Processing impairments in OCD: it is more than inhibition!
The study aimed to address a significant gap in the literature on inhibition impairments in OCD, by concurrently studying facilitation and inhibition processes and the effect of threat on these twin mechanisms. Participants were 20 persons with symptomatic OCD, 11 with remitted OCD, 20 with panic disorder and 20 normal control participants. Participants were required to respond to words that were either neutral or personally threatening, which during an immediately preceding trail, were responded to as targets (facilitation) or inhibited as non-targets (inhibition). OCD participants displayed greater facilitation and reduced inhibition, differences that were related to their diagnostic status but unrelated to symptomatic status. Threat had no effect on facilitation, but exacerbated inhibition problems in the symptomatic OCD and panic groups. This research suggests that underlying differences in both facilitation and inhibition, combined with influences of activated threat-schema on inhibition may play a role in the development and maintenance of OCD.


Optimisation of Fe2+/H2O2 ratio in Fenton process to increase dewaterability and solubilisation of sludge.
Fenton is one of the advanced oxidation processes that can oxide organic compounds efficiently increasing the dewaterability of sludge. This study reports the optimisation of two reagents, Fe2+ and H2O2, involved in the Fenton process in order to increase sludge dewaterability and solubilisation, which were evaluated in terms of SRF, CST and DS. The study was divided into two sets of tests. First the optimal ratio Fe2+/H2O2 was set varying from 0.5-2.0. Results showed that the best Fe2+/H2O2 was equal to 0.8 corresponding to 2.1 s of CST, 2.1·1013 m kg-1 of SRF and 3.1% of DS. In the second set of tests, the Fe2+/H2O2 ratio was maintained fixed to 0.8 while the concentration of reagents was decreased up to 98% in order to verify the efficiency of the process. Results showed that performing Fenton process with a concentration of H2O2 and Fe2+ of, respectively, 6000 and 5000 mg L-1 the SRF and CST could be reduced up to 88% and 76%, respectively, and a DS equal to 3.1% could be obtained. A reduction in the Fenton reagents down to 300 and 250 mg L-1, respectively, for H2O2 and Fe2+ showed a little decrease in efficiency of the process. However, the Fenton process could be still performed thus obtaining an economic saving.


Modulus of elasticity of randomly and aligned polymeric scaffolds with fiber size dependency.
The stiffness of a nano-fibrous scaffold is generally enhanced due to the size-dependency of the thin nanofibers contained in the scaffold. We proposed a model that incorporates size-dependency of single nanofibers to predict the scaffold effective modulus, in which the fibers' random or orientation distribution are considered. In the model the fiber segments between rigid fiber-fiber bonds can be stretching, shearing and bending. Using deformation energy equilibrium between sum of individual fibers and the plate of nano-fibrous scaffold, the scaffold effective modulus was derived explicitly. The model was verified via finite element analysis (FEA) and published experimental results. The parametric studies revealed that the fiber diameter is the dominant parameter to stiffen the scaffold beyond the fiber density and fiber aspect ratio when the fiber diameter is reduced below the onset value of size-dependencies. As a result, the scaffold stiffness can maintain its higher value and lower decrease rate because of the size-dependency with a decreasing diameter of the nanofiber as a result of biodegradation. This inspires the idea of selecting nanofibers near the onset value of size-dependency to obtain a controlled tuning of the scaffold stiffness in the design of novel nano-fibrous scaffolds.


HIF-1α/Beclin1-Mediated Autophagy Is Involved in Neuroprotection Induced by Hypoxic Preconditioning.
Hypoxic preconditioning (HPC) exerts a protective effect against hypoxic/ischemic brain injury, and one mechanism explaining this effect may involve the upregulation of hypoxia-inducible factor-1 (HIF-1). Autophagy, an endogenous protective mechanism against hypoxic/ischemic injury, is correlated with the activation of the HIF-1α/Beclin1 signaling pathway. Based on previous studies, we hypothesize that the protective role of HPC may involve autophagy occurring via activation of the HIF-1α/Beclin1 signaling pathway. To test this hypothesis, we evaluated the effects of HPC on oxygen-glucose deprivation/reperfusion (OGD/R)-induced apoptosis and autophagy in SH-SY5Y cells. HPC significantly attenuated OGD/R-induced apoptosis, and this effect was suppressed by the autophagy inhibitor 3-methyladenine and mimicked by the autophagy agonist rapamycin. In control SH-SY5Y cells, HPC upregulated the expression of HIF-1α and downstream molecules such as BNIP3 and Beclin1. Additionally, HPC increased the LC3-II/LC3-I ratio and decreased p62 levels. The increase in the LC3-II/LC3-I ratio was inhibited by the HIF-1α inhibitor YC-1 or by Beclin1-short hairpin RNA (shRNA). In OGD/R-treated SH-SY5Y cells, HPC also upregulated the expression levels of HIF-1α, BNIP3, and Beclin1, as well as the LC3-II/LC3-I ratio. Furthermore, YC-1 or Beclin1-shRNA attenuated the HPC-mediated cell viability in OGD/R-treated cells. Taken together, our results demonstrate that HPC protects SH-SY5Y cells against OGD/R via HIF-1α/Beclin1-regulated autophagy.


