Metalloproteinase activity is the sole factor responsible for the growth-promoting effect of conditioned medium in Trichoplusia ni insect cell cultures.
Conditioned medium (CM) taken from a serum-free culture of Trichoplusia ni (BTI-Tn-5B1-4, High Five) cells on days 2 and 3, shortened the lagphase and increased the maximum cell density when added to T. ni cultures with low-inoculum cell density. Gel filtration fractions of CM, eluting at around 45kDa, stimulated cell proliferation even better than CM. A protein in the gel filtration fraction was identified by N-terminal amino acid sequencing as a proteinase, related to a snake venom metalloproteinase. Casein zymography showed, multiple metalloproteinase bands between 48 and 25kDa, as well as precursor forms above 48kDa. Metalloproteinase bands below the main band at 48kDa were autocatalytic degradation products. Metalloproteinase activity was the sole factor responsible for the growth stimulating effect of CM as shown by using the specific metalloproteinase inhibitor dl-thiorphan. Metalloproteinases have recently been shown to release growth factors from sequestering extracellular proteins. We propose that the metalloproteinase is involved in autocrine regulation of T. ni proliferation in serum-free media. In addition, a gel filtration fraction of CM, eluting at about 10kDa, inhibited cell growth. Apart from a lysozyme precursor protein and a cyclophilin-like protein, a kazal-type proteinase inhibitor could be identified in this fraction.


Heat shock response to exercise in pancreatic islets of obese mice.
Chronic obesity imposes an organismal state of low-grade inflammation because the physiological resolution of inflammation is progressively repressed giving rise to cellular senescence and its accompanying Senescence-Associated Secretory Phenotype (SASP), which avoids apoptosis but perpetuates the relay of inflammatory signals from adipose tissue toward the rest of the body. Conversely, resolution of inflammation depends on the integrity of heat shock response (HSR) pathway that leads to the expression of cytoprotective and anti-inflammatory protein chaperones of the 70 kDa family (HSP70). However, chronic exposure to the aforementioned injuring factors leads to SASP, which, in turn, suppresses the HSR. A main metabolic tissue severely jeopardized by obesity-related dysfunctions is the endocrine pancreas, particularly β-cells of the islets of Langerhans. Because exercise is a powerful inducer of HSR and predicted to alleviate negative health outcomes of obesity, we sought whether obesity influence HSP70 expression in pancreatic islets and other metabolic tissues (adipose tissue and skeletal muscle) of adult B6.129SF2/J mice fed on a high-fat diet (HFD) for 13 weeks since the weaning and whether acute exercise as well as moderate-intensity exercise training (8 weeks) could interfere with this scenario. We showed that acute exercise of moderate intensity protects pancreatic islets against cytokine-induced cell death. In addition, acute exercise challenge time-dependently increased islet HSP70 that peaked at 12 h post-exercise in both trained and untrained mice fed on a control diet, suggesting an adequate HSR to exercise training. Unexpectedly, however, neither exercise training nor acute exercise challenges were able to increase islet HSP70 contents in trained mice submitted to HFD, but only in untrained HFD animals. In parallel, HFD disrupted glycemic status which is accompanied by loss of muscular mass resembling sarcopenic obesity that could not be rescued by exercise training. These results suggest that exercise influences HSR in pancreatic islets but obesity undermines islet, muscle and adipose tissue HSR, which is associated with metabolic abnormalities observed in such tissues.


Further additions to lichen genus buellia de not. In South Korea.
The paper describes two new records of the lichen genus Buellia (B. badia and B. nashii) from South Korea. A detailed taxonomic description and comments are presented for both taxa. An updated key representing all Buellia species known from South Korea is also provided.


Recovery of pyruvic acid from biotransformation solutions.
The aim of this investigation was to separate pyruvic acid of biotransformation solutions from lactic acid through complex extraction. For this purpose, complex extraction was investigated from model solutions. Tri-n-octanylamine (TOA) was used as the extractant. The effects of various diluents, the stoichiometry of pyruvic acid to TOA, and the initial pH of the aqueous phase on the extraction process were investigated in this study. The effects of sodium hydroxide (NaOH) and trimethylamine (TMA) on the back extraction process were also studied, respectively. The optimal conditions attained from the model solutions proved efficient on the biotransformation solutions of different concentrations. A total recovery of 71-82% of pyruvic acid was obtained, whereas 89-92% of lactic acid was removed. The purity of pyruvic acid reached 97% after the removal of TMA by a simple distillation.


CA125 as a predictor of endometrial cancer lymphovascular space invasion and lymph node metastasis for risk stratification in the preoperative setting.
Endometrial cancer (EC) is the most common malignancy of the female reproductive system. Cancer antigen 125 (CA125) is a serum tumor marker widely reported in EC patients, particularly those with poor prognostic factors such as grade 3 tumors, deep myometrial invasion, lymph node metastasis (LNM), and extra-uterine disease. This retrospective study stratifies pre-operative CA125 levels to evaluate odds ratios (OR) and relative risk (RR) between CA125 levels and the likelihood of +LNM, lymphovascular space invasion (LVSI), grade, and stage. Patient charts for women 18 years or older with a diagnosis of EC and pre-operative or within one week CA125 measurement from January 2000 to January 2015 at a regional hospital were reviewed. OR and RR were determined by unconditional maximum likelihood estimation for CA125 levels as the predictor with staging, grade, +LVSI and +LNM as outcomes. The largest increase in risk for patients having stage I/II/III disease was 52% greater (1.52-fold risk) while largest increase in risk for patients having stage III/IV disease was 67% greater (1.67-fold risk), both at CA125 ≥ 222U/ml. Patients with CA125 ≥ 122U/ml had significantly increased risk of +LNM, with maximum increase in risk of 98% (1.98-fold risk) at 222U/ml. Patients with CA125 ≥ 175U/ml had significantly increased risk of +LVSI, with maximum increase in risk of 39% (1.39-fold risk) at 222U/ml. This study shows that elevated CA125 levels correspond to increased stage, +LVSI, and +LNM in patients with EC.


Molecular epidemiology of canine parvovirus type 2 in Italy from 1994 to 2017: recurrence of the CPV-2b variant.
Canine parvovirus type 2 (CPV-2) is the most important enteric virus infecting canids. It is a rapidly evolving virus; after its emergence in the 1970s, new antigenic variants (called CPV-2a, 2b and 2c) emerged and replaced the original antigenic type. The three antigenic variants are globally distributed with different frequencies and levels of genetic variability. This study focused on VP2 gene sequence analysis and the phylodynamics of CPV-2 which were detected in 123 dogs showing clinical signs of gastroenteritis collected in Italy from 1994 to 2017. For the most part, the sick dogs were young, and a third of them (32.5%) had been vaccinated. No statistical association was found between the CPV-2 antigenic variants, and sex, age, breed and vaccination status. Sequence analysis showed that all three antigenic types circulated in Italy; the CPV-2a type was the prominent genotype, followed by CPV-2c and CPV-2b, with notable differences regarding regional bases and significant fluctuations over time. Nucleotide sequence data showed high genetic heterogeneity with 67 nucleotide sequence types (ntSTs) identified, corresponding to 21 amino acid sequence types (aaSTs). The aaSTs and ntSTs obtained were distributed differently among the three CPV-2 antigenic variants: CPV-2a grouped 12/21 (57.1%) aaSTs and 41/67 (61.2%) ntSTs; CPV-2b grouped 5/21 (23.8%) aaSTs and 6/67 (8.9%) ntSTs, and CPV-2c grouped 4/21 (19.1%) aaSTs and 20/67 (29.9%) ntSTs. Canine parvovirus 2a was characterised by the highest genetic variability while CPV-2c was characterised by notable stability with a predominant amino acid profile during the entire sampling time. Canine parvovirus 2b re-emerged in recent years, showing a new and distinctive amino acid profile of the VP2 protein. The findings of the present study provided new insights regarding the phylodynamics and evolution of CPV-2 in Italy, pointing out notable differences at the local level in the distribution of the CPV-2 variants and the selection of genetic subtypes. The evolution of CPV-2 has raised questions regarding the efficacy of vaccination; therefore, continuous monitoring regarding the evolution and spread of new CPV-2 variants should be a key aim of ongoing research.


Ethical considerations when co-analyzing ancient DNA and data from private genetic databases.
Ancient DNA studies have begun to explore the possibility of identifying identical DNA segments shared between historical and living people. This research requires access to large genetic datasets to maximize the likelihood of identifying previously unknown, close genetic connections. Direct-to-consumer genetic testing companies, such as 23andMe, Inc., manage by far the largest and most diverse genetic databases that can be used for this purpose. It is therefore important to think carefully about guidelines for carrying out collaborations between researchers and such companies. Such collaborations require consideration of ethical issues, including policies for sharing ancient DNA datasets, and ensuring reproducibility of research findings when access to privately controlled genetic datasets is limited. At the same time, they introduce unique possibilities for returning results to the research participants whose data are analyzed, including those who are identified as close genetic relatives of historical individuals, thereby enabling ancient DNA research to contribute to the restoration of information about ancestral connections that were lost over time, which can be particularly meaningful for families and groups where such history has not been well documented. We explore these issues by describing our experience designing and carrying out a study searching for genetic connections between 18th- and 19th-century enslaved and free African Americans who labored at Catoctin Furnace, Maryland, and 23andMe research participants. We share our experience in the hope of helping future researchers navigate similar ethical considerations, recognizing that our perspective is part of a larger conversation about best ethical practices.


[System analysis of heart rate variability, hemodynamics and bioelectrical activity of the human brain at moderate altitudes].
Heart rate variability (HRV), hemodynamics, cerebral alpha-rhythm and systemic relations between them were investigated in 35 normal human subjects at the age of 37.2 +/- 3.8 years. Results of comprehensive clinical, functional and instrumental HRV investigations, electroencephalography (EEG) using 21 monopolar electrodes and blood pressure (BP) monitoring were embodied in mathematical models describing the relations of these parameters, multiple regression equations, and generated 3-D diagrams. It was found that relative increase of LF and reductions of HF ranges occurred on the background of BP elevation. The EEG alpha amplitude was depressed and alpha index decreased. The HRV reduction and modification of the alpha-rhythm structure were demonstrated to affect BP values. These data point to interactions and tight relations between the vegetative and central nervous systems and BP.


