Folding and self-assembly of the TatA translocation pore based on a charge zipper mechanism.
We propose a concept for the folding and self-assembly of the pore-forming TatA complex from the Twin-arginine translocase and of other membrane proteins based on electrostatic "charge zippers." Each subunit of TatA consists of a transmembrane segment, an amphiphilic helix (APH), and a C-terminal densely charged region (DCR). The sequence of charges in the DCR is complementary to the charge pattern on the APH, suggesting that the protein can be "zipped up" by a ladder of seven salt bridges. The length of the resulting hairpin matches the lipid bilayer thickness, hence a transmembrane pore could self-assemble via intra- and intermolecular salt bridges. The steric feasibility was rationalized by molecular dynamics simulations, and experimental evidence was obtained by monitoring the monomer-oligomer equilibrium of specific charge mutants. Similar "charge zippers" are proposed for other membrane-associated proteins, e.g., the biofilm-inducing peptide TisB, the human antimicrobial peptide dermcidin, and the pestiviral E(RNS) protein.


Equine neonatal sepsis.
Neonatal infection remains a leading cause of morbidity and mortality in the equine industry, despite advances in prevention and treatment. Many factors can influence a foal's risk for the development of sepsis in the peripartum period. This article discusses those factors, causative organisms, and therapeutic options. Factors that influence prognosis and potential preventative strategies also are addressed.


Theoretical and practical aspects of risk communication in food safety: A review study.
Currently, food safety hazards have introduced as one of the most important threats to public health worldwide. Considering numerous crises in the field of food safety at global, regional, and national levels, and their impact on the physical and mental health of consumers, it is very vital to evaluate risk communication strategies in each country. Food safety risk communication (FSRC) aims to provide the means for individuals to protect their health from food safety risks and make informed decisions about food risks. The purpose of this study is to present FSRC as one of the key parts of risk analysis, its importance considering the prevalence of food contamination and recent crises related to food. Additionally, the stages of implementation of FSRC are mentioned. In FSRC, it is essential to comply with the principles and prerequisites. There are various strategies for FSRC nowadays. Different platforms for FSRC are rapidly evolving. Choosing and evaluating the appropriate strategy according to the target group, consensus of stakeholders, cooperation and coordination of risk assessors and risk managers have a significant impact in order to improve and implement FSRC.


Food-taking in the cat investigated with transection of the rubro- and corticospinal tracts.
In cats with the distal paw shaved food-taking from a horizontally or vertically placed tube was recorded with a video camera, supplementary results were obtained with a high frequency video system. Measurements were made of the dorsal contour of the digits to investigate angular movement in the proximal interphalangeal (PIP) joint and withdrawal of the paw before and after complete transection of the rubro- and corticospinal tracts just rostral to the forelimb segments. In the preoperative state PIP flexion occurs before withdrawal of the paw in the large majority of cats. Postsurgically the main part of PIP flexion is made during withdrawal of the paw. It is suggested that PIP flexion before withdrawal allows for accurate manipulative placement of the digits on the target which depends on the rubro- and corticospinal tracts, while PIP flexion during withdrawal, which may favour speed at the expense of accuracy, can be made without the rubro-and corticospinal tracts.


Ivermectin treatment in severe asymmetric reactive onchodermatitis (sowda) in Sudan.
Ivermectin efficacy and post-treatment reactions in asymmetric severe reactive ochodermatitis (sowda) were studied in 8 patients with sowda syndrome and 6 with mild generalized onchodermatitis in Sudan. Initial skin snips from 12 patients contained microfilariae (1-9 per mg skin). Patients were treated in hospital with a single oral dose of c. 150 micrograms/kg ivermectin (103-200 micrograms/kg) and monitored for frequency and severity of post-treatment reactions for 4 weeks. Serial samples of heparinized blood were collected over the first 24 h after treatment for determination of ivermectin pharmacokinetics. Skin snips from all patients on days 3 and 28 revealed no microfilariae. Post-treatment reactions were more common and severe in individuals with sowda; they consisted mainly of musculoskeletal pain, local swellings with pitting oedema, and lymph gland tenderness and enlargement. No relation was established between these reactions, the microfilarial infection intensity, or the plasma pharmacokinetic profiles. A single oral dose of ivermectin cleared the skin of microfilariae and led to improvement of symptoms and dermatological signs of sowda, but resulted in more marked reactions than in cases of generalized onchodermatitis.


Efficacy of maintaining low-tidal volume mechanical ventilation as compared to resting lung strategy during coronary artery bypass graft cardiopulmonary bypass surgery: A post-hoc analysis of the MECANO trial.
To compare a low-tidal-volume with positive end-expiratory pressure strategy (VENT strategy) to a resting-lung-strategy (i.e., no-ventilation (noV) strategy) during cardiopulmonary bypass for coronary artery bypass graft surgery on the incidence of postoperative pulmonary complications. Post-hoc analysis of the MECANO trial which was a prospective single-center, blind, randomized, parallel-group controlled trial. Tertiary care cardiac surgery center. Patients who underwent isolated on-pump coronary bypass surgery were randomized either to VENT or noV group. During the cardiopulmonary bypass phase of the cardiac surgery procedure, mechanical ventilation in the VENT group consisted of a tidal volume of 3 mL/kg, a respiratory rate of 5 per minute and a positive end-expiratory pressure of 5 cmH2O. Patients in the noV group received no ventilation during this phase. Primary composite outcome combining death, early respiratory failure, ventilation support beyond day 2 and reintubation. In this post-hoc analysis, we retained 725 patients who underwent isolated CABG surgery, from the 1501 patients included in the original study. There were 352 in the VENT group and 373 patients in the noV group. Post-hoc comparison yielded no differences in baseline characteristics between these two groups. The primary outcome occurred less frequently in the VENT group than in the noV group, with 44 (12.5%) and 76 (20.4%) respectively (odds-ratio (OR) = 0.56 (0.37-0.84), p = 0.004). There were fewer early respiratory dysfunctions and prolonged respiratory support in the VENT group (respectively, OR = 0.34 (0.12-0.96) p = 0.033 and OR = 0.51 (0.27-0.94) p = 0.029). Complications related to mechanical ventilation were similar in the two groups. In this post-hoc analysis, maintaining low-tidal ventilation compared to a resting-lung strategy was associated with fewer pulmonary postoperative complications in patients who underwent isolated CABG procedures.


Experimental and Analytical Investigations on Tribological Properties of PTFE/AP Composites.
The tribological properties of polytetrafluoroethylene (PTFE)/AP (poly(para-phenyleneterephthalamide) (PPTA) pulp) composites under different test conditions (load: 2N, 10N; frequency: 1 Hz, 4 Hz; amplitude: 2 mm, 8 mm) were holistically evaluated. PTFE/AP composites with different AP mass ratios of 3%, 6%, and 12% as a skeleton support material were prepared. The coefficient of friction (COF) and wear rate were determined on a ball-on-disk tribometer. Furthermore, the morphology, element composition, and chemical structure of the transfer membrane were analyzed accordingly. The relationships between load, frequency, amplitude, and tribological properties were further investigated. According to the wear mechanism, AP enables effective improvement in the stiffness and wear resistance, which is also conducive to the formation of transfer films.


Descending tentorial herniation: findings on computed tomography.
Descending tentorial herniation (DTH) can be diagnosed by computed tomography. Encroachment upon the lateral aspect of the suprasellar cistern is an early sign of impending tentorial herniation. Actual herniation is evidenced by rotation and shift of the brain stem with consequent widening of the crural and ambient cisterns on the side of the space-occupying lesion. In a more advanced stage of herniation, obliteration of cisternal spaces at the tentorial level will occur. Aqueductal compression secondary to the herniation will cause increased intraventricular pressure with widening of those parts of the lateral ventricles that are not exposed to the compression by the mass; a characteristic finding is widening of the temporal horn on the side opposite the space-occupying lesion. Infarction in the territory of the posterior cerebral artery may complicate DTH.


Developmental expression and subcellular localization of wallaby gonadotropin-releasing hormone receptor and its splice variants.
The developmental expression of gonadotropin-releasing hormone receptor (GnRH-R) and its splice variants was examined in the gonads of tammar wallaby pouch young in order to elucidate the functional role of GnRH-R in the developing testis and ovary. Wallaby GnRH-R, like eutherian GnRH-Rs, contains three exons and two introns. In the present study, the transcripts of two splice variants (GnRH-R Delta 1 and GnRH-R Delta 2) were cloned from the pituitary. GnRH-R Delta 1 contained a 291 bp deletion from nucleotide positions 232 to 522 within exon 1. This transcript appears to be distinctive in the wallaby and has not been reported in other species. GnRH-R Delta 2 contained a 220 bp deletion from nucleotide positions 523 to 742, corresponding to exon 2. We examined the subcellular localization of the wild type GnRH-R and its splice variants with confocal microscopy, showing that both the wild type receptor and the splice variants were membrane-associated molecules. The different pattern of expression of the wild type receptor and the variants transcripts found in adult and neonatal tissues suggests a specific developmental regulation of the GnRH-R Delta 2 transcript. In addition, the developmental expression of the GnRH-R and GnRH-R Delta 1 transcripts showed a possible association with key physiological events during gonadal development in the wallaby pouch young, suggesting that GnRH-R may be involved in the regulation of early development in the testis and ovary.


Unraveling the Numerous Biosynthetic Products of the Marine Sediment-Derived Fungus, Aspergillus insulicola.
A new tripeptide, pre-sclerotiotide F (3), was isolated from a marine sediment-derived fungus, Aspergillus insulicola, along with five known compounds, one of which was new at the time of isolation, scerotiotide F (4). The absolute configuration elucidation of the new compound was determined using a combination of NMR, HR-ESI-MS, and optical rotation analyses. Cytotoxicities were measured in vitro against selected cancer cells. The effects of pre-sclerotiotide F (3) and sclerotiotide F (4) on LPS-induced NF-κB and iNOS expression were also measured.


