Effect of β-Mannanase Supplementation on Growth Performance, Ileal Digestibility, Carcass Traits, Intestinal Morphology, and Meat Quality in Broilers Fed Low-ME Diets.
Experiment was designed to analyze the effect of low caloric diets, supplemented with β-mannanase on growth performance, carcass characteristics, nutrient digestibility, and other parameters in broilers. In this study, 400 broiler chicks were randomly divided into four treatments (Cont: without β-mannanase; LM-30, MM-60, and HM-90: supplemented with 200, 400, and 600 mg/kg β-mannanase, respectively). Dietary metabolizable energy (ME) in Cont was standard (starter diet 3100 kcal/kg; finisher diet 3200 kcal/kg) and reduced by 30, 60, and 90 kcal/kg, correspondingly in β-mannanase-supplemented treatments. The results exhibited that growth performance was not affected by reducing dietary energy levels with supplementation of β-mannanase. Ileal digestibility of DM and CF was improved (p < 0.01) by supplementation of β-mannanase at low dietary ME levels. Concerning carcass traits, the relative weight of breast meat, drumstick, and abdominal fat increased (p < 0.05) with β-mannanase supplementation in low-ME diets. Treatment HM-90 showed significantly (p < 0.05) better results regarding villus height and VH:CD. It could be concluded from the present results that supplementation of β-mannanase could improve the nutrient digestibility so that it is possible to reduce the dietary energy level without compromising production performance, carcass trails, and meat quality in broilers.


Uterine tube-ovary relationship and fimbrial development during the fetal period.
We aimed to evaluate the position, localization and development of the uterine tubes and their relationships to the ovaries. One hundred and fifty-four uterine tubes and ovaries taken from 77 human fetuses aged between 9-40 weeks of gestation have been included in this study. The study was performed in Department of Anatomy of Suleyman Demirel University Faculty of Medicine, Isparta, Turkey in 2004. The position and localization of the uterine tubes have been determined. Consequently, uterine tube - ovary relationship and fimbrial development has been investigated. It has been observed that the uterine tubes are transversely and obliquely positioned. The most commonly observed position was transverse position. When the relationship between the uterine tubes and ovaries was explored, it was observed that the ovaries were localized in the superior, anterior or posterior aspect of the uterine tubes. In addition, when relationship between the obliquely positioned uterine tubes and ovaries was assessed, we found that the ovaries are located at the middle, anterior, lateral or posterior of uterine tubes. Furthermore, it indicates that the fimbrial development begins only after the 20th week and the quantity of fimbriae increased by gestational age. We conclude that the uterine tubes are not positioned as in adults during the fetal period, some variants can be seen in the uterine tube - ovary relationship and fimbrial development begins after the 20th week of gestational age and continued after birth.


Mutated genes, pathways and processes in tumours.
Integration of the many available sources of cancer gene information--such as large-scale tumour-resequencing studies--identifies the 'usual suspect' genes, mutated in many tumour types, as well as different sets of mutated genes according to the specific tumour type. Scaling-up the analysis reveals that this large collection of mutated genes cluster into a smaller number of signalling pathways and processes. From this, we draw a map of the altered processes, and their combinations, in more than 10 tumours types. Literature searches identify pathways and processes that are covered sparsely in the literature, and invite the proposal of new hypotheses to investigate cancer initiation and progression.


Assessing Frailty in Chinese Nursing Home Older Adults: A Comparison between the Frail-NH Scale and Frailty Index.
(1) To establish appropriate FRAIL-NH cutoff points in nursing homes in Mainland China; (2) To compare the FRAIL-NH scale and Frailty Index in assessing frailty prevalence and associated factors in nursing homes. A cross-sectional study. Six nursing homes in Changsha, China. A total of 302 residents aged 60 years or older (mean aged 82.71±8.49, 71.2% female). Frailty was assessed using the 34-item Frailty Index and the FRAIL-NH scale. The appropriate FRAIL-NH cutoff points to classify frail status and frailest status were 1.5 (87.6% sensitivity, 63.3% specificity) and 7.5 (94.1% sensitivity, 73.4% specificity), respectively. Based on the FRAIL-NH and Frailty Index, 69.5% (48% for frail and 21.5% for frailest), and 66.5% (60.9% for frail and 5.6% for frailest) of residents were at risk of frailty, respectively. There was no statistically significant difference in the total frailty prevalence assessed by FRAIL-NH and Frailty Index (χ2=0.617, P=0.432). The FRAIL-NH Scale is significantly associated with the Frailty Index (correlation coefficient (r) = 0.74, P < 0.001), but there was a Kappa agreement of 0.39 for frailty classification between the FRAIL-NH and Frailty Index, with the Frailty Index classifying a larger number of individuals as frail. When using FRAIL-NH scale, disease and self-reported health status were associated with frail and frailest status while age was just associated with frailest status. regarding the Frailty Index, age, diseases, medications and self-reported health status were associated with frail and frailest status. The FRAIL-NH is a simple and effective tool to assess the overall frailty rate in nursing homes, and the Frailty Index may be more suitable capturing the multidimensionality of frailty at an individual level. Careful consideration in the selection of a frailty instrument, based on the intended purpose, is necessary.


Expectation and the placebo effect in inflammatory skin reactions: a randomised-controlled trial.
This study investigated the placebo effect on experimentally induced skin reactions via the manipulation of expectation. Fifty-eight healthy volunteers were randomised into either expectancy or control groups. All participants received a baseline administration of histamine on one arm (Time 1), then a second administration on the other arm, approximately 30 minutes later (Time 2). Prior to the second administration, the expectancy group was told that an antihistamine cream (the placebo) had been applied that would reduce their skin reaction to the histamine. Expected wheal area, actual wheal area, heart rate, and heart rate variability were measured at each time point. There was a positive relationship between expected and actual wheal area at Time 1. While the expectancy group expected a smaller skin reaction on the second arm they did not experience a greater reduction in wheal area, compared to control. The expectancy group had a greater reduction in heart rate during the second skin reaction, after the manipulation of expectation (p<.05). While wheal area was not modulated, it may be worth further investigating this possibility, with modifications to the protocol. The reduction of heart rate appears to be an expectation effect and future research could elucidate mechanisms involved. There is an indication that expectations and inflammatory skin reactions are associated. Further study might aim to clarify the direction and nature of this relationship.


A whole-genome massively parallel sequencing analysis of BRCA1 mutant oestrogen receptor-negative and -positive breast cancers.
BRCA1 encodes a tumour suppressor protein that plays pivotal roles in homologous recombination (HR) DNA repair, cell-cycle checkpoints, and transcriptional regulation. BRCA1 germline mutations confer a high risk of early-onset breast and ovarian cancer. In more than 80% of cases, tumours arising in BRCA1 germline mutation carriers are oestrogen receptor (ER)-negative; however, up to 15% are ER-positive. It has been suggested that BRCA1 ER-positive breast cancers constitute sporadic cancers arising in the context of a BRCA1 germline mutation rather than being causally related to BRCA1 loss-of-function. Whole-genome massively parallel sequencing of ER-positive and ER-negative BRCA1 breast cancers, and their respective germline DNAs, was used to characterize the genetic landscape of BRCA1 cancers at base-pair resolution. Only BRCA1 germline mutations, somatic loss of the wild-type allele, and TP53 somatic mutations were recurrently found in the index cases. BRCA1 breast cancers displayed a mutational signature consistent with that caused by lack of HR DNA repair in both ER-positive and ER-negative cases. Sequencing analysis of independent cohorts of hereditary BRCA1 and sporadic non-BRCA1 breast cancers for the presence of recurrent pathogenic mutations and/or homozygous deletions found in the index cases revealed that DAPK3, TMEM135, KIAA1797, PDE4D, and GATA4 are potential additional drivers of breast cancers. This study demonstrates that BRCA1 pathogenic germline mutations coupled with somatic loss of the wild-type allele are not sufficient for hereditary breast cancers to display an ER-negative phenotype, and has led to the identification of three potential novel breast cancer genes (ie DAPK3, TMEM135, and GATA4).


Oriented nucleation in formamidinium perovskite for photovoltaics.
The black phase of formamidinium lead iodide (FAPbI3) perovskite shows huge promise as an efficient photovoltaic, but it is not favoured energetically at room temperature, meaning that the undesirable yellow phases are always present alongside it during crystallization1-4. This problem has made it difficult to formulate the fast crystallization process of perovskite and develop guidelines governing the formation of black-phase FAPbI3 (refs. 5,6). Here we use in situ monitoring of the perovskite crystallization process to report an oriented nucleation mechanism that can help to avoid the presence of undesirable phases and improve the performance of photovoltaic devices in different film-processing scenarios. The resulting device has a demonstrated power-conversion efficiency of 25.4% (certified 25.0%) and the module, which has an area of 27.83 cm2, has achieved an impressive certified aperture efficiency of 21.4%.


Cytoplasmic alkalinization induced by insulin through an activation of Na(+)-H+ antiporter inhibits tyrosine hydroxylase activity in striatal synaptosomes.
Insulin dose-dependently inhibited tyrosine hydroxylase (TH) activity and increased intrasynaposomal pH (pHi) in rat striatal nerve endings. Both these effects of insulin on TH and pHi were prevented by the 5-(N-methyl-N-(guanidinocarbonylmethyl) amiloride (MGCMA), a putative selective inhibitor of the Na(+)-H+ antiporter. Interestingly when, by changing the extracellular pH (pHo), the pHi was increased, from 7.1 up to 7.5, an equivalent inhibition of TH activity occurred. The inhibitory action exerted from insulin on TH activity disappeared when the hormone was added to synaptosomes whose pHi was lowered to 6.83. Collectively, the results of the present study showed that insulin inhibited TH activity in striatal synaptosomes. This effect seems to involve the activation of the Na(+)-H+ antiporter. This exchange system once activated, may induce an intrasynaptosomal alkalinization, a condition in which TH activity is inhibited.


Quantitation of oil red O staining of the aorta in hypercholesterolemic rats.
A technique is described which provides morphologic and quantitative data on the amount of oil red O (ORO) staining in thoracic aortas of rats fed a high cholesterol diet. Samples are stained with ORO, the dye is extracted, and the concentration of ORO in the extract is measured colorimetrically. Wistar rats fed ad libitum either standard chow (control group: n = 15) or chow supplemented with 4% cholesterol, 1% cholic acid, and 0.5% thiouracil (CCT group: n = 23) were maintained on these diets for 1, 3, 6, 9, or 12 months. Plasma cholesterol levels averaged overall 87 and 737 mg/dl for the control and CCT groups, respectively. Animals were killed under anesthesia by perfusion fixation with formalin or glutaraldehyde, and samples of thoracic aorta were stained with ORO. After microscopic study en face and measurement of surface area, the ORO was extracted in chloroform-methanol (2:1). Concentrations of ORO (microM) were determined from a standard curve and expressed as microM/mm2 of aorta. Aortas of CCT animals showed progressive diet- and time-dependent increases in the amount of ORO staining compared to controls. We conclude that this method yields reliable quantitative data applicable to studying atherosclerosis in small animals.