Detection of the neuropathogenic variant of equine herpesvirus 1 associated with abortions in mares in Poland.
The incidence of reported cases of equine herpesvirus myeloencephalopathy (EHM) caused by infection with neuropathogenic strains of equine herpesvirus 1 (EHV-1) has markedly increased over the last decade in many Western countries. The purpose of this study was to estimate the prevalence of the neuropathogenic (G2254) and non-neuropathogenic (A2254) variants of EHV-1 among isolates associated with abortions in Polish stud farms. The results of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and sequencing were consistent, and showed that two out of 64 abortions (3.1%) were induced by the neuropathogenic genotype G2254. All remaining 18 EHV-1 positive abortion cases (28.1%) were caused by the non-neuropathogenic genotype A2254. Most of the abortions in mares in Poland from 1999 to 2012 were associated with non-neuropathogenic strains of EHV-1. However, the presented data indicate that the neuropathogenic genotype of the virus is also present in Polish stud farms. Such a presence suggests that the future emergence of EHM in Poland is probable.


Prognostic significance of ploidy, MIB-1 proliferation marker, and p53 in renal cell carcinoma.
Pathologic stage is currently the best prognostic factor for predicting outcomes in renal cell carcinoma. The objective of this study was to evaluate the role of DNA ploidy, p53, and Ki-67 (MIB-1) as individual and combined prognostic factors for survival in patients with renal cell carcinoma (RCC). From 1995 to 2004, 117 patients (78 men and 39 women; mean age 57.34 years), undergoing partial (n = 22) or radical (n = 95) nephrectomy for renal cell carcinoma were retrospectively analyzed. Analysis of MIB-1, p53, and DNA ploidy was performed. Disease-free and overall survival was calculated using Cox proportional hazard models. A combined score was given to incorporate p53, MIB-1, and ploidy as a single variable. On univariate analysis, tumor size, nuclear grade, MIB-1 <10% (p = 0.0059), ploidy (p = 0.0124), pathologic stage group, metastasis at time of operation, and combined score (p = 0.0024) were markedly associated with disease-free survival. On multivariate analysis, only metastasis and pathologic stage were pronounced. For overall survival, size, nuclear grade, MIB-1 <10% (p = 0.0167), pathologic stage group, metastasis, and combined score (p = 0.0456) were pronounced on univariate analysis. Only metastasis was pronounced on multivariate analysis. We incorporated a combined score to evaluate MIB-1, ploidy, and p53 as a single variable. A combined score is able to give a stronger predictive value of the cellular characteristics of each tumor. Individually and combined with p53, MIB-1, and ploidy were of prognostic significance on univariate analysis. Pathologic stage and presence of metastasis remain the best predictors of disease-free survival.


Influence of atrophy on the efficiency of muscle reinnervation.
The effectiveness of motor reinnervation carried out after an interval of 20 days between nerve transection and reimplantation onto a foreign muscle was studied in the rat. Sixty days after reimplantation the compound action potential, the maximal indirect twitch and tetanic tensions, and weight loss were evaluated. The functional data demonstrated an incomplete recovery which differed from the complete functional restoration observed in an acutely denervated muscle reinnervated with a chronically severed nerve. Time-dependent changes induced in the muscle by denervation seem therefore to influence the efficacy of motor reinnervation.


