks and at 5 degrees C in 2/3 weeks. The resulting data define growth/no growth boundaries with respect to low temperature, pH, NaCl and incubation time. This is important in assessment of the risk of growth and toxin production by non-proteolytic Cl. botulinum in minimally processed chilled foods.


Effects of miR-29a and miR-101a Expression on Myocardial Interstitial Collagen Generation After Aerobic Exercise in Myocardial-infarcted Rats.
Myocardial infarction (MI) is accompanied by increased collagen deposition, cell necrosis and angiogenesis in cardiac tissue, which results in reduced ventricular compliance. Both microRNA-29a (miR-29a) and microRNA-101a (miR-101a) target the mRNAs encoding collagens and other proteins involved in fibrosis. We assessed the effects of intermittent aerobic exercise on the expression of cardiac miR-29a and miR-101a and following effects on the TGFβ, fos, Smad2/3, COL1A1 and COL3A1 in MI model of rats. Intermittent aerobic exercise for MI rats was begun from the second week and ended at the ninth week postsurgery. Expressions of microRNAs (miRNAs) and fibrosis-associated genes were detected from the infarction adjacent region located in the left ventricle. The heart coefficient (HC = heart weight/body weight) and hemodynamics assay were used to evaluate cardiac function level. Intermittent aerobic exercise inhibited myocardial interstitial collagen deposition and significantly improved cardiac function of MI rats. The results of real-time PCR and Western blot indicate that intermittent aerobic exercise enhanced the expression of miR-29a and miR-101a and inhibited TGFβ pathway in the MI rats. Our results suggest that controlled intermittent aerobic exercise can inhibit TGFβ pathway via up-regulation to the expression of miR-29a and miR-101a and finally cause a reduced fibrosis and scar formation in cardiac tissue. We believe that controlled intermittent aerobic exercise is beneficial to the healing and discovery of damaged cardiac tissues and their function after MI.


The perception and use of chaperones by Nigerian gynecologists.
To determine how Nigerian gynecologists perceive and use chaperones during intimate gynecologic examinations. A cross-sectional survey of Nigerian gynecologists was conducted with the aid of self-administered, semi-structured questionnaires. Data were analyzed for descriptive and inferential statistics. In all, 97.6% of respondents considered the use of a chaperone necessary during intimate gynecologic examinations and recommended that the Society of Gynaecology and Obstetrics of Nigeria (SOGON) should endorse the routine offer of chaperones for such examinations. However, just 35.9% of male physicians always or often used chaperones, while 76.9% of female physicians used chaperones only under special circumstances. No female physician always or often used a chaperone during pelvic examination. The main obstacles to the use of chaperones were scarcity of personnel to serve in this capacity (87.6%) and patients' refusal to be examined in the presence of a third party (12.4%). Most Nigerian gynecologists use chaperones at least some of the time and also support a policy of routinely offering chaperones during intimate gynecologic examination while respecting patients' right to decline this offer. Scarcity of personnel to serve as chaperones is the greatest challenge to the implementation of this policy.


Endoluminal release of ureteral ligature after hysterectomy.
Iatrogenic ureteral injury is a well-recognized complication of abdominal total hysterectomy. We report a case of a 57-year-old female who underwent abdominal total hysterectomy for a uterine myoma and experienced severe right flank pain postoperatively. The imaging study displayed an obstruction of the right distal ureter. Under ureteroscopy, an extraluminal ligature was released with a holmium:yttrium-aluminum-garnet laser. The stenotic segment was immediately relieved. Two months later, the intravenous urogram illustrated patency of the distal ureter with regression of right hydronephrosis. There was no recurrent hydronephrosis during 1 year of follow-up.


Using near-infrared spectroscopy to monitor lower extremities in patients on venoarterial extracorporeal membrane oxygenation.
Patients on peripheral extracorporeal membrane oxygenation (ECMO) are at risk for lower extremity ischemia. Effective monitoring is needed to identify complications quickly and allow timely correction. Near-infrared spectroscopy has been used extensively in cerebral monitoring during cardiac surgery. We present its use in monitoring lower extremity perfusion in patients on ECMO. Five patients on ECMO had near-infrared spectroscopy monitors placed on the calf of both lower extremities. Continuous real-time tissue oxygen saturation data (stO2) was displayed and recorded. Two patients had lower extremity complications in the leg with the arterial cannula. The patients with complications had lower stO2 in the cannulated leg at the time of ECMO insertion, larger differences in stO2 between the legs at the time of insertion, lower nadir stO2s, and larger peak differences in stO2 between the legs than patients without limb complications. The use of near-infrared spectroscopy for continuous monitoring of tissue oxygenation in the lower extremities in patients on ECMO may allow early identification of patients with lower extremity complications.


Serratia liquefaciens as a new host superior for overproduction and purification using the N-acetylneuraminate lyase gene of Escherichia coli.
Serratia liquefaciens was screened as a host strain for effective gene expression and easy purification of the target protein. A model gene, N-acetylneuraminate lyase gene (nanA), fused with the promoter region of Escherichia coli lac operon successfully overproduced the protein independently from the inducer. Since S. liquefaciens grew at lower temperature than E. coli and its proteins were more heat sensitive than those of E. coli, simple incubation at 60 degrees C could inactivate most enzymes but the nanA protein. Subsequent column works for purification, then, became simple and rapid.


Determination of microRNAs associated with adverse left ventricular remodeling after myocardial infarction.
Increasing evidence indicates that microRNA (miRNA) regulated mechanisms in myocardial healing and ventricular remodeling following acute myocardial infarction (AMI). We aim to comprehensively investigate changes of exosomal miRNA profile during the post-MI period and determine potential miRNAs associated to adverse left ventricular remodeling (ALVR). We prospectively evaluated ST-elevated MI patients with cardiac magnetic resonance imaging at the 2 weeks and 6 months after AMI (n = 10). ALVR was defined as an increase in LV end-diastolic and end-systolic volume > 13%. The blood samples were taken for miRNA measurements at the baseline, 2 and 6 weeks after AMI. In the miRNA profile assessment, 8 miRNAs were identified that were associated ALVR (miR-199a-5p, miR-23b-3p, miR-26b-5p, miR-301a-3p, miR-374a-5p, miR-423-5p, miR-483-5p and miR-652-3p). Three of them (miR-301a-3p, miR-374a-5p and miR-423-5p) differed significantly between patients with and without ALVR during follow-up period and the rest of them during the acute phase of AMI. The detection of these miRNAs, which have different role in various pathways, necessitate future mechanistic studies unravel the complex remodeling process after AMI.


Transport of terrigenous polycyclic aromatic hydrocarbons affected by the coastal upwelling in the northwestern coast of South China Sea.
Coastal upwelling prevails in the coast of Hainan Island, the northern South China Sea (SCS) during summer. We studied the influences of the upwelling on the horizontal and vertical transport of terrigenous polycyclic aromatic hydrocarbons (PAHs). PAHs in dissolved and suspended particulate phase of water samples were determined in the upper (depth < 1 m) and water column (depth > 10 m). PAH levels decreased sharply from inshore to offshore to open sea. The results showed that terrestrial input was the main source of coastal PAHs. Perylene, an important indicator of land plant-derived PAH, showed the significant correlation with PAHs (p < 0.005). This implied that fluvial transport was the primary pathway of terrigenous PAHs into the coast of northern SCS. Variations of the concentrations, compositions and diagnostic ratios of PAHs, accompanied the partition equilibrium in the water column, could indicate the selective degradation of PAHs by the plankton affected by upwelling. Different from the "traditional" transport pathway of PAHs in the water column (surface enrichment-depth depletion distribution), the upwelling could provide the original driver to elevate the upward diffusion of sediment entrained contaminants towards the intermediate even the upper waters. It could also enhance the outward diffusion of terrigenous PAHs accompanied by the offshore transport of the upper waters. Therefore, the transport pathway of PAHs can be summarized by the coastal upwelling rising PAHs with their subsequent transport offshore and settling in the adjacent open sea.


Development of speed of repetitive movements in children is determined by structural changes in corticospinal efferents.
This study was aimed to determine the relationship between the maturation of corticospinal efferents, determined by transcranial stimulation of motor cortex, and the development of fastest repetitive voluntary motor activity in children. The development of fastest repetitive voluntary motor activity was assessed for 3 different types of movements including fastest repetitive tapping movements, aiming movements and a pegboard transportation task. These 3 motor activities were chosen as they were different as to their dependence on detailed sensory guidance. Despite these differences the speed of all 3 movements showed a very similar developmental profile, which was matched, however, by the developmental slope of the fastest cortico-motoneuronal efferents. Hence the development of central conduction times determines the speed of repetitive movements in children. In contrast, we could not observe significant effects of repetitive training on speed of these movements. We show for the first time that the development of fastest voluntary movements is a structure-bound phenomenon, being independent from learning.