PSTPIP1-associated myeloid-related proteinemia inflammatory syndrome: A rare cause of childhood neutropenia associated with systemic inflammation and hyperzincemia.
Neutropenia in pediatric patients can be due to a variety of disorders. We describe two patients who underwent extensive evaluation over many years for arthralgias and moderate neutropenia of unclear etiology. Genetic testing identified a pathogenic variant in PSTPIP1 (proline-serine-threonine phosphatase-interacting protein 1) in both patients. Markedly elevated inflammatory markers and zinc levels confirmed the rare diagnosis of PSTPIP1-associated myeloid-related proteinemia inflammatory (PAMI) syndrome, tailoring treatment. Neutropenia is common in patients with PAMI syndrome. Unique mutations seen in PAMI syndrome may account for the specific phenotypic features of this disorder.


Utilization of liposomes for correction of the metabolic and bactericidal deficiencies in chronic granulomatous disease.
IgG-coated liposomes containing glucose oxidase (GO) in order to provide a means of generating H2O2 were prepared. Leukocytes from patients with chronic granulomatous disease (CGD) which are lacking a means of generating H2O2, ingested the IgG-coated liposomes and metabolic oxidative deficiencies of glucose-1-14C oxidation and iodination were normalized. Both of these activities have been shown to depend upon the availability of H2O2 within polymorphonuclear leukocytes. Improvement in the capacity to kill Staphylococcus aureus by chronic granulomatous disease leukocytes were observed under similar conditions. Thus, it is possible to restore the oxidative metabolic capacities to CGD leukocytes by the introduction of glucose oxidase containing liposomes to these cells.


The first nationwide website survey of the availability and costs of medical and non-medical oocyte cryopreservation in Japan.
How does the cost-related oocyte cryopreservation (OoC) vary by the facility in Japan, and what data is provided on the websites about OoC procedures? Website survey. The websites of all 621 facilities that provide assistive reproductive technology registered in Japan were surveyed in 2021. Data included the rates of explicit statements regarding the provision of OoC for only medical reasons (medical only group) or non-medical reasons (non-medical group). Based on whether or not facilities that perform OoC clearly stated the cost on their websites, we compared the costs of OoC and annual storage cost between medical only and non-medical groups. Furthermore, we examined the stated number of OoC procedures performed and their clinical outcomes. Of the 621 facilities, 146 (23.5%) clearly stated that they offer OoC on their websites. Of the 88 medical only groups and 58 non-medical groups, 24 (27.3%) and 42 (72.4%) clearly stated the OoC cost, and 27 (30.7%) and 44 (75.9%) clearly states the annual oocyte storage cost, respectively. The OoC costs were significantly higher for the non-medical group than in the medical group. In the medical only group, the annual storage cost remained almost the same regardless of the number of oocytes, while in the non-medical group, the annual storage cost was 2-3 times higher than in the medical only group. Only 16 facilities (16/146, 11.0%) had mentioned the number of OoC procedures, and five facilities (3.4%) provided information on the clinical outcomes after OoC. Costs related to OoC are higher for the non-medical group in Japan. In addition, the websites contain scant information on the costs and clinical outcomes of OoC.


Efficacy and Safety of Sublingual Cyclobenzaprine for the Treatment of Fibromyalgia: Results From a Randomized, Double-Blind, Placebo-Controlled Trial.
To evaluate the efficacy and safety of TNX-102 SL, a once-nightly sublingual formulation of cyclobenzaprine, in reducing pain in patients with fibromyalgia (FM). RELIEF was a double-blind, randomized, placebo-controlled trial. Overall, 503 patients received TNX-102 SL 2.8 mg for 2 weeks, followed by 5.6 mg for 12 weeks (248 patients), or matching placebo (255 patients). The primary end point was change from baseline at week 14 in the weekly average of daily pain scores. Secondary end points included Patient Global Impression of Change (PGIC) scores, Fibromyalgia Impact Questionnaire Revised (FIQR) scores, Patient-Reported Outcomes Measurement Information System (PROMIS) Sleep Disturbance and Fatigue scores, and daily sleep quality. Safety was assessed by adverse event (AE) reporting. Reduction in daily pain from baseline at week 14 was significantly greater with TNX-102 SL (least squares [LS] mean change -1.9 [95% confidence interval (95% CI) -2.1, -1.7]) versus placebo (LS mean change -1.5 [95% CI -1.7, -1.3]; P = 0.01). TNX-102 SL was not associated with significant improvement in PGIC at week 14 but was associated with improvements in FIQR scores, PROMIS scores, and daily sleep quality. Overall, 59.7% of patients receiving TNX-102 SL and 46.3% receiving placebo reported treatment-emergent AEs; the most common were oral hypoesthesia (17.3% with TNX-102 SL versus 0.4% with placebo), oral paresthesia (5.6% versus 0.4%, respectively), and product taste abnormal (4.4% versus 0.4%, respectively). In this phase III, randomized, controlled trial of patients with FM, treatment with TNX-102 SL was associated with significant reductions in daily pain and was safe and well tolerated.


5-Chloro-1H-indole-3-carb-oxy-lic acid.
In the title compound, C(9)H(6)ClNO(2), the carboxyl group is twisted from the indole ring system by 9.00 (8)°. In the crystal, inversion dimers linked by pairs of O-H⋯O hydrogen bonds generate R(2) (2)(8) loops and N-H⋯O hydrogen bonds link the dimers into (001) sheets. Aromatic π-π stacking inter-actions [centroid-centroid distance = 3.7185 (12) A °] are also observed.


The MUC5B Promoter Polymorphism is Not Associated With Non-ILD Chronic Respiratory Diseases or Post-transplant Outcome.
The MUC5B promoter polymorphism (rs35705950) has been associated with interstitial lung disease (ILD) and with prolonged pre-transplant survival in idiopathic pulmonary fibrosis (IPF), but no information is available regarding its prevalence in other respiratory diseases and its influence on post-transplant outcome. We included the Leuven lung transplantation cohort between 1991 and 2015 (n = 801). We assessed the minor allele frequency (MAF) of the MUC5B variant in the entire study cohort and investigated the influence of recipient MUC5B promoter polymorphism on post-transplant outcome in patients who were transplanted after 2004. MUC5B was successfully genotyped in 746 patients. The MAF was significantly higher in ILD (17.6%) compared to chronic obstructive pulmonary disease (COPD)/emphysema (9.3%), cystic fibrosis (CF)/bronchiectasis (BRECT) (7.5%) and pulmonary hypertension (PHT) (7.4%) (p < 0.001). No association was observed between rs35705950 and chronic lung allograft dysfunction (CLAD)/graft loss in the ILD population [CLAD: HR 1.37 95% CI (0.70-2.68); graft loss: HR 1.02 95% CI (0.55-1.89)], nor the entire study cohort [CLAD: HR 0.96 95% CI (0.69-1.34); graft loss: HR 0.97 95% CI (0.70-1.35)]. The MUC5B promoter polymorphism is a very specific predictive factor for the presence of pulmonary fibrosis as it is only associated with pulmonary fibrosis and not with other chronic respiratory diseases. While the MUC5B promoter variant is associated with better pre-transplant survival among IPF patients, recipient MUC5B promoter variant does not play a role in post-transplant outcome.


Loop Diuretic Prescription and Long-Term Outcomes in Heart Failure: Association Modification by Congestion.
The effect of loop diuretics on clinical outcomes in heart failure has not been evaluated in randomized controlled trials. In hospitalized patients with heart failure, a discharge loop diuretic prescription has been shown to be associated with improved 30-day outcomes, which appears to be more pronounced in subgroups with congestion. In the current study, we examined these associations and association modifications during longer follow-up. We assembled a propensity score-matched cohort of 2191 pairs of hospitalized heart failure patients discharged with, vs without, a prescription for loop diuretics, balanced on 74 baseline characteristics (mean age 78 years; 54% women; 11% African American). Hazard ratio (HR) and 95% confidence interval (CI) for 6-year combined endpoint of heart failure readmission or all-cause mortality was 1.02 (0.96-1.09). HRs and 95% CIs for this combined endpoint in patients with no, mild-to-moderate, and severe pulmonary rales were 1.19 (1.07-1.33), 0.95 (0.86-1.04), and 0.77 (0.63-0.94), respectively (P for interaction, < .001). Respective HRs (95% CIs) for no, mild-to-moderate, and severe lower extremity edema were 1.16 (1.06-1.28), 0.94 (0.85-1.04), and 0.71 (0.56-0.89; interaction P < .001). The association between a discharge loop diuretic prescription and long-term clinical outcomes in hospitalized patients with heart failure is modified by admission congestion with worse, neutral, and better outcomes in patients with no, mild-to-moderate, and severe congestion, respectively. If these findings can be replicated, congestion may be used to risk-stratify patients with heart failure for potential optimization of loop diuretic prescription and outcomes.


Supercoiling as a Physical Process Providing Formation of Macroscopic Anisometric Supramolecular Structures.
Solutions of chiral and achiral trifluoroacetyl amino alcohols (TFAAA) contain anisometric structures with a diameter <1 nm and length ~7 nm. In homochiral solutions and xerogels, chiral TFAAA form strings with a diameter of ~30-100 nm and length more than ~1 μ, and achiral TFAAA condensate into isometric granule with diameter of ~1 μ. We conclude that molecular chirality determines helicity of strings within tens of nanometers or more. Stabilization of supramolecular structure of strings is presumably achieved via their supercoiling.