High precision measurement of electrical resistance across endothelial cell monolayers.
Effects of vasoactive agonists on endothelial permeability was assessed by measurement of transendothelial electrical resistance (TEER) of human umbilical vein endothelial cells (HUVECs) grown on porous polycarbonate supports. Because of the low values of TEER obtained in this preparation (< 5 omega cm2) a design of an Ussing type recording chamber was chosen that provided for a homogeneous electric field across the monolayer and for proper correction of series resistances. Precision current pulses and appropriate rates of sampling and averaging of the voltage signal allowed for measurement of < 0.1 omega resistance changes of the endothelium on top of a 21 omega series resistance of the support and bathing fluid layers. Histamine (10 microM) and thrombin (10 U/ml) induced an abrupt and substantial decrease of TEER, bradykinin (1 microM) was less effective, PAF (380 nM) and LTC4 (1 microM) had no effect. TEER was also reduced by the calcium ionophore A-23187 (10 microM). The technique allows for measurements of TEER in low resistance monolayer cultures with high precision and time resolution. The results obtained extend previous observations in providing quantitative data on the increase of permeability of HUVECs in response to vasoactive agonists.


Polymorph control by designed ultrasound application strategy: The role of molecular self-assembly.
Molecular self-assembly plays a vital role in the nucleation process and sometimes determines the nucleation outcomes. In this study, ultrasound technology was applied to control polymorph nucleation. For the first time, different ultrasonic application methods based on the nucleation mechanisms have been proposed. For PZA-water and DHB-toluene systems that the molecular self-assembly in solution resembles the synthon in crystal structure, ultrasound pretreatment strategy was conducted to break the original molecular interactions to alter the nucleated form. When the solute molecular self-associates can't give sufficient information to predict the nucleated polymorph like INA-ethanol system, the method of introducing continuous ultrasonic irradiation in the nucleation stage was applied. The induction of ultrasound during nucleation process can break the original interactions firstly by shear forces and accelerate the occurrence of nucleation to avoid the reorientation and rearrangement of solute molecules. These strategies were proved to be effective in polymorph control and have a degree of applicability.


Agro-active endo-therapy treated Xylella fastidiosa subsp. pauca-infected olive trees assessed by the first 1H-NMR-based metabolomic study.
Xylella fastidiosa is a xylem-limited bacterium causing a range of economically important plant diseases in hundreds of crops. Over the last decade, a severe threat due to Olive Quick Decline Syndrome (OQDS), caused by Xylella fastidiosa subspecies pauca, affected the Salento olive groves (Apulia, South-East Italy). Very few phyto-therapeutics, including a Zn/Cu citric acid biocomplex foliar treatment, were evaluated to mitigate this disease. However, the traditional foliar applications result in the agro-actives reaching only partially their target. Therefore the development of novel endo-therapeutic systems was suggested. Metabolite fingerprinting is a powerful method for monitoring both, disease progression and treatment effects on the plant metabolism, allowing biomarkers detection. We performed, for the first time, short-term monitoring of metabolic pathways reprogramming for infected Ogliarola salentina and Cima di Melfi olive trees after precision intravascular biocomplex delivery using a novel injection system. Upon endo therapy, we observed specific variations in the leaf content of some metabolites. In particular, the 1H NMR-based metabolomics approach showed, after the injection, a significant decrease of both the disease biomarker quinic acid and mannitol with simultaneous increase of polyphenols and oleuropein related compounds in the leaf's extracts. This combined metabolomics/endo-therapeutic methodology provided useful information in the comprehension of plant physiology for future applications in OQDS control.


Activation of the subthalamic region during emotional processing in Parkinson disease.
To elucidate the involvement of the human subthalamic nucleus (STN) region in the processing or transmission of emotional information. Local field potentials (LFPs) were recorded from this region in 10 patients with Parkinson disease (PD) undergoing bilateral implantation of the STN for high-frequency stimulation. LFP recordings were made while patients viewed pleasant and unpleasant emotionally arousing and neutral pictures. A significant decrease (event-related desynchronization [ERD]) in the local alpha power (8 to 12 Hz) was found for all stimulus categories starting at about 0.5 seconds after stimulus presentation. However, 1 to 2 seconds poststimulus, the ERD was larger in trials of pleasant (mean ERD: 21.6 +/- 2.8%; p < 0.009) and unpleasant (mean ERD: 15.0 +/- 4.2%; p = 0.018) stimuli compared with neutral stimuli (mean ERD: 4.4 +/- 4.2%). The delayed modulation of alpha activity recorded from the area of the subthalamic nucleus in PD may reflect the processing or transmission of information related to emotional stimuli. "Limbic" activation in the region of the subthalamic nucleus may explain why high-frequency stimulation of the subthalamic nucleus alters affect in some patients with PD.


Hydrolyzed whey protein prevents the development of food allergy to β-lactoglobulin in sensitized mice.
Food allergy is an adverse immune response to dietary proteins. Hydrolysates are frequently used for children with milk allergy. However, hydrolysates effects afterwards are poorly studied. The aim of this study was to investigate the immunological consequences of hydrolyzed whey protein in allergic mice. For that, we developed a novel model of food allergy in BALB/c mice sensitized with alum-adsorbed β-lactoglobulin. These mice were orally challenged with either whey protein or whey hydrolysate. Whey-challenged mice had elevated levels of specific IgE and lost weight. They also presented gut inflammation, enhanced levels of SIgA and IL-5 as well as decreased production of IL-4 and IL-10 in the intestinal mucosa. Conversely, mice challenged with hydrolyzate maintained normal levels of IgE, IL-4 and IL-5 and showed no sign of gut inflammation probably due to increased IL-12 production in the gut. Thus, consumption of hydrolysate prevented the development of clinical signs of food allergy in mice.


From diagnosis of colorectal cancer to diagnosis of Lynch syndrome: The RM Partners quality improvement project.
The UK National Institute for Health and Care Excellence guideline DG27 recommends universal testing for Lynch syndrome (LS) in all newly diagnosed colorectal cancer (CRC) patients. However, DG27 guideline implementation varies significantly by geography. This quality improvement project (QIP) was developed to measure variation and deliver an effective diagnostic pathway from diagnosis of CRC to diagnosis of LS within the RM Partners (RMP) West London cancer alliance. RM Partners includes a population of 4 million people and incorporates nine CRC multidisciplinary teams (MDTs), overseen by a Pathway Group, and three regional genetic services, managing approximately 1500 new CRC cases annually. A responsible LS champion was nominated within each MDT. A regional project manager and nurse practitioner were appointed to support the LS champions, to develop online training packages and patient consultation workshops. MDTs were supported to develop an 'in-house' mainstreaming service to offer genetic testing in their routine oncology clinics. Baseline data were collected through completion of the LS pathway audit of the testing pathway in 30 consecutive CRC patients from each CRC MDT, with measurement of each step of the testing pathway. Areas for improvement in each MDT were identified, delivered by the local champion and supported by the project team. Overall, QIP measurables improved following the intervention. The Wilcoxon signed rank test revealed significant differences with strong effect sizes on the percentile of CRC cases undergoing mismatch repair (MMR) testing in endoscopic biopsies (p = 0.008), further testing with either methylation or BRAF V600E (p = 0/03) and in effective referral for genetic testing (from 10% to 74%; p = 0.02). During the QIP new mainstreaming services were developed, alongside the implementation of systematic and robust testing pathways. These pathways were tailored to the needs of each CRC team to ensure that patients with a diagnosis of CRC had access to testing for LS. Online training packages were produced which remain freely accessible for CRC teams across the UK. The LS project was completed by April 2022. We have implemented a systematic approach with workforce transformation to facilitate identification and 'mainstreamed' genetic diagnosis of LS. This work has contributed to the development of a National LS Transformation Project in England which recommends local leadership within cancer teams to ensure delivery of diagnosis of LS and integration of genomics into clinical practice.


Regulation of dopamine and serotonin synthesis by acute administration of cocaine.
Because cocaine effectively increases extracellular levels of both dopamine (DA) and serotonin (5HT), it might be expected that this agent would inhibit transmitter biosynthesis in these monoamine neurons by activation of autoregulatory feedback pathways. This possibility was tested by measuring the effect of cocaine on 3,4-dihydroxyphenylalanine accumulation (DA synthesis) and 5-hydroxytryptophan accumulation (5HT synthesis) in vivo and in vitro after inhibition of aromatic amino acid decarboxylase with NSD-1015. In vivo, cocaine suppressed both DA and 5HT synthesis in a dose-dependent (10-60 mumols/kg, i.p.) and time-dependent fashion (maximum 60 min after administration, recovery by 120-150 min). Inhibition of DA and 5HT synthesis ranged from 35% to 60% depending on the brain region and was apparent in dopaminergic fields such as the medial prefrontal cortex, nucleus accumbens, piriform cortex, striatum, and in noradrenergic fields, such as the hippocampus and temporal cortex. Inhibition of DA, but not 5HT, synthesis was blocked by the D2 antagonist sulpiride in brain areas containing DA nerve terminals. Procaine (30 mumols/kg) did not inhibit DA or 5HT synthesis and prior treatment with reserpine diminished the effectiveness of cocaine in the medial prefrontal cortex, but not in the striatum. Cocaine did not reverse the gamma-butyrolactone-induced increase in striatal DA synthesis nor did cocaine block the ability of the D2 agonist quinpirole to reverse the increase. In vitro, cocaine inhibited DA synthesis in depolarized (K+ = 30 mM) striatal brain slices, an effect that was reversed by the D2 antagonist eticlopride. These results suggest that DA and 5HT neurons compensate in situ for cocaine-induced increases in synaptic transmitter levels by a transient inhibition of transmitter biosynthesis. Acute suppression of transmitter synthesis (and release) in mesoprefrontal DA neurons may represent the principal compensatory mechanism in this group of neurons.


Identification and characterization of a human transthyretin variant.
An apparent Mr variant of plasma transthyretin (TTR), previously detected using 2-D PAGE, is the first reported occurrence of this type of human TTR variant. We characterized the variant TTR to determine the nature of this difference. Comparative tryptic peptide maps of variant and normal TTR and sequencing of peptides which differed indicated the variant contained a single amino acid substitution of valine for tyrosine at position 116. Because such a change requires two nucleotide substitutions, we postulate the variant arose through mutation in codon 116 of a heretofore unrecognized polymorphic or rare variant allele of TTR.