Chronic hypoxia alters fatty acid composition of phospholipids in right and left ventricular myocardium.
Adult male Wistar rats were exposed to intermittent high altitude hypoxia of 7000 m simulated in a hypobaric chamber for 8 h/day, 5 days a week; the total number of exposures was 25. The concentration of individual phospholipids and their fatty acid (FA) profile was determined in right (RV) and left (LV) ventricles. Adaptation to hypoxia decreased the concentration of diphosphatidytglycerol (DPG) in hypertrophied RV by 19% and in non-hypertrophied LV by 12% in comparison with normoxic controls. Chronically hypoxic hearts exhibited lower phospholipid n-6 polyunsaturated FA(PUFA) content mainly due to decreased linoleic acid (18:2n-6), which was opposed by increased n-3 PUFA mainly due to docosahexaenoic acid (22:6n-3) in phosphatidylcholine (PC), phosphatidylethanolamine (PE) and phosphatidylinositol (PI). The content of arachidonic acid (20:4n-6) was unchanged in total phospholipids, but in PC it was increased in both ventricles (by 22%) and in PE decreased in LV only (by 20%). Chronic hypoxia increased the un-saturation index of PC and PE in both ventricles. The content of monounsaturated FA (MUFA) was increased and 18:2n-6 decreased in DPG. The proportion of saturated FA was increased in PC and PI of hypoxic RV but not LV. The FA composition of phosphatidylserine was not altered in hypoxic ventricles. It is concluded that chronic hypoxia led to only minor changes in individual phospholipid concentration in rat ventricular myocardium, but markedly altered their FA profile. These changes, in particular the greater incorporation of n-3 PUFA into phospholipids and increased un-saturation index, may lead to a better preservation of membrane integrity and thereby contribute to improved ischemic tolerance of chronically hypoxic hearts.


Scribble mutation disrupts convergent extension and apical constriction during mammalian neural tube closure.
Morphogenesis of the vertebrate neural tube occurs by elongation and bending of the neural plate, tissue shape changes that are driven at the cellular level by polarized cell intercalation and cell shape changes, notably apical constriction and cell wedging. Coordinated cell intercalation, apical constriction, and wedging undoubtedly require complex underlying cytoskeletal dynamics and remodeling of adhesions. Mutations of the gene encoding Scribble result in neural tube defects in mice, however the cellular and molecular mechanisms by which Scrib regulates neural cell behavior remain unknown. Analysis of Scribble mutants revealed defects in neural tissue shape changes, and live cell imaging of mouse embryos showed that the Scrib mutation results in defects in polarized cell intercalation, particularly in rosette resolution, and failure of both cell apical constriction and cell wedging. Scrib mutant embryos displayed aberrant expression of the junctional proteins ZO-1, Par3, Par6, E- and N-cadherins, and the cytoskeletal proteins actin and myosin. These findings show that Scribble has a central role in organizing the molecular complexes regulating the morphomechanical neural cell behaviors underlying vertebrate neurulation, and they advance our understanding of the molecular mechanisms involved in mammalian neural tube closure.


Cryopreservation of human lymphocytes for sequential testing of immune competence.
Frozen stored lymphocytes are frequently used for sequential testing of immunological function in patients. The reliability of this system was investigated. By varying combinations of factors, it has been shown that lymphocyte samples, taken at different times and subsequently tested as a batch, give the most consistent results, the means of the various immune parameters measured on different sampling days in normal persons lying on straight lines parallel with the time axis. It is also shown that storage at -90 degrees C is equivalent to storage at -196.5% C.


TXNIP potentiates Redd1-induced mTOR suppression through stabilization of Redd1.
The mammalian target of rapamycin (mTOR) is a highly conserved serine-threonine kinase activated in response to growth factors and nutrients. Because of frequent dysregulation of the mTOR signaling pathway in diverse human cancers, this kinase is a key therapeutic target. Redd1 is a negative regulator of mTOR, mediating dissociation of 14-3-3 from tuberous sclerosis complex (TSC)2, which allows formation of a TSC-TSC2 complex. In the present study, we identify TXNIP that inhibits mTOR activity by binding to and stabilizing Redd1 protein. Redd1 and TXNIP expression was induced by a synthetic glucose analog, 2-deoxyglucose (2-DG). Moreover, Redd1 expression in response to 2-DG was regulated by activating transcription factor 4 (ATF4). Overexpression of TXNIP was associated with reduced mTOR activity mediated by an increase in Redd1 level, whereas knockdown of TXNIP using small interfering RNA resulted in recovery of mTOR activity via downregulation of Redd1 during treatment with 2-DG. Interestingly, Redd1 was additionally stabilized via interactions with N-terminal-truncated TXNIP, leading to suppression of mTOR activity. Our results collectively demonstrate that TXNIP stabilizes Redd1 protein induced by ATF4 in response to 2-DG, resulting in potentiation of mTOR suppression. To the best of our knowledge, this is the first study to identify TXNIP as a novel member of the mTOR upstream that acts as a negative regulator in response to stress signals.


Novel nanomolar imidazo[4,5-b]pyridines as selective nitric oxide synthase (iNOS) inhibitors: SAR and structural insights.
Inducible arginine oxidation and subsequent NO production by correspondent synthase (iNOS) are important cellular answers to proinflammatory signals. Prolonged NO production has been proved in higher organisms to cause stroke or septic shock. Several classes of potent NOS inhibitors have been reported, most of them targeting the arginine binding site of the oxygenase domain. Here we disclose the SAR and the rational design of potent and selective iNOS inhibitors which may be useful as anti-inflammatory drugs.


Quantitative measurement of cell membrane receptor internalization by the nanoluciferase reporter: Using the G protein-coupled receptor RXFP3 as a model.
Nanoluciferase (NanoLuc) is a newly developed small luciferase reporter with the brightest bioluminescence to date. In the present work, we developed NanoLuc as a sensitive bioluminescent reporter to measure quantitatively the internalization of cell membrane receptors, based on the pH dependence of the reporter activity. The G protein-coupled receptor RXFP3, the cognate receptor of relaxin-3/INSL7, was used as a model receptor. We first generated stable HEK293T cells that inducibly coexpressed a C-terminally NanoLuc-tagged human RXFP3 and a C-terminally enhanced green fluorescent protein (EGFP)-tagged human RXFP3. The C-terminal EGFP-tag and NanoLuc-tag had no detrimental effects on the ligand-binding potency and intracellular trafficking of RXFP3. Based on the fluorescence of the tagged EGFP reporter, the ligand-induced RXFP3 internalization was visualized directly under a fluorescence microscope. Based on the bioluminescence of the tagged NanoLuc reporter, the ligand-induced RXFP3 internalization was measured quantitatively by a convenient bioluminescent assay. Coexpression of an EGFP-tagged inactive [E141R]RXFP3 had no detrimental effect on the ligand-binding potency and ligand-induced internalization of the NanoLuc-tagged wild-type RXFP3, suggesting that the mutant RXFP3 and wild-type RXFP3 worked independently. The present bioluminescent internalization assay could be extended to other G protein-coupled receptors and other cell membrane receptors to study ligand-receptor and receptor-receptor interactions.


The neural control of mood: the possible role of the adrenergic system in the medulla.
Mood in humans is a complex phenomenon that integrates emotion (e.g. happiness and sadness), cognition, perception, ideation, and action in a coherent manner. In bipolar disorder extremes of mood (up or down) occur outside the normal range, in which all the above functions are coherently affected. Mood is controlled by a series of separate but interactive brain circuits that involve much of the brain, but particularly the limbic system. The question addressed in this paper is whether the coordination of all these separate systems into one coherent functional mood is mediated by non-linear dynamics acting between these systems as equal participants; or whether it is affected by a single master regulator controlling the others. The possible roles, as master regulators, of non-linear dynamically linked populations of neurons, and of the C1-C3 adrenergic nuclei in the medulla is discussed.


Regenerating I messenger RNA and protein expression in the failing human testis: a potential molecular prognostic marker of seminoma.
Infertility has been stated as a risk factor for testicular cancer; but currently, there is no prognostic indicator of tumor development from the pathologic testis with impaired spermatogenesis. Regenerating proteins are expressed in many human tissues including the testis, and their role in carcinogenesis has been well documented. In the present work, regenerating I messenger RNA and protein expression and cellular protein localization were studied in testicular biopsies of patients with normal (obstructive azoospermia) or impaired spermatogenesis (nonobstructive azoospermia) and in seminoma testis by quantitative reverse transcriptase-polymerase chain reaction, Western blot, and immunofluorescence analyses. No significant differences in regenerating I transcripts were reported between the 3 groups studied. However, regenerating I protein was highly expressed in pure seminoma and in placental-like alkaline phosphatase-positive seminiferous tubules with in situ carcinoma. Regenerating I protein levels measured by Western blotting increased from the placental-like alkaline phosphatase-negative distal region of the seminoma to the pure placental-like alkaline phosphatase-positive tumoral region. Importantly, although cells localized in seminiferous tubules of obstructive azoospermic patients with normal spermatogenesis were very slightly labeled, persisting germ, Sertoli, and myoid cells and fibrous tissues were strongly regenerating I positive in seminiferous tubules of nonobstructive azoospermia. These results suggest the possibility to use regenerating I as a prognostic marker of tumoral development in the infertile testis.