Exploring approaches to facilitate family communication of genetic risk information after cystic fibrosis population carrier screening.
Population carrier screening for cystic fibrosis (CF) enables individuals with no known family history of the condition to ascertain their risk of having a child with CF. When an individual is identified as a carrier of CF, a life-shortening condition, they are encouraged to inform their relatives who are at increased risk of being a carrier. Research suggests that the uptake of CF carrier testing amongst relatives of carriers or people with CF is low. This study aimed to explore approaches to facilitate the process of family communication of genetic information after an individual is identified as a carrier of CF through population screening. Five key informants were interviewed to inform the development of a telephone survey which was administered to 21 individuals identified as carriers of CF through population carrier screening at Victorian Clinical Genetics Services. This study suggests that providing carriers with additional information and follow-up support would be appreciated by carriers and could result in more accurate information being disseminated more widely within families, which could lead to more at-risk relatives accessing testing. Suggested strategies to enhance current practice include mailing a fact sheet to carriers and a follow-up telephone call provided by a genetic counsellor to carriers to offer further support in communicating this information to their relatives.


Widespread applications of host-guest interactive cyclodextrin functionalized polymer nanocomposites: Its meta-analysis and review.
Cyclodextrins are cyclic oligosaccharides, having tyroid shape of the molecule which has a hydrophobic cavity and outer hydrophilic surface. This characteristic feature of the dextrins allows it to function as a functionalizing as well as a stabilizing agent. Polymer nanocomposites are nanoscale composites of polymers with enhanced and synergized properties of its components and have been known to have applications in various fields of chemistry, biomedical, pharmaceutical and environmental purposes to name a few. To impart specificity, thermal, mechanical stability, resistance to solvents and biodegradability to the polymers, cyclodextrins have been incorporated in the nanocomposites. The utilization of the aforementioned properties of cyclodextrins to the polymer nanocomposites, implications of the incorporation of cyclodextrins to polymer nanocomposites and their subsequent applications in various fields have been discussed in this review systematically, using PRISMA guidelines.


Elimination of lead dislodgement by the use of tined transvenous electrodes.
Pacemaker lead dislodgement has accounted for a large proportion of the postoperative complications seen after transvenous pacemaker insertion. Ninety-two patients underwent implantation of a tined transvenous electrode over a three-year period without a single dislodgement. Excellent thresholds were obtained and no difficulties related to electrode insertion were encountered. Tined transvenous pacemaker leads are preferred for routine use at this time.


Twenty-five years experience of the drug treatment of tuberculosis of the female genital tract.
A study has been made of women with proved, tuberculosis of the genital tract who were treated with drugs between 1st January, 1951, and 1st July, 1976. Seven different drug programmes were employed and 566 women were treated. Apart from the last two schedules employing the newer antituberculosis drugs, which were too recent for a follow-up to be available, the best results were obtained with a combination of streptomycin, PAS and isoniazid for 18 months or two years. In this group, 87.7 per cent were regarded as cured after an average follow-up of six years and six months. Drug cover was employed in 79 patients in whom surgery was found to be necessary and the results were uniformly satisfactory. Toxic drug reactions occurred in 18.2 per cent of the patients treated.


Squamous cell carcinoma of the uterine cervix in association with stage 0 chronic lymphocytic leukemia/small lymphocytic lymphoma.
There have been many cases of multiple malignant neoplasms involving the female genital tract reported, but involvement by epithelial and hematologic malignancy is extremely rare. A 52-year-old woman, who was followed for stage 0 chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), had developed invasive squamous cell carcinoma of the uterine cervix. Microscopic examination of the hysterectomy specimen disclosed invasive squamous cell carcinoma in the cervix and monotonous populations of small lymphoid cells with proliferation centers, which are consistent with CLL/SLL, in the cervix as well as parametrium. Thirty months after the initial diagnosis of CLL/SLL, the patient died with systemic dissemination of squamous cell carcinoma, but the CLL/SLL remained a local disease. The clinical course of squamous cell carcinoma in this case appeared to be aggressive, but it was unclear whether the outcome was associated with an altered immune status due to the presence of concurrent CLL/SLL.


The effects of ventral tegmental administration of GABA(A), GABA(B), NMDA and AMPA receptor agonists on ventral pallidum self-stimulation.
The ventral pallidum (VP) is a basal forebrain structure that is interconnected with motor and limbic structures and may be considered as an interface between motivational and effector neural signals. Results from a considerable number of studies suggest that this structure is critically involved in reward-related behavior. The VP shares reciprocal connections with other reward-implicated regions, such as the ventral tegmental area (VTA). This anatomy predicts that drug-induced neuronal alterations in the VTA could profoundly alter the function of the VP. Here, using the curve-shift intracranial self-stimulation method, we studied the effects of muscimol (GABA(A) agonist), baclofen (GABA(B) agonist), NMDA and AMPA, microinjected bilaterally into the VTA on the rewarding efficacy of VP self-stimulation. Central injections of the highest dose of muscimol (0.128 microg) resulted in significant elevations in VP self-stimulation thresholds, indicating a reduction in the rewarding efficacy of the stimulation. Elevations in VP self-stimulation thresholds were also evident after intrategmental injections of higher doses of baclofen (0.12, 0.48 microg). By contrast, intrategmental activation of NMDA and AMPA receptors did not affect reward thresholds. These findings suggest that GABAergic and glutamatergic transmission in the VTA activate different circuits that may mediate different functions. Thus, the VTA--VP projection activated by GABA modulates VP stimulation reward, while the projection activated by glutamate may be involved in reward-unrelated effects, rather than in the processing of reward. The decreased rewarding efficacy of VP self-stimulation following intrategmental injections of muscimol and baclofen may be due to GABAergic modulation of ventral tegmental dopaminergic and nondopaminergic neurons projecting to the VP.


A Negative Feedback Loop Controlling bHLH Complexes Is Involved in Vascular Cell Division and Differentiation in the Root Apical Meristem.
Controlling cell division and differentiation in meristems is essential for proper plant growth. Two bHLH heterodimers consisting of LONESOME HIGHWAY (LHW) and TARGET OF MONOPTEROS 5 (TMO5)/TMO5-LIKE1 (T5L1) regulate periclinal cell division in vascular cells in the root apical meristem (RAM). In this study, we further investigated the functions of LHW-T5L1, finding that in addition to controlling cell division, this complex regulates xylem differentiation in the RAM via a novel negative regulatory system. LHW-T5L1 upregulated the thermospermine synthase gene ACAULIS5 (ACL5), as well as SUPPRESSOR OF ACAULIS5 LIKE3 (SACL3), which encodes a bHLH protein, in the RAM. The SACL3 promoter sequence contains a conserved upstream open reading frame (uORF), which blocked translation of the main SACL3 ORF in the absence of thermospermine. Thermospermine eliminated the negative effect of uORF and enhanced SACL3 production. Further genetic and molecular biological analyses indicated that ACL5 and SACL3 suppress the function of LHW-T5L1 through a protein-protein interaction between LHW and SACL3. Finally, we showed that a negative feedback loop consisting of LHW-T5L1, ACL5, SACL3, and LHW-SACL3 contributes to maintain RAM size and proper root growth. These findings suggest that a negative feedback loop regulates the LHW-T5L1 output level to coordinate cell division and differentiation in a cell-autonomous manner.


[Prophylaxis of post-operative pneumonia after surgery for cancer of the esophagus and esophagogastric junction].
Purulent endobronchitis was identified as a significant causative factor of post-operative development of pneumonia in 113 patients operated on for cancer of the esophagus and esophagogastric junction. Development of purulent endobronchitis was in turn influenced by extent of lymph node dissection. Timely catheterization and sanitation of the trachea and bronchi are a major tool of treatment.


Gangliosides, sialoglycoproteins and glucocerebroside in the spleen and bone marrow of patients with beta-thalassemia major.
Bone marrow and spleen samples were studied biochemically to elucidate the nature of the material stored in the large histiocytes present in beta-thalassemic patients. Only the protein-bound N-acetylneuraminic acid (NANA) content of the spleen of homozygous beta-thalassemic patients was significantly higher than that of controls. In the bone marrow, which contained a large number of thalassemic storage cells, the lipid-bound NANA and the glucocerebroside showed a moderate increase, while the amount of protein-bound NANA was much greater than that in controls. These results, in agreement with ultrastructural and histochemical observations, differentiate thalassemic storage cells from other storage cells found in diseases characterized by an increased destruction of blood cells and suggest that there may also be an impairment of the sialoglycoprotein metabolism of the red blood cells in homozygous beta-thalassemia.


Restrictive Mitral Valve Annuloplasty: Prognostic Implications of Left Ventricular Forward Flow.
Surgical mitral valve repair for severe secondary mitral regurgitation (MR) remains controversial. The association of MR reduction and changes in left ventricular (LV) hemodynamics with survival has not been investigated. We investigated the independent associates of outcomes in heart failure patients with severe secondary MR who underwent surgical mitral valve repair. Patients (n = 130, 62 ± 12 years old, 55% men) with chronic severe secondary MR and impaired LV ejection fraction (<0.50, mean 0.31 ± 0.10) treated with surgical mitral valve repair were included. Echocardiographic LV forward stroke volume and LV forward ejection fraction were measured at baseline and at discharge. All-cause mortality was the primary endpoint, and the combination of major adverse cardiac-related events and all-cause mortality was the secondary endpoint. At hospital discharge, 77% of patients showed no residual MR and 23% showed mild MR. LV volumes reduced significantly, whereas LV ejection fraction remained unchanged. In contrast, LV forward stoke volume (53 ± 24 mL versus 64 ± 22 mL, p < 0.001) and LV forward ejection fraction (0.32 ± 0.16 versus 0.48 ± 0.24, p < 0.001) significantly increased at discharge. During a median follow-up of 3.44 years, 33 patients (29%) died and 40 had major adverse cardiac-related events. On multivariable analysis, LV forward stroke volume after repair was independently associated with all-cause mortality (hazard ratio 0.98, p = 0.047) and with the combined endpoint (hazard ratio 0.98, p = 0.045) after correcting for other baseline, procedural, and postrepair characteristics. In patients with severe secondary MR treated with surgical repair, LV forward flow was independently associated with better survival and lower risk of the combined endpoint.


Stages of change for perceived stress in a Swiss population sample: an explorative study.
Data from a cross-sectional survey of the Swiss general population were used in an explorative attempt to apply the transtheoretical model of behavioural change to perceived stress. The sample comprised 575 respondents who reported having experienced stressful situations in the previous month. Other variables assessed included gender, age, education, reported symptoms, and three constructs representing stages and processes of change as well as self-efficacy. Findings indicated that (1) about one third of respondents appeared to cope successfully with the stressful situations they experienced, one third intended to do so, while one quarter appeared to have no intention of managing their stress more effectively. (2) There was no difference in stage of change distribution by gender or age, while those with higher education were more frequently represented in the latter stages than those with lower education. (3) Those in the maintenance stage reported significantly less symptoms than others. We conclude that the assessment of readiness to change could be of valuable support in designing stage-specific interventions in the area of stress management.