STX-478, a Mutant-Selective, Allosteric PI3Kα Inhibitor Spares Metabolic Dysfunction and Improves Therapeutic Response in PI3Kα-Mutant Xenografts.
Phosphoinositide 3-kinase α (PIK3CA) is one of the most mutated genes across cancers, especially breast, gynecologic, and head and neck squamous cell carcinoma tumors. Mutations occur throughout the gene, but hotspot mutations in the helical and kinase domains predominate. The therapeutic benefit of isoform-selective PI3Kα inhibition was established with alpelisib, which displays equipotent activity against the wild-type and mutant enzyme. Inhibition of wild-type PI3Kα is associated with severe hyperglycemia and rash, which limits alpelisib use and suggests that selectively targeting mutant PI3Kα could reduce toxicity and improve efficacy. Here we describe STX-478, an allosteric PI3Kα inhibitor that selectively targets prevalent PI3Kα helical- and kinase-domain mutant tumors. STX-478 demonstrated robust efficacy in human tumor xenografts without causing the metabolic dysfunction observed with alpelisib. Combining STX-478 with fulvestrant and/or cyclin-dependent kinase 4/6 inhibitors was well tolerated and provided robust and durable tumor regression in ER+HER2- xenograft tumor models. These preclinical data demonstrate that the mutant-selective, allosteric PI3Kα inhibitor STX-478 provides robust efficacy while avoiding the metabolic dysfunction associated with the nonselective inhibitor alpelisib. Our results support the ongoing clinical evaluation of STX-478 in PI3Kα-mutated cancers, which is expected to expand the therapeutic window and mitigate counterregulatory insulin release. See related commentary by Kearney and Vasan, p. 2313. This article is featured in Selected Articles from This Issue, p. 2293.


Reliability and validity of the positive mental health literacy scale in Chinese adolescents.
Mental health literacy (MHL) is not only the necessary knowledge and ability to promote mental health, but also an important determinant of mental health. Traditionally, the MHL Scale focuses on measuring knowledge and beliefs about mental disorders. In China, there are very few scales for assessing positive MHL. The present study aimed to evaluate the reliability and validity of a Chinese version of the Positive MHL Scale (MHPK-10) in Chinese adolescents. Chinese adolescents (n = 1,247) completed the MHPK-10 online. The validation included the translation and cultural adaptation of the MHPK-10 original version into Chinese and assessment of its psychometric properties: reliability-test-retest and internal consistency, construct validity and criterion validity. Participant's mean score on the revised positive MHL scale was 3.75 (SD = 0.69) which was a unidimensional scale. The correlation coefficients between each item and the total score were between 0.639 and 0.753. Scale item loadings ranged between 0.635 and 0.760 based on confirmatory factor analysis. Cronbach's α coefficient of the scale was 0.869, and the test-retest intraclass correlation coefficient was 0.721 (p < 0.01). Criterion validity was assessed by comparing results of the revised MHPK-10 against those of other validated scales and resulting correlations ranged between 0.342 and 0.615. The revised Chinese version of the MHPK-10 has sound reliability and validity and can be used to measure Chinese adolescents' positive MHL.


SUMO-1 enhancing the p53-induced HepG2 cell apoptosis.
In order to investigate the effect of small ubiquitin-like modifier-1 (SUMO-1) on the p53-induced HepG2 cell apoptosis, HepG2 cells were transfected by recombinant plasmids as pwtp53, pMDM2 and pSUMO-1 respectively. Western blot was employed to detect the protein expression of the transfected recombinant plasmids and the rate of apoptosis was measured by flow cytometry. The results showed that in cells transfected with pwtp53 and pwtp53 + pSUMO-1, the apoptosis rate was (16.79+/-1.62) % and (18.15+/-1.36) % respectively, while transfected with pwtp53+ pMDM2, the rate was decreased to (5.17+/-1.23) %. The apoptosis rate was (14.06+/-1.84) % in the cells transfected with pwtp53+pMDM2+pSUMO-1, significantly higher than that in the cells Transfected with pwtp53+pMDM2 (P<0.01). The apoptosis rates in the cells were all less than 2 % and had no significant difference among the groups. It was suggested that in the HepG2 cells, SUMO-1 can increase the apoptosis induced by wild-type p53 through binding to p53 protein, posttranslational modification and inhibiting the p53 degradation by MDM2.


Transmission of Trypanosoma theileri to cattle by Tabanidae.
Tabanids were collected in an area in northern Germany, where pastured cattle were abundant. Trypanosomatidae were identified in 14% of tabanids examined. Twelve cattle became infected with Trypanosoma theileri after applying usually 2-5 infected tabanids, to the intact oral mucosa. Haematopota pluvialis, Haematopota italica, Hybomitra micans and Tabanus bromius were identified as vectors. Infective stages of Trypanosoma theileri were identified in the gut and in the faeces of tabanids by transmission experiments. The minimum prepatent period was less than 4 days. No apparent signs of disease were observed in the infected cattle.


PCDD/F and PCB water column partitioning examination using natural organic matter and black carbon partition coefficient models.
A 9-year water dataset from the Houston Ship Channel (HSC) was analyzed to understand partitioning in polychlorinated biphenyls (PCBs) and polychlorinated dibenzo-p-dioxins/polychlorinated dibenzofurans (PCDD/Fs). Total PCBs had more mass as dissolved (74%) whereas total PCDD/Fs did not (11%). Generally, the limited number of PCDD/Fs (only 2378 substituted) explained these differences though differences in chemical behavior beyond log K ow also likely influence partitioning. The particular fractionation seen in the HSC also seemed related to a wide variation in particulate organic carbon (POC)/dissolved organic carbon (DOC) ratio (0.42-180%). Published and unaltered linear free energy and linear solvation energy relationships for DOC, POC, and particulate black carbon (BC) resulted in predictions that were at best 27% (PCB) and 25% root-mean-square error (RMSE) (PCDD/F) partition fraction compared to observed (using estimated BC/POC fractions of 10 and 25%, respectively). These results show, at least in light of the uncertainties in this data (e.g., precise fraction of BC), that a 25% accuracy in model prediction of operationally dissolved or suspended fraction for any one PCB or PCDD/F congener is the best prediction that may be expected. It is therefore recommended that site-specific data be used to calibrate most any water column-partitioning model if it is to be expected to describe what actually occurs in field conditions.


Expression profile of a clonal insulin-expressing epithelial cell in the thymus.
Type 1 diabetes is an autoimmune disease resulting from the destruction of pancreatic beta-cells. One of the main antigens targeted in this auto reactive response is insulin. It has been shown that insulin is expressed in small amounts in the thymus, and more specifically in the medullary thymic epithelial cells (mTECs), which also express a variety of other tissue-specific antigens. This thymic expression enables the maintenance of self-tolerance, and is essential in preventing auto-immune disease. Our laboratory has created a mouse mTEC clonal cell line specifically expressing insulin in order to better understand the regulatory mechanisms of this ectopic expression of insulin. In this study, we compared the insulin expressing cell line to an insulin non-expressing mTEC line by genome-wide expression profiling. The most important difference was overexpression of CD34 in the insulin expressing clone, confirmed by Real-time Rt-PCR and flow cytometry. Cells in the thymus expressing higher levels of CD34 were found to contain higher levels of insulin and, to a lesser extent, Aire, a master regulator of self-antigen expression in the thymus. The cells expressing CD34 were not enriched in CD80, a known mTEC maturity marker. CD34 may be a specific marker for functionality, with some specificity for insulin.


External application of mirabilite before surgery can reduce the inflammatory response and accelerate recovery in mild acute biliary pancreatitis.
Mild acute biliary pancreatitis (MABP) is one of the most common diseases that require surgical treatment. Previous studies have focused on the timing of laparoscopic cholecystectomy (LC) for MABP. However, the impact of its inflammatory response process on the clinical outcome has been rarely reported. This study aimed to investigate the effect of preoperative external application of mirabilite on the inflammatory response and clinical efficacy in MABP. Medical records of patients undergoing LC due to MABP from November 2017 to June 2022 were retrospectively reviewed. Prior to surgery, the control group received the same baseline treatment measures as the study group. The difference was the addition of external application of mirabilite in the study group. A total of 75 patients were included in the final analysis: 38 patients in the mirabilite group and 37 patients in the control group. Repeated-measures ANOVA (P < 0.01) showed that the white blood cell count (WBC) on the 3rd day of admission and the WBC and C-reactive protein (CRP) level on the 5th day of admission decreased rapidly and significantly in the mirabilite group, compared with the control group. The mirabilite group had earlier anal exhaust time. The number of patients in the mirabilite group and control group with gallbladder wall ≥ 3 mm before the operation was 16 (42.11%) vs. 24 (64.86%), p = 0.048, respectively; and the number of cases with surgical drain placement was 2 (5.26%) vs. 9 (24.32%), p = 0.020, respectively. The intraoperative modified American Fertility Society (mAFS) score of adhesions was lower in the mirabilite group (1.08 ± 0.59 points) than in the control group (1.92 ± 0.60 points), p = 0.000. The mirabilite group, compared to the control group, p = 0.000, had a short waiting time for surgery (5.68 ± 0.70 days vs. 6.54 ± 0.59 days), short operation time (38.03 ± 5.90 min vs. 48.51 ± 8.37 min), and reduced hospitalization time (8.95 ± 0.96 days vs. 9.84 ± 1.07 days). This study demonstrated that preoperative external application of mirabilite can reduce the inflammatory response, decrease the edema and peribiliary adhesions at the surgical site, and accelerate recovery in MABP.


Alteration in crossbridge kinetics caused by mutations in actin.
The generation of force during muscle contraction results from the interaction of myosin and actin. The kinetics of this force generation vary between different muscle types and within the same muscle type in different species. Most attention has focused on the role of myosin isoforms in determining these differences. The role of actin isoforms has received little attention, largely because of the lack of a suitable cell type in which the myosin isoform remains constant yet the actin isoforms vary. An alternative approach would be to examine the effect of actin mutations, however, most of these cause such gross disruption of muscle structure that mechanical measurements are impossible. We have now identified two actin mutations which, despite involving conserved amino acids, can assemble into virtually normal myofibrils. These amino-acid changes in actin significantly affect the kinetics of force generation by muscle fibres. One of the mutations is not in the putative myosin-binding site, demonstrating the importance of long-range effects of amino acids on actin function.


Adverse childhood experiences, diabetes and associated conditions, preventive care practices and health care access: A population-based study.
Our objective was to examine how Adverse Childhood Experiences (ACEs) are associated with diabetes mellitus, diabetes-related conditions, and preventive care practices. We used data from the Behavioral Risk Factor Surveillance System (BRFSS) 2009-2012, a cross-sectional, population-based survey, to assess ACEs, diabetes, and health care access in 179,375 adults. In those with diabetes (n = 21,007), we assessed the association of ACEs with myocardial infarction, stroke, and five Healthy People 2020 (HP2020) diabetes-related preventive-care objectives (n = 13,152). Healthcare access indicators included lack of a regular health care provider, insurance, and difficulty affording health care. Regression analyses adjusted for age, sex, and race. The adjusted odds ratio (AOR) of diabetes increased in a stepwise fashion by ACE exposure, ranging from 1.2 (95% CI 1.1-1.3) for 1 ACE to 1.7 (95% CI 1.6-1.9) for ≥4 ACEs, versus having no ACEs. In persons with diabetes, those with ≥4 ACEs had an elevated adjusted odds of myocardial infarction (AOR = 1.6, 95% CI 1.2-2.0) and stroke (AOR = 1.8, 95% CI 1.3-2.4), versus having no ACEs. ACEs were also associated with a reduction in the adjusted percent of HP2020 diabetes objectives met: 72.9% (95% CI 71.3-74.5) for those with no ACEs versus only 66.5% (95% CI 63.8-69.3%) for those with ≥4 ACEs (p = 0.0002). Finally, ACEs predicted worse health care access in a stepwise fashion for all indicators. In conclusion, ACEs are associated with greater prevalence of diabetes and associated disease conditions, and with meeting fewer HP2020 prevention goals. Implementing ACE screening and trauma-informed health care practices are thus recommended.