Studies on the procoagulant activity of human amniotic fluid. I. Stability and coagulation factor requirements.
A fraction of human amniotic fluid possessing procoagulant activity was purified 35-70 fold by gel filtration on Sepharose 4B. The activity eluted in the void volume indicating a particle size in excess of 5 X 10(6) daltons. The amniotic fluid factor (AFF) activity is stabilized on storage in the presence of Ca++ ions which could not be replaced by Mg++. Addition of phospholipids resulted in accelerated loss of activity. Steps taken to remove factor VII did not affect the activity, but factor X and V are required.


Capabilities of asymmetrical flow field - Flow fractionation on-line coupled to different detectors for characterization of water-stabilized quantum dots bioconjugated to biomolecules.
The asymmetric flow field-flow fractionation (AF4) coupled on-line with elemental (inductively coupled plasma-mass spectrometry, ICP-MS) and molecular (fluorescence and UV) detection has been investigated as a powerful tool for the characterization of bioinorganic nano-conjugates. In this study, we described methods for the characterization of biotin-antibody complexes bioconjugated with streptavidin quantum dots (QDs-SA-b-Ab). Operating parameters of AF4 separation technique were optimized and two procedures are proposed using a channel thickness of 350 μm and 500 μm. The use of a 500 μm spacer allowed to achieve an efficient AF4 separation of the QDs-SA-b-Ab complexes from the excess of individual species used in the bioconjugation that was required for a proper characterization of the bioconjugates. Optimization of the AF4 allowed a separation resolution good enough to isolate the QDs-SA-b-Ab bioconjugates from the free excess of b-Ab and QD-SA. The efficiency of the bioconjugation process could be then calculated, obtaining a value of 86% for a 1 QDs-SA: 5 b-Ab bioconjugation ratio. In addition, sample recovery around 90% was achieved.


[Timeline trends in surgery of bronchogenic carcinoma].
The aim of our study was to determine how patient preoperative status and outcomes of resection have changed over last 12 years. This retrospective study of prospective database included 1412 patients operated from January 1,1998 through December 31,2009. Patient characteristics and outcomes were compared for two time periods (1998-2003 and 2004-2009). We performed 985 lobectomies with 30-days mortality 1.8% and 300 pneumonectomies with 30-days mortality 5.7%. Median of survival of all 1412 patients was 4.3 year and 5-year survival was 45%. The percentage of female patients, lobectomies and adenocarcinoma increased over time, as well as age of our patients. Outcome improved over time, with significant decrease in 30-days mortality after pneumonectomy (8.2% vs. 2.3%, p = 0.029). The overall 3-year survival improved in patients with III. stage (30 % vs. 40%, p = 0.012). Our study identified time trends which are in-line with increased incidence of lung cancer among women and with improvement of preoperative evaluation, preoperative and postoperative care


Efficient regulation of gene expression using self-contained fiber-modified adenovirus vectors containing the tet-off system.
Previously, we developed single adenovirus (Ad) vectors that contained the gene of interest in the E1 deletion region and the transactivator gene for the tetracycline-controllable expression system in the E3 deletion region. In the present study, we improved the Ad vector-mediated tetracycline-controllable expression system by the fiber modification of Ad. We developed fiber-modified Ad vectors containing the tet-off system, which are effective in overcoming the limitations of conventional Ad vectors, specifically their inefficient gene transfer into cells lacking the primary receptor, the coxsackievirus and adenovirus receptor (CAR). Ad vectors containing the tet-off system with an Arg-Gly-Asp (RGD) peptide in the HI loop of the fiber knob or the Ad type 35 fiber greatly improved transduction efficiency (more than 1-2-log orders) into the cells lacking CAR expression but expressing alphav integrin or CD46, respectively. They exhibited vastly higher regulation of gene expression by doxycycline. The combination of fiber-modified Ad vectors and the tetracycline-controllable expression system should offer a powerful tool for gene therapy and gene transfer experiment.


Surgical Construct Type Is Associated With Time to Fusion and Reoperation Rate in Double and Isolated Talonavicular Arthrodeses.
This study evaluates the effect of surgical construct on postoperative outcomes in patients undergoing isolated talonavicular (TN) or double (TN and subtalar ST) arthrodesis. TN constructs included plate and screw, screw and staple, and isolated staple constructs. Subtalar constructs included 1- and 2-screw constructs. Retrospective chart review identified 52 patients who underwent double or isolated TN arthrodesis between 2016 and 2021 by a single fellowship-trained foot and ankle surgeon with minimum 6 months of follow-up (mean = 1.62 years, range = 0.50-4.39 years). Data collected included demographics, medical history, surgical indication, surgical constructs used, complications, reoperations, patient-reported outcome measures, and radiographic measures. Overall complication and reoperation rates were 26.3% and 12.3%, respectively. Among TN constructs, time to ST (P = .026) and TN (P = .018) fusion was significantly slower among patients receiving a plate and screw construct. Complication rate did not differ, but reoperation rate was significantly higher for plate and screw TN constructs (P = .039). Postoperative Foot and Ankle Outcome Score (FAOS) Quality of Life (P = .028) and Total (P = .016) scores were significantly better among plate and screw TN constructs. Utilization of screw and staple or isolated staple construct have significantly quicker time to fusion and lower reoperation rates than plate and screw constructs for the TN joint. Level III: Retrospective cohort study.


DEC1/STRA13/SHARP2 and DEC2/SHARP1 coordinate physiological processes, including circadian rhythms in response to environmental stimuli.
Daily physiological and behavioral rhythms are regulated by endogenous circadian molecular clocks. Clock proteins DEC1 (BHLHe40) and DEC2 (BHLHe41) belong to the basic helix-loop-helix protein superfamily, which contains other clock proteins CLOCK and BMAL1. DEC1 and DEC2 are induced by CLOCK:BMAL1 heterodimer via the CACGTG E-box in the promoter and, thereafter, suppress their own expression by competing with CLOCK:BMAL1 for the DNA binding. This negative feedback DEC loop together with the PER loop involving PER and CRY, the other negative clock regulators, maintains the circadian rhythm of Dec1 and Dec2 expression. DEC1 is induced by light pulse and adjusts the circadian phase of the central clock in the suprachiasmatic nucleus, whereas DEC1 upregulation by TGF-β resets the circadian phase of the peripheral clocks in tissues. Furthermore, DEC1 and DEC2 modulate the clock output signals to control circadian rhythms in behavior and metabolism. In addition to the functions in the clocks, DEC1 and DEC2 are involved in hypoxia responses, immunological reactions, and carcinogenesis. These DEC actions are mediated by the direct binding to the E-box elements in target genes or by protein-protein interactions with transcription factors such as HIF-1α, RXRα, MyoD, and STAT. Notably, numerous growth factors, hormones, and cytokines, along with ionizing radiation and DNA-damaging agents, induce Dec1 and/or Dec2 in a tissue-specific manner. These findings suggest that DEC1 and DEC2 play a critical role in animal adaptation to various environmental stimuli.


Hydroxyl radical reactions and the radical scavenging activity of β-carboline alkaloids.
β-Carbolines are bioactive pyridoindole alkaloids occurring in foods, plants and the human body. Their activity as hydroxyl radical (OH) scavengers is reported here by using three different methods: deoxyribose degradation, hydroxylation of benzoate and hydroxylation of 2'-deoxyguanosine to give 8-hydroxy-2'-deoxyguanosine (8-OHdG) as assessed by RP-HPLC (MS). Fenton reactions (Fe(2+)/Fe(3+) plus H2O2) were used for OH generation, and the radical increased in the presence of ascorbic acid or 6-hydroxydopamine as pro-oxidants. β-Carbolines were scavengers of OH in the three assays and in the presence of pro-oxidants. Tetrahydro-β-carboline-3-carboxylic acids were active against the hydroxylation of 2'-deoxyguanosine. β-Carbolines reacted with hydroxyl radicals (OH) affording hydroxy-β-carbolines, whereas tetrahydro-β-carbolines gave oxidative and degradation products. On the basis of IC50 and reaction rates (k), β-carbolines (norharman and harman), and tetrahydro-β-carbolines (tetrahydro-β-carboline, 1-methyltetrahydro-β-carboline and pinoline) were good OH radical scavengers and their activity was comparable to that of the indole, melatonin, which is an effective hydroxyl radical scavenger and antioxidant.


Effect of prefrontal transcranial magnetic stimulation on spontaneous truth-telling.
Brain-process foundations of deceptive behaviour have become a subject of intensive study both in fundamental and applied neuroscience. Recently, utilization of transcranial magnetic stimulation has enhanced methodological rigour in this research because in addition to correlational studies causal effects of the distinct cortical systems involved can be studied. In these studies, dorsolateral prefrontal cortex has been implied as the brain area involved in deceptive behaviour. However, combined brain imaging and stimulation research has been concerned mostly with deceptive behaviour in the contexts of mock thefts and/or denial of recognition of critical objects. Spontaneous, "criminally decontextuated" propensity to lying and its dependence on the activity of selected brain structures has remained unexplored. The purpose of this work is to test whether spontaneous propensity to lying can be changed by brain stimulation. Here, we show that when subjects can name the colour of presented objects correctly or incorrectly at their free will, the tendency to stick to truthful answers can be manipulated by stimulation targeted at dorsolateral prefrontal cortex. Right hemisphere stimulation decreases lying, left hemisphere stimulation increases lying. Spontaneous choice to lie more or less can be influenced by brain stimulation.