Coronary artery bypass graft surgery: clinical comparison of cold blood potassium cardioplegia, warm cardioplegic induction, and secondary cardioplegia.
An analysis of myocardial protection was performed in 45 low-risk patients undergoing coronary bypass procedures who were divided into three equal groups with similar preoperative ejection fractions and coronary artery obstructions. Group 1 (N = 15) received cold blood cardioplegia, Group 2 received cold blood cardioplegia and secondary cardioplegia, and Group 3 received cold blood cardioplegia plus warm cardioplegic induction. The aortic cross-clamp time and the number of bypass grafts were similar among the groups. The following variables were measured serially: electrocardiographic changes, serum myocardial-specific isoenzyme of creatine kinase, cardiac output, left ventricular filling pressure, ejection fraction, and left ventricular wall motion. The three methods evaluated were all effective in protecting the myocardium during global myocardial ischemia. Patients who received secondary cardioplegia (Group 2) were more likely to exhibit spontaneous defibrillation (12/15) than those in Group 1 (5/15) or Group 3 (6/15) (p less than 0.05). However, measurements of left ventricular performance and evidence of perioperative myocardial infarction were similar among all three groups. These data suggest that a standard technique of cold potassium cardioplegia alone should be the method of choice in elective, low-risk coronary bypass operations rather than this technique in combination with either of the other two more costly and complex methods evaluated in this study.


Association Between the Overall Risk of Prostate Cancer and Use of Calcium Channel Blockers: A Systematic Review and Meta-analysis.
Although calcium channel blockers (CCBs) are now commonly prescribed to treat hypertension as a first-line drug therapy, their impact on prostate cancer (PCa) is unclear. This systematic review and meta-analysis was conducted to determine the association between CCB use and the overall risk of PCa. PubMed, EMBASE, and Cochrane were searched up to December 26, 2019, stratified according to statistical method of outcome [odd ratios (ORs), relative ratios (RRs), hazard ratios (HRs)] and cumulative duration of CCB use. The quality assessment of included studies was evaluated by using the Newcastle-Ottawa Scale. Fixed effects models were used to study the association between CCB use and the risk of PCa. Between-study heterogeneity was quantified by using Cochran's Q-statistic and I2 statistics. Sensitivity analysis was performed by excluding the studies one by one, and publication bias was analyzed by using funnel plots. Nineteen studies with 1,418,407 patients were identified for inclusion in the meta-analysis, which was based on the comparison of cohort studies, nested case-control studies, and case-control studies. Pooled estimates showed a RR of 1.08 (95% CI, 1.05-1.11; P < 0.00001) and a HR of 1.07 (95% CI, 1.02-1.13; P = 0.008) for association between CCB use and the risk of PCa. In addition, the results of subgroup analysis showed that CCB users of <5 years had an 8% increased overall risk of PCa (RR, 1.08; 95% CI, 1.04-1.12; P = 0.0001), and CCB users of 5-10 years had a 13% increased overall risk of PCa (RR, 1.13; 95% CI, 1.04-1.23; P = 0.003). CCB use had a tendency to increase the overall risk of PCa, and cumulative duration of CCB use might also be positively correlated with the overall risk of PCa.


Wiskott-Aldrich syndrome with IgA nephropathy: a case report and literature review.
The pathogenesis of renal involvement in Wiskott-Aldrich syndrome (WAS) is unclear and renal outcome is generally poor in such situations. Here we present the case of an 8-year-old boy with WAS who developed hematuria, proteinuria, and declining renal function that did not improve with the combined use of immunosuppressive agents and angiotensin-converting-enzyme inhibitor. Renal pathology revealed IgA nephropathy (IgAN). The patient underwent splenectomy for refractory thrombocytopenia. The proteinuria remitted and renal function improved after splenectomy, long-term antibiotic prophylaxis, and tapering of immunosuppressive agents.


Effect of papillary muscle approximation on acute ovine functional tricuspid regurgitation.
Ring annuloplasty represents the standard surgical treatment, but offers suboptimal results in patients with severe functional tricuspid regurgitation. Addition of papillary muscles (PMs) approximation may improve clinical outcomes. Eight healthy adult male sheep (56 ± 4 kg) underwent cardiopulmonary bypass and implantation of sonomicrometry crystals on the tricuspid annulus, PM tips and right ventricular (RV) free wall. Papillary muscles approximation sutures were anchored between anterior-posterior and anterior-septal PMs and their loose ends externalized through RV free wall to epicardial tourniquets. After weaning from cardiopulmonary bypass, acute right heart failure and tricuspid regurgitation were induced, and subsequent sequential anterior-posterior and anterior-septal PM approximations were performed. Echocardiographic, haemodynamic and sonomicrometry data were collected. Tricuspid regurgitation at baseline in eight sheep was none or trace in 3 and mild in 5, and after induction of acute right heart failure increased significantly to moderate in 5, moderately severe in 1 and severe in 2 (P = 0.011). RV pressure increased from 31 [28; 43] to 51 [47; 55] mmHg (P = 0.012). Anterior-posterior PM approximation decreased regurgitation grade to none or trace in 1, mild in 4 and moderate in 3 (P = 0.016) and reduced PM area from 208 [160; 241] to 108 [48; 181] mm2 (P = 0.008), and anterior-posterior PM distance from 18 [16; 20] to 10 [7; 13] mm (P = 0.037). Anterior-septal approximation also significantly reduced PM area but had no effect on regurgitation grade. Anterior-posterior but not anterior-septal PM approximation alleviated acute ovine tricuspid regurgitation. Selective PM approximation may offer better control of tricuspid regurgitation.


Psychological reactions to cancer risks after the Chernobyl accident.
This is a report on an investigation of people's reactions to the Chernobyl accident. Interviews and mail surveys were conducted in July-September 1986 with pregnant women, parents of newborn children, farmers, adolescents and men who were not parents, in various areas of Sweden, differing as to the amount of Chernobyl fallout they had received. The accident had probably doubled the number of people who were negative to nuclear power in the most affected area. Radiation risks were highly salient in most groups. Areas differed in the expected direction, people in the more exposed areas being more concerned. Women were more worried and more negative to nuclear power than men while adolescents appeared to be the group least affected by the accident. Farmers were also strongly opposed to nuclear power and concerned about its risks. Nuclear attitude could be well accounted for by attitude statements and rated basic life values. It was quite stable over a 1 month period.


Alloantigens expressed on a subset of unstimulated human T lymphocytes that generate suppressor function.
Human alloantisera were tested for antibodies reacting with T-cell subpopulations. T-cell subsets were separated using the monoclonal antibodies OKT4 and OKT8. Five sera reacting with the T4-T8+ subset and two sera reacting with T4+T8- lymphocytes were identified. Serum Z. G. reacted with T4-T8+ cells from 8 of a panel of 19 donors. T cells treated with Z. G. serum and rabbit complement lost the capacity to generate suppressor cells but showed no decrease in the development of cytotoxic effector cells. ZG antigens were demonstrated by absorption also on monocytes but not on B cells. Their reactions on T cells were blocked by chicken anti-human Ia serum, but not by turkey anti-beta 2-microglobulin or by a monoclonal anti-human DR (L227). Studies in four informative families suggested that the ZG determinants are inherited in linkage with HLA. Although the similarities between ZG antigens and mouse I-J products are striking, structural studies are needed to establish their homology.


A LISREL analysis of work-related risk factors and health complaints in the nursing profession.
To fit a model which describes the complex interaction between various work-related factors and both musculoskeletal and psychosomatic complaints of nurses simultaneously and to compare the results with those of two LISREL models, in which the health outcome variables are analyzed separately in terms of their correlation with the same set of work-related factors. Nurses (n=718) working in four Dutch nursing homes completed a questionnaire about work-related factors and musculoskeletal and psychosomatic complaints (response 81%). LISREL was used to describe and analyse the models. The full model had a reasonable overall fit. The strongest (and statistically significant) correlations were found between work postures and musculoskeletal complaints and between psychosocial work demands and psychosomatic complaints. In the two single models, health outcomes showed statistically significant correlations with the same work-related factors as they did in the full model. The full model could be slightly improved when the variable somatized complaints (e.g., dizzyness, headache) was related both to musculoskeletal complaints and to psychosomatic complaints. Although a model that simultaneously describes more dependent variables appears to provide a better approximation of the complexity of the actual relationship between work-related factors and health effects, the models in which only one health outcome is studied seem to give a proper description of the data at hand. This is an important finding because these single health outcome models resemble the usual analysis strategy by means of standard regression analysis. The adapted version of the full model suggests that musculoskeletal complaints of nurses can partly be understood as non-specific health complaints.


Alteration of in vitro bone metabolism and tooth formation by zinc.
1. The effects of zinc on bone metabolism and tooth formation was examined in organ cultures of calvaria and tooth germ, and in cell cultures of osteoblast-like cells, MC3T3-E1. 2. Treatment of calvaria with zinc (10, 100 microM) for 4 days both increased alkaline phosphatase (ALP) activity in bone and reduced the secretion of N-acetyl beta-glucosaminidase from bone, without affecting bone mineral or collagen content. The increase in ALP activity produced by zinc (10 microM) was inhibited neither by actinomycin D (5 micrograms/ml) nor by cycloheximide (0.5 micrograms/ml). 3. Treatment of MC3T3-E1 cells with zinc (50, 100 microM) for 25 days also increased ALP activity, but reduced calcium content in cells and in the matrix layer. 4. These results indicate that zinc increases ALP activity in osteoblasts without affecting de novo enzyme synthesis, and that it inhibits bone mineralization, in accordance with the inhibition of osteoclastic activity. 5. Treatment of tooth germ with zinc (100 microM) for 7 days also produced an increase in ALP activity and inhibition of mineralization. These results indicate that the increased ALP activity produced by zinc is a common phenomenon in hard tissues, and, further, that zinc inhibits mineralization during tissue formation.