Appendiceal tumor incidence and an in-depth look at appendiceal neuroendocrine neoplasm in a cohort of 8,162 appendectomies: Full dataset.
Data describing appendiceal tumor incidence and epidemiology is limited. We collated data from appendectomy pathology reports between 2005 and 2018 in our institution and examined patient epidemiological and appendectomy pathological features [1]. Overall, 8,328 appendectomies were performed at our institution over the pre-specified time period and 8,162 patients had sufficient epidemiological data to be included in the analysis. A total of 153 patients (1.9%) were diagnosed with appendiceal tumors, of which 57 (37.3%) were Appendiceal Neuroendocrine Neoplasm (ANEN), 35 (22.9%) were mucinous cystadenoma and 34 (22.2%) ovarian cancer metastases. We further examined the ANEN cases in order to characterize initial patient and tumor characteristics, to evaluate the performance of further investigations and interventions, and ultimately to study the behavior of these tumors over time.


Traffic noise inhibits inhibitory control in wild-caught songbirds.
Anthropogenic noise is ubiquitous across environments and can have negative effects on animals, ranging from physiology to community structure. Recent work with captive-bred zebra finches demonstrated that traffic noise also affects cognitive performance. We examined whether these results extend to animals that have experienced noise in the wild. We collected black-capped chickadees from areas frequently exposed to road traffic noise and tested them on a detour reaching task, a commonly used measure of inhibitory control. Those chickadees exposed to traffic noise playback had much lower performance on the task than control birds, indicating that noise negatively impacts inhibitory control. These data corroborate previous findings in lab-reared zebra finches. Furthermore, these results suggest that prior experience with traffic noise is not sufficient for animals to habituate to noise and overcome its negative effects on cognitive performance. Instead, noise-induced cognitive effects might have broad impacts on animal species living in noise-polluted habitats.


Side-effect of ancillary ligand on electron transfer and photodynamics of a dinuclear valence tautomeric complex.
A cobalt complex [[Co(dpqa)]2(dhbq)](PF6)3 ((PF6)3, dhbq = deprotonated 2,5-dihydroxy-1,4-benzoquinone, dpqa = di(2-pyridylmethyl)-N-(quinolin-2-ylmethyl)amine) was prepared and studied by X-ray diffraction, electrochemistry, ESR, thermally and photo-induced magnetic measurements; the results show that the ancillary ligand finely tuned structural factors as well as intermolecular interactions that affect the VT behavior.


Fingertip reconstruction by palmar bipedicular island flap in long fingers (modified neurovascular Tranquilli-Leali flap): A dual-center study.
When bone is exposed, fingertip defects may require a flap procedure. Many types are available, with little consensus about which one is best. But each one has its own disadvantages: esthetic (claw nail deformity), neurological (sensory disorders) or functional (stiffness). The purpose of this study was to evaluate a palmar bipedicular island flap (our modification of the Tranquilli-Leali flap) for fingertip reconstruction. We retrospectively analyzed the prospective data of 42 patients with a mean follow up of 16.4 months (6-30 months) operated in two hospital facilities. Thirty-three patients were men. Mean age was 39.5 years (12-83 years) and 24 (57.1%) were smokers. In 23 cases (54.8%), the trauma was work-related. A crush mechanism was identified in 29 patients (69%). According to Allen's classification of fingertip injuries, there were 26 cases of stage II, 14 cases of stage III and 2 cases of stage IV. All procedures were performed on an emergency basis, within 24 hours of the trauma. No claw nail deformity was observed. The mean discrimination in the Weber test was 3.8mm (2-6mm). The mean Total Active Motion (TAM) was 268.3° (255-275°). The patient satisfaction was graded at 8.7 on a 10-point scale. Results were considered as excellent in 15 cases and good in 23 cases. The modified palmar bipedicular island flap makes the old Tranquilli-Leali flap - which has a poor reputation in the hand surgeon community-simpler and safer to use. This flap restores proper balance between skin, bone and nail in Allen stage II and III fingertip amputations.


Structure and Activity of the Thermophilic Tryptophan-6 Halogenase BorH.
Flavin-dependent halogenases carry out regioselective aryl halide synthesis in aqueous solution at ambient temperature and neutral pH using benign halide salts, making them attractive catalysts for green chemistry. BorH and BorF, two proteins encoded by the biosynthetic gene cluster for the chlorinated bisindole alkaloid borregomycin A, are the halogenase and flavin reductase subunits of a tryptophan-6-halogenase. Quantitative conversion of l-tryptophan (Trp) to 6-chlorotryptophan could be achieved using 1.2 mol % BorH and 2 mol % BorF. The optimal reaction temperature for Trp chlorination is 45 °C, and the melting temperatures of BorH and BorF are 48 and 50 °C respectively, which are higher than the thermal parameters for most other halogenases previously studied. Steady-state kinetic analysis of Trp chlorination by BorH determined parameters of kcat =4.42 min-1 , and KM of 9.78 μm at 45 °C. BorH exhibits a broad substrate scope, chlorinating and brominating a variety of aromatic substrates with and without indole groups. Chlorination of Trp at a 100 mg scale with 52 % crude yield, using 0.2 mol % BorH indicates that industrial scale biotransformations using BorH/BorF are feasible. The X-ray crystal structure of BorH with bound Trp provides additional evidence for the model that regioselectivity is determined by substrate positioning in the active site, showing C6 of Trp juxtaposed with the catalytic Lys79 in the same binding pose previously observed in the structure of Thal.


Lymphoproliferative disorders after renal transplantation: role of medical imaging.
Post-transplantation lymphoproliferative disorders (PTLD) are a complication of immunosuppressed transplant recipients, and their incidence is reported to be 20-120 times greater than the rate in the general population. After kidney transplantation, PTLD more likely arise within the renal transplant fossa. Radiological patterns of these forms are presented and discussed, according to a review of the literature, and illustrated by cases from our institution. Ultrasound plays an essential role in the early diagnosis of PTLD by detecting a urinary obstruction associated with adenopathy or an ill-defined mass not previously seen. However, in the case of an inconclusive US examination, CT or MRI should be performed to confirm the presence of a mass. Both techniques are useful in evaluating the extension of the process within the transplantation fossa; MRI seems more accurate and can be used for the follow-up, especially after reduction in immunosuppressive therapy without transplant removal.


Closure of subarachnoid-pleural fistulae with fibrin sealant.
Subarachnoid-pleural fistulae are rare and require closure if conservative therapy has failed. A simple and effective method is described using a pleural graft sealed with fibrin glue. The closure is immediate and long lasting.


Descending colon fistula: Unusual complication of severe acute pancreatitis a case report.
The incidence of colonic complications from acute pancreatitis (AP) and severe AP are 3.3% and 15%, respectively. We report a case of descending colon fistula secondary to severe AP and its management. We report a case of a 35-year-old male hospitalized in our department for severe acute pancreatitis (grade E of Balthazar classification).Initially, the evolution was favorable under medical management. Two months later, he was readmitted for infection of the necrosis with a descending colon fistula. As we did not have the possibility of performing a CT scan drainage, our plan was to do surgical drainage under general anesthesia. The colonic involvement following AP or severe AP is rare and difficult to diagnoses. Conservative treatment when some conditions are available should be the best choice; it is associated with lower risk of morbidity and mortality.


Bisphenol S increases the obesogenic effects of a high-glucose diet through regulating lipid metabolism in Caenorhabditis elegans.
Bisphenol S (BPS), a structural analog of Bisphenol A (BPA), has been widely used as a substitute for epoxy resin, food packaging materials, and other products due to the limited application of BPA. Studies in vivo and in vitro have indicated that BPA could induce fat accumulation like an obesogen. The main goal of this study was to investigate the role and mechanism of BPS in lipid metabolism using Caenorhabditis elegans (C. elegans) as a model. Results showed that both the overall fat deposition and the triglyceride level were significantly increased in a non-monotonically increasing trend, and the low dose of BPS (0.01 μM) exhibited a stronger influence. Additionally, BPS enhanced fat synthesis depending on daf-16, fat-5, fat-6 and fat-7, and inhibited fatty acid oxidation via nhr-49 and acs-2. This study further indicate that fat accumulation induced by BPS requires nhr-49, which also mediated the nuclear hormone signaling pathway.


Genome survey, high-resolution genetic linkage map construction, growth-related quantitative trait locus (QTL) identification and gene location in Scylla paramamosain.
Scylla paramamosain is one of the most economically important crabs in China. In this study, the first genome survey sequencing of this crab was performed, and the results revealed that the estimated genome size was 1.21 Gb with high heterozygosity (1.3%). Then, RAD technology was used to construct a high-resolution linkage map for this species. A total of 24,444 single nucleotide polymorphism (SNP) makers were grouped into 47 linkage groups. The total length of the linkage groups was 3087.53 cM with a markers interval of 0.92 cM. With the aid of transcriptome and genome scaffold data, 4,271 markers were linked to genes, including several important growth-related genes such as transforming growth factor-beta regulator I, immune related-gene C-type lectin and ecdysone pathway gene broad-complex-like protein. Further, 442 markers, representing 279 QTLs, associated with 24 traits were identified, and of these markers, 78 were linked to genes. Some interesting genes, such as dedicator of cytokinesis protein 3, tenascin-X and DNA helicase MCM8, were believed to have important relationship with specific traits and merit further exploration. The results of this study will accelerate the genetic improvement and genome sequencing analysis of the mud crab.