A Systems-Based Morbidity and Mortality Conference Was Associated With a Transient Reduction in ECG Completion Times.
During its monthly morbidity and mortality conference (MMC), the University of Colorado Division of Cardiology reviewed a "near-miss" patient safety event involving the delayed completion of a Stat-priority (ie, statim, meaning high priority) electrocardiogram (ECG). Because critical and interprofessional stakeholders participated in the conference, we hypothesized that the MMC would be associated with reduced ECG completion times. Data were collected for in-hospital ECGs performed at the University of Colorado Hospital between January 1, 2017, and June 30, 2018. An interrupted time series analysis was used to estimate the immediate and ongoing impact of the MMC (held on February 28, 2018) on ECG completion times, stratified by order priority (Stat, Now, or Routine). The percentage of delayed Stat-priority ECGs was analyzed as a secondary outcome. Before the MMC, ECG completion times were stable for all order priorities ( P > .2), but the proportion of delayed Stat-priority ECGs increased from 5% in January 2017 to 20% in February 2018 ( P < .01). The MMC was associated with an immediate reduction in average daily ECG completion times for Routine (-18.4 minutes, P = .03) and Now (-8 minutes, P = .024) priority ECGs. No reduction was seen for Stat ECGs ( P = .97), though the percentage of delayed Stat ECGs stopped increasing ( P = .63). In the post-MMC period, completion times for Routine-priority ECGs increased and approached pre-MMC levels. The MMC was associated with an immediate, but temporary, improvement in ECG completion times. Although the observed clinical benefit of the MMC is novel, these data support the need for more durable reforms to sustain initial improvements.


Automated imaging and quantitation of tumor cells and CFU-GM colonies in microcapillary cultures: toward therapeutic index-based drug screening.
Human colony forming units (CFUs) from both malignant and hematopoietic tissues can be assayed in vitro in microcapillary cultures, an alternative cloning system to the Petri dish methodology. For technical reasons, microcapillary culture may be ideally suited for new drug screening by therapeutic index. To achieve the high output required by screening programs, automated quantitation of CFUs is required. Toward this end, this paper reports the development of a prototype CapScan, an image analysis system that uses a novel axial laser illumination system to detect tumor cell colonies and, with technical modifications, CFU-granulocyte-macrophage (CFU-GM) colonies in microcapillary cultures. As currently configured, the CapScan can quantify colonies grown in a rack of 18 microcapillary cultures in 30 minutes or less. The sensitivity and detection specificity of tumor cell colonies is >90% with a coefficient of variance of 5-40%, dependent upon colony number. Over a range of colony numbers, CapScan and manual colony counts showed a linear correlation > -0.9, and yielded identical results in assays of doxorubicin inhibition of clonogenic P388 cells. As an additional advantage, the growth kinetics of individual colonies can also be monitored with the CapScan, making distinctions between cytotoxic and cytostatic drugs possible; colonies of freshly isolated human tumor cells can also be quantified. Thus, a microcapillary-based human tumor cloning assay that tests for resistance and/or sensitivity to chemotherapeutic agents may be useful in drug development programs and may also facilitate the development of chemotherapy for individual patient tumors, especially when tumor availability is limited.


Arterio-ureteric fistula following iliac angioplasty.
Arterio-ureteric fistulae are rare but can be associated with significant morbidity and mortality. We describe a novel case in which an arterio-ureteric fistula occurred as a complication following external iliac artery angioplasty and stenting, in a patient who had undergone previous pelvic surgery, radiotherapy, ureteric stenting, and urinary diversion surgery. Prompt recognition enabled successful endovascular management using a covered stent.


Correction to: Dual contributions of noradrenaline to behavioural flexibility and motivation.
The article Dual contributions of noradrenaline to behavioural flexibility and motivation written by Caroline I. Jahn, Sophie Gilardeau, Chiara Varazzani, Bastien Blain, Jerome Sallet, Mark E. Walton, Sebastien Bouret was originally published electronically on the publisher's internet portal.


Ionic mechanisms involved in the strontium-induced spike and plateau in the smooth muscle of rat portal vein.
The action of Sr on the smooth muscle of rat portal vein was studied electrophysiologically using micro-electrodes. By replacing Ca with Sr (2.5 mM), the spontaneous membrane activity was altered and spikes were followed by a long lasting plateau potential. The mechanisms which generated the spike and the plateau in the Sr-induced activity were elucidated. As the concentration of Sr was increased, the peak potential and the maximum rates of rise and fall of the initial spike in each discharge increased. The peak potential varied by 15.2 mV with a 10-fold change in [Sr]o. As there was a decrease in the membrane resistance during the plateau, an increase in the permeability of the membrane for Sr, Cl or Na could be responsible for generation of the plateau. The amplitude of the plateau decreased with increase in the concentration of Sr, remained unchanged in a low-Cl solution, but was diminished in a low-Na solution. Mn (1-2 mM) inhibited not only the spike but also the plateau. TEA (20 mM) shifted the plateau potential in a positive direction and the plateau became permanent. When inward currents were applied in the presence of TEA, spikes with large overshoots and small rates of fall were induced. These results indicate that Sr and K conductances of the membrane generate the spike and that slow-inactivating voltage-dependent Na conductance produces the plateau.


Exploring gene-deleted adenoviral vectors for delivery of short hairpin RNAs and reduction of hepatitis B virus infection in mice.
RNA interference based therapeutic approaches hold promise for the treatment of patients chronically infected with hepatitis B virus (HBV). To conquer HBV infection, long-term suppression of target transcripts in all hepatocytes without toxic effects may be required. The present study explored gene-deleted adenoviral vectors (GD-AdV) lacking all viral coding sequences for delivery of the previously described short hairpin RNA (shRNA) HBVU6no.2, which was demonstrated to result in post-transcriptional knock-down of HBV transcripts. We established conditions for shRNA delivery expressed from GD-AdV in vitro and in vivo and observed up to 96% shRNA-mediated knockdown of luciferase expressed in mouse liver. To investigate in vivo efficacy of HBVU6no.2 expressed from a GD-AdV, we explored a transient and a transgenic mouse model for HBV infection. We observed an up to 68% drop in serum HBV surface antigen (HBsAg) levels in the transient and the transgenic mouse model for HBV infection, respectively. Interestingly, we detected an up to 86% drop in HBsAg levels in both animal models after administration of a control GD-AdV encoding beta-galactosidase. In concordance with reduced serum HBsAg levels, we observed reduced HBV replication as demonstrated by Southern blot analysis of HBV genomes. The present study demonstrates that GD-AdV can be used against HBV infection but the design of DNA sequences including shRNAs contained in the vector and virus-host interactions during superinfection needs to be carefully considered.


Temporal patterns of cotton Fusarium and Verticillium wilt in Jiangsu coastal areas of China.
Cotton diseases caused by soil-borne pathogenic fungi present a major constraint to cotton production not only in China but also worldwide. A long-term field inventory was made of the prevalence of Fusarium and Verticillium wilt of cotton in the Jiangsu coastal area of China from 2000 to 2014. Various factors (crop varieties, rotation and weather) were analyzed to explore the dynamics of these diseases in cotton. The results showed that the prevalence of Fusarium and Verticillium wilt increased before 2005 and that Verticillium wilt remained at a high incidence over most of the past 10 years, while Fusarium wilt began to gradually decrease after 2005. The dynamics of Fusarium and Verticillium wilt were closely associated with the introduced cotton varieties and the intensive cropping history. In addition, weather conditions occurring during some of the years appeared to coincide with a substantial variation in the wilt diseases. Our study highlighted epidemiological dynamics of Fusarium and Verticillium wilt in a long-term survey.


Correction: Separating extracellular vesicles and lipoproteins via acoustofluidics.
Correction for 'Separating extracellular vesicles and lipoproteins via acoustofluidics' by Mengxi Wu et al., Lab Chip, 2019, 19, 1174-1182, DOI: .


[The adaptation of four protein determination methods to flow injection analysis (FIA)].
The adaptation of 4 manual methods to the flow-injection analysis is described for the determination of proteins (Biuret- and Exton-method, albumin and hemoglobin determination). The comparison of analytical results of FIA with the manual methods shows a very good agreement of values. Flow-injection-analysis appears not only as an excellent possibility to automate these 4 investigated methods but it also shows unlike the manual methods a considerable better precision and accuracy of the analytical results and a reduction of time and materials.


Effects of soluble dietary fiber on low-density lipoprotein cholesterol and coronary heart disease risk.
Strong epidemiologic and experimental data suggest that increasing dietary fiber may help to lower low-density lipoprotein cholesterol (LDL-C) and decrease the risk of coronary heart disease. Recent studies have highlighted the role of dietary fiber, particularly water-soluble varieties, in decreasing the risk of cardiovascular disease. Several types of soluble fiber, including psyllium, beta-glucan, pectin, and guar gum, have been shown to decrease LDL-C in well-controlled intervention studies, whereas the soluble fiber content of legumes and vegetables has also been shown to decrease LDL-C. Current investigations continue to explore this area in depth and examine potential synergies between dietary fiber and other phytochemicals that may lower cholesterol. These studies, along with recent analyses of ongoing prospective cohort studies, have provided new insights into the probable protective role of dietary fiber in the development of coronary heart disease and other cardiovascular diseases.


Mycobacterium avium infection in freeliving hedgehogs (Erinaceus europaeus L).
Mesenteric lymph nodes were examined from five hedgehogs captured on the Berkshire Downs. The single culture obtained was identified as Mycobacterium avium type 2.


Directing attention to movement effects enhances learning: a review.
Studies investigating the influence of the learner's focus of attention, induced by instructions or feedback, on motor skill learning are reviewed. In general, directing performers' attention to the effects of their movements (external focus of attention) appears to be more beneficial than directing their attention to their own movements (internal focus of attention). Preliminary evidence is presented indicating that an internal attentional focus constrains the motor system by interfering with natural control processes, whereas an external focus seems to allow automatic control processes to regulate the movements. Support for the view that actions are controlled by their anticipated effects comes from research demonstrating functional variability in motor control, as well as the benefits of purposeful activity in occupational therapy. We explain these results in terms of the ideomotor principle of human actions (James, 1890) and its more modern derivatives (Hommel, 1996; Prinz, 1990, 1997).


Incidence and root causes of medication errors by anesthetists: a multicenter web-based survey from 8 teaching hospitals in Ethiopia.
The operating room is a demanding and time-constrained setting, in comparison to primary care settings, where perioperative medication administration is more complicated and there is a high risk that the patient will experience a medication error. Without consulting the pharmacist or seeking assistance from other staff members, anesthesia clinicians prepare, deliver, and monitor strong anesthetic drugs. The purpose of this study was to determine the Incidence and root causes of medication errors by anesthetists in Amhara region, Ethiopia. A multi-center cross sectional web-based survey study was conducted from October 1 to November 30, 2022, across eight referral and teaching hospitals of Amhara region. A self-administered semi structured questionnaire was distributed using survey planet. Data analysis was conducted using SPSS version 20. Descriptive statistics were computed and binary logistic regression was used for data analysis. A p-value < 0.05 was considered statistically significant. The study included 108 anesthetists in total, yielding a response rate of 42.35%. Out of 104 anesthetists, Majority of participants (82.7%) were male. During their clinical practice, more than half (64.4%) of participants experienced atleast one drug administration error. 39 (37.50%) of the respondents revealed that they experienced more medication errors while on night shifts. Anesthetists who did not always double-check their anesthetic drugs before administration had a 3.51 higher risk of developing MAEs compared to those who always double-check anesthetic drugs before administration (AOR = 3.51; 95% CI: 1.34, 9.19). Additionally, participants who administer medications that have been prepared by someone else are about five times more likely to experience MAEs than participants who prepare their own anesthetic medications prior to administration (AOR = 4.95; 95% CI: 1.54, 15.95). The study found a considerable rate of errors in the administration of anaesthetic drugs. The failure to always double-check medications before administration and the use of drugs prepared by another anaesthetist were identified to be underlying root causes for drug administration errors.