Dendritic structure varies as a function of eccentricity in V1: a quantitative study of NADPH diaphorase neurons in the diurnal South American rodent agouti, Dasyprocta prymnolopha.
The cerebral cortex is often described as a composite of repeated units or columns, integrating the same basic circuit. The 'ice-cube' model of cortical organization, and 'canonical' circuit, born from insights into functional architecture, still require systematic comparative data. Here we probed the anatomy of an individual neuronal type within V1 to determine whether or not its dendritic trees are consistent with the 'ice-cube' model and theories of canonical circuits. In a previous report we studied the morphometric variability of NADPH-diaphorase (NADPH-d) neurons in the rat auditory, visual and somatosensory primary cortical areas. Our results suggested that the nitrergic cortical circuitry of primary sensory areas are differentially specialized, probably reflecting peculiarities of both habit and behavior of the species. In the present report we specifically quantified the dendritic trees of NADPH-d type I neurons as a function of eccentricity within V1. Individual neurons were reconstructed in 3D, and the size, branching and space-filling of their dendritic trees were correlated with their location within the visuotopic map. We found that NADPH-d neurons became progressively smaller and less branched with progression from the central visual representation to the intermediate and peripheral visual representation. This finding suggests that aspects of cortical circuitry may vary across the cortical mantle to a greater extent that envisaged as natural variation among columns in the 'ice-cube' model. The systematic variation in neuronal structure as a function of eccentricity warrants further investigation to probe the general applicability of columnar models of cortical organization and canonical circuits.


Effects of interleukin-17A in nucleus pulposus cells and its small-molecule inhibitors for intervertebral disc disease.
Intervertebral discs (IVD) degeneration, which is caused by ageing or mechanical stress, leads to IVD disease, including back pain and sciatica. The cytokine interleukin (IL)-17A is elevated in NP cells during IVD disease. Here we explored the pharmacotherapeutic potential of IL-17A for the treatment of IVD disease using small-molecule inhibitors that block binding of IL-17A to the IL-17A receptor (IL-17RA). Treatment of NP cells with IL-17A increased expression of cyclooxygenase-2 (COX-2), IL-6, matrix metalloproteinase (MMP)-3 and MMP-13. These increases were suppressed by an IL-17A-neutralizing antibody, and small molecules that were identified as inhibitors by binding to the IL-17A-binding region of IL-17RA. IL-17A signalling also altered sulphated glycosaminoglycan deposition and spheroid colony formation, while treatment with small-molecule inhibitors of IL-17A attenuated this response. Furthermore, mitogen-activated protein kinase pathways were activated by IL-17A stimulation and induced IL-6 and COX-2 expression, while small-molecule inhibitors of IL-17A suppressed their expression. Taken together, these results show that IL-17A is a valid target for IVD disease therapy and that small-molecule inhibitors that inhibit the IL-17A-IL-17RA interaction may be useful for pharmacotherapy of IVD disease.


Stress-induced alterations in coagulation: assessment of a new hemoconcentration correction technique.
For the examination of psychological stress effects on coagulation, the Dill and Costill correction (DCC) for hemoconcentration effects has been used to adjust for stress-induced plasma volume changes. Although the correction is appropriate for adjusting concentrations of various large blood constituents, it may be inappropriate for time-dependent or functional coagulation assays. Two new plasma reconstitution techniques for correcting hemoconcentration effects on stress-induced changes in coagulation were compared with the DCC. Blood was collected from 31 men during baseline, the Trier Social Stress Test (TSST), and after 20-minute recovery. For the reconstitution techniques, TSST plasma samples were reconstituted with either baseline plasma or physiological saline equal to the amount of plasma lost during stress. Uncorrected activated partial thromboplastin time (APTT) decreased, whereas fibrinogen, factor VIII clotting activity (FVIII:C), D-dimer and prothrombin time (PT%) increased significantly during the TSST. The DCC produced a significantly greater decrease in APTT during stress compared to uncorrected APTT, a significant decrease in PT% compared to uncorrected PT%, and stress D-dimer and fibrinogen and FVIII:C being no different than baseline. APTT, fibrinogen, D-dimer and PT% after saline reconstitution were not different from baseline, whereas FVIII:C after saline reconstitution remained elevated. APTT, PT%, fibrinogen and D-dimer after plasma reconstitution were no different from uncorrected values, whereas FVIII:C remained significantly elevated. The observed changes in coagulation are likely in part a consequence of stress and hemoconcentration, but the DCC seems to be an inappropriate hemoconcentration correction technique of time-dependent assays. The saline reconstitution technique may be more biologically relevant when examining stress-hemoconcentration effects on coagulation.


Evaluating Serum Proteome in Women with Obsessive-Compulsive Disorder/Bipolar Disorder Compared to Pure Obsessive- Compulsive Disorder Subjects and Healthy Controls.
The present study aimed to evaluate the serum proteome of women with obsessive-compulsive disorder (OCD)/bipolar disorder (BP) compared to pure OCD subjects and healthy controls. Serum proteome of women with OCD/BP, pure OCD individuals, and healthy controls were subjected to 2DE-based proteomics accompanied with MALDI-TOF-TOF mass spectrometry. Further evaluation of the identified protein spots with the significance of p<0.05 and fold≥1.5 was done by applying protein interaction mapping via Cytoscape v. 5.3.1 and its plugins. The results indicate that vitamin D binding protein (GC) and haptoglobin spots (HP) significantly changed expression in OCD and OCD/BP with different expression patterns. These identified spots may contribute to OCD/BP and act as differentially recognized biomarkers comparing pure OCD and OCD/BP. The Findings imply that these proteins in the serum of the patients could be potential distinguishable biomarkers in clinical usage after related validation experiments. Therefore, this study provides a preliminary evaluation to understand OCD/BP proteome behavior better.


Periodic bursting of cultured cortical neurons in low magnesium: cellular and network mechanisms.
The origin of the 0.1 Hz bursting of cultured rat cortical neurons in zero Mg2+ was studied by whole-cell recording, fluo-3 Ca2+ imaging, and multi-unit electrode array recording. A model is proposed in which spontaneous synaptic currents act as a random pacemaker.


Effects of maintenance implant therapy with and without periodic removal and decontamination of prosthetic components on inflammatory peri-implant parameters.
This retrospective clinical study compared two different professional maintenance therapy (MT) approaches (with and without periodic removal and decontamination of prosthetic components) on peri-implant inflammatory clinical and biochemical parameters after 5 years of implant function. A retrospective analysis based on patient records was used to assess inflammatory clinical and biochemical parameters around dental implants placed by the same clinician in a private practice. The Plaque Index (PI), peri-implant probing depth (PPD), mucosal recession (REC), bleeding on probing (BOP), and radiographic marginal bone level were determined at baseline and at each follow-up year. Moreover, at the last follow-up visit, the peri-implant intrasulcular levels of active metalloproteinasis 8 (aMMP-8) were also assessed. All participants were under MT with a 6-month recall interval. A total of 92 patients with 132 implants were selected. At the end of the study period, 12 patients with 12 implants were classified as dropouts. The remaining 80 patients and 120 implants were classified into two groups: Group 1 (42 patients, 62 implants) received MT with periodic removal and decontamination of prosthetic components; Group 2 (38 patients, 58 implants) received MT without periodic removal and decontamination of prosthetic components. No statistical differences were found between the groups regarding PI, PPD, and REC. Group 1 presented a statistically significant higher number of sites with BOP (12.4% vs 6.2%). Marginal bone loss was statistically higher in Group 2 than in Group 1 (0.23 ± 0.6 mm vs 0.78 ± 0.3 mm). Intrasulcular levels of aMMP-8 were statistically higher in Group 1 than in Group 2. The supplemental application of periodic removal and decontamination of prosthetic components during MT had a significantly positive effect on the inflammatory status of peri-implant tissues.


Discordance in lumbar bone mineral density measurements by quantitative computed tomography and dual-energy X-ray absorptiometry in postmenopausal women: a prospective comparative study.
Level-specific lumbar bone mineral density (BMD) evaluation of a single vertebral body can provide useful surgical planning and osteoporosis management information. Previous comparative studies have primarily focused on detecting spinal osteoporosis but not at specific levels. To compare the detection rate of lumbar osteoporosis between quantitative computed tomography (QCT) and dual-energy X-ray absorptiometry (DXA); to explore and analyze the distribution models of QCT-derived BMD and DXA T-score at the specific levels; and to evaluate the diagnostic accuracy of level-specific BMD thresholds for the prediction of osteoporotic vertebral compression fracture (OVCF) in postmenopausal women. A comparative analysis of prospectively collected data comparing QCT-derived BMD with DXA T-score. A total of 296 postmenopausal women who were referred to the spine service of a single academic institution were enrolled. QCT-derived BMD and DXA T-score at specific levels, with or without osteoporotic vertebral compression fracture. Postmenopausal women who underwent QCT and DXA within a week of admission from May 2019 to June 2022 were enrolled. The diagnostic criteria for osteoporosis recommended by the World Health Organization and the American College of Radiology were used for lumbar osteoporotic diagnosis. To evaluate differences in lumbar BMD measurements at specific levels, a threshold of T score=-2.5 and QCT-derived BMD = 80 mg/cm3 were used to categorize level-specific lumbar BMD into low and high BMD. Disagreements in BMD categorization between DXA and QCT were classified as a minor or major discordance based on the definition by Woodson. Data between QCT and DXA were visualized in a stacked bar plot and analyzed. Correlations between DXA and QCT at the specific levels were evaluated using Pearson's linear correlation and scatter plots. Curve fitting of BMD distribution, receiver operating characteristic (ROC) and area under the curve (AUC) for each single vertebral level was performed. Of the 296 patients, QCT diagnosed 61.1% as osteoporosis, 30.4% as osteopenia and 8.4% as normal. For those screened with DXA, 54.1% of the patients had osteoporosis, 29.4% had osteopenia and 16.6% had normal BMD. Diagnoses were concordant for 194 (65.5%) patients. Of the other 102 discordant patients, 5 (1.7%) were major and 97 (32.8%) were minor. Significant correlations in level-specific BMD between DXA and QCT were observed (p<.001), with Pearson's correlation coefficients ranging from 0.662 to 0.728. The correlation strength was in the order of L1 > L2 > L3 > L4. The low BMD detection rate for QCT was significantly higher than that for DXA at the L3 and L4 levels (65% vs. 47.9% and 68.1% vs 43.7, respectively, p<.001). Patients with OVCF showed significantly lower QCT-derived BMD (47.2 mg/cm3 vs. 83.2 mg/cm3, p<.001) and T-score (-3.39 vs. -1.98, p<.001) than those without OVCF. Among these patients, 82.8% (101/122) were diagnosed with osteoporosis by QCT measurement, while only 74.6% (91/122) were diagnosed by DXA. For discrimination between patients with and without OVCF, QCT-derived BMD showed better diagnosed performance (AUC range from 0.769 to 0.801) than DXA T-score (AUC range from 0.696 to 0.753). QCT provided a more accurate evaluation of lumbar osteoporosis than DXA. The QCT-derived BMD measurements at a specific lumbar level have a high diagnostic performance for OVCF.