Categorisation of EEG suppression using enhanced feature extraction for SUDEP risk assessment.
Sudden Unexpected Death in Epilepsy (SUDEP) has increased in awareness considerably over the last two decades and is acknowledged as a serious problem in epilepsy. However, the scientific community remains unclear on the reason or possible bio markers that can discern potentially fatal seizures from other non-fatal seizures. The duration of postictal generalized EEG suppression (PGES) is a promising candidate to aid in identifying SUDEP risk. The length of time a patient experiences PGES after a seizure may be used to infer the risk a patient may have of SUDEP later in life. However, the problem becomes identifying the duration, or marking the end, of PGES (Tomson et al. in Lancet Neurol 7(11):1021-1031, 2008; Nashef in Epilepsia 38:6-8, 1997). This work addresses the problem of marking the end to PGES in EEG data, extracted from patients during a clinically supervised seizure. This work proposes a sensitivity analysis on EEG window size/delay, feature extraction and classifiers along with associated hyperparameters. The resulting sensitivity analysis includes the Gradient Boosted Decision Trees and Random Forest classifiers trained on 10 extracted features rooted in fundamental EEG behavior using an EEG specific feature extraction process (pyEEG) and 5 different window sizes or delays (Bao et al. in Comput Intell Neurosci 2011:1687-5265, 2011). The machine learning architecture described above scored a maximum AUC score of 76.02% with the Random Forest classifier trained on all extracted features. The highest performing features included SVD Entropy, Petrosan Fractal Dimension and Power Spectral Intensity. The methods described are effective in automatically marking the end to PGES. Future work should include integration of these methods into the clinical setting and using the results to be able to predict a patient's SUDEP risk.


Sustained selective attention to chromatic information enhances visuocortical gain at the population level.
Prior work in selective attention research has shown that colour-selective attention enhances neural activity in visuocortical areas sensitive to the attended colour while suppressing activity in areas sensitive to ignored colours. However, it is currently unclear whether this effect is limited to attending to specific colour hues or extends to chromatic information more broadly. To investigate this question, we used steady-state visual evoked potentials (ssVEPs) frequency tagging to quantify participants' visuocortical responses to specific elements embedded in arrays of flickering, randomly moving mid-complex patterns. Participants were instructed to attend to either coloured or greyscale patterns while ignoring the others. We found that attending to either coloured or greyscale patterns produced robust increases in ssVEP amplitudes both compared to ignored stimuli and to baseline. There was however no evidence of suppressed responses to ignored patterns. These findings demonstrate that attentional selection based on the presence or absence of chromatic information prompts selectively enhanced visuocortical processing but this selective amplification is not accompanied by suppression of unattended stimuli. Findings are consistent with theoretical notions that predict strong competition between specific exemplars within a given feature dimension, such as red or green, but weak competition between broadly defined stimulus categories, such as chromatic versus non-chromatic.


Induction of immunomodulating cytokines by a new polysaccharide-peptide complex from culture mycelia of Lentinus edodes.
The immunomodulating effect of a new polysaccharide-peptide complex from culture mycelia of Lentinus edodes (LE) was studied for elucidation of the mechanism of augmentation of cell-mediated immunity. RNA samples were isolated from the untreated and treated murine splenocytes and human peripheral blood mononuclear cells. RT-PCR was used to analyze the cytokine gene expression and bioassay was used to analyze the cytokine production. By administration of LE, the expression levels of IL-2 and TNF-alpha genes were augmented in the treated murine spleen mononuclear cells and human peripheral blood mononuclear cells. The production of IL-2 were augmented in the treated murine spleen mononuclear cells, and the production of TNF-alpha were augmented in the treated murine peritoneal exudate macrophages. The production of IL-2 and TNF-alpha were augmented in the treated human peripheral blood mononuclear cells. These results suggest that LE may induce Th immune responses.


A simplified definition of diastolic function in sepsis, compared against standard definitions.
Guidelines for grading diastolic dysfunction poorly categorize septic patients. We compared how well the American Society of Echocardiography (ASE) 2009 and 2016 definitions and a simplified definition categorized septic patients. We studied septic patients who received a transthoracic echocardiogram within 24 h of admission to an ICU. We categorized patients according to ASE 2009 and 2016 definitions and a definition using E/e', a surrogate for left ventricular filling pressure. We assessed 28-day all-cause mortality and the presence of pre-existing diabetes, hypertension, or myocardial infarction. We tested for associations among diastolic grade, comorbidities, and outcomes using logistic regression. We studied 398 patients. Mortality was 23%. The simplified definition categorized more patients than ASE 2016 (78% vs. 71%, p = 0.035); both definitions categorized more patients than ASE 2009 (34%, p < 0.001 for both comparisons). Higher grades of diastolic dysfunction were associated with hypertension (ASE 2016, simplified), myocardial infarction (ASE 2009, simplified), and diabetes (simplified). Grade of diastolic dysfunction was not associated with mortality by any definition. Of 199 patients categorized as normal by ASE 2016, 40% had an abnormal E/e' > 9 and 7% had a severely abnormal E/e' > 13. The ASE 2016 definition categorizes more septic patients than the ASE 2009 definition, but it does not categorize the diastolic function of a third of septic patients. ASE 2016 designates many patients with elevated E/e' as normal. A simplified definition categorized patients with less ambiguity and is associated with relevant comorbidities.


Pathology, genetics and precursors of human and experimental pancreatic neoplasms: An update.
Over the past decade, there have been substantial improvements in our knowledge of pancreatic neoplasms and their precursor lesions. Extensive genetic analyses, recently using high-throughput molecular techniques and next-generation sequencing methodologies, and the development of sophisticated genetically engineered mouse models closely recapitulating human disease, have improved our understanding of the genetic basis of pancreatic neoplasms. These advances are paving the way for refined, molecular-based classifications of pancreatic neoplasms with the potential to better predict prognosis and, possibly, response to therapy. Another major development resides in the identification of subsets of pancreatic exocrine and endocrine neoplasms which occur in the context of hereditary syndromes and whose genetic basis and tumor development have been at least partially defined. However, despite all molecular progress, correct and careful morphological characterization of tissue specimens both in the context of experimental and routine diagnostic pathology represents the basis for any further genetic investigation or clinical decision. This review focuses on the current and new concepts of classification and on the current models of tumor development, both in the field of exocrine and endocrine neoplasms, and underscores the importance of applying standardized terminology to allow adequate data interpretation and promote scientific exchange in the field of pancreas research.


Endothelin-1 and protein kinase C co-expression in the pathogenesis of diabetic retinopathy.
Diabetic retinopathy (DR) is becoming one of the most important complications of diabetes at present. Endothelin-1 (ET-1) and protein kinase C (PKC) are the two important proteins involved in the pathogenesis of DR. A clarification on the interaction between ET-1 and PKC has not yet been made. Here, the author used a new gene ontology technology to predict the molecular function of ET-1 and PKC in an episode of co-expression. With the use of the GoFigure server, the molecular function of ET-1 and PKC is predicted. According to this study, different pathways can be derived from ET-1 and PKC; however, ET-1-PKC produces the same pathway as PKC. This could mean that the interaction between ET-1 and PKC results in increased activity of the PKC pathway but does not generate any new pathway. This finding can be a good explanation for the co-expression between ET-1 and PKC in the pathogenesis of DR.


Prediction and identification of novel IBV S1 protein derived CTL epitopes in chicken.
Infectious bronchitis virus (IBV) is a major pathogen common in the poultry industry. Broad cytotoxic T lymphocyte (CTL) response against IBV is one of the crucial factors that help to control viral replication. Spike glycoproteins on the surface of the IBV virion harbor major T cell epitopes. In this study, based on the peptide-binding motifs of chicken MHC I molecules for the BF2*4, BF2*12, BF2*15, and BF2*19 haplotypes, potential CTL epitopes were predicted using S1 proteins from different IBV strains. Twenty-one peptides were predicted to be potential CTL epitopes; they were manually synthesized and the CTL responses to them tested in vitro. Spleen lymphocytes were collected from specific-pathogen free (SPF) chicken that had been immunized with the S1 protein expression plasmid, pV-S1, and were stimulated by the synthesized peptides. IFN-γ secretion and CD8(+) T cell proliferation in chickens were tested by ELISpot array and flow cytometry, respectively. Four epitopes (P8SRIQTATDP, P9SRNATGSQP, P18GAYAVVNV, and P19SRIQTATQP) were identified to stimulate CD8(+) T cell proliferation and IFN-γ secretion, indicating their efficacy as CTL epitopes in chicken. Poly-CTL-epitope DNA vaccine (pV-S1T) was constructed by inserting nucleotide sequences encoding the P8, P9, P18, and P19 CTL epitopes into the pVAX1 vector. Chickens were vaccinated with either pV-S1, pV-S1T, or pVAX1 and the protection efficacy was analyzed, revealing that ninety percent of chickens immunized with pV-S1T were protected after challenge with 10(6) ELD50 of IBV, demonstrating that these novel CTL epitopes were effective against IBV challenge. This study provides a new method to screen virus CTL epitopes in chicken and to develop poly-CTL-epitope DNA vaccines.


Reduced insulin binding to hepatic plasma membranes in D-galactosamine-treated rats.
Six to 12 hr after IP injection of 400 mg/kg of D-galactosamine in rats a 5-fold increase in plasma insulin was observed. In addition, impaired glucose assimilation was present after an IV Load in spite of unchanged fasting glucose levels. In streptozotocin-diabetic rats (100 mg/kg IV) plasma insulin remained diminished 12 h after induction of D-galactosamine hepatitis. Under identical conditions of preparation and incubation, the liver plasma membranes of D-galactosamine-treated rats, in both normal and diabetic states, bound only 40--60% as much insulin per mg of membrane protein as those of the control rats. Scatchard analysis suggested that this was due to a decrease in the number of receptor sites in the membranes of the D-galactosamine-injected rats. No difference in the insulin degrading capacity and in insulin-receptor dissociation of the plasma membranes between control and D-galactosamine-treated groups was found. These data suggest that a reduction in the number of hepatic insulin receptors in galactosamine hepatitis can lead to insulin resistance and hyperinsulinaemia.


Pesticides in roof runoff: study of a rural site and a suburban site.
The quality of stored roof runoff in terms of pesticide pollution was assessed over a one-year period. Two tanks, located at a rural and suburban site, respectively, were sampled monthly. The two studied collection surface were respectively a tile slope roof and a bituminous flat roof. Four hundred and five compounds and metabolites were screened using liquid and gas chromatography coupled with various detection systems. Principal Component Analysis was applied to the data sets to elucidate patterns. At the rural site, two groups of compounds associated with two different types of agriculture, vineyard and crops, were distinguished. The most frequently detected compound was glyphosate (83%) which is the most commonly used herbicide in French vineyards. At the suburban site, quantified compounds were linked to agriculture rather than urban practices. In addition, all samples were contaminated with mecoprop which is a roof-protecting agent. Its presence was attributed to the nature of roofing material used for rainwater collection. For both sites, the highest number and concentrations of compounds and metabolites were recorded at the end of spring and through summer. These results are consistent with treatment periods and higher temperatures.