Inhibition of GABA-gated chloride channel function by arachidonic acid.
The effects of arachidonic acid and its metabolites on gamma-aminobutyric acid (GABAA) receptor function were determined in rat cerebral cortical synaptoneurosomes. Incubation of synaptoneurosomes with phospholipase A2 decreased muscimol-induced 36Cl- uptake. Arachidonic acid, the major unsaturated fatty acid released by phospholipase A2, also inhibited muscimol-induced 36Cl uptake. Similar inhibition was obtained with other unsaturated fatty acids (docosahexaenoic, oleic) but not with saturated fatty acids (stearic, palmitic). The effect of arachidonic acid on muscimol responses was inhibited by bovine serum albumin (BSA), and BSA enhanced muscimol responses directly, indicating the generation of endogenous arachidonic acid in the synaptoneurosome preparation. The generation of endogenous arachidonic acid was also indicated by the ability of 2 inhibitors of arachidonic acid metabolism, indomethacin and nordihydroguaiaretic acid (NDGA), to inhibit muscimol-induced 36Cl uptake. We conclude that arachidonic acid probably has both direct and indirect actions on muscimol responses since both enzyme inhibitors inhibited muscimol responses but did not prevent the effect of exogenously added arachidonic acid. In additional experiments, arachidonic acid metabolites generated by cyclooxygenase, prostaglandins D2, E2 and F2 alpha, each decreased muscimol responses; prostaglandins F2 alpha was the most potent inhibitor. Since the unsaturated fatty acids and their metabolites are most susceptible to peroxidation, a generating system of superoxide radicals was tested on muscimol responses. A combination of xanthine and xanthine oxidase inhibited muscimol-induced 36Cl uptake in a concentration-dependent manner. We propose that the inhibition of GABAA neurotransmission by arachidonic acid and its metabolites can lead to increased neuronal excitability. This mechanism may play an important role in the development of neuronal damage following seizures or cerebral ischemia.


Effect of halothane, enflurane and isoflurane on body temperature during and after surgery.
The superficial and deep body temperatures of 40 healthy females undergoing total abdominal hysterectomy were measured during surgery and for 4 h afterwards. The patients were allocated randomly to one of five groups and anaesthetized to produce an end-tidal concentration of 1% halothane, 1% enflurane, 2% enflurane, 1% isoflurane or 2% isoflurane. The patients received also 70% nitrous oxide in oxygen and neuromuscular blockade. The theatre temperature was maintained at 22.0 degrees C. There were significant body temperature changes during operation in all groups. The mean (SD) decrease in core temperature over 85 min was approximately 1.1 (0.3) degrees C in the 1% halothane, 2% enflurane and 2% isoflurane groups, and 0.6 (0.4) degrees C in the 1% enflurane and 1% isoflurane groups (P less than 0.05). During the recovery period the 1% halothane, 2% enflurane and 2% isoflurane groups took 2 h to rewarm to preoperative temperatures, and the rate of rewarming during this time was similar for all groups.


The challenge of providing holistic care in a viral epidemic: opportunities for palliative care.
To determine, using the perspective of a hospital-based palliative care service (PCS), the spiritual and psychosocial impact of a novel and potentially fatal viral epidemic on patients, their families and health care workers. Qualitative study using semi-structured interviews. The data were analysed using the constant comparative method and were validated using respondent validation. Eight palliative care workers. Tan Tock Seng Hospital (TTSH), the hospital designated to manage all cases of Severe Acute Respiratory Syndrome (SARS) in Singapore. Disease containment resulted in isolation, where isolation meant the disruption of connectedness. This disruption of connectedness took place at multiple levels: in the patient himself, between the patient and the family, within the family, between the patient and the health care worker, between the patient and society, and between health care workers. As the nature of the disease was uncertain, prognostication was inaccurate. This created difficulties in helping patients and their families prepare for death. The fear of facing the unknown led to safety-seeking behaviours, which could be overcome by repeated exposure to the feared situation. The process of bereavement was disturbed, as traditional death rituals could not be performed by the family. Informants perceived themselves to be suffering as they suffered the same anxieties, fears and grief as the patient. Dealing with a novel viral epidemic creates spiritual and psychosocial issues similar to those encountered in a palliative care practice. Palliative care workers would do well to be aware of such issues and act proactively when such epidemics arise.


"What does this mean?" How Web-based consumer health information fails to support information seeking in the pursuit of informed consent for screening test decisions.
The authors analyzed online consumer health information related to screening tests to see how well this information meets known standards for supporting the understanding of test uncertainty. MedlinePlus documents regarding maternal serum screening (6), prostate-specific antigen testing (6), and screening mammography (6) were analyzed. The content of the documents was analyzed. This study showed that most sites conscientiously report that tests are less than 100% accurate, but few provide important details about the level of uncertainty associated with test results. In particular, few resources give information about the predictive value of screening tests and have little mention of the fact that predictive value is influenced by the a priori likelihood of having the condition. These results suggest that online consumer health information does not adequately support decisions about medical screening. We suggest a potential solution to the problem: metadata harvesting coupled with optimized presentation techniques to format personalized information about screening tests. Using these techniques, the empowerment of personal choice in matters of health decisions could become the de facto standard.


Detection of orientationally multimodal textures.
Oriented textures were produced with the use of probability density functions modulated sinusoidally over orientation. Orientational contrast sensitivity functions (OCSFs) for a task involving the discrimination of these patterns from orientationally-random textures were found for several human observers. An inverse Fourier transform of this OCSF yielded a weighting function, or filter, defined over orientation. The weighting function is broad, with a half-height full-width of 34 deg. This orientational filter was able to predict human performance in further discrimination tasks employing a variety of probability density functions over orientation.


Extended HLA-DPB1 polymorphism: an RNA approach for HLA-DPB1 typing.
Most of the 119 human leukocyte antigen (HLA)-DPB1 alleles are defined by polymorphism in six hypervariable regions (HVRs) in exon 2 of the HLA-DPB1 gene. We investigated how DPB1 polymorphism is represented in the entire coding region. An RNA sequencing-based typing (SBT) approach was developed for the identification of HLA-DPB1 polymorphism from the 5' untranslated region (UTR) through the 3'-UTR. B-cell lymphoblastoid cell lines, encoding 16 different DPB1 alleles, were studied. Results show additional HLA-DPB1 polymorphism in exons 1, 3, 4 and 5 and the 5' and 3'-UTR. Four new HLA-DPB1 alleles were identified, DPB1*0502, DPB1*0602, DPB1*0802 and DPB1*0902, which have exon 2 sequences identical to other DPB1 alleles but differ in the extended region. The additional polymorphism represents two main polymorphic lineages in the DPB1 alleles. Among the HVRs in exon 2, only HVR F correlates with these two main lineages.


[Research report of common oral diseases of 800 old people in Jing'an District, Shanghai].
To find out the condition of the oral health of the old people in Jing'an district, Shanghai and explore new measures for their oral health taken by the community. The method employed by us involves visiting 800 old people aged from 60 to 74 to inspect their oral health, using indexes and standards with reference to the standards used at the 2nd national oral epidemiological survey. Of the 800 old people investigated, 80.15% suffered from dental caries, 66.24% from gingivitis, 32.38% from periodontitis, 88.13% from impaired teeth, 16.25% from missing teeth and 54.63% from wedge-shaped damages of teeth. The old people have a rather poor oral-health condition and lack a self oral health awareness. The investigation suggests that in our communal health service, propaganda and education for oral hygiene should be carried out to the old people in a planned and targeted manner, along with preventive and restoration treatments.


[Phylogenetic relationships among holarctic populations of Chironomus entis and Chironomus plumosus in view of possible horizontal transfer of mitochondrial genes].
In eight Holarctic populations of two typical chironomid sibling species of the plumosus group, Chrionomus entis and Chironomus plumosus, nucleotides sequences of mitochondrial (cytb) and nuclear (gb2b) gene regions were examined. The phylogenetic trees reflecting the evolutionary histories of the nuclear and mitochondrial markers exhibited significant differences. On the tree based on the nuclear gene sequences the populations clustered according to their species affiliation, whereas on the tree based on the mitochondrial gene sequences the populations were grouped according to their geographic position. This discrepancy is probably explained by mitochondrial gene flow between sympatric species with incomplete reproductive isolation (sibling species). Based on our results together with the earlier data on nuclear and mitochondrial gene sequences of some other species from the phylogenetic group plumosus, a scheme of phylogenetic relationships within this group is proposed. This scheme is in many ways different from the traditional view on the evolutionary relationships among species of the plumosus group.


The influence of odor type on the discrimination and identification of odorants in multicomponent odor mixtures.
Using a limited set of odorants, previous studies have indicated that the ability of humans to discriminate and identify the components of olfactory mixtures is limited to approximately four. However, the ability to generalize these results may have been limited by specific neural or cognitive interactions among the particular odorants used. In the present experiment, 41 subjects examined the influence of odor type (different individual odorants), from two very different odor sets, on the perception of the components of complex mixtures. One set contained odors that were selected by an expert panel to blend well in mixtures (good blenders), whereas the other contained odors that blended poorly in mixtures (poor blenders). The stimuli were common, dissimilar odorants of equivalent, moderate intensity, each of which was a single chemical. A computer-controlled air dilution olfactometer delivered a single odorant or a mixture containing up to eight odorants. Although the poor blenders were more easily discriminated, this superiority was displayed within a narrow range, and the ability of subjects to identify mixture components with either odor set was limited to approximately four. The results indicate that, whereas odor type can alter which odorants will be perceived in a mixture, the limited capacity to discriminate mixture components is independent of the type of odorants. These findings are discussed in terms of their implications for olfactory coding.