Determination by photoreduction of flip-flop kinetics of spin-labeled stearic acids across phospholipid bilayers.
Spin-labeled stearic acid derivatives (N-DS) can be used to determine the rate at which lipid-derived drugs can cross a phospholipid bilayer (flip-flop). The flip-flop rate of N-DS (where N=5, 6, 7, 9, 10, 12, 16), was measured using vectorial photoreduction of nitroxides to their corresponding hydroxylamine by FMN, a charged, membrane-impermeable flavin, by hydrogen atom transfer from EDTA. From the time difference in the photoreduction rates of N-DS located in the outer and inner half of the bilayer, the flip-flop rate of N-DS across the bilayer can be determined. The results show that at pH 8.0 or lower, the photoreduction of 5-DS on one side of the membrane by FMN is slower than the flip-flop rate of 5-DS across phospholipid bilayers. For 5-DS at pH 7.0, this rate is at least 33.8+/-4.24 s or faster. Stearic acids with the spin label at different positions along the acyl chain (N=5, 6, 7, 9, 10, 12) have similar flip-flop rates in the liposomes at pH 7.0 although 16-DS is slower, probably due to the inaccessibility of the nitroxide moiety to FMN. It is most likely that the fast distribution of 5-DS in cells is due to the fast movement of acidic form, but not the salt form, of 5-DS across membrane bilayers. The oxazolidine (nitroxide moiety) does not seem to affect the pKa ( approximately 8.3) of stearic acid at air-water interface. Thus, N-DS are good probes for studying the distribution kinetics of stearic acid derivatives in biological systems.


A new antiserum with conformational specificity for LHRH: usefulness for radioimmunoassay and immunocytochemistry.
We have produced and characterized a new high titer, highly specific antiserum for luteinizing hormone-releasing hormone (LHRH), and demonstrated its usefulness for radioimmunoassay (RIA) and immunocytochemistry. The antiserum can be used at a final dilution of 1:500,000 to 1:600,000 for RIAs with a sensitivity of 0.2 pg/tube. Both the amino and carboxy terminal ends of the LHRH molecule are required for antibody recognition, and the antigenic determinant appears to be part of a three-dimensional structure of LHRH. Fragments of LHRH and other brain peptides are not recognized by the antiserum. Using immunocytochemical techniques, we have localized LHRH-containing neurons in the medial basal hypothalamus of the rhesus monkey, guinea pig, and rat. Staining of LHRH fibers and cell bodies was eliminated by preabsorbtion of the immune serum with synthetic LHRH. This antiserum should be useful in studies that require quantification of very low amounts of LHRH and in studies that require correlation between immunocytochemical localization and tissue content or secretion of LHRH.


Interaction of dendritic cells and T lymphocytes for the therapeutic effect of Dangguiliuhuang decoction to autoimmune diabetes.
In traditional Chinese medicine (TCM), Dangguiliuhuang decoction (DGLHD) is an effective treatment of autoimmune diabetes. Here, we studied potential anti-diabetic mechanisms of DGLHD in a non-obese diabetic (NOD) mouse model. In vitro, DGLHD and individual active ingredients enhanced glucose uptake in HepG2 cells, inhibited T lymphocyte proliferation, and suppressed dendritic cells (DCs) function. In vivo, DGLHD significantly inhibited insulitis, delayed the onset and development of diabetes, promoted insulin secretion and sensitivity, and balanced partially normalized Th1 and Th2 cytokines in NOD mice. In addition, DGLHD increased α1-antitrypsin (AAT-1), Bcl-2, and CyclinD1, and decreased Bax levels in pancreas, spleen, thymus, DCs, and a NIT-1 cell line, all consistent with protecting and repairing islet β cell. More detailed studies indicated that DGLHD regulated the maturation and function of DCs, decreased the percentage of merocytic dendritic cells (mcDCs) subset, and increased programmed death ligand-1 (PD-L1) expression in DCs. DGLHD also impeded T lymphocyte proliferation and promoted regulatory T cells (T(regs)) differentiation in vivo. A JAK2-STAT3-dependent pathway was involved in the suppression by DGLHD of interactions between DCs and T lymphocyte. The experiments implicated five active ingredients in specific anti-diabetic actions of DGLHD. The results demonstrated the reasonable composition of the formula.


National reduction in porcine circovirus type 2 prevalence following introduction of vaccination.
Porcine circovirus type 2 (PCV2), a small, single-stranded circular DNA virus and the causative agent of porcine circovirus associated disease (PCVAD), was first observed in the mid-1990s in pigs with a post-weaning wasting disease. In 2006 the number of PCVAD cases greatly increased, marking it as an important viral pathogen for the United States (US) swine industry. PCV2 vaccines were introduced to the US in 2006 in response to widespread outbreaks of PCVAD. These vaccines were effective in preventing disease, but did not eliminate virus from the animals. In 2006, prior to vaccine use, a study of PCV2 prevalence in pig herds across the US was performed in conjunction with the US National Animal Health Monitoring System. In 2012, 6 years after widespread PCV2 vaccination, this study was repeated. Since the introduction of PCV2 vaccines in 2006, viral presence and viral loads have greatly decreased, and a genotypic shift dominated by PCV2b has occurred. Antibody levels have decreased in the pig population, but approximately 95% of sites continue to be antibody-positive. Widespread vaccination has controlled PCVAD and decreased PCV2 prevalence to the point that viremia is not detected on many sites. Thus, continued vaccination may lead to PCV2 elimination in the national herd over time.