Can the singularity of chronic peptic ulcers be described by catastrophe theory and explained by biofeedback?
The damaging effect of hydrochloric acid within the lumen of the stomach and duodenum should be diffuse, but chronic peptic ulcers are discrete and usually single. The search for localizing effects on acid attack, or localized defects in mucosal defense have so far been fruitless. If attacking forces increase, or mucosal defense diminishes to the point where ulceration occurs, mucosal breakdown should be progressive. In chronic peptic ulceration, however, the process usually seems to be self-limiting. The catastrophe theory of René Thom may describe the progressive change in the forces that leads to eventual breakdown in mucosal continuity. Possibly this catastrophe triggers off biofeedback mechanisms that hold in check further progress of the ulcer.


Prevention of alcohol-induced developmental delays and learning abnormalities in a model of fetal alcohol syndrome.
Prenatal alcohol exposure results in fetal death and neurobehavioral complications including learning impairment. Previously synthetic peptides derived from activity-dependent neurotrophic factor have been shown to prevent aspects of alcohol-induced damage in pregnancy. The objective of this work was to evaluate whether activity-dependent neurotrophic factor-12 could prevent alcohol-induced damage in a model of fetal alcohol syndrome. Using a well-characterized model, C57Bl6/J mice on gestational day 8 were treated with placebo, alcohol (30% volume/volume alcohol 0.03 mL/kg), alcohol plus activity-dependent neurotrophic factor-12 30 minutes prior to alcohol, or activity-dependent neurotrophic factor-12 alone. Fetal death was assessed on gestational day 18 (25 litters were evaluated: alcohol, n = 5; placebo, n = 9; alcohol plus activity-dependent neurotrophic factor-12, n = 11). Neonatal behavior tests were performed on postnatal days 1 through 21 with the offspring of 12 dams (alcohol, n = 16; placebo, n = 46; alcohol plus activity-dependent neurotrophic factor-12, n = 23; and activity-dependent neurotrophic factor-12, n = 35). Adult males were tested in the Morris water maze for learning assessment and with the hole punch activity test for exploratory activity. Statistical analysis included Kruskal-Wallis and analysis of variance. Fetal death was greater in alcohol (67% +/- 13%) vs placebo (8.4% +/- 3%, P < .001). Pretreatment with activity-dependent neurotrophic factor-12 prevented the alcohol-induced fetal death (2.2% +/- 8.1%) with levels similar to control (P = .12). Alcohol exposure caused a delay in achieving developmental milestones, with alcohol achieving milestones later than all other groups (all P < .001). Pretreatment with activity-dependent neurotrophic factor-12 prevented the alcohol-induced milestone delays. In the Morris water maze, the placebo learned, decreasing their latency to find the hidden platform over 70% (P < .01). Alcohol plus activity-dependent neurotrophic factor-12 also significantly learned, with a learning curve not different from placebo (all P > .5) and significantly better than alcohol on days 4, 6, and 7 (all P < .05). Alcohol exposure resulted in significantly less time in hole punch activity (P < .02) than control. Activity-dependent neurotrophic factor-12 pretreatment prevented the alcohol-induced decline, with levels the same as control (P = .1). The novel peptide activity-dependent neurotrophic factor-12 prevents alcohol-induced fetal death and developmental and learning abnormalities in a model of fetal alcohol syndrome. This demonstrates that a single treatment with a peptide is efficacious and may be of value in the prevention of alcohol-induced damage.


Scoring System Development and Validation for Prediction Choledocholithiasis before Open Cholecystectomy.
Accurate precholecystectomy detection of concurrent asymptomatic common bile duct stones (CBDS) is key in the clinical decision-making process. The standard preoperative methods used to diagnose these patients are often not accurate enough. The aim of the study was to develop a scoring model that would predict CBDS before open cholecystectomy. We retrospectively collected preoperative (demographic, biochemical, ultrasonographic) and intraoperative (intraoperative cholangiography) data for 313 patients at the department of General Surgery at Gornji Milanovac from 2004 to 2007. The patients were divided into a derivation (213) and a validation set (100). Univariate and multivariate regression analysis was used to determine independent predictors of CBDS. These predictors were used to develop scoring model. Various measures for the assessment of risk prediction models were determined, such as predictive ability, accuracy, the area under the receiver operating characteristic curve (AUC), calibration and clinical utility using decision curve analysis. In a univariate analysis, seven risk factors displayed significant correlation with CBDS. Total bilirubin, alkaline phosphatase and bile duct dilation were identified as independent predictors of choledocholithiasis. The resultant total possible score in the derivation set ranged from 7.6 to 27.9. Scoring model shows good discriminatory ability in the derivation and validation set (AUC 94.3 and 89.9%, respectively), excellent accuracy (95.5%), satisfactory calibration in the derivation set, similar Brier scores and clinical utility in decision curve analysis. Developed scoring model might successfully estimate the presence of choledocholithiasis in patients planned for elective open cholecystectomy.


Long-term graft-versus-tumor effect following reduced intensity hematopoietic stem cell transplantation in a child with metastatic renal cell carcinoma.
Pediatric renal cell carcinoma (RCC) is rare and different from adult RCC. Although target agents have recently been introduced, allogeneic hematopoietic stem cell transplantation exploiting graft-versus-tumor effect still remains an important treatment option for metastatic RCC. A 2-year-old male with RCC developed hepatic metastases 6 months following radical nephrectomy and subsequent cytokine therapy. Allogeneic reduced-intensity stem cell transplantation (RIST) with early withdrawal of immunosuppression and delayed donor lymphocyte infusions was performed. A second transplantation was undertaken following marrow aplasia. Now he remains progression-free with regression of hepatic metastases 5.7 years after RIST, along with complete donor chimerism.


A phase I study of 3-day topotecan and cisplatin in elderly patients with small-cell lung cancer.
The aim of this phase I study was to determine the maximum-tolerated dose (MTD) in elderly patients with small-cell lung cancer (SCLC). Patients aged over 75 years with previously untreated SCLC were enrolled in this study. Both topotecan and cisplatin were administered on days 1-3 and repeated every 3 weeks. The starting dose of topotecan was 0.5 mg/m2/day, while cisplatin was fixed at the dose of 20 mg/m2/day. Patients with limited disease (LD) SCLC received thoracic irradiation after the completion of chemotherapy. Twenty-one elderly patients were enrolled in this study and received a total of 59 cycles. The major hematological toxicity was neutropenia and non-hematological toxicities including diarrhea were generally mild and reversible. The MTD of topotecan was determined as 1.2 mg/m2/day. The recommended phase II study dose of topotecan was determined as 1.0 mg/m2/day with cisplatin 20 mg/m2/day daily for 3 days. An objective response was observed in 6 of 10 patients (60%) with LD-SCLC and 6 of 11 (55%) with extensive disease (ED) SCLC. The median survival time in patients with LD-SCLC and those with ED-SCLC were 16.0 and 11.0 months, respectively. The combination chemotherapy of 3-day topotecan and cisplatin appears to be tolerable and effective in elderly patients with SCLC.


Pollination: Multimodal signaling in a co-dependent thermogenic gymnosperm system.
Plant-pollinator interaction research commonly focuses on more apparent traits, floral morphology and odor. A new study of a thermogenic gymnosperm brood-site pollination system via a specialist beetle reveals intricate long- and short-range multimodal signals are involved in host finding.


On chronic rhinosinusitis and the prevalence of fungal sinus disease: problems of diagnostic accuracy and a proposed classification of chronic rhinosinusitis.
There is considerable controversy in the diagnosis and classification of the type of inflammation that is attributed to various forms of chronic rhinosinusitis (CRS). Specimens obtained during surgical treatment of CRS have been invaluable resources for identifying the underlying inflammatory process. The classification of sinus inflammation is based on histopathologic examination of these surgical specimens. Accurate identification of the pathology and standardized reporting are invaluable for postsurgical treatment options and our understanding of CRS. In a large multispecialty referral hospital where multiple surgeons and pathologists are involved in clinical practice, the lack of standardization in specimen collection, specimen processing, and reporting introduce several variables that make it extremely difficult for retrospective analysis. This report focuses on consecutive endoscopic sinus surgical procedures performed by 4 different sinus surgeons over a period of 4 years in a Central Texas multispecialty hospital. This is an analysis of the reality of clinical practice without intervention. At the core of this analysis are pathology reporting practices for fungal sinus disease and the undesirable variables introduced by nonstandardized reporting. A practical classification of CRS based on pathology is proposed.


Amino acids 1-1,680 of ryanodine receptor type 1 hold critical determinants of skeletal type for excitation-contraction coupling. Role of divergence domain D2.
To identify domains of the ryanodine receptor (RyR1) that are functionally relevant for excitation-contraction (EC) coupling in vivo, we have studied the ability of RyR1/RyR3 chimera to rescue skeletal EC coupling in dyspedic myotubes. In this work we show that chimeric receptors containing amino acids 1-1,680 of RyR1 were able to render depolarization-induced Ca2+ release to RyR3. Within this region, residues 1,272-1,455, containing divergent domain D2 of RyR1, proved to be a critical element because the absence of this region selectively abolished depolarization-evoked Ca2+ transients without affecting chemically induced activation. Although the D2 domain by itself failed to restore skeletal EC coupling to RyR3, the addition of the D2 region resulted in a dramatic enhancement of EC coupling restored by an RyR3 chimera containing amino acids 1,681-3,770 of RyR1. These results suggest that although the D2 domain of RyR1 plays a key role during EC coupling, additional region(s) from the N-terminal end of RyR1 as well as previously identified regions of the central portion of the receptor are needed in order to allow normal EC coupling.


Wide-field polygon-scanning photoacoustic microscopy of oxygen saturation at 1-MHz A-line rate.
We report wide-field polygon-scanning functional OR-PAM that for the first time achieves 1-MHz A-line rate of oxygen saturation in vivo. We address two technical challenges. The first is a 1-MHz dual-wavelength pulsed laser that has sufficient pulse energy and ultrafast wavelength switching. The second is a polygon-scanning imaging probe that has a fast scanning speed, a large field of view, and great sensitivity. The OR-PAM system offers a B-scan rate of 477.5 Hz in a 12-mm range and a volumetric imaging rate of ∼1 Hz over a 12 × 5 mm2 scanning area. We image microvasculature and blood oxygen saturation in a 12 × 12 mm2 scanning area in 5 s. Dynamic imaging of oxygen saturation in the mouse ear is demonstrated to monitor fast response to epinephrine injection. The new wide-field fast functional imaging ability broadens the biomedical application of OR-PAM.