Trochanteric impingement: is it a source of pain after THR?
While uncommon, trochanteric-pelvic impingement may lead to significant lateral hip pain. We defined "impingement distance" as the radiographic distance from the medial aspect of the greater trochanter and the corresponding lateral edge of the acetabular bone or component and compared this to the contralateral normal hip. We present two painful total hip replacement (THR) cases, each featuring a patient with severe lateral hip pain when walking and sitting. Both patients had diminished femoral offset and trochanteric-pelvic clearance, compared to the contralateral normal hip. The impingement distance was increased an average of 10 mm with the exchange to a longer femoral head. Both patients had immediate and complete pain relief with operative treatment to increase the impingement distance.


Diagnosis and management of fetal cardiac anomalies: 10 years of experience at a single institution.
To assess the diagnostic accuracy of fetal echocardiography and the outcome of cardiac malformations diagnosed in utero. A retrospective study. The archives of our ultrasound laboratory were searched for fetal cardiac abnormalities in the period 1991-2001. Diagnosis of a fetal cardiac anomaly was made in 339 pregnancies at a mean gestational age of 26.2 weeks. Pathology or a detailed postnatal follow-up was available in 260 cases, and the prenatal diagnosis was accurate in 236 cases (91%). Discrepancies included nine false positive diagnoses (six ventricular septal defects and three coarctation of the aorta) and 15 cases in which a cardiac anomaly different from the one suspected in utero was documented. Of the 142 fetuses with isolated cardiac malformations (no extracardiac anomalies, normal chromosomes) that were delivered in our center, 114 were alive (80.2%) at a mean follow-up of 38 months (range, 1-120 months). In this group of patients, conotruncal anomalies and univentricular lesions were the most frequent types of anomaly, and had a survival rate of 87% and 57%, respectively. Hypoplastic left heart was the most frequent isolated congenital heart defect in infants that were delivered (19 cases) and it was associated with a survival rate of 37%. In expert hands, fetal echocardiography is highly accurate. The long-term prognosis of cardiac lesions diagnosed in utero is similar to that reported in series of infants diagnosed after birth. The only exception is hypoplastic left heart in which the survival rate is much lower than expected from postnatal studies.


Integrin α11β1 in tumor fibrosis: more than just another cancer-associated fibroblast biomarker?
There is currently an increased interest in understanding the role of the tumor microenvironment (TME) in tumor growth and progression. In this context the role of integrins in cancer-associated fibroblasts (CAFs) will need to be carefully re-evaluated. Fibroblast-derived cells are not only in the focus in tumors, but also in tissue fibrosis as well as in inflammatory conditions. The recent transcriptional profiling of what has been called "the pan-fibroblast cell lineage" in mouse and human tissues has identified novel transcriptional biomarker mRNAs encoding the secreted ECM proteins dermatopontin and collagen XV as well as the phosphatidylinositol-anchored membrane protein Pi16. Some of the genes identified in these fibroblasts scRNA-seq datasets will be useful for rigorous comparative characterizations of fibroblast-derived cell subpopulations. At the same time, it will be a challenge in the coming years to validate these transcriptional mRNA datasets at the protein-(expression) and at tissue-(distribution) levels and to find useful protein biomarker reagents that will facilitate fibroblast profiling at the cell level. In the current review we will focus on the role of the collagen-binding integrin α11β1 in CAFs, summarizing our own work as well as published datasets with information on α11 mRNA expression in selected tumors. Our experimental data suggest that α11β1 is more than just another biomarker and that it as a functional collagen receptor in the TME is playing a central role in regulating collagen assembly and matrix remodeling, which in turn impact tumor growth and metastasis.


Akebia saponin D attenuates ibotenic acid-induced cognitive deficits and pro-apoptotic response in rats: involvement of MAPK signal pathway.
Cholinergic deficit is one of the most remarkable symptoms and plays an important role in Alzheimer's disease. In the present study, the protective effects of Akebia saponin D (ASD) on learning and memory impairments induced by excitatory neurotoxin ibotenic acid injection were examined in vivo. Our findings suggest that ASD (90 mg/kg, p.o.) would exert a rescue effect on rats both in behavioral performances in Morris water maze and Y maze and cholinergic functions detected by chemical methods. We further investigated in the hippocampus and found ASD could regulate apoptosis-related proteins expression following ibotenic acid injection. Additionally, mitogen-activated protein kinase (MAPK) family phosphorylations were inhibited after ASD treatment, implicating that the MAPK signaling pathway could be involved in the mechanism underlying neuroprotection of ASD against ibotenic acid-induced excitotoxicity.


Exploring the limits for the survival of DNA in blood stains.
It is generally recognized that usable DNA may be retained in dry biological stains for years. We have explored the environmental limits for this property. Air-dried blood stains were incubated at different conditions of relative humidity (RH) and temperature. The quality of the extracted DNA was assessed by the ability to amplify 273 bp and 1600 bp DNA fragments by PCR, and by quantitative estimation of a 147 bp DNA fragment using real time PCR. Despite the fact that the availability of water is important for processes that degrade DNA, no significant difference was observed in the stability of DNA at 50%, 80% or 93% RH at room temperature or at 35 °C, and even the 1600 bp fragment was amplifiable after one year. Microbial growth was not observed at these conditions and the number of template molecules did not drop significantly over time. At 100% RH, however, microbial growth was observed after varying amounts of time. This may explain the decreased stability of DNA observed at these conditions. Even so, the 273 bp fragment was amplifiable for at least 3 months, and the 1600 bp fragment for at least two months. Microbial growth was not observed at higher temperatures (45-65 °C) at 100% RH, and the 1600 bp fragment was amplifiable after eight months at 45 °C, but only survived for one month at 55 °C or 65 °C. Thus DNA remains amplifiable in blood stains for many months, even at extreme RH and temperatures up to 45 °C. Even in humid climates the average RH is usually not more than 80% and RH rarely exceeds 93%; therefore we conclude that normal climatic conditions are not critical for the long time survival of DNA in untreated blood stains.


New advances in invasive aspergillosis immunobiology leading the way towards personalized therapeutic approaches.
Invasive aspergillosis (IA) remains a devastating disease in immune compromised patients despite significant advances in our understanding of fungal virulence and host defense mechanisms. In this review, we summarize important research advances in the fight against IA with particular focus on early events in the interactions between Aspergillus fumigatus and the host that occur in the respiratory tract. Advances in understanding mechanisms of immune effector cell recruitment, antifungal effector mechanisms, and how the dynamic host-fungal interaction alters the local microenvironment to effect outcomes are highlighted. These advances illustrate exciting new therapeutic opportunities, but also emphasize the importance of understanding each unique fungus-host interaction for improving patient outcomes.


Microsatellite-centromere mapping in the loach, Misgurnus anguillicaudatus.
Primer sets for 15 polymorphic microsatellite loci were developed in the loach, Misgurnus anguillicaudatus (Cobitidae) by molecular cloning and sequencing techniques. Mendelian inheritance was confirmed for the 15 loci by examining the genotypic segregation produced with the primer sets in two full-sib families. The loci were mapped in relation to their centromere in four gynogenetic diploid lines, which were induced by inhibition of the second meiotic division after fertilization with genetically inert sperm. Microsatellite-centromere recombination rates ranged between 0.06 and 0.95 under the assumption of complete interference. Thus, these loci are distributed from the centromeres to the telomeres of their respective chromosomes. The success of mitotic gynogenesis, produced by suppression of the first cleavage, was verified by homozygosity at three diagnostic microsatellite loci that exhibited high gene-centromere meiotic recombination rates in the same family. The differences in heterozygosity levels observed with these markers were attributed to differences in the temporal application of heat shock following inert sperm activation.


A comparative study on the effect of tumor promoters on poly ADP-ribosylation in A431 cells.
Poly ADP-ribosylation is a post-translational modification of chromatin proteins catalyzed by the enzyme poly-ADPR transferase (poly-ADPRT) and affects the structure as well as the functional properties of chromatin. It is of particular relevance in carcinogenesis, as it represents an epigenetic mechanism for modulation of gene expression. In the present study, A431 cells were exposed to tumor promoters phorbol-12-myristate-13-acetate (PMA), benzoyl peroxide (BP), mezerein and 6-keto-lithocholic acid (KA), and their effect on poly-ADP-ribosylation was studied. All these tumor promoters increased the activity of poly-ADPRT in these cells--PMA 2.3-fold, BP and mezerein 2.2-fold each and KA 1.3-fold. The enzyme inhibitor 3-amino benzamide (3AB) partially prevented the stimulation of poly-ADPRT by these promoters. There was a concomitant decrease in NAD levels, the substrate for poly-ADPRT. The decrease was 44% for PMA, 46% for BP, 21% for KA and 34% for mezerein. The induction of poly-ADP-ribose synthesis by PMA and BP appears to be mediated at least in part by active oxygen species, as they induced an increase in superoxide anions and anti-oxidants prevented the increase of poly-ADPRT activity to varying extents.


[Additive nature of the stimulating effects of alloxan diabetes and fasting on the specific binding of insulin with its receptors in the plasma membranes of adipose and hepatic cells in the rat].
Properties of insulin receptors were studied in rat fatty tissue and in plasmatic membranes of liver cells under conditions of alloxan diabetes (within 3 days) and in fasting (within 2 days) as well as under conditions of simultaneous effect of these factors. In the diabetes amount of receptors in plasmatic membranes of both these tissues, affinity of fatty cell membranes as well as amount of the receptors and their specific affinity in hepatic cell membranes were increased. Specific binding of insulin was distinctly increased under conditions of simultaneous influence of diabetes and fasting due to elevation in content of the receptors in liver cell membranes and in both their content and affinity in fatty cell membranes. The data obtained suggest that alloxan diabetes and fasting caused additive effect on expression of insulin receptors in fatty and hepatic cell plasmatic membranes as well as that the content of receptors on the cell surface was regulated by means of several mechanisms.


Effect of Olibanum Extract/Graphene Oxide on Differentiation of Bone Marrow Mesenchymal Stem Cells into Neuron-Like Cells on Freeze Dried Scaffolds.
One of the challenges in using stem cells to neural repair is to induce their differentiation into neurons and lack of glial formation. Mesenchymal stem cells have revealed great potential for neural reorganization and renewal by taking advantage of differentiation capabilities. Here we explored the potential use of olibanum extract in freeze-dried scaffolds for induction of stem cells differentiation. In this study, gelatin/ collagen/olibanum/ graphene oxide (GEL/COL/OL/GO) freeze-dried scaffolds were synthesized and then adult rat bone marrow mesenchymal stem cells (BMMSCs) were seeded on scaffolds. The viability of cells was evaluated using MTT test on days 1, 3 and 5. The morphology of the cells seeded on scaffolds was studied using SEM and specific protein expression detected by immunohistochemical analysis. Real-time PCR was applied to detect the expression of Chat, Pax6, Hb-9, Nestin, Islet-1, and neurofilament-H (NF-H). The data were analyzed using Tukey test and one-way ANOVA and the means difference was considered significant at P<0.05, P<0.01, and P<0.001. Showed that the pore size is increased in GEL/COL/OL/GO scaffolds compared with GO-free scaffolds and higher attachment and proliferation of BMMSCs on GEL/COL/OL /1.5% GO scaffolds compared to GEL/COL/OL/3% GO scaffolds. The cell viability results after 5 days of incubation showed the significant biocompatibility of GEL/COL/OL /1.5% GO freeze-dried scaffold. The results of immunohistochemical and PCR analysis revealed positive role of GEL/COL/OL/1.5% GO scaffolds in upregulation of neuron-specific markers. These results reveal the great potential of GEL/COL/OL/GO scaffolds for nerve regeneration. Our data suggested that both OL extract and GO can regulate the MSCs differentiation into neurons.