Influence of spatial frequency and handedness on hemispheric asymmetry in visually steady-state evoked potentials.
Recent suggestions on the involvement of the spatial frequency of visual stimuli in the hemispheric lateralization were investigated by recording steady-state evoked potentials in two groups of subjects: five right-handers and five left-handers. Sinusoidal gratings at spatial frequency of 0.5, 1, 3, 4, 6, 8, 10, 12 or 16 cpd were phase reversed at 4 Hz or 12 Hz. Evoked potentials recorded from temporal leads over each hemisphere were submitted to a FFT analysis. Results concern the amplitude of the fundamental component. In right-handers, the temporal frequency was the deciding factor of the lateralization: the evoked activities were greatest in the RH at 4 Hz and in the LH at 12 Hz. This effect was obvious for the range of spatial frequencies from 3-12 cpd. Results, discussed in terms of global/local information, suggested the existence of two transient and sustained systems. In left-handers, both the spatial and temporal parameters were relevant to the lateralization. A spatio-temporal interaction was observed which was reversed at 6 cpd.


Comparative evaluation of Ca(OH)2 plus points and Ca(OH)2 paste in apexification.
The aim of this study was to compare calcium hydroxide plus points (CHPPs) with the conventional calcium hydroxide paste (CHP) clinically and radiographically as materials used in apexification treatment. Sixteen children, each with at least one necrotic permanent central incisor requiring apexification treatment, were selected for this study. Twenty-two selected teeth were divided into two test groups (10 CHP and 12 CHPP). The children were recalled for clinical evaluations every 3 weeks, and their radiographical evaluations were carried out every 3 months. Mann-Whitney U and Fisher's exact tests were used to evaluate the differences between the groups. The follow-up evaluations revealed that the success rate was 100% for CHP and 92% for CHPP. No statistically significant difference between the groups was observed (P > 0.05). CHPP-treated central incisors requiring apexification demonstrated good success. CHPP can be used for cases in which traditional Ca(OH)(2) apexification is indicated as it has a similar outcome with CHP.


How Can I Survive This?: Coping During Coronavirus Disease 2019 Pandemic.
Worldwide, health-care professionals are experiencing unprecedented stress related to the coronavirus disease 2019 pandemic. Responding to a new virus for which there is no effective treatment yet and no vaccine is beyond challenging. Moral distress, which is experienced when clinicians are unable to act in the way that they believe they should, is often experienced when they are dealing with end-of-life care issues and insufficient resources. Both factors have been widespread during this pandemic, particularly when patients are dying alone and there is a lack of personal protection equipment that plagues many overburdened health-care systems. We explore here, guided by evidence, the concept and features of moral distress and individual resilience. Mitigation strategies involve individual and institutional responsibilities; the importance of solidarity, peer support, psychological first aid, and gratitude are highlighted.


Value of Multimodal Data From Clinical and Sonographic Parameters in Predicting Recurrence of Hepatocellular Carcinoma After Curative Treatment.
The objective of the work described here was to assess the value of the combination of pre-operative multimodal data-including clinical data, contrast-enhanced ultrasound (CEUS) information and liver stiffness measurement (LSM) based on 2-D shear wave elastography (SWE)-in predicting early (within 1 y) and late (after 1 y) recurrence of hepatocellular carcinoma (HCC) after curative treatment. We retrospectively included 101 patients with HCC who met the Milan criteria and received curative treatment. The multimodel data from clinical parameters, LSM by 2-D SWE and CEUS enhancement patterns were collected. The association between different variables in HCC recurrence was accessed using a Cox proportional hazard model. On the basis of the independent factors of early recurrence, models with different source variables were established (Clinical Model, CEUS-Clinical Model, SWE-Clinical Model, CEUS-SWE-Clinical Model). The goodness-of-fit of models was evaluated and the performance trends of different models were calculated by time-dependent area under the curve (AUC). Two-dimensional SWE, CEUS enhancement patterns and clinical parameters (spleen length, multiple tumors, α-fetoprotein, albumin and prothrombin time) were independently associated with early recurrence (all p values <0.05). Multiple tumors and a decrease in albumin independently contributed to the late recurrence. The model fit of CEUS-SWE-Clinical Model was superior to other models in predicting early recurrence (all p values <0.05). The AUCs of the CEUS-Clinical Model were higher from 2 mo to 7 mo, while the SWE-Clinical Model had higher AUCs from 9 mo to 12 mo. CEUS enhancement patterns and 2-D SWE were independent predictors of HCC early recurrence as the two factors contributed to the predictive performance at different times. The multimodal model, which included diverse data in predicting early HCC recurrence, had the best goodness-of-fit.