Response of transcortin and alpha 2u-globulin to turpentine-induced inflammation in the rat: influence of corticosteroids and prolactin.
Evidence is presented that (transcortin and alpha 2u-globulin react as negative acute-phase proteins in the rat. Thirty-six hours after turpentine injection, the serum concentration of these proteins showed a two- to threefold decrease. Thereafter, transcortin rapidly returned to normal values, whereas alpha 2u-globulin remained low. This reaction pattern was still present after adrenalectomy, adrenalectomy and administration of glucocorticoids, and after treatment with bromocriptine, a suppressor of prolactin secretion. It is concluded that changes in the secretion of glucocorticoids and prolactin are not required for the observed turpentine-induced decrease of transcortin and alpha 2u-globulin.


Biodiesel production as a solution to waste cooking oil (WCO) disposal. Will any type of WCO do for a transesterification process? A quality assessment.
Biodiesel production can be the solution to the problem of how to deal with waste cooking oils (WCO) and the associated problem of environmental contamination. Every year, tonnes of WCO are poured into toilets and drains, contaminating water supplies and creating serious problems in waste water treatment plants. WCO is a waste material that can be used to produce biodiesel. The main aim of this study is to determine how the type of WCO (and how much it has been used) affect the quality of the biodiesel obtained. Four types of WCO (sunflower, maize, olive and a blend of soybean, palm and sunflower) with two different levels of degradation were used to produce biodiesel. The WCO were subjected to a transesterification process, using NaOH and methanol as reagents, reaction temperatures of between 50 and 67.5 °C, a 60 min reaction time and magnetic stirring. The quality of the biodiesel that was obtained was measured on the basis of four parameters as set out in the UNE-EN 14214 standard: density at 15 °C, kinematic viscosity at 40 °C, acid number and iodine value. This characterisation forms part of the second aim of this research, namely to determine which types of WCO can produce a quality biodiesel via a single stage transesterification process. The results show that the biodiesel quality is closely related to that of the WCO, and that the transesterification method can be recommended for WCO with densities (at 15 °C) of up to 930 kg/m3, kinematic viscosity (at 40 °C) of up to 38.46 mm2/s, and acid numbers of up to 4.19 mg KOH/g. The production method used is a simple, economic and effective way of adding value to a hazardous and difficult to manage waste material like WCO.


Inhibition of microRNA-196a might reverse cisplatin resistance of A549/DDP non-small-cell lung cancer cell line.
We aimed to explore the possible mechanism of microRNA-196a (miR-196a) inhibition and reversion of drug resistance to cisplatin (DDP) of the A549/DDP non-small-cell lung cancer (NSCLC) cell line. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect expression differences of miR-196a in the drug-resistant A549/DDP NLCLC cell line and the parental A549 cell line, and expressions of miR-196a in the A549/DDP NLCLC cell line transfected with miR-196a inhibitor (anti-miR-196a group) and the miR-196a negative control (miR-NC) group and blank group (without transfection). 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test was applied in examining the cell viability of A549/DDP cell line before and after transfection. Clonogenic assay was used to detect cell proliferation ability. Flow cytometry was applied in detecting apoptosis rate of assayed tumor cell and rhodamine-123 changes in cells. Western blot was applied in detecting proteins of drug-resistant related gene in A549/DDP cell line. Significantly higher expression of miR-196a was detected in the drug-resistant A549/DDP cell line than that in the parental A549 cell line (P < 0.05). However, miR-196a expression in the anti-miR-196a group decreased obviously compared to that in the blank group and the miR-NC group (both P < 0.05); The value of IC50 in the anti-miR-196a group showed remarkably lower than that in the blank group and the miR-NC group (both P < 0.05); Rh-123 absorbing ability in the anti-miR-196a group increased 2.51 times and 2.49 times respectively compared to that in the blank group and the miR-NC group (both P < 0.05). No statistical differences in the apoptosis rate of A549/DDP cell line in the early stage were found among the three groups (all P > 0.05), but the late-stage apoptosis rate in the anti-miR-196a group was significantly higher than that in the blank group and the miR-NC group (both P < 0.05); The expressions of human multidrug resistance 1 (MDR1), multidrug resistance protein 1 (MRP1), excision repair cross-complementation 1 (ERCC1), survivin, and B cell lymphoma 2 (Bcl-2) decreased significantly while RhoE increased significantly in the anti-miR-196a group than the blank group and the miR-NC group (all P < 0.05). Inhibition of miR-196a could reverse cisplatin resistance of A549/DDP cell lines, which might relate with inhibition of drug efflux, down-regulation of drug-resistant protein expression, cell apoptosis, and cell proliferation suppression.


A Study of Application of Preoperative Clinical Predictors of Difficult Laryngeal Exposure for Microlaryngoscopy: The Laryngoscore in the Indian Population.
Good exposure for visualisation of the glottis is an essential prerequisite for effective microlaryngoscopy. There is no definitive clinical predictor scoring system to predict difficult microlaryngoscopy. The aim of the study was to study the validity of the Laryngoscore scoring system as a preoperative clinical predictor score in Indian population for difficult laryngeal exposure during microlaryngoscopy. A prospective study was carried out in 32 patients undergoing microlaryngoscopy in a tertiary care hospital who were evaluated by a standardized preoperative assessment protocol (Laryngoscore) which included 11 parameters interincisors gap, thyro-mental distance, upper jaw dental status, trismus, mandibular prognathism, macroglossia, micrognathia, degree of neck flexion-extension, history of previous open-neck and/or radiotherapy, Mallampati's modified score, and body mass index. Each parameter was assessed to obtain a total score (Maximum-17). Patients were divided into five classes according to the anterior commissure visualization: class 0 to class IV. Class 0 being complete and class IV being impossible AC visualization. When the Laryngoscore was < 6, good laryngeal exposure was observed in 94% of patients. Laryngoscore had a sensitivity of 87.5% and specificity of 75% in predicting difficult laryngeal exposure. The positive and negative predictive values of the same are 53.8% and 94.7% respectively. Our study found that the Laryngoscore scoring system as a preoperative indicator for predictor of Difficult Laryngeal Exposure during Micro Laryngeal surgeries is very useful in the Indian population.


Evaluation of the effects of selamectin against adult and immature stages of fleas (Ctenocephalides felis felis) on dogs and cats.
The adulticidal, ovicidal, and larvicidal effects of selamectin against flea (Ctenocephalides felis felis) infestations on dogs and cats were evaluated in a series of seven controlled and masked studies (three in cats, four in dogs). Animals were randomly allocated to treatment with either selamectin at a minimum dosage of 6mgkg(-1) in the commercial formulation or one of two negative-controls (0.9% NaCl solution or the vehicle from the commercial formulation). Treatments were administered topically in a single spot on the skin at the base of the neck in front of the scapulae. Speed of kill, measured by flea comb counts at 12h intervals during the 48h immediately following a single treatment on day 0, was evaluated in two studies. One study was in dogs and the other in cats, and each animal was infested with approximately 100 unfed viable adult fleas prior to treatment. Reductions in geometric mean flea counts for selamectin compared with saline were >98% between 24 and 36h after treatment in dogs, and between 12 and 24h after treatment in cats (P< or =0.0006). Efficacy in reducing flea egg hatch and larval development was evaluated in four studies, in which dogs and cats were treated once on day 0 and then repeatedly infested with approximately 600 fleas. Flea eggs were collected approximately for 72h after each infestation, on days 3, 7, 14, 21, and 30, counted, and cultured to determine their hatchability and subsequent larval development. Compared with the vehicle, selamectin was highly effective in reducing flea egg hatch (>92% in cats) and larval development (> or =95% for dogs and cats), and emergence of adults (97.8-100% for dogs, 85.6-100% for cats) for 30 days. Effects of exposure to hair coat debris were investigated in a study with dogs treated once on day 0 and repeatedly infested with 100 adult fleas. Debris (dander, flea faeces, hair, scales) was collected on days 1, 7, 14, 21, and 30 and added to normal flea eggs or larvae for incubation. Compared with debris from vehicle-treated dogs, debris from selamectin-treated dogs was highly effective in preventing egg hatch (>96%), in killing larvae (>98%) and in preventing larval development to adults (>99%) (P</=0.0033). Selamectin was shown to be highly effective in the treatment and control of flea infestations (C. felis) on dogs and cats. The adulticidal, ovicidal, and larvicidal effects of selamectin will be important in interrupting the flea life cycle by preventing the introduction and establishment of new flea infestations in a household environment.


Immunotoxicology of non-functionalized engineered nanoparticles in aquatic organisms with special emphasis on fish--review of current knowledge, gap identification, and call for further research.
The rapid increase in use of nanotechnology products is increasing the presence of metal, metal-oxide and carbon-based nanoparticles in the aquatic environment. These non-functionalized engineered nanoparticles can interact with the immune system of fish and invertebrates, and tip the ecological balance of population sustainability. Most nanoparticle types present in the aquatic environment, such as titanium dioxide, do not exhibit or have very low direct toxicity, but instead display silent or concealed sub-lethal effects on the immune system with serious implications. There is a gap in current available information regarding the immunotoxic potential of engineered nanoparticles toward aquatic organisms. Therefore, there is a critical need to provide the first comprehensive review of the effects of engineered non-functionalized nanoparticles on the immune system of aquatic animals, address the major gaps in current existing information, and recommend the future focus of research. This manuscript identifies cell mediated immunity and the phagocytic cells as the primary target of nanoparticle immunotoxicity. The immunotoxicity is primarily govern by lysosomal destabilization, frustrated phagocytosis, and change in function of the phagocytic cells, which decrease the ability of animals to defend themselves against pathogens and infectious diseases. Humoral immune system is a lesser target of direct immunotoxicity, but plays a critical role in dissemination of the nanoparticles through the body and their presentation to the phagocytic cells. The external innate immunity and the acquired immunity have not been connected with overly important and direct immunotoxic effects, but instead a big gap in current targeted research has been acknowledged.