[Prevalence of metastatic lymph nodes in the central compartment of the neck following prophylactic clearance for papillary thyroid cancer].
Clinical suspicion of regional lymph nodes' involvement is present in approximately 10% of patients with papillary thyroid cancer (PTC). Nevertheless, among the remaining 90% of individuals staged pre-, or intraoperatively as node negative, some cases of metastatic lymph nodes from PTC are found on final pathological report. Both quality of life and survival can be influence by eventual nodal recurrence in this group of patients. To evaluate the prevalence of metastatic lymph nodes in patients with PTC in stage cT1-3NxMx undergoing prophylactic central compartment lymph nodes' clearance, and to assess associated morbidity. Clinical database of patients with thyroid cancer undergoing surgery in 2009 and 2010 was retrospectively analyzed. 116 (78.9%) patients with PTC, with pre-, or intraoperatively not suspected lymph nodes were identified. Total extracapsular thyroidectomy with one-stage prophylactic bilateral level VI lymph nodes clearance was performed in all patients. The numbers of excised and metastatic lymph nodes within the surgical specimen were analyzed. In addition, surgical morbidity was evaluated. Metastatic level VI lymph nodes' involvement was found in 22 of 116 (19%) patients. Mean number of lymph nodes within the surgical specimen was 4.5 +/- 3.3 (1-17, median 4). Mean number of 1 +/- 2 metastatic lymph nodes were identified (0-7, median 1). Transient vs. permanent hypoparathyroidism was found in 31 (26.7%) vs. 2 (1.7%) and temporary vs. permanent recurrent laryngeal nerve injury was found in 7 (3.0%) vs. 2 (0.9%) of 232 nerves at risk. One fifth of PTC patients with clinically and intraoperatively non-suspected lymph nodes within the central compartment are positive for metastatic nodal de- posits in surgical specimen following prophylactic level VI clearance.


Neural evidence that disengaging memory retrieval is modulated by stimulus valence and rumination.
To remember information from our personal past we need to be in a cognitive state where we treat stimuli as cues for memory retrieval. In this study we considered whether participants could exert control and disengage from a memory state when it was no longer required for the task at hand. In particular, we examined whether this ability was affected by the valence of the stimuli and participant's rumination scores. After a study phase participants completed test blocks where the task switched every two trials between a memory task (retrieving information from the study phase) and a perceptual task. Even though there was no episodic memory requirement in the perceptual task, a well-established event-related potential (ERP) index of memory retrieval was present for both trials when the stimuli were negative valenced pictures but not for neutral pictures. Furthermore, there was a positive correlation between the magnitude of this ERP memory index in the perceptual task and rumination scores but only for neutral stimuli and not negative. Thus, in this study participants generally had difficultly suppressing memory retrieval when negative stimuli were presented. However, for neutral stimuli only ruminators were more susceptible to memory intrusions.


Isolation and genomic characterization of five novel strains of Erysipelotrichaceae from commercial pigs.
Members of the Erysipelotrichaceae family have a high abundance in the intestinal tract of mammals, and have been reported to be associated with host metabolic disorders and inflammatory diseases. In our previous study, we found that the abundance of Erysipelotrichaceae strains in the cecum was associated with the concentration of N-acetylgalactosamine (GalNAc). However, only a few members of Erysipelotrichaceae have been isolated and cultured, and their main characteristics, genomic information and the functional capacity of carbohydrate metabolism remain unknown. In this study, we tested 10 different kinds of commercially available media and successfully isolated five Erysipelotrichaceae strains from healthy porcine feces. The five isolates were Gram-positive, and their colonies on Gifu anaerobic medium (GAM) or modified GAM were approximately 0.25-1.0 mm in diameter, and they were circular, white, convex, moist, translucent, and contained colony margins. These isolates were subjected to Oxford Nanopore and Illumina whole-genome sequencing, genome assembly, and annotation. Based on whole-genome sequences, the five strains belong to Erysipelotrichaceae bacterium OH741_COT-311, Eubacterium sp. AM28-29, and Faecalitalea cylindroides. The GC content of the five strains ranged from 34.1 to 37.37%. Functional annotation based on the Kyoto encyclopedia of genes and genomes pathways revealed tens to hundreds of strain-specific proteins among different strains, and even between the strains showing high 16S rRNA gene sequence identity. Prediction analysis of carbohydrate metabolism revealed different capacities for metabolizing carbohydrate substrates among Erysipelotrichaceae strains. We identified that genes related to the GalNAc metabolism pathway were enriched in the genomes of all five isolates and 16 Erysipelotrichaceae strains downloaded from GenBank, suggesting the importance of GalNAc metabolism in Erysipelotrichaceae strains. Polysaccharide utilization loci (PUL) analysis revealed that the strains of Erysipelotrichaceae may have the ability to utilize plant polysaccharides. The present study not only reports the successful isolation of novel Erysipelotrichaceae strains that enrich the cultured strains of Erysipelotrichaceae, but also provided the genome information of Erysipelotrichaceae strains for further studying the function roles of Erysipelotrichaceae in host phenotypes.


Dogs are more permissive than cats or guinea pigs to experimental infection with a human isolate of Bartonella rochalimae.
Bartonella rochalimae was first isolated from the blood of a human who traveled to Peru and was exposed to multiple insect bites. Foxes and dogs are likely natural reservoirs for this bacterium. We report the results of experimental inoculation of two dogs, five cats and six guinea pigs with the only human isolate of this new Bartonella species. Both dogs became bacteremic for 5-7 weeks, with a peak of 10(3)-10(4) colony forming units (CFU)/mL blood. Three cats had low bacteremia levels (< 200 CFU/mL) of 6-8 weeks' duration. One cat that remained seronegative had two bacterial colonies isolated at a single culture time point. A fifth cat never became bacteremic, but seroconverted. None of the guinea pigs became bacteremic, but five seroconverted. These results suggest that dogs could be a reservoir of this strain of B. rochalimae, in contrast to cats and guinea pigs.


Charge transport and optical properties of MOCVD-derived highly transparent and conductive Mg- and Sn-doped In2O3 thin films.
Mg- and Sn-doped In2O3 (MgIn(x)Sn(y)O(z), 6.0 < x < 16.0; 3.0 < y < 8.0) thin films were grown by low-pressure metal-organic chemical vapor deposition using the volatile metal-organic precursors tris(2,2,6,6-tetramethyl-3,5-heptanedionato)indium(III) [In(dpm)3], bis(2,4-pentanedionato)tin(II) [Sn(acac)2], and bis(2,2,6,6-tetramethyl-3,5-heptanedionato)(N,N,N',N'-tetramethylethylenediamine)magnesium(II) [Mg(dpm)2(TMEDA)]. Films in this compositional range retain the cubic In2O3 bixbyite crystal structure. The highest conductivity is found to be approximately 1000 S/cm for an as-grown film with a nominal composition MgIn14.3Sn6.93O(z). Annealing of such films in a vacuum raises the conductivity to approximately 2000 S/cm. The optical transmission window of the present films is significantly wider than that of typical indium tin oxide (ITO) films from 300 to 3300 nm, and the transmittance is also greater than or comparable to that of commercial ITO films.


Effects of dietary dandelion (Taraxacum mongolicum Hand.-Mazz.) polysaccharides on the performance and gut microbiota of laying hens.
This experiment was designed to evaluate the influences of dietary dandelion polysaccharides (DP) on the performance and cecum microbiota of laying hens. Three hundred laying hens were assigned to five treatment groups: the basal diet group (CK group), three DP groups (basal diets supplemented with 0.5, 1.0, and 1.5 % DP), and the inulin group (IN group, basal diet supplemented with 1.5 % inulin). Increased daily egg weight and a decreased feed conversion rate were observed when the diets were supplemented with inulin or DP. The calcium metabolism rate in the 0.5 % and 1.0 % DP groups was greater than that in the CK group. The DP groups increased the short-chain fatty acid concentration, decreased pH, and enhanced the relative abundances of Parabacteroides, Alloprevotella, and Romboutsia in the cecum. These results showed that DP supplementation in the diets of laying hens can improve their performance, which might be associated with the regulation of the cecal microbiota.


Falcine meningioma masquerading as biliary colic - Case report and literature review.
Right upper quadrant (RUQ) abdominal pain and discomfort is a common presenting complaint often associated with abdominal pathology. We report a rare presentation of structural intracranial pathology in a patient initially presenting with RUQ abdominal discomfort. While initial investigations concentrating on abdominal causes revealed no likely culprit, progression of symptoms to involve right lower limb weakness eventually prompted the patient's re-presentation and eventual definitive diagnosis. This case depicts a hitherto unreported cause for abdominally-manifested seizures.