A simplified scleral reinforcement technique.
A simplified scleral reinforcement technique performed on 52 eyes with myopic degeneration prevented further visual loss by strengthening of the sclera over the posterior pole. This scleral homograft was useful not only in older patients with high myopia and posterior staphyloma, but also in younger patients in whom the degenerative process could be stopped at an earlier stage. In all cases in which follow-up was possible, the visual acuity remained at the preoperative level before surgery was performed or it improved.


Observed attention allocation processes in category learning.
In two empirical studies of attention allocation during category learning, we investigate the idea that category learners learn to allocate attention optimally across stimulus dimensions. We argue that "optimal" patterns of attention allocation are model or process specific, that human learners do not always optimize attention, and that one reason they fail to do so is that under certain conditions the cost of information retrieval or use may affect the attentional strategy adopted by learners. We empirically investigate these issues using a computer interface incorporating an "information-board" display that collects detailed information on participants' patterns of attention allocation and information search during learning trials. Experiment 1 investigated the effects on attention allocation of distributing perfectly diagnostic features across stimulus dimensions versus within one dimension. The overall pattern of viewing times supported the optimal attention allocation hypothesis, but a more detailed analysis produced evidence of instance- or category-specific attention allocation, a phenomenon not predicted by prominent computational models of category learning. Experiment 2 investigated the strategies adopted by category learners encountering redundant perfectly predictive cues. Here, the majority of participants learned to distribute attention optimally in a cost-benefit sense, allocating attention primarily to only one of the two perfectly predictive dimensions. These results suggest that learners may take situational costs and benefits into account, and they present challenges for computational models of learning that allocate attention by weighting stimulus dimensions.


The effects of temperature, humidity, photoperiod and weight of the engorged female on oviposition of Boophilus annulatus (Say, 1821).
At a constant temperature of 25 degrees C and 84% relative humidity the pre-oviposition period of Boophilus annulatus was 2-5 days (mean 2.7 days) and the oviposition lasted 11-17 days (mean 15 days). The peak egg laying occurred 1-6 days (mean 3.5 days) after the start of oviposition. The daily egg output was 135 (range 90-190) and the total egg production was 2004 (range 1432-2664). Light had no significant effect on oviposition. There was a highly significant correlation between the weight of the engorged female and the total egg yield (r = 0.78; P less than 0.01). The pre-oviposition and oviposition periods were not influenced by the weight of the engorged females. The relative humidity (25, 62, 93%) had no effect on the oviposition, but the temperature (16, 25, 35 degrees C) had a significant influence on it. The pre-oviposition and oviposition periods increased with the decrease of temperature. The course of oviposition was similar at 25 and 35 degrees C, with a peak occurring within a few days of the start of egg-laying, followed by a gradual decline. At 16 degrees C, the egg production curve was flat, without a peak. However, the total number of eggs produced was not significantly different at the three temperature regimes.


Binding divergence of polystyrene nanoparticles with serum albumin caused by surface functionalization.
Using a combination of spectroscopy, we devised an integrated structural strategy to comprehensively profile the molecular details of the impact of differently functionalized (plain, aminated, and carboxylated) polystyrene nanoparticles (PSNPs) on human serum albumin (HSA). The binding isotherms obtained from fluorescence and UV-vis absorption measurements demonstrate that surface functionalization can distinguish the interaction of PSNPs with HSA. Three-dimensional fluorescence and circular dichroism analysis of the effect of interaction with PSNPs on the native conformation and secondary structures of the protein reveals a diminution in the skeleton structure of HSA induced by the PSNPs. In accordance with this, it is discovered that the esterase activity of protein-PSNPs aggregates is diminished compared to that of the native protein. The carboxylated PSNPs exhibited the strongest protein binding and perturbation effects compared to other particles. Plain PSNPs exhibited significant hydrophobic interaction properties, as evidenced by spectral blue shifts and a diminished Stokes shift in the three-dimensional fluorescence assay. Our results exclusively highlight that the hydrophobic and surface charge characteristics of PSNPs govern the extent of interaction with the protein, which is beneficial to understanding microplastic toxicology.