Design, synthesis and evaluation of novel 1,4-naphthoquinone derivatives as antifungal and anticancer agents.
A series of 1,4-naphthoquinone derivatives were synthesized and tested for antifungal and antitumor activity against a number of fungal disease causative species and Walker 256 carcinoma cell lines. The results show that the compounds 8a,e and 11b possess pronounced antifungal profile where as 7b and f were found to be active against Walker 256 carcinoma cell lines. Moreover 7c and 11a showed inhibitory effect against reverse transcriptase enzyme from Rauscher Murine Leukemia Virus.


Spinal intramedullary cavernous angioma patient in a pain clinic - A case report.
Spinal intramedullary cavernous angioma is a rare form of spinal cord tumor that is associated with myelopathy and significant morbidity and surgical treatment is almost always required. We report a case of spinal intramedullary cavernous angioma in a pain clinic with initial symptoms of unilateral interdigital space sensory change. Morton's neuroma and piriformis syndrome were clinically suspected, however, symptoms acutely aggravated, and paraplegia developed following the patient's COVID-19 vaccination. Vaccine-associated side effects were ruled out and spinal intramedullary cavernous angioma was confirmed through magnetic resonance image. The patient underwent surgery for complete mass excision. Recent reports of COVID-19 vaccine-associated side effects have raised sensitive concerns to both health care providers and the public, that in some cases when the symptoms coincide with vaccination history, it may delay time-sensitive diagnosis and treatment and spend unnecessary costs.


Dynamics of DNA replication in mammalian somatic cells: nucleotide pool modulates origin choice and interorigin spacing.
Selection of active origins and regulation of interorigin spacing are poorly understood in mammalian cells. Using tricolor analysis of combed DNA molecules, we studied an amplified locus containing the known origin, oriGNAI3. We visualized replication firing events at this and other discrete regions and established a strict correlation between AT richness and initiation sites. We found that oriGNAI3 is the prominent origin of the domain, the firing of which correlates with silencing of neighboring sites and establishes large interorigin distances. We demonstrate that cells reversibly respond to a reduction in nucleotide availability by slowing the rate of replication fork progression; in addition, the efficiency of initiation at oriGNAI3 is lowered while other normally dormant origins in the region are activated, which results in an overall increase in the density of initiation events. Thus, nucleotide pools are involved in the specification of active origins, which in turn defines their density along chromosomes.


Arthroscopic Repair of Humeral Avulsion of the Glenohumeral Ligaments Based on Location.
Humeral avulsion of the glenohumeral ligament (HAGL) can be a difficult problem to treat. HAGL lesions can be particularly challenging to repair when approached arthroscopically. Because of the technical difficulties of HAGL repair, the surgeon must be strategic to successfully address these lesions arthroscopically. The purpose of this article is to propose a surgical technique that can be used in the arthroscopic treatment of HAGL lesions based on their location.


Basement membrane invasion by first trimester human trophoblast: requirement for branched complex-type Asn-linked oligosaccharides.
Trophoblast cells of normal first trimester human placenta share with malignant tumor cells the ability for significant cellular proliferation and invasion of basement membranes. Because tumor cell metastasis in vivo and invasion of basement membranes in vitro have recently been shown to require the expression of -GlcNAc beta 1-6 Man alpha 1-6 Man beta 1-branched complex type Asn-linked oligosaccharides in tumor cell surface glycoproteins, we decided to determine if such structures were also necessary for invasion by trophoblast cells. We report here that invasive first trimester trophoblasts express leukoagglutinin-reactive beta 1-6 branched Asn-linked oligosaccharides on their surface. Moreover, basement membrane invasion by trophoblast was significantly inhibited by pretreating the cells with swainsonine, a non-toxic inhibitor of Golgi alpha-mannosidase II which blocks beta 1-6 branching of Asn-linked oligosaccharides. The first trimester trophoblast cells pretreated with swainsonine attached more avidly to the amnion basement membrane and to an extracellular matrix (ECM) preparation compared to control non-treated erophoblast cells. Swainsonine treatment did not inhibit secretion of gelatinase or plasminogen activator activities by trophoblast cells. These results suggest that expression of beta 1-6 branched oligosaccharides in trophoblast cells may be functionally important for the implantation and placentation processes by reducing cell adhesion to ECM and thereby facilitating trophoblast cell invasion.


Effects of intramuscularly injected plant-derived antimicrobials in the mouse model.
With increasing antibiotic resistance, the use of plant derived antimicrobials (PDAs) has gained momentum. Here, we investigated the toxicity of trans-cinnamaldehyde, eugenol, and carvacrol after intramuscular injection in mice. Two doses of each PDA-300 and 500 mg/kg body weight-and vehicle controls were injected into the muscle of the right hind limb of CD-1 adult mice (n = 8/treatment). Ten physical/behavioral parameters were monitored hourly for 2 h and twice daily for 4 days post-injection together with postmortem examination of leg muscles and organs. Within the first 2 days of carvacrol treatment, one male died in each dose level and a third male receiving 500 mg/kg was removed from the study. No mortality was seen with any other treatment. Among all 81 parameters examined, significant higher relative liver weights (300 and 500 mg/kg eugenol groups; P < 0.05) and relative kidney weights (300 mg/kg carvacrol group; P < 0.001) were observed. Taken together, little to mild toxicity was seen for trans-cinnamaldehyde and eugenol, respectively, while carvacrol exerted more toxicity in males. This study lays the foundation for future extensive work with large sample size, varied treatment durations, and additional treatment levels.


Tophaceous gout in the cervical spine.
Gout is a common metabolic disorder typically affecting the distal joints of the appendicular skeleton. Involvement of the axial skeleton, particularly the facet joints and posterior column of the cervical spine, is rare. This case report highlights such a presentation in a 76-year old female who presented with cervical spine pain following a fall. Her radiological findings were suggestive of a destructive metastatic process. Histological diagnosis confirmed tophaceous gout.


Comparative elucidation on the phenolic fingerprint, sugars and antioxidant activity of white, orange and purple-fleshed sweet potatoes (Ipomoea batatas L.) as affected by different cooking methods.
In this study, three cooking methods (baking, boiling, sous vide (SV)) were applied to Turkish sweet potatoes with three flesh colors (white, orange, purple) to examine the effects of the product color and cooking methods on the total phenolics, antioxidant activity, sugars, phenolic acids, and anthocyanins. LC-MS-MS was employed in the characterization of these compounds. It was observed that the product color and cooking method significantly affected the concentrations of bioactive compounds like polyphenols. Both the highest total phenolic content (11.36 mg/g) and antioxidant activity (DPPH (50.3 μM TE/g) and ABTS (63.53 μM TE/g)) were determined in the purple sweet potato cooked with the SV method. 10 phenolic acids were quantified in all samples which were in the highest amounts in the orange colored samples followed by the purple samples. Baking resulted in the highest total phenolic acids in all samples. 13 anthocyanins were detected in the purple-colored samples, while the SV cooking best preserved the anthocyanins. In sum, purple sweet potatoes cooked by SV are recommended for higher phenolic contents, antioxidant capacity and anthocyanins.


Annular pancreas in adults: embryological development, morphology and clinical significance.
Three cases (two male, one female) of annular pancreas are presented, which were found and operated on within the last three decades. Diagnosis was made using imaging techniques, especially ultrasonography and computed tomography. In two cases there was incomplete obstruction, while in the other obstruction was complete. It is characteristic that in the case of complete obstruction the annular portion of the pancreas attached to a circular band of connective tissue, while in the two cases of incomplete obstruction there was a complete ring of pancreatic tissue. In all cases surgical intervention was needed in order to create a bypass. In the first case gastroenterostomy and truncal vagotomy was performed, in the second latero-lateral duodeno-jejunostomy and in the third latero-lateral antropyloroduodeno-jejunostomy. The embryology and morphology of the annular pancreas, the morphology of its duct system, diagnosis, differential diagnosis and the surgical treatment of this rare condition are reviewed.


Fabrication of hierarchical flower-like WO3 nanoparticles for effective metal ions sensing and catalytic degradation of organic dyes.
In this work, we report on the synthesis of flower-like tungsten oxide nanoparticles (WO3 NPs) using a simple precipitation method. This paper reports a simple method for synthesizing flower-like WO3 NPs, which can be used for environmentally treating hazardous organic pollutants. The photocatalytic degradation of model artificial Orange II and Congo red was assessed under natural sunlight irradiation. The surface morphologies, crystallinity, and binding energy of the synthesized WO3 NPs were determined. The synthesized WO3 NPs exhibited good photodegradation percentages of approximately Orange II (97.6%) and Congo red dye (98.2%) after 120 min of irradiation. Furthermore, the WO3 NPs maintained their degradation ability for up to three cycles. In addition, WO3 NPs were examined in different metal ions sensing (Hg2+, Fe2+, Cu2+, Ni2+, and Cd2+) in an aqueous solution. The results showed that the WO3 NPs exhibited excellent Cd2+ ion sensing. Based on the investigations, WO3 NPs proved to be an efficient photocatalyst and hold promise as the best material for future applications in preventing water pollution.


Pizotifen increases 5-HIAA urinary excretion in male healthy volunteers.
A single dose of 0.5 mg pizotifen or a placebo was administered to 10 healthy male volunteers in a double blind cross-over trial. 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA) in hourly urine samples were determined by liquid chromatography with amperometric detection. The 5-HIAA levels were strongly correlated with the HVA levels in control samples (r = 0.95, p less than 0.001). Pizotifen produced a significant increase in the urinary 5-HIAA/HVA ratio over the 3 hours following absorption of the drug (+0.21, +0.18, +0.19, p less than 0.05). The increase demonstrates an interaction between pizotifen and 5-HT metabolism, which may be involved in its antimigraine effect.


Purification and characterization of smooth muscle myosin-associated phosphatase from chicken gizzards.
Myosin light chain phosphatase associated with smooth muscle myosin (MAPP) was isolated from chicken gizzard. The MAPP was tightly associated with myosin and was not dissociated from myosin under the physiological ionic conditions. The phosphatase was dissociated from myosin in the presence of high MgCl2, i.e. 80 mM MgCl2. The binding site of the enzyme on the myosin molecule was the subfragment-2 region, since the enzyme did bind to the myosin rod and heavy meromyosin but not to the subfragment-1 affinity column. MAPP was purified with a heparin-Sepharose 6B column, and two activity peaks were obtained, i.e. MAPP I and MAPP II. The major activity peak, MAPP I, was further purified to homogeneity by thiophosphorylated myosin light chain-Sepharose 4B column chromatography. MAPP I was a tetramer composed of four 34-kDa subunits. The enzyme preferentially dephosphorylated the beta-subunit of phosphorylase kinase and was strongly inhibited by the heat- and acid-stable protein phosphatase inhibitor-1, whereas it was partially inhibited by the inhibitor-2. The IC50 (concentration of inhibitor giving 50% inhibition) value for the inhibition of the enzyme by okadaic acid was 70 nM which was about eight times higher than skeletal muscle type-1 and 390 times higher than type-2 protein phosphatase. These results demonstrate that the MAPP I is a type-1-like protein phosphatase, although the properties are not the same as type-I phosphatase. The properties of the myosin-associated phosphatase were distinct from the phosphatases reported previously, although some properties were similar to smooth muscle phosphatase-IV. Therefore, it is concluded that MAPP I is a novel smooth muscle protein phosphatase. Since it strongly associated with smooth muscle myosin, it is likely that MAPP I is responsible for the dephosphorylation of smooth muscle myosin in situ.