Could woodworking have driven lithic tool selection?
Understanding early stone tools, particularly relationships between form and function, is fundamental to understanding the behavioral evolution of early hominins. The oldest-claimed flake tools date to ca. 3.3 million years ago, and their development may represent a key step in hominin evolution. Flake form, and its relationship to function, has long been a focus of Paleolithic studies, almost exclusively with respect to meat acquisition. However, evidence for woodworking is now known from sites dating to 1.5 Ma. Additionally, Pan troglodytes are known to manufacture wooden tools for hunting and foraging, thus creating a phylogenetic (parsimony) argument for more ancient woodworking. However, few studies examining woodworking and Paleolithic tools have been completed to date. Indeed, it remains an open question whether woodworking may have instigated specific selective demands on the form of early stone tools. Here, we conducted an experiment testing the comparative woodworking efficiency (measured by time) of small and large flakes. Two groups of participants used either a relatively small or large unretouched flake to remove a predefined area from standardized samples of wood. Those using larger flakes were significantly more efficient (i.e., required less time) during this woodworking task. Our results demonstrate that larger flakes could have been preferentially chosen by hominins for woodworking, consistent with previous data generated experimentally in other (non-woodworking) tasks. Moreover, the production of relatively large flakes, such as those at Lomekwi, could have been motivated by woodworking, rather than, or in addition to, butchery. Such issues may also have encouraged the use of Levallois production strategies in later times.


Influence of progressive salt restriction on urinary bicarbonate wasting in uremic acidosis.
In steady state, the acidosis in the majority of 17 uremic patients was characterized by a persistent bicarbonaturia (FEHCO3 ranging between 0% and 17.65%). An NH4Cl loading test in 17 patients revealed two distinct groups: group A (n = 11) with complete disappearance of the urinary bicarbonate loss and a mean UpH of 5.39 +/- 0.10 at a PHCO3 level of 13.3 +/- 0.5 mEq/L; and group B (n = 6) with urinary acidification disturbances with a persistent FEHCO3 ranging between 1.06% and 3.15% and a mean UpH of 6.53 +/- 0.06 at a PHCO3 level of 13.5 +/- 0.7 mEq/L. Between the two groups, there were no differences in CCr, plasma Na, K, Cl, Ca, PO4, PCO2, and aldosterone levels. Calculation of the THCO3/TNa reabsorption ratio over a wide range of PHCO3 levels revealed no differences between the two groups. The mean levels of circulating PTH were significantly higher in group B compared with group A (40.1 +/- 10.8 mU/dL v 19.3 +/- 4.4 mU/dL; P less than .05), and the spontaneous steady-state FENa was more pronounced in group B than in group A (12.1% +/- 1.5% v 4.9% +/- 0.7%; P less than .05). Four patients from group B with a well-documented salt-losing nephropathy (FENa ranging from 10.20% to 15.10%) were submitted to a progressive dietary salt restriction over several weeks. At this stage, the four patients no longer had bicarbonaturia, and the urinary pH decreased to levels between 5.15 and 5.65 during NH4Cl-induced acidosis.(ABSTRACT TRUNCATED AT 250 WORDS)


Temporal and spatial variations in the relationship between urbanization and water quality.
With the development of economy, most of Chinese cities are at the stage of rapid urbanization in recent years, which has caused many environmental problems, especially the serious deterioration of water quality. Therefore, the research of the relationship between urbanization and water quality has important theoretical and practical significance, and it is also the main restriction factor in the urbanization advancement. In this work, we investigated the impact of urbanization on the water quality of the nearby river. We established a comprehensive environmental assessment framework by combining urbanization and water quality, and one model was designed to examine the impact of urbanization on the water quality in Jinan from 2001 to 2010 with factor component analysis. The assessment of urbanization level was accomplished using a comprehensive index system, which was based on four aspects: demographic urbanization, economic urbanization, land urbanization, and social urbanization. In addition, synthetic pollution index method was utilized to assess the water pollution of Xiaoqing River in the study area. Through the analysis of regression curves, we conclude that (1) when the urbanization level is below 25 %, the relationship is low and irregular; (2) if the urbanization level varies between 25 and 40 %, there will be an irreversible degradation of stream water quality; (3) there is a positive correlation between urbanization and pollution levels of urban river after the adjustment period; and (4) land and demographic aspects have the highest independent contribution. This study is a useful reference for policymakers in terms of economic and environmental management.


Accelerating Cu and Cd removal in soil flushing assisted by regulating permeability with electrolytes.
Soil flushing is one of the common in-situ remediation technologies, in which the permeability of the soil determines its feasibility. Batch extractions showed that deionized water extracted about 20% Cu and 30% Cd from a soil. Electrolytes of 100 mmol/l NaCl, 500 mmol/l NaCl, and 167 mmol/l CaCl2 promoted the extractions to about 60% and 90%, respectively, with higher concentration and valence of cations being more effective. Presence of 100 mmol/l EDTA as a chelant further enhanced the extractions to near completion. Extractions appeared to occur concurrently via ion exchange, complexation with Cl- and predominantly chelation with EDTA. Column leaching in dynamic setups with electrolyte solutions in the presence of EDTA showed similar Cu and Cd removal degrees to the batch extractions. The permeability of soils during leaching decreased by up to 80%, decelerating time-dependent Cu and Cd removal, due to soil swelling by Na+. Electrolytes in leaching solutions well defended the permeability of soil against its decrease to as low as 3.5%, maintaining Cu and Cd removal rates. Formulating flushing solution with EDTA and proper electrolytes have advantages of not only enhancing extraction degrees but accelerating heavy metal removal from soil by regulating the permeability, with the potential to be extended to soils with high clay contents and thus low natural permeability.


Bone marrow derived stromal cells from myelodysplastic syndromes are altered but not clonally mutated in vivo.
The bone marrow (BM) stroma in myeloid neoplasms is altered and it is hypothesized that this cell compartment may also harbor clonal somatically acquired mutations. By exome sequencing of in vitro expanded mesenchymal stromal cells (MSCs) from n = 98 patients with myelodysplastic syndrome (MDS) and n = 28 healthy controls we show that these cells accumulate recurrent mutations in genes such as ZFX (n = 8/98), RANK (n = 5/98), and others. MDS derived MSCs display higher mutational burdens, increased replicative stress, senescence, inflammatory gene expression, and distinct mutational signatures as compared to healthy MSCs. However, validation experiments in serial culture passages, chronological BM aspirations and backtracking of high confidence mutations by re-sequencing primary sorted MDS MSCs indicate that the discovered mutations are secondary to in vitro expansion but not present in primary BM. Thus, we here report that there is no evidence for clonal mutations in the BM stroma of MDS patients.


Molecular analysis of genetic fidelity in Cannabis sativa L. plants grown from synthetic (encapsulated) seeds following in vitro storage.
The increasing utilization of synthetic (encapsulated) seeds for germplasm conservation and propagation necessitates the assessment of genetic stability of conserved propagules following their plantlet conversion. We have assessed the genetic stability of synthetic seeds of Cannabis sativa L. during in vitro multiplication and storage for 6 months at different growth conditions using inter simple sequence repeat (ISSR) DNA fingerprinting. Molecular analysis of randomly selected plants from each batch was conducted using 14 ISSR markers. Of the 14 primers tested, nine produced 40 distinct and reproducible bands. All the ISSR profiles from in vitro stored plants were monomorphic and comparable to the mother plant which confirms the genetic stability among the clones. GC analysis of six major cannabinoids [Δ(9)-tetrahydrocannabinol, tetrahydrocannabivarin, cannabidiol, cannabichromene, cannabigerol and cannabinol] showed homogeneity in the re-grown clones and the mother plant with insignificant differences in cannabinoids content, thereby confirming the stability of plants derived from synthetic seeds following 6 months storage.


Biostimulation of sulfate-reducing bacteria used for treatment of hydrometallurgical waste by secondary metabolites of urea decomposition by Ochrobactrum sp. POC9: From genome to microbiome analysis.
Sulfate-reducing bacteria (SRB) are key players in many passive and active systems dedicated to the treatment of hydrometallurgical leachates. One of the main factors reducing the efficiency and activity of SRB is the low pH and poor nutrients in leachates. We propose an innovative solution utilizing biogenic ammonia (B-NH3), produced by urea degrading bacteria, as a pretreatment agent for increasing the pH of the leachate and spontaneously stimulating SRB activity via bacterial secondary metabolites. The selected strain, Ochrobactrum sp. POC9, generated 984.7 mg/L of ammonia in 24 h and promotes an effective neutralization of B-NH3. The inferred metabolic traits indicated that the Ochrobactrum sp. POC9 can synthesize a group of vitamins B, and the production of various organic metabolites was confirmed by GC-MS analysis. These metabolites comprise alcohols, organic acids, and unsaturated hydrocarbons that may stimulate biological sulfate reduction. With the pretreatment of B-NH3, sulfate removal efficiency reached ~92.3% after 14 days of incubation, whereas SRB cell count and abundance were boosted (~107 cell counts and 88 OTUs of SRB) compared to synthetic ammonia (S-NH3) (~103 cell counts and 40 OTUs of SRB). The dominant SRB is Desulfovibrio in both S-NH3 and B-NH3 pretreated leachate, however, it belonged to two different clades. By reconstructing the ecological network, we found that B-NH3 not only directly increases SRB performance but also promotes other strains with positive correlations with SRB.