Lighting the way to interdisciplinary primary health care.
Between 2004 and 2006, the Enhancing Interdisciplinary Collaboration in Primary Health Care (EICP) initiative undertook research on interdisciplinary collaboration. The last report prepared by the Initiative, Interdisciplinary Primary Health Care: Finding the Answers - A Case Study Report, offers a research-based blueprint for action by showcasing some current successful collaborative practices in primary health care. Several key learnings are discussed, especially in areas such as health human resources, funding, liability, regulation, information and communication technologies, management and leadership and planning and evaluation. Each of the primary health care organizations that were studied has created very different organizational cultures and teams. Each has faced different obstacles and developed innovative solutions to overcome them, indicating that there is no single right way, no step-by-step prescription as how to best pursue this method of care. Their innovative approaches are enlightening the way to interdisciplinary primary health care.


A rapid, simple, and humane method for submandibular bleeding of mice using a lancet.
Methods for obtaining blood samples from mice tend to be difficult, inhumane, or both. The authors describe an inexpensive, disposable, single-use lancet for submandibular bleeding of mice that allows investigators to quickly draw 0.2-0.5 ml of blood without the use of anesthesia.


A two dimensional 1H NMR study of the solution conformation of gastrin releasing peptide.
An almost complete assignment of the 1H NMR spectrum of gastrin releasing peptide in dimethyl sulphoxide solution and aqueous solution has been carried out using two dimensional NMR techniques. The chemical shifts in both solvents have been compared with the corresponding values in random coil polypeptides and it is concluded that gastrin releasing peptide adopts little short or long range order under either solvation conditions.


False negative histochemical reaction for myophosphorylase activity in fulminant sepsis due to methicillin resistant Staphylococcus aureus.
We report a false negative histochemical reaction for myophosphorylase in the case of an 11 year old with fulminant Staphylococcus aureus. Due to increased creatine kinase levels and marked myoglobinuria a muscle biopsy was performed prior to death. The biopsy revealed rhabdomyolysis, glycogen depletion and absent myophosphorylase reactivity. Subsequent myophosphorylase quantification was normal. This unique case of a false negative myophosphorylase histochemical reaction is apparently related to sepsis.


Neoliberalism, Control of Trans and Gender Diverse Bodies and Social Work.
This paper explores how neoliberal ideologies inform both social and political agendas that influence how social workers can provide support to trans and gender diverse people attempting to access gender-affirming healthcare, using an analysis of social workers' experiences working in mental health in Nova Scotia, Canada. Qualitative semi-structured interviews provide a perspective of the experiences of social workers in Nova Scotia and how their ability to provide mental health services to trans and gender diverse people is impacted by neoliberalism. Most social workers attributed the structural context of working within a bio-medical system as contributing to social workers being disempowered, undermined, and not able to practice according to the values of their profession thus limiting their ability to provide affirming mental health supports to trans and gender diverse people in ways that align with their social work professional ethics and values. Through examining how neoliberal ideologies create notions of ideal social citizens by controlling the body, the paper explores how lived experience of neoliberal practices in mental health social work reinforce transnormativity. This paper highlights the necessity for social workers to resist dominant neoliberal and medicalized discourses which serve as mechanisms of power and control. The paper concludes with recommendations for social work practice with trans and gender diverse populations.


Molecular characterization of the high-affinity [3H]neuropeptide Y-binding component from the venom of Conus anemone.
The venom of the marine snail Conus anemone contains the 'ANPY toxin' which binds neuropeptide Y (NPY) and related insect peptides with nanomolar affinity. This toxin has initially been proposed to be a major 18.5 kDa component of the venom. Here we demonstrate that the 18.5 kDa proteins of venom produce at least five different bands in native electrophoresis and that none of them binds [3H]NPY. Instead, the ANPY toxin migrates as a distinct band on native electrophoresis and is only present as a minor component in the venom. Its approximate molecular weight is 17.5 kDa and its [3H]NPY binding activity is extremely stable below 37 degrees C, even in the absence of protease inhibitors.


Hypercalcaemia in adult hospital population: comparison of inpatients of 1966 with those of 1976.
During 1976, inpatients with hypercalcaemia at The Royal Melbourne Hospital were identified from the worksheets of the Department of Biochemistry and compared with those discovered in a similar study in 1966. In 1966, the estimation of plasma calcium level had to be ordered specifically, whereas in 1976, for technical reasons, the measurement of plasma calcium level was frequently performed when not requested. Despite a six-fold increase in plasma calcium in the rate of detection of hypercalcaemia. In both studies, malignant disease was the most common casue of hypercalcaemia, but primary common cause of hypercalcaemia, but primary hyperparathyroidism was found slightly more frequently in 1976. This study suggests that screening inpatients for hypercalcaemia is of little value.