Evaluating the Psychometric Properties and Clinical Utility of a Digital Psychosocial Self-Screening Tool (HEARTSMAP-U) for Postsecondary Students: Prospective Cohort Study.
Existing screening tools for mental health issues among postsecondary students have several challenges, including a lack of standardization and codevelopment by students. HEARTSMAP-U was adapted to address these issues. This study aimed to evaluate the suitability of HEARTSMAP-U as a self-screening tool for psychosocial issues among postsecondary students by evaluating its validity evidence and clinical utility. A prospective cohort study was conducted with University of British Columbia Vancouver students to evaluate HEARTSMAP-U's predictive validity and convergent validity. Participating students completed baseline and 3-month follow-up assessments via HEARTSMAP-U and a clinician-administered interview. In a diverse student sample (n=100), HEARTSMAP-U demonstrated high sensitivity (95%-100%) in identifying any psychiatric concerns that were flagged by a research clinician, with lower specificity (21%-25%). Strong convergent validity (r=0.54-0.68) was demonstrated when relevant domains and sections of HEARTSMAP-U were compared with those of other conceptually similar instruments. This preliminary evaluation suggests that HEARTSMAP-U may be suitable for screening in the postsecondary educational setting. However, a larger-scale evaluation is necessary to confirm and expand on these findings.


The ubiquitin-modifying enzyme A20 restricts ubiquitination of the kinase RIPK3 and protects cells from necroptosis.
A20 is an anti-inflammatory protein linked to multiple human diseases; however, the mechanisms by which A20 prevents inflammatory disease are incompletely defined. We found that A20-deficient T cells and fibroblasts were susceptible to caspase-independent and kinase RIPK3-dependent necroptosis. Global deficiency in RIPK3 significantly restored the survival of A20-deficient mice. A20-deficient cells exhibited exaggerated formation of RIPK1-RIPK3 complexes. RIPK3 underwent physiological ubiquitination at Lys5 (K5), and this ubiquitination event supported the formation of RIPK1-RIPK3 complexes. Both the ubiquitination of RIPK3 and formation of the RIPK1-RIPK3 complex required the catalytic cysteine of A20's deubiquitinating motif. Our studies link A20 and the ubiquitination of RIPK3 to necroptotic cell death and suggest additional mechanisms by which A20 might prevent inflammatory disease.


Primary intraosseous fibrosarcoma of jaw.
This paper reports one case of primary fibrosarcoma affecting the mandible in a 41-year-old woman. Microscopically, the tumor was cellularized with an intense mitotic activity, and areas of necrosis and hemorrhage, and the cells showed immunoreactivity only for vimentin, establishing the diagnosis of primary intraosseous fibrosarcoma. The patient underwent tumor surgical resection, supraomohyoid neck dissection and mandible reconstruction with fibula flap and titanium bar. She also received post-surgical radiotherapy and is in follow up for 36 months without signs of recurrence or metastases.


Electrophysiological Evaluation of Audiovestibular Pathway Dysfunction in Parkinson's Disease and Its Correlates: A Case Control Study.
Parkinson's disease (PD) is associated with brainstem dysfunction causing non-motor symptoms. Vestibular evoked myogenic potential (VEMP) and brainstem auditory evoked potential (BAEP) are electrophysiological tests to assess the vestibular and auditory pathways in the brainstem. To study the abnormalities of cervical VEMP (cVEMP) and BAEP in PD and to correlate the findings with the symptoms related to brainstem involvement. cVEMP and BAEP were recorded in 25 PD patients and compared 25 age matched controls. The PD patients were assessed with the following clinical scales: REM Sleep Disorder Screening Questionnaire (RBD-SQ), Epworth Sleepiness Scale (ESS), mini-BESTest, Geriatric Depression Scale (GDS-15) and MMSE (Mini-mental state examination). The P13 and N23 peak latencies and the P13/N23 amplitude of cVEMP, the latencies of waves I, III and V, and the inter-peak latencies (IPL) of waves I-III, III-V and I-V of BAEP were measured. The PD patients showed prolonged latencies and reduced amplitude in cVEMP responses. They had abnormal BAEP in the form of prolonged absolute latencies of wave V, followed by wave III and I-V IPL with no significant difference in waves I and I-III IPL. The cVEMP abnormality was correlated directly with RBD-SQ and inversely with mini-BESTest scores. There were no correlations between cVEMP/BAEP abnormality and disease severity, GDS-15, ESS and MMSE. PD is associated with cVEMP and BAEP abnormalities that suggest auditory and vestibular pathway dysfunction in the brainstem and cVEMP correlates with the symptoms of brainstem degeneration like RBD and postural instability.


Maternal infection during pregnancy and risk of autism spectrum disorders: A systematic review and meta-analysis.
Conflicting evidence exists with regard to the relationship between maternal infection during pregnancy and the risk of autism spectrum disorder (ASD) in offspring. The aim of this meta-analysis was to systematically assess this relationship. To identify relevant studies, we conducted systematic searches in PubMed and Embase of scientific articles published through March 2016. Random-effects models were adopted to estimate overall relative risk. A total of 15 studies (2 cohort and 13 case-control studies) involving more than 40,000 ASD cases were included in our meta-analysis. Our results showed that maternal infection during pregnancy was associated with an increased risk of ASD in offspring (OR=1.13, 95% confidence interval (CI): 1.03-1.23), particularly among those requiring hospitalization (OR=1.30, 95% CI: 1.14-1.50). Subgroup analyses suggested that risk may be modulated by the type of infectious agent, time of infectious exposure, and site of infection. These findings indicate that maternal infection during pregnancy increases the risk of ASD in offspring. Possible mechanisms may include direct effects of pathogens and, more indirectly, the effects of inflammatory responses on the developing brain.


Capillary electrophoretic focusing of covalently derivatized protein induced by surfactant.
In this communication, we present a very simple strategy to focus covalently derivatized proteins for high sensitivity CE analysis by LIF detection. We demonstrated that the covalently tagged protein can be focused just by adding SDS at a concentration above the CMC in the derivatized sample. Under specific injection conditions, SDS concentration below the CMC is also sufficient to induce the focusing of the tagged protein. This method allows the quantification and detection of the covalently tagged protein in a narrow zone with an efficiency approaching 220 000 plates/m. Very good linearity was obtained for the ubiquitin in a concentration range of 2-25 μM.


Cardiac output effects of high-frequency oscillatory ventilation in normal dogs.
We compared the hemodynamic effects of high-frequency oscillatory ventilation (HFOV) with conventional continuous positive pressure ventilation (CPPV). Six mongrel dogs were anesthetized with chloralose and evaluated over a range of mean airway pressures (Pao) during CPPV and HFOV. Pao during HFOV was measured by allowing alveolar pressure to come into equilibrium with airway opening pressure and was set to equal mean Pao during CPPV. Pao during CPPV was set by adding positive end-expiratory pressure (PEEP) of 0, 5, 10, and 15 cm H2O. Transmural pulmonary capillary wedge pressures (Pwp) were maintained at near 11 mm Hg in both groups during all four ventilatory periods. Cardiac output as measured in triplicate by thermal dilution was similar between HFOV and CPPV at each level of mean airway pressure. After matching mean airway pressure and transmural Pwp we were unable to find any sparing effect of HFOV on cardiac output over a wide range of airway pressures. We conclude that there is not an independent effect of HFOV on cardiac output.


Receptor-targeting mechanisms of pain-causing toxins: How ow?
Venoms often target vital processes to cause paralysis or death, but many types of venom also elicit notoriously intense pain. While these pain-producing effects can result as a byproduct of generalized tissue trauma, there are now multiple examples of venom-derived toxins that target somatosensory nerve terminals in order to activate nociceptive (pain-sensing) neural pathways. Intriguingly, investigation of the venom components that are responsible for evoking pain has revealed novel roles and/or configurations of well-studied toxin motifs. This review serves to highlight pain-producing toxins that target the capsaicin receptor, TRPV1, or members of the acid-sensing ion channel family, and to discuss the utility of venom-derived multivalent and multimeric complexes.


Critical access: the need to connect. Connecting midsize hospitals to rural critical access hospitals is important to the growth of both--but there are things larger hospitals need to know.
Many small, rural critical access hospitals are reaching out to each other and to larger hospitals as a way of setting up affordable health information technology systems that will meet meaningful use requirements. CIOs who have followed this strategy weigh in on its benefits and potential pitfalls.


Step-by-step guide to creating the best syncope units: From combined United States and European experiences.
Syncope can be caused by many physiological and pathophysiological conditions. Causes of syncope encompass a wide range of conditions from benign vasovagal syncope to life-threatening arrhythmias. The lack of a standardized method of evaluation and management of this large patient population leads to a wide practice variation which results in broad-based testing, frequent hospital admission and high healthcare cost. The concept of a syncope observational unit was created for inpatients and outpatients in the United States and Europe. Studies have demonstrated that syncope units, staffed by trained health care providers with sufficient resources could expedite and improve diagnostic yield, reduce hospital admission, and result in decreased healthcare cost with favorable clinical outcomes. The implementation of a standardized syncope unit has been challenging because resources and health care systems are variable regionally, nationally, and internationally. In this review, we provide an overview of the evidences that support a standardized syncope unit practice. We provide step-by-step algorithms for the "best syncope units" in the inpatient and outpatient settings by combining the synergistic experiences from the United States and Europe.


Delayed enterocutaneous fistula formation secondary to an inverted non-absorbable suture post midline laparotomy closure.
Enterocutaneous fistula is a well recognised complication of intra-abdominal surgery. Postoperatively, it may occur due to a small bowel injury or an anastomotic leak and usually presents within days or weeks after surgery. We present a case report. Information was obtained through a retrospective review of the notes, clinic letters, images and the histology report. We present a case of a patient who developed an enterocutaneous fistula 34 years after panproctocolectomy for ulcerative colitis. Imaging was consistent with an enterocutaneous fistula arising from mid-small bowel. A laparotomy and small bowel resection was performed. The enterocutaneous fistula occurred due to an inverted non-absorbable suture post midline laparotomy closure. Suture-related enterocutaneous fistula can be a rare delayed complication of a midline laparotomy closure when a knot is inverted intra-peritoneally. Consideration should be given to either leaving a knot in the subcutaneous fat tissue or feeding it between the rectus sheath and the suture bites.