Peripheral intravenous catheter infiltration: anesthesia providers do not adhere to their own ideas of best practice.
To survey anesthesia providers for their opinion on "best practice" in perioperative peripheral intravenous catheter (PIV) management, and to determine if they follow those opinions. Survey instrument. Academic medical center. 266 United States (U.S.) anesthesia provider respondents (attending anesthesiologists, anesthesiology residents, anesthesia assistants, certified registered nurse-anesthetists and student registered nurse-anesthetists). Between May 2009 and October 2010 a national survey was distributed to individuals who provide intraoperative anesthesia care to patients. Results were gathered via the SurveyMonkey database. 266 anesthesia providers from across the U.S. took part in the survey. The majority (70%) had less than 5 years' experience. Nearly 90% of respondents cared for a patient with an intravenous catheter infiltration at some point during their training; 7% of these patients required medical intervention. Intravenous assessment and documentation practices showed great variability. Management and documentation of PIVs was more aggressive and vigilant when respondents were asked about "best practice" than about actual management. There is no commonly accepted standard for management and documentation of PIVs in the operating room. From our survey, what providers think is "best practice" in the management and documentation of PIVs is not what is being done.


Bladder mucosal autograft: An effective method for repair of vesicovaginal fistula.
To investigate the effectiveness of bladder mucosal autograft for the treatment of vesicovaginal fistulae. Between March 2005 and June 2011, 21 patients with a single vesicovaginal fistula above the trigone, not involving the ureters, underwent surgery. Bladder was approached extraperitoneally and opened in the midline. The mucosa around the fistula was incised and inverting sutures were placed over the fistula opening. The mucosal defect was covered by a free mucosal graft from the edge of cystotomy incision. After catheter removal at 2 weeks, 18 patients (85 %) remained dry while one patient experienced urge incontinence, which resolved in a few days and another one still had urine leakage (although less than before the operation) that improved after another 3 weeks of bladder drainage. Only in one patient, the operation failed. Short duration of hospitalization, simplicity of the procedure, avoidance of extensive bladder dissection, and extraperitoneal nature of the operation, along with a high success rate are the advantages of this procedure. This technique could be recommended for single fistulae not involving the ureters and not secondary to malignancies.


CRTH2 is a critical regulator of neutrophil migration and resistance to polymicrobial sepsis.
Although arachidonic acid cascade has been shown to be involved in sepsis, little is known about the role of PGD(2) and its newly found receptor, chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2), on the septic response. Severe sepsis is associated with the failure of neutrophil migration. To investigate whether CRTH2 influences neutrophil recruitment and the lethality during sepsis, sepsis was induced by cecal ligation and puncture (CLP) surgery in mice. CRTH2 knockout (CRTH2(-/-)) mice were highly resistant to CLP-induced sepsis, which was associated with lower bacterial load and lower production of TNF-α, IL-6, and CCL3. IL-10, an anti-inflammatory cytokine, was higher in CRTH2(-/-) mice, blunting CLP-induced lethality in CRTH2(-/-) mice. Neutrophil accumulation in the peritoneum was more pronounced after CLP in CRTH2(-/-) mice, which was associated with higher CXCR2 levels in circulating neutrophils. Furthermore, sepsis caused a decrease in the level of acetylation of histone H3, an activation mark, at the CXCR2 promoter in wild-type neutrophils, suggesting that CXCR2 expression levels are epigenetically regulated. Finally, both pharmacological depletion of neutrophils and inhibition of CXCR2 abrogated the survival benefit in CRTH2(-/-) mice. These results demonstrate that genetic ablation of CRTH2 improved impaired neutrophil migration and survival during severe sepsis, which was mechanistically associated with epigenetic-mediated CXCR2 expression. Thus, CRTH2 is a potential therapeutic target for polymicrobial sepsis.


Design and management of humanitarian supply chains: challenges, solutions, and frameworks.
The design and management of the humanitarian supply chain are the most critical aspects of the humanitarian aid supply chain. Despite enormous interest among the academic community and the practitioners, the design of a humanitarian supply chain is still not well understood. Most of the publications have attempted to address the mechanisms of the humanitarian relief operations. However, the elements of the humanitarian supply chain designs are not well understood in an integrated manner. In this special issue, we have accepted the articles based on six factors that shape the design and management of the humanitarian supply chain and the influencing factors (see Fig. 4). We have noted the research gaps and offered rich directions for future research.


A prothrombinase complex of mouse peritoneal macrophages.
Addition of prothrombin to mouse peritoneal macrophages in vitro resulted in the formation of a thrombin-like enzyme, as demonstrated by use of the luminogenic peptide substrate S-2621. The prothrombinase activity was sedimented by high-speed centrifugation following homogenization of the cells and was abolished by treatment of the cells with the nonionic detergent Triton X-100 at 0.02% concentration. Moreover, the activity was drastically reduced by maintaining cultures in the presence of warfarin and, presumably due to competitive substrate inhibition, by adding S-2222, a chromogenic peptide substrate for Factor Xa. These findings suggest that prothrombin cleavage is catalyzed by Factor Xa at the macrophage surface. The generated thrombin was inhibited by antithrombin, and this reaction was accelerated by heparin with high affinity for antithrombin but not by the corresponding oligosaccharides composed of 8-14 monosaccharide units. Such oligosaccharides which are capable of accelerating the inactivation of Factor Xa by antithrombin, inhibited thrombin formation from prothrombin in the macrophage cultures, presumably by promoting inactivation by antithrombin of Factor Xa in a prothrombinase complex. Activation of the macrophage coagulation system, as proposed to occur in certain inflammatory conditions, thus may be modulated at various levels by heparin, or heparin oligosaccharides, released from mast cells.


Expression of human insulin gene wrapped with chitosan nanoparticles in NIH3T3 cells and diabetic rats.
To study the expression of human insulin gene wrapped with chitosan nanoparticles in NIH3T3 cells and diabetic rats. pCMV.Ins, an expression plasmid of the human insulin gene, was constructed. In total, 100 microg pCMV.Ins wrapped with chitosan nanoparticles (chitosan-pCMV.Ins) was transfected to NIH3T3 cells and diabetes rats through lavage and coloclysis, respectively. The transfected cells were grown in Dulbecco's modified Eagle's medium, containing G418, for 72 h after transfection. The clones were selected and continued to grow in G418 medium for 24 d. The expression of human insulin was detected by immunohistochemistry. Human insulin in the culture medium of transfected cells was measured. Fasting blood glucose and plasma human insulin of diabetic rats were measured for 5 d after transfection. RT-PCR and Western blotting were performed to confirm the expression of the human insulin gene in diabetic rats. Approximately 10% of NIH3T3 cells transfected by chitosan-pCMV.Ins expressed human insulin. Human insulin in the culture medium of NIH3T3 cells transfected by chitosan-pCMV.Ins significantly increased compared with that of the control group (P<0.01). Fasting blood glucose levels of the lavage group and the coloclysis group decreased significantly in 5 d (P<0.01) in comparison, while plasma insulin levels were much higher (P<0.01). The human insulin gene mRNA and human insulin were only detected in the lavage and the coloclysis groups. The human insulin gene can be transfected and expressed successfully by chitosan- pCMV.Ins in NIH3T3 cells and diabetes rats, which indicates that chitosan is a promising, non-viral vector for gene expression.


Recombinant Production and Characterization of SAC, the Core Domain of Par-4, by SUMO Fusion System.
Prostate apoptosis response-4 (Par-4), an anticancer protein that interacts with cell surface receptor GRP78, can selectively suppress proliferation and induce apoptosis of cancer cells. The core domain of Par-4 (aa 137-195), designated as SAC, is sufficient to inhibit tumor growth and metastasis without harming normal tissues and organs. Nevertheless, the anticancer effects of SAC have not been determined in ovarian cancer cells. Here, we developed a novel method for producing native SAC in Escherichia coli using a small ubiquitin-related modifier (SUMO) fusion system. This fusion system not only greatly improved the solubility of target protein but also enhanced the expression level of SUMO-SAC. After purified by Ni-NTA affinity chromatography, SUMO tag was cleaved from SUMO-SAC fusion protein using SUMO protease to obtain recombinant SAC. Furthermore, we simplified the purification process by combining the SUMO-SAC purification and SUMO tag cleavage into one step. Finally, the purity of recombinant SAC reached as high as 95% and the yield was 25 mg/L. Our results demonstrated that recombinant SAC strongly inhibited proliferation and induced apoptosis in ovarian cancer cells SKOV-3. Immunofluorescence analysis and competitive binding reaction showed that recombinant SAC could specifically induce apoptosis of SKOV-3 cells through combination with cell surface receptor, GRP78. Therefore, we have developed an effective strategy for expressing bioactive SAC in prokaryotic cells, which supports the application of SAC in ovarian cancer therapy.


β1,3-galactosyltransferase on chromosome 6 is essential for the formation of Lewis a structure on N-glycan in Oryza sativa.
β1,3-galactose is the component of outer-chain elongation of complex N-glycans that, together with α1,4-fucose, forms Lewis a structures in plants. Previous studies have revealed that N-glycan maturation is mediated by sequential attachment of β1,3-galactose and α1,4-fucose by individual β1,3-galactosyltransferase (GalT) and α1,4-fucosyltransferase (1,4-FucT), respectively. Although GalT from several species has been studied, little information about GalT from rice is available. I therefore characterized three GalT candidate genes on different chromosomes in Oryza sativa. Seeds of rice lines that had T-DNA insertions in regions corresponding to individual putative GalT genes were obtained from a Rice Functional Genomic Express Database and plants grown until maturity. Homozygotes were selected from the next generation by genotyping PCR, and used for callus induction. Callus extracts of two independent T-DNA mutant rice which have T-DNA insertions at the same gene on chromosome 6 but in different exons showed highly reduced band intensity on a western blots using an anti-Lewis a antibody. Cell extracts and cultured media from suspension culture of the one of these mutant rice were further analysed by N-glycan profiling using matrix-associated laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF). Identified N-glycan species containing β1,3-galactose from both cell extracts and cultured media of knock-out mutant were less than 0.5% of total N-glycans while that of WT cells were 9.8% and 49.1%, respectively. This suggests that GalT located on rice chromosome 6 plays a major role in N-glycan galactosylation, and mutations within it lead to blockage of Lewis a epitope formation.