Laparoscopic staging of the patient with incompletely staged early adenocarcinoma of the endometrium.
To determine the feasibility of laparoscopic staging in patients with presumed early stage but incompletely surgically staged adenocarcinoma of the endometrium. Thirteen patients with incompletely staged adenocarcinoma of the endometrium underwent laparoscopic staging. The women ranged in age from 36-74 years (mean age 64) and weighed 132-201 lb (mean 147.5). The interval between hysterectomy and laparoscopic staging ranged from 14-63 days, for an average of 47. All patients underwent inspection of the entire intraperitoneal cavity, procurement of pelvic washings, and/or pelvic or para-aortic lymphadenectomy, and two patients had remaining ovaries removed. Extrauterine disease was found in three patients: One had intraperitoneal washings positive for adenocarcinoma, and two had pelvic lymph nodes positive for microscopic carcinoma. The average number of lymph nodes removed was 17.5. There were no intraoperative complications. Estimated blood loss averaged less than 50 mL, and the mean hospital stay was 1.5 days. Our initial experience indicates that this is a safe, effective procedure that offers a short hospital stay. We consider laparoscopic staging an attractive option for some patients with incompletely staged early adenocarcinoma of the endometrium.


Atrazine exposure decreases cell proliferation in Chinese Hamster Ovary (CHO-K1) cell line.
The aim of this study was to determine the toxic effect of atrazine at the ovarian cellular level. Chinese Hamster Ovary (CHO-K1) cell line was used to evaluate the degree of in vitro atrazine cytotoxicity and the morphological changes were followed during the cell death. Application of four bioassays confirmed that atrazine decreases ovarian cell proliferation and IC(50) were determined with each assay after 72 h of exposure. The level of apoptosis in atrazine treated cells was low.


A micrometer-sized ultrasound contrast agent with nanometer-scale polygonal patterning surfaces.
To develop a smaller micro-sized bubble ultrasound contrast agent which composed of an insoluble, less-dense, self-assembled surfactant with a condensed crystallized nanometer-scale polygonal patterning surface. The microbubble was prepared by high-shear mixing a mixture of sucrose esters, glucose sugar, and water. The coulter counter was used to measure the size and concentration of the microbubble. Surface patterns of the microbubble were determined using vitrified samples under cryo-transmission electron microscopy. Myocardial contrast effects of six normal dog's myocardium were assessed. The diameter of the developed microbubble was smaller than Sonovue(®). Direct imaging of cryo-transmission electron microscopy revealed that the developed microbubble has a nanometer-scale polygonal surface pattern. Both the developed microbubble and Sonovue(®) effectively enhanced the myocardial contrast. The difference in the peak video intensity, the longevity of the contrast effect, and time-to-peak interval between both microbubbles were not statistically significant (NS). The microbubble with nanometer-scale polygonal patterning surfaces is a feasible and promising contrast agent for the ultrasound imaging.


Survival in unresectable AJCC stage I and II HCC and the effect of DEB-TACE: SEER versus tertiary cancer center cohort study.
To evaluate overall survival (OS) in unresectable American Joint Committee on Cancer (AJCC) stage I/II hepatocellular carcinoma (HCC) treated with drug-eluting-bead transarterial chemoembolization (DEB-TACE) versus best supportive care. OS in consecutive patients with AJCC stage I/II unresectable HCC diagnosed in 2005-2010 who underwent DEB-TACE and similar patients from SEER with no surgery/radiation recommended/performed was evaluated. Median OS from HCC diagnosis was 28.9 months (DEB-TACE) versus 10.0 months (SEER), p < 0.0001. Median OS was 36.3 months (DEB-TACE) versus 12.0 months (SEER) in AJCC I, and 27.9 months (DEB-TACE) versus 10.0 months (SEER) in AJCC II, p < 0.0001. Significant independent prognostic factors for OS were single primary tumor, no vascular invasion, normal α-fetoprotein and DEB-TACE. DEB-TACE in patients with unresectable AJCC stage I/II HCC was a significant independent prognostic factor for greater OS in a population-based study.


NADH-Activated Dual-Channel Fluorescent Probes for Multicolor Labeling of Live Cells and Tumor Mimic Spheroids.
The 1,4-dihydronicotinamide adenine dinucleotide (NADH) is one of the key coenzymes that participates in various metabolic processes including maintaining the redox balance. Early information on the imbalance of NADH is crucial in the context of diagnosing the pathogenic conditions. Thus, a dual-channel fluorescent probe (MQN) is developed for tracking of NADH/NAD(P)H in live cells. In the presence of NADH, only it showed emission signals at 460 and 550 nm upon excitation at 390 and 450 nm, respectively. The probe could provide accurate information on NADH levels in cancer cells (HeLa) and normal cells (WI-38). We observed that the NADH level in cancer cells (HeLa) is relatively higher than that in normal WI-38 cells. We received similar information on NADH upon calibrating with a commercial NADH kit. Moreover, we evaluated substrate-specific NADH expression in the glycolysis pathway and oxidative phosphorylation process. Also, the dual-channel probe MQN has visualized NADH manipulation in the course of depletion of GSH to maintain cellular redox balance. This dual-channel molecular probe MQN comes out as a new detection tool for NADH levels in live cells and tumor mimic spheroids.