Molecular cloning of an acrosomal sperm antigen gene and the production of its recombinant protein for immunocontraceptive vaccine.
A monoclonal antibody, HS-63, which reacts specifically with a highly conserved sperm acrosome antigen, was shown to inhibit in vitro fertilization of mouse and human. The corresponding sperm antigen designated as MSA-63 was purified to homogeneity from mouse testes and used as an immunogen to generate polyclonal antisera in rabbits. The cDNA fragments of MSA-63 gene were cloned from mouse testis cDNA library by an immunoscreening method using polyclonal antisera specific for MSA-63. Using the established cDNA clone as a probe, the gene encoding for MSA-63 protein was found to be conserved among different mammalian species. Only one specific mRNA 1.5 kb in size was identified from the adult mouse testis among different mouse tissues. The recombinant fusion protein containing MSA-63 protein fragment was produced in Escherichia coli and used to immunize female mice. Similar to the original HS-63 monoclonal antibody, the antisera thus produced reacted only with the sperm acrosome and revealed significant inhibition to the in vitro fertilization of mouse oocytes. The results of this preliminary study suggest that it is feasible to mass produce sperm-specific antigens or their antigenic fragments by recombinant DNA technology for the development of sperm antigen-based immunocontraceptive vaccines.


Subjective donor deferral as a tool for increased blood transfusion safety: A cross-sectional observational study.
This study aims at evaluating whether subjective donor deferral (SDD) has the potential for increasing blood transfusion safety. Appropriate donor selection via clinical and serologic screening is necessary to prevent transfusion-transmissible infections (TTIs). One additional strategy adopted by some Brazilian blood transfusion centers (BTCs) is the rejection of a donation by the pre-donation interviewer based on subjective factors. We conducted a STROBE-guided cross-sectional study including 105 005 prospective donors who presented to our BTC between 1 January 2013, and 31 December 2015. Donors were evaluated for age, gender, education level, donation type and history, confidential unit exclusion, SDD, and results of serologic screening for TTIs. Even after controlling for potential confounding variables, subjectively deferred donors were more likely to have at least one reactive serology in the standard screening (OR: 2.80; 95% CI: 2.13-3.69; P < .001). They also had a higher risk for testing positive for syphilis (OR: 4.47; 95% CI: 3.05-6.55; P < .001), hepatitis B (OR: 5.69; 95% CI: 2.48-13.08; P < .001), and HIV (OR: 6.14; 95% CI: 3.22-11.69; P < .001). Routine implementation of SDD in donor selection may be an effective additional measure to avoid TTIs, highlighting the importance of interviewer experience, perspicacity, and face-to-face contact with donors for blood safety assurance.


Current perspective on the regulation of FOXO4 and its role in disease progression.
Forkhead box O4 (FOXO4) is a member of the FOXO family that regulates a number of genes involved in metabolism, cell cycle, apoptosis, and cellular homeostasis via transcriptional activity. It also mediates cell responses to oxidative stress and treatment with antitumor agents. The expression of FOXO4 is repressed by microRNAs in multiple cancer cells, while FOXO4 function is regulated by post-translational modifications and interaction with other proteins. The deregulation of FOXO4 is closely linked to the progression of several types of cancer, senescence, and other diseases. In this review, we present recent findings on the regulation of FOXO4 in physiological and pathological conditions and provide an overview of the complex role of FOXO4 in disease development and response to therapy.


Association of admission frailty and frailty changes during cardiac rehabilitation with 5-year outcomes.
Examine the association between (1) admission frailty and (2) frailty changes during cardiac rehabilitation (CR) with 5-year outcomes (i.e. time to mortality, first hospitalization, first emergency department (ED) visit, and number of hospitalizations, hospital days, and ED visits). Data from patients admitted to a 12-week CR programme in Halifax, Nova Scotia, from May 2005 to April 2015 (n = 3371) were analysed. A 25-item frailty index (FI) estimated frailty levels at CR admission and completion. FI improvements were determined by calculating the difference between admission and discharge FI. CR data were linked to administrative health data to examine 5-year outcomes [due to all causes and cardiovascular diseases (CVDs)]. Cox regression, Fine-Gray models, and negative binomial hurdle models were used to determine the association between FI and outcomes. On average, patients were 61.9 (SD: 10.7) years old and 74% were male. Mean admission FI scores were 0.34 (SD: 0.13), which improved by 0.07 (SD: 0.09) by CR completion. Admission FI was associated with time to mortality [HRs/IRRs per 0.01 FI increase: all causes = 1.02(95% CI 1.01,1.04); CVD = 1.03(1.02,1.05)], hospitalization [all causes = 1.02(1.01,1.02); CVD = 1.02(1.01,1.02)], ED visit [all causes = 1.01(1.00,1.01)], and the number of hospitalizations [all causes = 1.02(95% CI 1.01,1.03); CVD = 1.02(1.00,1.04)], hospital days [all causes = 1.01(1.01,1.03)], and ED visits [all causes = 1.02(1.02,1.03)]. FI improvements during CR had a protective effect regarding time to all-cause hospitalization [0.99(0.98,0.99)] but were not associated with other outcomes. Frailty status at CR admission was related to long-term adverse outcomes. Frailty improvements during CR were associated with delayed all-cause hospitalization, in which a larger effect was associated with a greater chance of improved outcome.


Neuroimaging markers of chronic fatigue in older people: a narrative review.
Chronic fatigue is a common symptom in older adults. Although some studies have attempted to identify the neuronal correlates of fatigue associated with chronic diseases, the scientific evidence is scarce regarding fatigue in older people not suffering from a specific disease. To gather available evidence of neuroimaging studies investigating the associations between fatigue and brain health in older adults out of the context of a specific disease, and to identify potential brain structures associated with this symptom. Studies considering exclusively patients with a specific disease and/or studies focusing on physiological mechanisms of acute fatigue induced by the realization of cognitive and physical tasks were excluded. Very few studies on the associations of fatigue with neuroimaging markers are currently available. Fatigue was associated with reduced hippocampus volumes and with hippocampal amyloid deposition. Regarding the association between fatigue and the circuit of basal ganglia, putamen and thalamus were associated with physical fatigability, whereas amygdala and thalamus with mental fatigability. Very limited evidence about white matter integrity found that healthy individuals with high levels of fatigue had a greater total volume of leukoaraiosis. This review suggests that hippocampus damage and potentially loss of function in basal ganglia networks could play a role on chronic fatigue during aging. Further studies are needed to assess the associations of fatigue with white matter alterations.


Prolonged binding of radiolabeled recombinant tissue-type plasminogen activator after angioplasty and enclosed thrombolysis of the femoropopliteal arteries.
The authors measured the binding of indium-111-labeled recombinant tissue-type plasminogen activator (rt-PA) within the recanalized femoropopliteal segment after percutaneous transluminal angioplasty (PTA) and enclosed thrombolysis. In patients with long occlusions (n = 3), 91 micrograms of rt-PA was bound 1 hour after the procedure, and the half-time of the final washout curve averaged 114 hours. After PTA in patients with multiple stenoses (n = 6), 45 micrograms of rt-PA was bound, and the half-time averaged 32 hours. These values were significantly smaller than those in patients with occlusions (P < .01). In patients with a single stenosis (n = 4), 19 micrograms of rt-PA was bound, and the half-time averaged 5 hours. These values were significantly smaller than those in patients with multiple stenoses (P < .01). The progressive accumulation of rt-PA at the sites of PTA therapy is most likely related to increasing presence of fibrin with increasing lesion severity. Fibrin accumulation may be partly responsible for early failures after PTA in extensive lesions. Removal of this fibrin with enclosed thrombolysis might improve patency.


Addiction severity and MMPI-derived typologies in cocaine abusers.
This study replicated the two Minnesota Multiphasic Personality Inventory subtypes (psychopathic and severe psychiatric) found in inpatient male cocaine abusers in an outpatient sample of 132 men and women. The Addiction Severity Index validated these subtype differences on the basis of psychiatric severity.