Leveraging cardiac resynchronization therapy devices to monitor patients with heart failure.
Cardiac resynchronization therapy is a standard therapy for heart failure patients with cardiac dyssynchrony. The implantable device provides a convenient and continuous platform for heart failure monitoring. Information such as heart rate variability and activity status retrieved from the device allows physicians to more comprehensively evaluate these high-risk patients. Several registries and prospective observational studies have evaluated the value of intrathoracic impedance monitoring in predicting exacerbation of heart failure. With its sensitivity and positive predictive power, the fluid index--derived from the raw intrathoracic impedance--may alert clinicians to subclinical or clinical heart failure deterioration. Uncertainty remains as to whether the additional device-derived information will translate into clinical benefit by reducing the number of hospitalizations for heart failure. An ongoing randomized controlled clinical trial is expected to clarify the role of the device-based pulmonary fluid index in the management of heart failure.


Prenatal testosterone causes shift of asymmetry in neonatal tail posture of the rat.
Neonatal tail posture is a sexually dimorphic behavior with females more biased leftwards than males. Prenatal exposure of female pups to testosterone propionate (TP) but not dihydrotestosterone propionate (DHTP) shifts the population pattern of tail posture to the right. No effects were found with male pups. Since TP is aromatizable and DHTP is not, it is concluded that TP exerts its effects on tail posture via the CNS.


The inhibitory effect of magnolol on cutaneous permeability in mice is probably mediated by a nonselective vascular hyporeactivity to mediators.
In the present study, we demonstrated the inhibitory effect of magnolol on the plasma leakage in passive cutaneous anaphylactic (PCA) reaction, neurogenic inflammation, dorsal skin and ear edema in mice. Hind-paw skin plasma extravasation caused by antidromic stimulation of the saphenous nerve was reduced in mice pretreated with magnolol, diphenydramine or methysergide, but not with indomethacin. Ear edema formation in the PCA reaction was reduced by magnolol in dose-dependent manner. In addition, histamine-, serotonin-, compound 48/80-, bradykinin- and substance P-induced ear edema in mice was also suppressed by magnolol. A dose- and time-dependency of the inhibitory effect of magnolol was demonstrated in histamine- and compound 48/80-induced dorsal skin edema. The maximal inhibitory effect produced by a single dose of magnolol (10 mg/kg) persisted for 1 h, and significant suppression lasted for at least 3 h. In compound 48/80-pretreated mice, the histamine content of the ear was greatly reduced. Bradykinin- and substance P-induced ear edema in compound 48/80-pretreated mice was less severe than that seen in normal mice, but was still significantly reduced by magnolol pretreatment. Moreover, the inhibitory effect of magnolol was more marked than that of diphenhydramine combined with methysergide. These results suggest that the inhibitory effect of magnolol on local edema formation probably occurs through a nonselective inhibition on vascular tissue to prevent the permeability change caused by various mediators.


The high prevalence of intestinal parasitic infections is associated with stunting among children aged 6-59 months in Boricha Woreda, Southern Ethiopia: a cross-sectional study.
Prior studies reported controversial results about the association between intestinal parasitic infections and childhood under-nutrition. We investigated the association of intestinal parasitic infections with under-nutrition among children aged 6-59 months in Boricha Woreda, Southern Ethiopia. This community-based prospective cross-sectional study was carried out from January 1-30, 2019 among 622 children aged 6-59 months. A two-stage stratified sampling procedure was used. Data were collected using a structured, face-to-face interviewer-administered questionnaire and standard anthropometric measurements. The stool specimens were collected using standard technique and examined for the existence and species of intestinal parasites using direct wet mount, Kato Katz and staining technique. We have entered data using Epi Data 3.1 and WHO Anthro software and all analyses were conducted using SPSS version 20. The descriptive analyses were done to find descriptive measures for the socio-demographic and other important variables. Multivariable logistic regression analysis was used to identify factors associated with under-nutrition. Adjusted odds ratios (AORs) with a 95% confidence interval (CI) were computed to assess the presence and strength of associations. The total prevalence of intestinal parasitic infection was 48.7% (95% CI, 44.77-52.62). Approximately one-fourth (22%) of the children were infected with moderate intensity infections. Prevalence of stunting, underweight, wasting were 39.3, 24 and 11.6%, respectively. The prevalence of stunting among children infected with the intestinal parasite (59.4%) was significantly higher than the prevalence in non-infected children (20.6%) (p < 0.001). The absence of sanitation facility, living in medium and large family size, lack of shoes wearing practice, consuming raw vegetables and fruits were positively associated with intestinal parasitic infections. The presence of intestinal parasitic infections was positively associated with stunting (AOR = 2.18, 95% CI: 1.36-3.50) but not with wasting (AOR = 0.58, 95% CI: 0.3-1.13) and underweight (AOR: 0.92, 95% CI = 0.55-1.54). Under-nutrition and intestinal parasitic infections were serious public health concerns. Consolidating the prevailing water, sanitation and hygiene packages and routine deworming of children aged 6-59 months may aid to decrease the burden of both stunting and intestinal parasitic infection in children. Also, improving modern contraceptive methods utilization to reduce family size is recommended.


The need to discontinue the use of the term "accident" when referring to unintentional injury events.
Inconsistencies in the common usage of the words "accident" and "injury" are examined. The practical difficulties in applying some commonly accepted definitions are illustrated. It is shown how common notions of "accident" are not supported by the facts and are counter-productive to preventive measures. It is argued that the phrase "injury control" provides a more comprehensive perspective of the problem than the phrase "accident prevention", but its use also has disadvantages. It is concluded that health professionals should discontinue using the term "accident" and associated phrases, when referring to unintentional injury events.


Effects of chronic exposure to microplastics of different polymer types on early life stages of sea trout Salmo trutta.
The aim of the present study was to determine the effect of a long-term (113 days) exposure to microplastics on the development and induction of endocrine, geno- and cytotoxic responses in early life stages of sea trout Salmo trutta. Microplastic particles (3000 μm) of three most commonly mass-produced polymers (polystyrene - PS, polyethylene terephthalate - PET and polyethylene - PE) were applied in environmentally realistic concentrations (0.1% of sediment dry weight) in a laboratory experiment imitating the natural environment, typical for sea trout spawning grounds. The exposure of the sea trout, from fertilized eggs to mobile yolk-sac larvae, to microplastics did not affect the hatching success (the survival of embryos), hatching rate and the incubation period. Microplastics of any tested polymer type also had no adverse effect on the larvae survival, growth rate and the rate of yolk sack absorption. Similarly, no changes in frequencies of detected cytotoxicity endpoints compared to the control group were recorded. Exposure to polymer particles induced however the formation of genotoxicity endpoints (nuclear buds, micronuclei and blebbed nuclei cells). The level of total genotoxicity (ΣGentox) in fish larvae erythrocytes increased significantly in the following sequence: PS > PET > PE. No significant changes in the whole body corticosterone, dehydrocorticosterone and cortisone concentrations due to exposure to microplastics were recorded, while cortisol was detected in larvae exposed to PS. Our results show that long-term, non-ingestion related exposure to microplastics does not affect development of S. trutta early life stages but may lead to genotoxic responses. PS seems to be the most hazardous among all polymers studied. This is the first study demonstrating non-ingestion related toxicity of microplastics to the early life stages of fish.


Induction of hepatic peroxisome proliferation in mice by lactofen, a diphenyl ether herbicide.
A technical grade of lactofen (1'[carboethoxy]ethyl 5-[2-chloro-4-[trifluoro-methyl] phenoxy]-2-nitrobenzoate) has been shown to induce liver tumors in mice. To determine a possible mechanism of action, the effect of exposure for 7 weeks to dietary concentrations of 2, 10, 50, and 250 ppm technical grade lactofen and 250 ppm of pure lactofen was studied for various liver parameters in groups of male and female CD-1 mice. Liver-weight to body-weight ratio, liver catalase, liver acyl-CoA oxidase, liver cell cytoplasmic eosinophilia, nuclear and cellular size, and peroxisomal staining were increased by the tumorigenic dose of lactofen, i.e., 250 ppm, in a fashion similar to the comparison chemical nafenopin (500 ppm), which is a peroxisome proliferator. Lower doses of lactofen that were reported as nontumorigenic had little or no effect on these parameters. Thus, pure and technical grade lactofen appear to induce murine liver tumors through a mechanism similar to epigenetic hepatocarcinogens of the peroxisome proliferating type.


Antitumor activity of irofulven monotherapy and in combination with mitoxantrone or docetaxel against human prostate cancer models.
Irofulven (6-hydroxymethylacylfulvene, HMAF, MGI 114) is a novel antitumor agent currently undergoing clinical trials in hormone-refractory prostate cancer. This report examines the efficacy of irofulven alone or in combination with mitoxantrone or docetaxel against androgen-independent prostate cancer cell lines. To elucidate the activity of irofulven monotherapy and in combination, PC-3 and DU-145 cell lines were utilized in cellular viability assessments and tumor growth inhibition studies. Viability assays with irofulven and mitoxantrone show additive to synergistic activity. Furthermore, irofulven and mitoxantrone in combination exhibit enhanced antitumor activity against PC-3 and DU-145 xenografts. Additive combination effects are also observed when irofulven and docetaxel were tested against PC-3 xenografts and curative activity (8/10 CR) is observed in DU-145 xenografts. These studies demonstrate that irofulven displays strong activity as monotherapy and in combination with mitoxantrone or docetaxel against androgen-independent prostate cancer in vitro and in vivo; thus, supporting the clinical investigation of irofulven against hormone-refractory prostate cancer.