A tunable monochromatic X-ray source for metrological studies in the 1-20 keV energy range: application to the measurement of attenuation coefficients.
A tunable monochromatic X-ray source operating in the 1-20 keV energy range is described. An X-ray tube provides initial photons. A dispersive crystal performs the energy selection, according to Bragg's law. An X-ray detector is connected to the monochromator fixed exit. This setup can be used for metrological studies. A first application consists in measuring attenuation coefficients in the 4-10 keV energy range. Results for aluminum and copper are given, with average relative uncertainties (1sigma) of 1% and 3% respectively.


Using Shared Medical Appointments to Increase Access to Buprenorphine Treatment.
This study examines patient experiences with shared medical appointments for buprenorphine treatment at a safety net primary care clinic. This is a cross-sectional observational study of 28 participants in a primary care buprenorphine shared medical appointments program. Participants reported appreciating the group visit format, gaining increased coping skills, and having more stable housing and less legal difficulty after starting the program. The implementation of shared medical appointments for buprenorphine treatment benefits clinicians and patients. The nurse care manager and buprenorphine prescriber can efficiently attend to the clinical needs of multiple patients.


Visual, auditive and somatosensory pathways alterations in geriatric rhesus monkeys (Macaca mulatta).
Synapses loss during aging is associated to neurophysiologic alterations that impair organism's health span, thus making the study and prevention of sensory decline relevant for healthy aging and welfare. Therefore the aim of this study was to obtain normative data related to the electrophysiological responses of the different neurosensory components in the visual, auditory and somatosensory pathways in healthy geriatric rhesus monkeys in captivity. Twenty-four rhesus monkeys were divided in two groups: (i) Geriatric monkeys, 20-30 years of age, and (ii) Young monkeys, 7 years of age. Evoked potentials were obtained from the visual, auditory and somatosensory pathways. Regardless the sensory pathways evaluated, a significant delay in nerve conduction was observed in the geriatric group in comparison to the young group. Evoked potentials allowed identifying changes generated during aging in rhesus monkeys and normative data for this species were obtained.


Interferon-gamma inhibits lipoprotein lipase in human monocyte-derived macrophages.
Lipoprotein lipase (LPL) (EC 18.104.22.168) hydrolyzes triacylglycerols of very low density lipoproteins and chylomicrons. It is produced by several cell types, including macrophages, which are frequent in atherosclerotic lesions. The atherosclerotic plaque also contains activated T lymphocytes. We therefore investigated the possible regulatory effect of the T lymphocyte-derived lymphokine interferon-gamma (IFN-gamma) on macrophage LPL. Human monocyte-derived macrophages were treated with recombinant IFN-gamma or conditioned medium from activated peripheral blood mononuclear cells for 3 days. LPL activity was thereafter measured in the culture medium and in cell homogenates. The enzyme protein was detected at a cellular level by immunocytochemistry and immunopredicipitation. Recombinant IFN-gamma caused a profound decrease in macrophage LPL secretion. The IFN-gamma-treated cells, however, still contained immunodetectable enzyme and the decrease in secretion was apparently only partly due to an inhibited synthesis. Conditioned medium from activated peripheral blood mononuclear cells also drastically decreased the macrophage LPL secretion. When the conditioned medium was treated with antibodies against IFN-gamma, its down-regulating effect on macrophage LPL was totally removed. The data indicate that IFN-gamma is inhibiting macrophage LPL at least in part via a reduction of LPL synthesis. A local release of IFN-gamma may be important in the pathogenesis of atherosclerosis by affecting the lipid accumulation in the lesion.


Compensation procedures for facial asymmetries.
Why would a patient complain of "fuzzy and uncomfortable" vision with a variety of glasses? Perhaps because the practitioner has failed to take facial asymmetry into account. Methods of measuring facial asymmetry and optically correcting for it are discussed.


Geographic variation in work injuries: a multilevel analysis of individual-level data and area-level factors within Canada.
This study sought to examine provincial variation in work injuries and to assess whether contextual factors are associated with geographic variation in work injuries. Individual-level data from the 2003 and 2005 Canadian Community Health Survey was obtained for a representative sample of 89,541 Canadians aged 15 to 75 years old who reported working in the past 12 months. A multilevel regression model was conducted to identify geographic variation and contextual factors associated with the likelihood of reporting an activity limiting work injury [corrected], while adjusting for demographic and work variables. Provincial differences in work injuries were observed, even after controlling for other risk factors. Workers in western provinces such as Saskatchewan (adjusted odds ratio [AOR], 1.30; 95% confidence interval [CI], 1.09-1.55), Alberta (AOR, 1.31; 95% CI, 1.13-1.51), and British Columbia (AOR, 1.46; 95% CI, 1.26-1.71) had a higher risk of work injuries compared with Ontario workers. Indicators of area-level material and social deprivation were not associated with work injury risk. Provincial differences in work injuries suggest that broader factors acting as determinants of work injuries are operating across workplaces at a provincial level. Future research needs to identify the provincial determinants and whether similar large area-level factors are driving work injuries in other countries.


[Smoking initiation in Italian regions, 2014, and Regional Prevention Plans].
to evaluate smoking prevalence in adolescents by Italian region from the Health Behaviour Study in School-aged Children (HBSC) of 2014 and to correlate it with the presence, in the 2014-2018 Regional Prevention Plans (PRPs), of school-based smoking prevention interventions. the 2014 HBSC surveillance system provided data on 48,000 adolescents aged 11, 13, and 15 years; Ministry of Health provided data for each PRP on interventions with a tobacco control component and, among them, school-based smoking prevention interventions. weekly smoking prevalence; proportion of school-based smoking prevention interventions out of prevention interventions with tobacco control measures. regions with the highest weekly smoking prevalence were Sardinia and Apulia for all age groups, Abruzzo for 11- and 15-year-old children, Basilicata for 15-year-old children, Bolzano for girls aged 13 years old; Liguria for females, Molise, Calabria, and Veneto for males. In the regions with the highest prevalence of smoking in 2014, in girls aged 11 and 13 years (Sardinia, Apulia, Basilicata, Liguria, Bolzano), a greater proportion of school-based smoking prevention interventions to be developed in the period 2014-2018 have been recorded. smoking prevalence in Italian adolescents is high, especially in 15-year-old children. Implementing policies recommended by the World Health Organization - Framework Convention on Tobacco Control (higher tobacco taxes, anti-tobacco mass media campaigns, plain tobacco package) could work synergistically with school-based interventions in order to decrease tobacco initiation among adolescents in Italy.


Malignant tracheoesophageal fistula.
Malignant tracheoesophageal fistula occurs infrequently in patients with esophageal and lung cancer. However, the occurrence of this entity is very distressing for the patient since it leads to rapid deterioration and death due to overwhelming pulmonary infection. A review of cases reported in the recent world literature is presented. The only effective treatment is to exclude the fistula from the alimentary tract. This may be achieved by intubation or operation. Intubation is probably associated with a lower mortality but is less certain to control the fistula. Single-stage operative exclusion and bypass is preferred under ideal circumstances. However, the patient's condition may dictate that a two-stage operation be performed--first, operative exclusion of the fistula and then, if the patient's respiratory and nutritional state improves sufficiently, restoration of alimentary continuity at a later date.


Single-unit responses selective for whole faces in the human amygdala.
The human amygdala is critical for social cognition from faces, as borne out by impairments in recognizing facial emotion following amygdala lesions [1] and differential activation of the amygdala by faces [2-5]. Single-unit recordings in the primate amygdala have documented responses selective for faces, their identity, or emotional expression [6, 7], yet how the amygdala represents face information remains unknown. Does it encode specific features of faces that are particularly critical for recognizing emotions (such as the eyes), or does it encode the whole face, a level of representation that might be the proximal substrate for subsequent social cognition? We investigated this question by recording from over 200 single neurons in the amygdalae of seven neurosurgical patients with implanted depth electrodes [8]. We found that approximately half of all neurons responded to faces or parts of faces. Approximately 20% of all neurons responded selectively only to the whole face. Although responding most to whole faces, these neurons paradoxically responded more when only a small part of the face was shown compared to when almost the entire face was shown. We suggest that the human amygdala plays a predominant role in representing global information about faces, possibly achieved through inhibition between individual facial features.


Subsequent risky driving behaviors, recidivism and crashes among drivers with a traffic violation: A scoping review.
Drivers who have committed a traffic violation are a particularly high-risk group, yet studies conducted among this group are scarce. We analyzed and synthesized the current literature concerning subsequent risky driving behaviors, recidivism, and crashes among drivers with a traffic violation. We searched PubMed, Education Resources Information Center (ERIC), Academic Search Complete, Web of Science, and Scopus for articles published in English between January 1, 1999, and May 31, 2023. A total of 25 articles met the selection criteria and were included in the final analysis. Two coders independently extracted and analyzed the selected articles to identify common categories across the articles, including study design, study population, type of traffic violation, and study outcomes including subsequent driving behaviors, recidivism, and crash risks. Of the 25 selected articles, 19 (76%) involved both male and female participants. Fourteen (56%) studies were interventions/evaluation studies, with the other 11 (44%) being observational. Nineteen (76%) studies included alcohol-impaired driving violations, and 23 (92%) studies examined recidivism as an outcome measure. Over half of the observational studies demonstrated that traffic offenders were more likely to commit a subsequent traffic violation or had elevated risk of crashes. Most of the intervention/evaluation studies demonstrated a significant reduction in driving under the influence (DUI) of alcohol among the study participants. However, such positive effects observed during the active intervention period were not always sustained. Traffic offenders are a high-risk group for subsequent violations and crashes. Evidence from this review calls for more effective interventions implemented following a traffic violation to prevent recidivism, crashes, and crash-related injuries and deaths.