Treatment device for neonatal birth asphyxia related Hypoxic Ischemic Encephalopathy.
Birth asphyxia is a leading cause of neonatal brain injury, morbidity, and mortality globally. It leads to a multi-organ dysfunction in the neonate and to a neurological dysfunction called Hypoxic Ischemic Encephalopathy (HIE). Cooling therapy is commonly used to slow or stop the damaging effects of birth asphyxia. However, most of the cooling devices used in the healthcare facility do not have a rewarming functionality after cooling therapy. A separate rewarming device, usually a radiant warmer or incubator is used to rewarm the infant after therapy, causing additional burden to the healthcare system and infant families. The objective of this project was, therefore, to design and develop a cost-effective and efficient total body cooling and rewarming device. Our design includes two water reservoirs that operate by pumping cold and warm sterile water to a mattress. After decreasing the infant's core body temperature to 33.5 °C, the system is designed to maintain it for 72 h. Feedback for temperature regulation is provided by the rectal and mattress temperature sensors. Once the cooling therapy is completed, the system again rewarms the water inside the mattress and gradually increases the neonate temperature to 36.5-37 °C. The water temperature sensors' effectiveness was evaluated by adding 1000 ml of water to the reservoir and cooling and warming to the required level of temperature using Peltier. Then a digital thermometer was used as a gold standard to compare with the sensor's readings. This was performed for five iterations. The prototype was built and gone through different tests and iterations. The proposed device was tested for accuracy, cost-effectiveness and easy to use. Ninety-three point two percent accuracy has been achieved for temperature sensor measurement, and the prototype was built only with a component cost of less than 200 USD. This is excluding design, manufacturing, and other costs. A device that can monitor and regulate the neonate core body temperature at the neuroprotective range is designed and developed. This is achieved by continuous monitoring and regulation of the water reservoirs, mattress, and rectal temperatures. The device also allows continuous monitoring of the infant's body temperature, mattress temperature, reservoir temperature, and pulse rate. The proposed device has the potential to play a significant role in reducing neonatal brain injury and death due to HIE, especially in low resource settings, where the expertise and the means are scarce.


Alatae production and population increase of aphid vectors on virus-infected host plants.
Zucchini yellow mosaic virus (ZYMV) and Aphis gossypii Glover are two components of a recently identified plant-parasite system that provides an excellent opportunity to study interrelations between a virus and a vector that share the same host, but have no direct physiological interaction. In a field experiment we documented numbers of alate and apterous A. gossypii on healthy Cucurbita pepo and on plants inoculated with virus 0, 7, 14, and 21 days before aphid infestation. When plants were inoculated and infested simultaneously, more than twice as many alatae were produced after 20 days of colony growth than on any other treatment. This indicates that properties unique to the early stages of viral infection somehow stimulated wing formation. Because it is spread by the activities of alatae, virus dispersal would be greater as a result of these properties. Developmental rate, total numbers of aphids, and numbers of alatae and apterae decreased as the time between virus inoculation and aphid colonization increased.


Hydantoinases and related enzymes as biocatalysts for the synthesis of unnatural chiral amino acids.
A cascade of hydantoinase, N-carbamoylase and hydantoinracemase can be used for the production of natural and unnatural chiral D- and L-amino acids from chemically synthesized hydantoin derivatives. Potentially, 100% conversion and 100% optically pure amino acids can be obtained at the same time if racemic substrates are used. Recent research activities concentrate on newly isolated or improved enzymes and include directed evolution techniques, structure elucidation, studies of fusion proteins and the use of specially designed whole cell biocatalysts.


Cadmium, zinc, copper, sodium and potassium concentrations in rooster and turkey semen and their correlation.
The purpose of this study was to assess concentration of selected elements (cadmium, zinc, copper, sodium and potassium) in rooster and turkey semen and to find possible correlations between these elements. Samples were analyzed on the atomic absorption spectrophotometer. The analysis of cadmium showed that the concentration in rooster is 9.06 +/- 7.70 and in turkey 4.10 +/- 3.59 microg/mL. In zinc 5.25 +/- 1.96 microg/mL in rooster and 3.70 +/- 1.26 microg/mL in turkey were detected. Higher concentration of copper was found in rooster semen (6.79 +/- 6.42 microg/mL) in comparison with turkey semen (4.29 +/- 5.43 microg/mL). The level of sodium (3.96 +/- 1.02 microg/mL; 3.14 +/- 0.85 microg/mL) and potassium (2.88 +/- 0.65 microg/mL; 3.42 +/- 1.41 microg/mL) was very similar in both species. Correlation analysis detected high positive correlation between cadmium and zinc (r = 0.701) in rooster and between sodium and potassium (r = 0.899) in turkey semen.


Too close for comfort: screening strategy to detect methicillin-resistant Staphylococcus aureus conversion in exposed roommates.
All 899 roommates exposed to methicillin-resistant Staphylococcus aureus (MRSA) index cases were studied over 57 months. MRSA detection is better at approximately 3 days (50%-55%) or 7 days (56%) after contact has been broken than day 0 (30%). Polymerase chain reaction testing at day 3 performs similarly to culture at day 7. Nasal/rectal screening provides superior detection than nasal alone. Those exposed >48 hours are at significantly greater risk of colonization.


Device-Algorithm Co-Optimization for an On-Chip Trainable Capacitor-Based Synaptic Device with IGZO TFT and Retention-Centric Tiki-Taka Algorithm.
Analog in-memory computing synaptic devices are widely studied for efficient implementation of deep learning. However, synaptic devices based on resistive memory have difficulties implementing on-chip training due to the lack of means to control the amount of resistance change and large device variations. To overcome these shortcomings, silicon complementary metal-oxide semiconductor (Si-CMOS) and capacitor-based charge storage synapses are proposed, but it is difficult to obtain sufficient retention time due to Si-CMOS leakage currents, resulting in a deterioration of training accuracy. Here, a novel 6T1C synaptic device using only n-type indium gaIlium zinc oxide thin film transistor (IGZO TFT) with low leakage current and a capacitor is proposed, allowing not only linear and symmetric weight update but also sufficient retention time and parallel on-chip training operations. In addition, an efficient and realistic training algorithm to compensate for any remaining device non-idealities such as drifting references and long-term retention loss is proposed, demonstrating the importance of device-algorithm co-optimization.


Increased air temperature decreases high-speed, but not total distance, in international field hockey.
This study investigated the effect of heat stress on locomotor activity within international field hockey at team, positional and playing-quarter levels. Analysis was conducted on 71 matches played by the Malaysia national men's team against 24 opponents. Fixtures were assigned to match conditions, based on air temperature [COOL (14 ± 3°C), WARM (24 ± 1°C), HOT (27 ± 1°C), or VHOT (32 ± 2°C), p < 0.001]. Relationships between locomotor metrics and air temperature (AIR), absolute and relative humidity, and wet bulb globe temperature (WBGT) were investigated further using correlation and regression analyses. Increased AIR and WBGT revealed similar correlations (p < 0.01) with intensity metrics; high-speed running (AIR r = -0.51, WBGT r = -0.45), average speed (AIR r = -0.48, WBGT r = -0.46), decelerations (AIR r = -0.41, WBGT r = -0.41), sprinting efforts (AIR r = -0.40, WBGT r = -0.36), and sprinting distance (AIR r = -0.37, WBGT r = -0.29). In comparison to COOL, HOT, and VHOT matches demonstrated reduced high-speed running intensity (-14-17%; p < 0.001), average speed (-5-6%; p < 0.001), sprinting efforts (-17%; p = 0.010) and decelerations per min (-12%; p = 0.008). Interactions were found between match conditions and playing quarter for average speed (+4-7%; p = 0.002) and sprinting distance (+16-36%; p < 0.001), both of which were higher in the fourth quarter in COOL versus WARM, HOT and VHOT. There was an interaction for "low-speed" (p < 0.001), but not for "high-speed" running (p = 0.076) demonstrating the modulating effect of air temperature (particularly >25°C) on pacing within international hockey. These are the first data demonstrating the effect of air temperature on locomotor activity within international men's hockey, notably that increased air temperature impairs high-intensity activities by 5-15%. Higher air temperatures compromise high-speed running distances between matches in hockey.


Immune suppressive mechanisms in the tumor microenvironment.
Effective immunotherapy, whether by checkpoint blockade or adoptive cell therapy, is limited in most patients by a key barrier: the immunosuppressive tumor microenvironment. Suppression of tumor-specific T cells is orchestrated by the activity of a variety of stromal myeloid and lymphoid cells. These often display inducible suppressive mechanisms that are triggered by the same anti-tumor inflammatory response that the immunotherapy intends to create. Therefore, a more comprehensive understanding of how the immunosuppressive milieu develops and persists is critical in order to harness the full power of immunotherapy of cancer.


Impact of comorbidities and surgery on health related transitions in pancreatic cancer admissions: a multi state model.
Pancreatic cancer is one of the least common tumors, nevertheless it is one of the most lethal. This lethality is mainly due to the fact that the vast majority of patients are diagnosed in an advanced stage. The objective of this work is investigate how different covariates affect the transition to death after a first admission due to pancreatic cancer. We analyze the impact of different factors on health related transitions after a first hospital admission related to pancreatic cancer based on a multi state model. Transitions of interest include the transition to death (i.e. survival time), but also the time between a first admission and discharge or between discharge and readmission. We consider comorbidities, the type of admission, and especially the performance of pancreas surgery as covariates with a potential effect on the transition intensities. The multi state model allows for a very detailed analysis since all covariate effects may change depending on the current state of the patient.


Control of the cultivation process of antithrombin III and its characterization by capillary electrophoresis.
The production by baby hamster kidney cells of recombinant antithrombin III (r-AT III), the main inhibitor of thrombin, factor Xa and other proteases of the clotting cascade, was monitored by capillary isotachophoresis using mixtures of continuous spacers. The results were compared with those obtained by capillary zone electrophoresis (CZE). The downstream process, which incorporated anion-exchange and heparin affinity chromatography, was monitored by CZE under acidic conditions and voltage ramping. The purified product was characterized by its isoelectric point and molecular mass. Isoelectric points of the three major and three minor isoforms of AT III were evaluated by capillary isoelectric focusing using a pH range of 4-6 and various mobilization procedures. The molecular mass of AT III was investigated by capillary gel electrophoresis (CGE), applying removable dextran gels. Both parameters could be determined within 30 min using only one coated capillary. The results showed an excellent correspondence with those achieved with conventional slab gels. The affinity complex between AT III and thrombin could also be detected by CGE and the heparin dependence of the affinity reaction could be investigated.