Retention of the spacing effect with mental practice in hemiparetic stroke.
Mental practice (MP) is a promising adjuvant to physical practice that involves many of the same mechanisms and takes on many of the same properties as physical practice. This study compared efficacy of a "massed" MP regimen versus a "distributed" MP regimen on upper extremity (UE) motor impairment and functional limitation. Twenty-seven chronic stroke survivors were administered the UE section of the Fugl-Meyer (FM) and Action Research Arm Test (ARAT), followed by standardized physical practice and MP regimens. One group was administered "massed" MP (60 min of MP during a single daily session) and a second group administered distributed MP (20 min of MP occurring three times/day). After intervention, changes in FM and ARAT scores of subjects in the distributed condition were significantly higher than those of subjects in the massed condition (FM 3.65, 95 % CI 0.82-6.49, p value = 0.01; ARAT 3.95, 95 % CI 1.24-6.67, p value = 0.006). Likewise, at POST 3, subjects in the distributed group showed significantly higher change in ARAT scores (ARAT 4.90, 95 % CI 0.57-9.22, p value = 0.03); the change in FM scores at POST 3 was 3.18 points higher among subjects in the distributed condition, but only approached significance (95 % CI -1.27 to 7.63, p value = 0.15). Results suggest that a distributed MP schedule is more efficacious in bringing about paretic UE changes than a massed practice schedule, especially in terms of reducing UE functional limitation.


Effect of pre- and postnatal nicotine exposure on vasopressinergic system in rats.
Timed pregnant Sprague-Dawley rats were infused subcutaneously either with nicotine (NIC, 6 mg kg-1 day-1; n=17) or saline (control, n=15) on the 3rd day of gestation, via Alzet osmotic pumps, for 28 days. After the parturition, the pups of both, control and NIC infused dams, were each randomly divided into 2 groups and placed to be nursed as following: (1) control dams nursing pups born to control mother (control group); (2) control dams nursing pups born to NIC-infused mother (prenatal NIC group); (3) NIC-infused dams nursing pups born to control mother (postnatal NIC group); (4) NIC-infused dams nursing pups born to NIC-infused mother (pre- and postnatal NIC group). Vasopressin (VP) was measured by RIA in plasma, neurointermediate lobe (NIL) and hypothalamus (HT) in the pups of both sexes, at the following age: 0 (within 24 h after birth); 1, 2, 3, 4 and 6 weeks. At the age of 3, 4 and 6 weeks, the isolated NILs were individually superfused and VP was measured as a basal release and the response to a 10-min 56 mM potassium stimulation. A marked suppression in the activity of VP-ergic system was observed in both sexes of offspring exposed to NIC prenatally, being first detectable at the age of 3 weeks, when the HT-NIL system becomes fully developed. However, the significant changes were observed at the age of 6 weeks: decreased serum VP concentration, lower VP contents in the HT and NIL, and suppressed VP release, basal and stimulated, from the isolated NIL. Postnatal exposure to nicotine was ineffective.


Genetic studies of the Macushi and Wapishana Indians. I. Rare genetic variants and a "private polymorphism' of esterase A.
Blood samples from 509 Macushi and 623 Wapishana Amerindians of of Northern Brazil and Southern Guyana have been analyzed with reference to the occurrence of rare variants and genetic polymorphisms of the following 25 systems: (i) Erythrocyte enzymes: acid phosphatase-1, adenosine deaminase, adenylate kinase-k, carbonic anhydrase-1, carbonic anhydrase-2, esterase A1,2,3, esterase D, galactose-1-phosphate uridyltransferase, isocitrate dehydrogenase, lactate dehydrogenase, malate dehydrogenase, nucleoside phosphorylase, peptidase A, peptidase B, phosphoglucomutase 1, phosphoglucomutase 2, phosphogluconate dehydrogenase, phosphohexoseisomerase, triosephosphate isomerase and (ii) Serum proteins: albumin, ceruloplasmin, haptoglobin, hemoglobin A2 and transferrin. Fifteen different rare variants were detected, involving 11 of these systems. In addition, a previously undescribed variant of ESA 1,2,3 which achieves polymorphic proportions in both these tribes is described. Excluding this variant, the frequency of rare variants is 1.1/1000 in 12510 determinations in the Macushi and 4.7/1000 in 15396 determinations in the Wapishana. The ESA 1,2,3 polymorphism was not observed in 382 Makiritare, 232 Yanomama, 146 Piaroa, 404 Cayapo, 190 Kraho and 112 Moro. Irregularities in the intratribal distribution of this polymorphism in the Macushi and Wapishana render a decision as to the tribe of origin impossible at present. Gene frequencies are also given for previously described polymorphisms of 5 systems: haptoglobin, phosphoglucomutase 1, erythrocyte acid phosphatase, esterase D, and galactose-1-phosphate-uridyl-transferase.


Redo minimally invasive direct coronary artery bypass grafting.
Conventional redo coronary artery bypass grafting is associated with an increased risk of mortality and morbidity as a result of manipulation of patent grafts, mediastinitis, and the presence of pericardial adhesions. Minimally invasive direct coronary artery bypass grafting may be an alternative approach in selected patients. From January 1997 to October 2003, 46 patients (mean age, 66 +/- 7.4 years) underwent minimally invasive direct coronary artery bypass grafting using the left internal thoracic artery to the left anterior descending artery on the beating heart as a reoperation. Patients after previous cardiac operation by means of median sternotomy without use of the left internal thoracic artery presenting with a significant left anterior descending artery stenosis ("culprit lesion") were included. Predicted mortality was 13.6% (range, 2.4% to 72.8%) as calculated by the logistic Euroscore; ejection fraction was 0.531 (range, 0.14 to 0.81). Surgical results were analyzed for mortality, morbidity, duration of the procedure, hospital stay, and event-free survival. Mean operating time was 103 +/- 34 minutes. There were two in-hospital deaths (4.6%), one for malignant ventricular arrhythmia (Euroscore, 60.9%) and the second as a result of severe gastrointestinal bleeding (Euroscore, 29.2%). One patient (2.3%) was successfully reoperated on because of perianastomotic hematoma using the same approach after 6 days. Patients were discharged after 9.4 +/- 2.6 days. There were no other serious adverse events, no stroke, and no myocardial infarction. During follow-up (37 +/- 21 months, complete in 92.1%), 1 patient experienced angina and 6 patients died. The actuarial 4-year survival is 74.8% (95% confidence interval, 51% to 92%), and the actuarial 4-year event-free survival including freedom from angina, major adverse cardiac events, and reintervention is 81% (95% confidence interval, 54% to 97%). Minimally invasive direct coronary artery bypass grafting can be considered as an alternative approach for redo coronary artery bypass grafting in selected patients.


Novel Insight into the Effect of Probiotics in the Regulation of the Most Important Pathways Involved in the Pathogenesis of Type 2 Diabetes Mellitus.
Type 2 diabetes mellitus (T2DM) is considered one of the most common disorders worldwide. Although several treatment modalities have been developed, the existing interventions have not yielded the desired results. Therefore, researchers have focused on finding treatment choices with low toxicity and few adverse effects that could control T2DM efficiently. Various types of research on the role of gut microbiota in developing T2DM and its related complications have led to the growing interest in probiotic supplementation. Several properties make these organisms unique in terms of human health, including their low cost, high reliability, and good safety profile. Emerging evidence has demonstrated that three of the most important signaling pathways, including nuclear factor kappa B (NF-κB), phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt), and nuclear factor erythroid 2-related factor 2 (Nrf2), which involved in the pathogenesis of T2DM, play key functions in the effects of probiotics on this disease. Hence, we will focus on the clinical applications of probiotics in the management of T2DM. Then, we will also discuss the roles of the involvement of various probiotics in the regulation of the most important signaling pathways (NF-κB, PI3K/Akt, and Nrf2) involved in the pathogenesis of T2DM.


[The role of cellular immunity in gingival inflammation through a study of the cells of Langerhans].
The purpose of this semiquantitative study was to evaluate the number of Langerhans cells in correlation with gingival inflammation and the use of two antisera: anti-T6 and anti-HLA/DR reacting with two different membrane antigens. Results indicate that HLA/DR is a better functional marker, and that the number of Langerhans cells is higher in the moderate inflammation of the gingiva (G.I. 1 to 2).


DACO: Distortion/artefact correction for diffusion MRI data.
In this paper, we propose a registration-based algorithm to correct various distortions or artefacts (DACO) commonly observed in diffusion-weighted (DW) magnetic resonance images (MRI). The registration in DACO is accomplished by means of a pseudo b0 image, which is synthesized from the anatomical images such as T1-weighted image or T2-weighted image, and a pseudo diffusion MRI (dMRI) data, which is derived from the Gaussian model of diffusion tensor imaging (DTI) or the Hermite model of mean apparent propagator (MAP)-MRI. DACO corrects (1) the susceptibility-induced distortions and (2) the misalignment between the dMRI data and anatomical images by registering the real b0 image to the pseudo b0 image, and corrects (3) the eddy current-induced distortions and (4) the head motions by registering each image in the real dMRI data to the corresponding image in the pseudo dMRI data. DACO estimates the models of artefacts simultaneously in an iterative and interleaved manner. The mathematical formulation of the models and the estimation procedures are detailed in this paper. Using the human connectome project (HCP) data the evaluation shows that DACO could estimate the model parameters accurately. Furthermore, the evaluation conducted on the real human data acquired from clinical MRI scanners reveals that the method could reduce the artefacts effectively. The DACO method leverages the anatomical image, which is routinely acquired in clinical practice, to correct the artefacts, omitting the additional acquisitions needed to conduct the algorithm. Therefore, our method should be beneficial to most dMRI data, particularly to those acquired without field maps or reverse phase-encoding images.


Reorganization of sensorimotor representations of the intact limb after upper but not lower limb traumatic amputation.
It is becoming increasingly clear that limb loss induces wider spread reorganization of representations of the body that are nonadjacent to the affected cortical territory. Data from upper extremity amputees reveal intrusion of the representation of the ipsilateral intact limb into the former hand territory. Here we test for the first time whether this reorganization of the intact limb into the deprived cortex is specific to the neurological organization of the upper limbs or reflects large scale adaptation that is triggered by any unilateral amputation. BOLD activity was measured as human subjects with upper limb and lower limb traumatic amputation and their controls moved the toes on each foot, open and closed each hand and pursed their lips. Subjects with amputation were asked to imagine moving the missing limb while remaining still. Bayesian pattern component modeling of fMRI data showed that intact ipsilateral movements and contralateral movements of the hand and foot were distinctly represented in the deprived sensorimotor cortex years after upper limb amputation. In contrast, there was evidence reminiscent of contralateral specificity for hand and foot movements following lower limb amputation, like that seen in controls. We propose the cortical reorganization of the intact limb to be a function of use-dependent plasticity that is more specific to the consequence of upper limb loss of forcing an asymmetric reliance on the intact hand and arm. The contribution of this reorganization to phantom pain or a heightened risk of overuse and resultant maladaptive plasticity needs investigating before targeting such reorganization in intervention.