Inhibition of oxidative phosphorylation by an oligomer of prostaglandin B1, PGBx.
PGBx is a synthetic, oligomeric derivative of prostaglandin B1 that has been shown to protect rat liver mitochondria from the deleterious effects of aging. In fresh mitochondria, PGBx inhibits reactions involving the F1F0-ATPase. It prevents the stimulation of respiration by ADP and inhibits ATP-driven Ca2+ transport. It has no effect, however, on Ca2+-stimulated respiration and associated proton movements, or on respiration-driven Ca2+ transport, indicating that PGBx is not an inhibitor of the electron transport chain. The ATPase activity of submitochondrial particles is inhibited by PGBx with mixed type kinetics in which both Km and V are affected. PGBx has no effect on the ATPase activity of soluble F1, but induces respiratory control in F1-deficient submitochondrial particles, indicating a mode of action similar to oligomycin and DCCD. The binding of DCCD to its proteolipid receptor is inhibited by PGBx, suggesting that this is the binding site for PGBx. It is concluded that PGBx inhibits reactions involving the F1F0-ATPase by binding at or near the DCCD-binding protein and blocking proton conduction through the F0 moiety of the complex.


Pre-infection of pigs with Mycoplasma hyopneumoniae modifies outcomes of infection with European swine influenza virus of H1N1, but not H1N2, subtype.
Swine influenza virus (SIV) and Mycoplasma hyopneumoniae (Mhp) are widespread in farms and are major pathogens involved in the porcine respiratory disease complex (PRDC). The aim of this experiment was to compare the pathogenicity of European avian-like swine H1N1 and European human-like reassortant swine H1N2 viruses in naïve pigs and in pigs previously infected with Mhp. Six groups of SPF pigs were inoculated intra-tracheally with either Mhp, or H1N1, or H1N2 or Mhp+H1N1 or Mhp+H1N2, both pathogens being inoculated at 21 days intervals in these two last groups. A mock-infected group was included. Although both SIV strains induced clinical signs when singly inoculated, results indicated that the H1N2 SIV was more pathogenic than the H1N1 virus, with an earlier shedding and a greater spread in lungs. Initial infection with Mhp before SIV inoculation increased flu clinical signs and pathogenesis (hyperthermia, loss of appetite, pneumonia lesions) due to the H1N1 virus but did not modify significantly outcomes of H1N2 infection. Thus, Mhp and SIV H1N1 appeared to act synergistically, whereas Mhp and SIV H1N2 would compete, as H1N2 infection led to the elimination of Mhp in lung diaphragmatic lobes. In conclusion, SIV would be a risk factor for the severity of respiratory disorders when associated with Mhp, depending on the viral subtype involved. This experimental model of coinfection with Mhp and avian-like swine H1N1 is a relevant tool for studying the pathogenesis of SIV-associated PRDC and testing intervention strategies for the control of the disease.


Effect of ultra-processed food intake on metabolic syndrome components and body fat in children and adolescents: A systematic review based on cohort studies.
The aim of this study was to thoroughly review the scientific literature related to cohort studies that evaluated the association between the intake of ultra-processed foods, according to the NOVA classification, and the increase in the components of metabolic syndrome and body fat in children and adolescents. We consulted the PubMed, Scielo, Lilacs, and ScienceDirect databases and selected cohort studies that met the main objective of this review and included the age group of interest. We used an adaptation of the Newcastle-Ottawa scale to evaluate cohort studies. Of 383 articles identified, 367 were excluded after reading the title, abstract, and methodology. Only nine met the selection criteria defined for this review. Of the nine articles, two reported a positive association between high consumption of ultra-processed foods and total cholesterol levels; one reported a positive association with low-density lipoprotein cholesterol, one with triacylglycerols, one with diastolic blood pressure, three with body mass index, two with waist circumference, and two with body fat. Seven of nine studies found at least one association with components of metabolic syndrome. This highlights the importance of early intervention to prevent non-communicable diseases in the future.


Selective extraction by 1-butanol of surface glycoprotein antigens from human melanoma cells.
The butanol extraction method has previously been used to achieve selective release of tumor-specific transplantation antigens from mouse sarcoma cells. In this study we investigated the feasibility of this method for extracting four surface glycoprotein antigens (87K, 95-150K, HLA-DR, and HLA-A,B,C) from cultured human melanoma cells. Of the four antigens examined, only 95-150K and HLA-DR antigens could readily be detected in material extracted by 2%, 3%, or 5% butanol. The 3% butanol was found to be most effective in releasing these two antigens. Treatment of melanoma cells with less than or equal to 3% butanol did not decrease the viability of extracted cells as judged by either Trypan Blue dye exclusion or plating efficiency. Thus the noncytolytic butanol extraction method offers a promising approach to the isolation of certain glycoproteins such as 95-150K and HLA-DR from viable human melanoma cells for further purification and structural analysis.


Pharmacokinetic comparison of three clindamycin phosphate dosing schedules.
In a randomized, three-way crossover study, six male volunteers received clindamycin phosphate 600 mg iv q6h (treatment A), 600 mg iv q8h (treatment B), or 900 mg iv q8h (treatment C). Plasma clindamycin concentrations were determined periodically for eight hours after achieving steady state. The results indicate that treatment C yielded significantly higher peak plasma clindamycin concentrations than treatments A or B. There were no significant differences in minimum plasma clindamycin concentrations (Cmin) or area under the plasma concentration versus time curve (AUC24) between treatments A and C. However, both treatments A and C yielded significantly greater Cmin and AUC24 values than treatment B. There were no significant differences among treatments for clindamycin clearance. It is concluded that clindamycin phosphate 900 mg q8h is a pharmacokinetically acceptable alternative to clindamycin phosphate 600 mg q6h.


Pierre Robin syndrome and pulmonary hypertension.
Five infants with Pierre Robin syndrome developed evidence of carbon dioxide retention and congestive cardiac failure despite measures to alleviate upper airway obstruction. Investigations included chest radiography, electrocardiography, echocardiography, and cardiac catheterization; pulmonary hypertension was diagnosed. In two cases raised main pulmonary artery pressures of 40 mm Hg and 120 mm Hg were recorded. Relief of upper airway obstruction was achieved by tracheostomy in three cases and nasopharyngeal intubation in two cases, with reversal of signs of cor pulmonale in each. Four patients progressed well with no recurrence of cardiac problems but one died suddenly one month after apparently successful management by tracheostomy.


Antithetic roles of proteoglycans in cancer.
Proteoglycans (PGs), a family of complex post-translationally sculptured macromolecules, are fundamental regulators of most normal and aberrant cellular functions. The unparalleled structural-functional diversity of PGs endows them with the ability to serve as critical mediators of the tumor cells' interaction with the host microenvironment, while directly contributing to the organization and dynamic remodeling of this milieu. Despite their indisputable importance during embryonic development and in the adult organism, and their frequent dysregulation in tumor lesions, their precise involvement in tumorigenesis awaits a more decisive demonstration. Particularly challenging is to ascertain to what extent selected PGs may catalyze tumor progression and to what extent they may inhibit it, implying antithetic functions of individual PGs. Integrated efforts are needed to consolidate the routine use of PGs in the clinical monitoring of cancer patients and to broaden the exploitation of these macromolecules as therapeutic targets. Several PGs have the required attributes to be contemplated as effective antigens for immunotherapeutic approaches, while the tangible results obtained in recent clinical trials targeting the NG2/CSPG4 transmembrane PG urge further development of PG-based cancer treatment modalities.


Alterations in brain 5HT and tryptamine content during indoleamine-induced myoclonus in guinea pigs.
L-5-Hydroxytryptophan (5HTP) (with or without carbidopa pretreatment), L-tryptophan (plus pargyline pretreatment), or tryptamine (plus pargyline pretreatment) all induced dose-dependent myoclonus in guinea pigs. At the time of maximal behavioural response animals were killed for determination of brain indoleamine content. Administration of 5HTP (50-200 mg/kg) to naive guinea pigs, or of 5HTP (20-80 mg/kg) to carbidopa- (25 mg/kg 1 hr previously) pretreated animals, markedly elevated brain 5-hydroxytryptamine (5HT) concentrations but depressed whole brain tryptamine content. L-Tryptophan (50-200 mg/kg) administration to pargyline- (75 mg/kg 30 min previously) pretreated animals also increased cerebral 5HT levels. L-Tryptophan (200 mg/kg plus pargyline), elevated whole brain tryptamine content. Administration of tryptamine (40 mg/kg) to pargyline-pretreated guinea pigs caused a small increase in brain 5HT levels, but markedly elevated cerebral tryptamine content. 5HT appears to be the indoleamine mainly responsible for 5HTP-induced myoclonus but tryptamine predominates in tryptamine-induced myoclonus. Both 5HT and tryptamine may contribute to myoclonus induced by L-tryptophan.


Exercise therapy after ultrasound-guided corticosteroid injections in patients with subacromial pain syndrome: a randomized controlled trial.
Subacromial pain syndrome (SAPS) accounts for around 50 % of all cases of shoulder pain. The most commonly used treatments are glucocorticosteroid (steroid) injections and exercise therapy; however, despite treatment SAPS patients often experience relapse of their symptoms. Therefore the clinical effect of combining steroid and exercise therapy is highly relevant to clarify. The aim of this randomized controlled trial was to investigate if exercise therapy added to steroid injection in patients with SAPS will improve the effect of the injection therapy on shoulder pain. In this two-arm randomized trial running over 26 weeks, patients with unilateral shoulder pain (> 4 weeks) and thickened subacromial bursa (> 2 mm on US) were included. At baseline all participants received two steroid injections into the painful shoulder with an interval of one week. Subsequently they were randomized (1:1) to either 10 weeks exercise of the involved shoulder (intervention group) or exercise of the uninvolved shoulder (control group). The patients were re-examined after the exercise program (at week 13) and again at week 26. The primary outcome assessed after 26 weeks was change in shoulder pain analyzed using the intention-to-treat principle (non-responder imputation). Ninety-nine SAPS patients (58 female) participated (49 intervention/50 control). At both follow up visits (week 13 and 26) no statistically significant between-group differences in pain changes on a visual analog scale (mm) were seen (13 weeks: pain at rest 1.7 (95 % CI -3.6 to 7.0; P = 0.53); pain in activity 2.2 (95 % CI -6.5 to 10.9; P = 0.61), 26 weeks: rest 5.6 (95 % CI -0.9 to 12.1; P = 0.09); activity 2.2 (95 % CI -6.8 to 11.2; P = 0.62). The reduction in pain was most evident in the control group at all four pain measurements. The only difference between groups was seen by US examination at week 13, where fewer participants with impingement were observed in the intervention group compared with the controls (9 vs. 19 participants; P = 0.03). Exercise therapy in the painful shoulder in SAPS patients did not improve the effectiveness of steroid injections for shoulder pain in patients with unilateral SAPS and enlarged subacromial bursa on US examination. ClinicalTrials.gov ( NCT01506804 ). Registration date 5 May 2011.