The audiologist's role in university hearing conservation programs: Gaps and opportunities in U.S. universities.
All universities that meet state and/or federal requirements for employees' noise exposure must have a hearing conservation program (HCP). Universities with HCPs and Doctor of Audiology (AuD) programs could reap a range of benefits from interprofessional collaboration between these programs, including enhanced learning opportunities for AuD students; however, it is unclear whether this collaboration occurs consistently in different university settings. Despite a relatively robust literature around occupational audiology and the audiologist's role in hearing conservation in general, few studies examine this subject in the university setting. This study seeks to provide insights into the role of the university audiologists in university HCPs that could help inform further exploration and potential pilot studies to enhance university-based occupational HCPs, ultimately supporting more rigorous professional training in occupational audiology in AuD programs. This study's primary method was a survey questionnaire delivered to audiologists at U.S. universities. Survey questions explored university audiologists' role, involvement with their universities' HCPs, and benefits and barriers to collaboration with the HCPs. The results indicate that although audiologists report that they have participated in hearing conservation generally at their universities, the majority of respondents were not actively involved with occupational HCPs. Further research is needed to understand how university HCPs are managed and how effective they are. With greater awareness of audiologists' contributions to university HCPs, their role in this important workplace program could merit expansion.


Pharmacokinetic interactions and tolerability of rosuvastatin and ezetimibe: an open-label, randomized, multiple-dose, crossover study in healthy male volunteers.
Rosuvastatin is a synthetic 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor that effectively reduces low-density lipoprotein cholesterol levels. However, statin monotherapy does not always achieve acceptable low-density lipoprotein cholesterol levels in patients with severe hypercholesterolemia. Ezetimibe, a selective cholesterol-absorption inhibitor, is approved for use as a monotherapy or combination therapy with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors for patients with hypercholesterolemia. The aim of this study was to examine the pharmacokinetics (PKs) of drug interactions between rosuvastatin and ezetimibe, and the tolerability of combined administration in healthy Korean male volunteers. Healthy subjects (n=24) were randomly allocated to 3 treatment groups: rosuvastatin (20 mg) alone, ezetimibe (10 mg) alone, and rosuvastatin (20 mg) plus ezetimibe (10 mg). The drugs were taken once every 24 hours over a period of 10 days. Blood samples were collected to analyze steady-state PKs. All adverse events observed during the study were mild, and the frequency was no higher for combined administration than for mono administration. For rosuvastatin, the steady-state mean ratios (90% CI) of the combined over the single dose were 1.076 (1.019-1.136) for AUCτ,ss and 1.099 (1.003-1.204) for concentration at steady-state, respectively. In the case of free and total ezetimibe, the steady-state ratios of AUCτ,ss and concentration at steady-state were 1.131 (1.051-1.218) and 1.182 (1.038-1.346), and 1.055 (0.969-1.148) and 0.996 (0.873-1.135), respectively. Combined administration of rosuvastatin and ezetimibe was well tolerated. No clinically significant PK interactions between rosuvastatin and ezetimibe were observed when the 2 drugs were administered concomitantly.


Supplemental oxygen reduces intimal hyperplasia after intraarterial stenting in the rabbit.
Supplemental oxygen can reduce intimal hyperplasia (IH) after stent deployment in a rabbit model. Endovascular stent placement is technically feasible, but long-term durability in vessels outside the aortoiliac system is compromised with postinterventional IH, which causes restenosis and failure of the arterial conduit. Groups (n = 4 to 6) of female New Zealand white rabbits underwent placement of a 3-mm intraaortic stent with laparotomy and were placed in either normoxic (21% inspired oxygen concentration) or supplemental-oxygen (40% inspired oxygen concentration) environments for 0, 7, 14, and 28 days. The transarterial wall oxygen gradient was measured at 0, 7, and 28 days with an oxygen microelectrode. 5-Bromo-2'deoxyuridine (BrdU) was injected into the peritoneum before death to assess cellular proliferation. Aortic specimens were harvested en bloc and sectioned for analysis of cellular proliferation and intimal thickness. Intraaortic stent placement significantly decreased the transarterial wall oxygen gradient in the outer 70% of the vessel wall and was easily reversed at 7, 14, and 28 days with application of supplemental oxygen. Cellular proliferation was significantly decreased at 14 days (0.5% +/- 0.001% versus 2.3% +/- 0.002%; P <.001) and 28 days (0.4% +/- 0.001% versus 1.0% +/- 0.001%; P <.025) as measured with count of nuclei staining for 5-Bromo-2'deoxyuridine in the intima and media. Intimal thickness was significantly decreased at 28 days in oxygen-supplemented rabbits (intimal area/medial area = 0.50 +/- 0.07) as compared with controls (intimal area/medial area = 0.89 +/- 0.11; P <.025). This study shows the ability of supplemental oxygen to reverse arterial wall hypoxia, decrease cellular proliferation, and control IH at the deployment site of an intraarterial stent in a rabbit model. Forty-percent supplemental oxygen suppresses IH by 44% at 28 days as compared with normoxic control values. Cellular proliferation is reduced four-fold at 14 days and two-fold at 28 days in oxygen-supplemented rabbits as compared with control media after deployment. The clinical implications of these findings are significant, especially as the role of endovascular interventions continues to expand.


Disease-related death in patients who were considered free of macroscopic disease after initial treatment of well-differentiated thyroid carcinoma.
Death from well-differentiated thyroid cancer (WDTC) is rare, and over the past century there has been a trend away from local recurrence as the primary cause of death. The objective of our study was to report the cause of death from thyroid cancer in patients with WDTC treated with curative intent with surgery ± adjuvant radioactive iodine. An institutional database of 1811 patients with WDTC treated surgically for WDTC between 1986 and 2005 was analyzed and identified 165 (9.4%) who had died. Case records were studied to determine the cause of death in each patient. Of the 165 deaths, 17 (10%) patients were confirmed to have died of thyroid cancer and 6 (4%) died of an unknown cause but had thyroid cancer present at the time of last follow-up. The remaining 142 (86%) died from other causes and were considered free of thyroid cancer at their last follow-up. We therefore identified only 23 cause-specific deaths from the entire cohort (1.3%). Of the 17 patients known to have died of thyroid cancer, all had distant recurrence. Ninety-four percent had pulmonary metastases. Of these, 47% also had bony metastasis at the time of death. Two patients had recurrent disease in the neck at the time of death, but both also had distant disease. Of the six patients (4%) who died of unknown causes but had thyroid cancer at last follow-up, four (67%) had distant disease alone, one (17%) had local and regional recurrence, and one had local and distant recurrence at last follow-up. After successful resection of WDTC, we report a low disease-specific death rate (1.3%). In contrast to earlier reports, death caused by central compartment disease in this recent series is very rare, with metastatic disease accounting for almost all fatalities.


Glucose to Platelet Ratio: A Potential Predictor of Hemorrhagic Transformation in Patients with Acute Ischemic Stroke.
Glucose and platelet are two easily obtained clinical indicators; the present research aimed to demonstrate their association with hemorrhagic transformation (HT) in acute ischemic stroke (AIS) patients without thrombolytic or thrombectomy therapy. This was a single-center retrospective study. Patients who were diagnosed with HT after AIS were included in the HT group. Meanwhile, using the propensity score matching (PSM) approach, with a ratio of 1:2, matched patients without HT were included in the non-HT group. Serum G/P levels were measured on the first morning after admission (at least eight hours after the last meal). Characteristics were compared between the two groups. Multivariate logistic regression was used to determine the independent relationship between G/P and HT after AIS, with G/P being divided into quartiles. From January 2013 to March 2022, we consecutively included 643 AIS patients with HT (426/643 [66.25%] with HI and 217/643 [33.75%] with PH), and 1282 AIS patients without HT, at the First Affiliated Hospital of Wenzhou Medical University. The HT group had higher G/P levels than the non-HT group (0.04 ± 0.02 vs. 0.03 ± 0.02, p < 0.001). However, there was no difference in G/P levels between HI and PH subgroups (0.04 ± 0.02 vs. 0.04 ± 0.02, p > 0.05). Moreover, the G/P levels were divided into quartiles (Q1 ≤ 0.022; Q2 = 0.023−0.028; Q3 = 0.029−0.039; Q4 ≥ 0.040), with Q1 being settled as the reference layer. After controlling the confounders, multivariate regression analyses showed that the Q4 layer (Q4: G/P ≥ 0.040) was independently associated with elevated HT risk (odds ratio [OR] = 1.85, 95% CI = 1.31−2.63, p < 0.001). G/P levels on admission were independently associated with HT risk in AIS patients. In clinical practice, adequate attention should be paid to AIS patients with elevated G/P levels (G/P ≥ 0.040).


Seroprevalence of an antibody against diphtheria, tetanus, and pertussis among the elderly in Khon Kaen, Thailand.
Owing to a declining birth rate and longer lifespan, the number of elderly people (≥ 60 years) in Thailand has grown rapidly. However, the elderly are at significant risk of infectious diseases because they have never been immunized, because they have not been completely immunized, or because their immunity has waned. Immunity against infectious diseases in the elderly is an important means of controlling diseases in the community. Our objective was to evaluate the seroprotective rate against diphtheria, tetanus, and pertussis in the elderly Thai population. In total, 430 healthy individuals from the northeastern region of Thailand were enrolled in this study and stratified into five age groups: 60-65, 66-70, 71-75, 76-80, and > 80 years. Serum samples were collected and quantitatively analyzed for diphtheria, tetanus, and pertussis IgG antibody by using commercial ELISA kits. For anti-diphtheria toxoid and anti-tetanus toxoid ELISA, values < 0.01 IU/ml were interpreted as seronegative, and for anti-Bordetella pertussis toxin ELISA, values < 5 IU/ml were interpreted as seronegative; these definitions were in accord with previous studies. For diphtheria toxoid Ab, the majority of the population had antibody levels > 0.01 IU/ml. For tetanus anti-toxoid Ab, the majority of the population had antibody levels of > 0.01 IU/ml, of which approximately 34% had durable antibody protection levels (DAPL) of ≥ 1 IU/ml. Meanwhile, nearly 45% of the population had an Ab level against pertussis lower than the protectivity level. In total, 97.2%, 83.5%, and 55.8% of the population had a higher antibody level than the minimal protective level for diphtheria, tetanus, and pertussis, respectively. In order to prevent an outbreak of these diseases in the future, the elderly should be administered with Tdap revaccination to provide diphtheria herd immunity in the population; this will increase cocoon phenomenon for pertussis and protect the population from tetanus-prone injury.


Phage Microarrays for Screening of Humoral Immune Responses.
Chronic diseases are the leading cause of disability and responsible for about 63% of deaths worldwide. Among the noninfectious chronic diseases with the highest incidence are cancer and neurodegenerative diseases. Although they have been extensively studied in the last years, there is still an urgent need to find and elucidate the molecular mechanisms underlying their formation and progression to get an early diagnosis and find new therapeutic targets of intervention. Beyond other microarray-based proteomic techniques more extensively used because of their commercial availability, such as protein and antibody microarrays, phage microarrays are another kind of protein microarrays useful for the identification and characterization of disease-specific humoral immune responses and to get further insights into these devastating diseases. Here, we describe the integration and utilization of phage microarrays, which offer such a combination of sensitivity and cost-effective multiplexing capabilities that makes them an affordable strategy for the characterization of humoral immune responses in multiple diseases.


An Economic Evaluation of the All New Zealand Acute Coronary Syndrome Quality Improvement Registry Program (ANZACS-QI 28).
The All New Zealand Acute Coronary Syndrome Quality Improvement (ANZACS-QI) program comprises a clinical quality registry of acute coronary syndrome patients admitted to hospitals across New Zealand. Its primary purpose is to improve quality of care by promoting evidence- and guidelines-based practice, and benchmarking against performance targets. Few studies have examined the cost-effectiveness attributed to clinical quality registries. We aimed to evaluate the clinical and cost impacts of the ANZACS-QI program in New Zealand from both a societal and health care system perspective. Using decision analytic Markov models, we estimated the effectiveness and costs of the ANZACS-QI program in each year over 4 years (2013-2016), against a hypothetical scenario where the registry did not exist. We assumed that the ANZACS-QI contributed to 15% of the temporal changes to patient mortality and hospital readmissions for myocardial infarction observed in the study period. Marginal costs of the registry and years of life saved were estimated. Over a one-year period, the return on investment (ROI) ratio for the ANZACS-QI program was 1.53; thus, every dollar spent on the program resulted in a return of NZD $1.53. (All dollars are in 2017 New Zealand dollars [NZD] unless otherwise stated). The estimated incremental cost-effectiveness ratio (ICER) was $113,327 per year of life saved (YoLS). Extending the time horizon to 5 years, reduced the ICER to $19,684 per YoLS. The ANZACS-QI program represents a sound investment for New Zealand. Even based on highly conservative assumptions, the program is cost saving for society, at a ROI ratio of about 1.5 each year.


Clowning during COVID-19 - A survey of European Healthcare Clowning Organisations highlights the role of humour and art in the healthcare system.
This paper presents the findings of a Europe-wide survey that investigates the impact of COVID-19 on Healthcare Clowning Organisations and encourages the healthcare community to reflect on the role of medical clowning within the healthcare system. Online survey. The survey was conducted in June 2020. Forty organisations from 21 countries across Europe responded through a mix of closed and open-ended answers. During the pandemic, 36 out of 39 of the surveyed organisations (with one non-response) had to postpone or cancel their artistic activities. As the crisis continued, 34 out of 40 of them managed to adapt their in-person activities, but the impact of virtual and distanced interactions with the beneficiaries was generally perceived as lower than that of in-person activities. In open responses, many Healthcare Clowning Organisations criticised the exclusion of medical clowns from healthcare institutions in times when the need for psychosocial support was particularly acute. The healthcare sector should reconsider the important role the medical clowns play within healthcare settings, and allow for more inclusive and flexible safety regulations that take into consideration the holistic well-being of vulnerable groups, especially children, the elderly, and medical staff.


Neurotoxic Effect of Fipronil in Male Wistar Rats: Ameliorative Effect of L-Arginine and L-Carnitine.
The ameliorative effect of L-arginine (LA) and L-carnitine (LC) against fipronil (FPN)-induced neurotoxicity was explored. In this case, 36 adult male rats were randomly divided into six groups: group I received distilled water, group II received 500 mg/kg LA, group III received 100 mg/kg LC, group IV received 4.85 mg/kg FPN, group V received 4.85 mg/kg FPN and 500 mg/kg LA and group VI received 4.85 mg/kg FPN and 100 mg/kg LC for 6 weeks. Cognitive performance was assessed using Barnes maze (BM). Serum corticosterone, brain total antioxidant capacity (TAC), malondialdehyde (MDA) and dopamine were measured. Histopathology and immunohistochemistry of ionized calcium-binding adaptor (Iba-1), doublecortin (DCX) and serotonin (S-2A) receptors were performed. Fipronil induced noticeable deterioration in spatial learning and memory performance. In addition, FPN significantly (p < 0.05) diminished brain antioxidant defense system and dopamine coincide with elevated serum corticosterone level. Histopathological examination revealed degenerative and necrotic changes. Furthermore, Iba-1 and DCX were significantly expressed in cortex and hippocampus whereas S-2A receptors were significantly lowered in FPN group. However, administration of LA or LC alleviated FPN-induced deteriorations. In conclusion, LA and LC could be prospective candidates for mitigation of FPN-induced neurotoxicity via their antioxidant, anti-inflammatory and neuropotentiating effects.


Myocardial infarction in the 31st week of pregnancy--case report.
The occurrence of acute myocardial infarction (AMI) during pregnancy is rare. The authors describe the case of MI in a 31-week pregnant woman and the importance of a multidisciplinary team for its approach. Thirty-one week pregnant woman with history of smoking, alcoholism and hypertension was admitted after an episode of syncope. On admission she was conscious and asymptomatic, although hypotensive. The electrocardiogram showed marked ST-segment elevation in D1, aVL, V1-V6. The cardiac enzymes were positive. The transthoracic echocardiogram showed reduction in septal and left ventricular contractility and an ejection fraction of 30%. Angiography revealed proximal occlusion of the left anterior descending artery. After a non-successful balloon angioplasty, a metallic stent was placed. The patient started therapy with beta-blockers, aspirin and clopidogrel. As for the delivery, we chose to perform a cesarean section four weeks after MI. Clopidogrel was suspended seven days before delivery. The preoperative cardiac function was improved by infusion of levosimendan started the day before. Cesarean section occurred under epidural block. The intraoperative period showed no complications, except for mild hypotension easily corrected with phenylephrine. The Apgar score for the newborn was 9/10. This is one of the few cases of myocardial infarction and angioplasty reported during pregnancy. The authors discuss the decisions taken by the multidisciplinary team consisting of anesthesiologists, obstetricians, neonatologists and cardiologists, particularly with regard to dual antiplatelet therapy, the type of delivery and anesthesia.


Coding of image contrast in central visual pathways of the macaque monkey.
Measurements of contrast sensitivity were obtained from isolated neurons in the lateral geniculate nucleus, striate cortex, and middle temporal visual area of macaque monkeys. Between the lateral geniculate nucleus and the middle temporal area contrast sensitivity functions become progressively steeper. Furthermore, many neurons in the middle temporal area are more sensitive than any cell encountered in early stages. Measurements made with stimuli of different sizes show that this high sensitivity depends on areal summation across the receptive field.


Treatment outcomes and quality-of-life assessment in a university-based fertility preservation program: results of a registry of female cancer patients at 2 years.
To explore patient goals and quality of life (QOL) via a prospective registry and compare fertility preservation (FP) outcomes before, during, and after cancer therapy. Of 35 patients entering the registry from 3/2008 to 3/2010, 29/35 completed the study survey and agreed to follow-up, and 31/35 completed treatment. Survey results and FP outcomes were analyzed. Most patients rated the impact of cancer treatment on fertility of highest importance at baseline and 1-year follow-up. QOL scores were overall positive at both intervals. Patients naïve to any cancer treatment (n = 12) had more gametes frozen than patients with prior cancer treatment (n = 19) with no difference in age or gonadotropin dosage. For patients awaiting cancer treatment, the median time from consultation to oocyte retrieval was 25 days. Cancer treatment sequalae posed challenges to optimal FP outcomes. Fertility preservation remains a significant issue for cancer patients. With early reproductive endocrinologist referral, cancer treatment delay is minimized and FP outcomes are optimized.