[Effect of pH of Adsorption Buffers on the Number and Antigen-Binding Activity of Monoclonal Antibodies Immobilized on the Surface of Polystyrene Microplates].
The change in the concentration and antigen-binding activity of 28 monoclonal antibodies was studied after their adsorption on the surface of polystyrene microplates in buffers with different pH values (1.0, 2.8, 7.5, 9.6, and 11.9). We used 16 clones to the HIV p24 protein and 12 clones to the surface antigen of Hepatitis B Virus. The binding efficiency of adsorbed antibodies to the labeled antigen was evaluated by the slope of the linear region of the binding curve to the concentration axis. It was shown that the antigen-binding activity of six antibodies (21.5%) statistically significantly increased after adsorption at pH 2.8 and 11.9 as compared to pH 7.5 and 9.5. The maximum amount of antibodies was found to be adsorbed on the solid surface at pH 7.5. The analysis of the binding of 125I-HBs-antigen to adsorbed antibodies made it possible to evaluate the concentration of active antibodies on the polystyrene surface. It was shown that the increase in the antigen-binding activity was due to an increase in the proportion of antibodies with retained activity after adsorption at pH 2.8 and 11.9. Under these conditions, about 20% of the antibodies retained their antigen-binding activity, and 6% did so after immobilization at pH 7.5.


Design, baseline results of Irbid longitudinal, school-based smoking study.
To compare patterns of water pipe and cigarette smoking in an eastern Mediterranean country. In 2008, 1781 out of 1877 seventh graders enrolled in 19 randomly selected schools in Irbid, Jordan, were surveyed. Experimentation with and current water pipe smoking were more prevalent than cigarette smoking (boys: 38.7% vs 26.8%; 20.2% vs 9.0%, girls: 21.2% vs 9.5%; and 7.5% vs 2.3%, P<0.05 for all). Parent- and peer-smoking correlated more strongly with water pipe than with cigarette smoking. Water-pipe smoking is more prevalent than cigarette smoking at this early age.


Hyperglycemia exacerbates ischemic stroke not through increased generation of hydrogen peroxide.
Diabetes is one of the significant risk factors for ischemic stroke. Hyperglycemia exacerbates the pathogenesis of stroke, leading to more extensive cerebral damage and, as a result, to more severe consequences. However, the mechanism whereby the hyperglycemic status in diabetes affects biochemical processes during the development of ischemic injury is still not fully understood. In the present work, we record for the first time the real-time dynamics of H2O2 in the matrix of neuronal mitochondria in vitro in culture and in vivo in the brain tissues of rats during development of ischemic stroke under conditions of hyperglycemia and normal glucose levels. To accomplish this, we used a highly sensitive HyPer7 biosensor and a fiber-optic interface technology. We demonstrated that a high glycemic status does not affect the generation of H2O2 in the tissues of the ischemic core, while significantly exacerbating the consequences of pathogenesis. For the first time using Raman microspectroscopy approach, we have shown how a sharp increase in the blood glucose level increases the relative amount of reduced cytochromes in the mitochondrial electron transport chain in neurons under normal conditions in awake mice.


National incidence rate and related mortality for acute respiratory distress syndrome in France.
Despite many efforts to improve mechanical ventilation strategies and the use of rescue strategies, ARDS-related mortality remains high. The primary objective of this study was to determine the incidence and 90-day mortality of ARDS patients admitted to all French ICUs following the introduction of the Berlin definition of ARDS. The data source for this nationwide cohort study was the French national hospital database (Programme de Médicalisation des Systèmes d'Information (PMSI)), which systematically collects administrative and medical information related to all patients hospitalised and hospital stays. Patient-level data were obtained from the PMSI database for all patients admitted to an ICU from the 1st of January 2017, through the 31st of December 2017. The inclusion criteria were as follows: ICU patients ≥ 18 years old with at least one International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10) diagnosis code of J80 (ARDS), either as a primary diagnosis or a secondary diagnosis, during their ICU stay. A total of 12,846 ICU adult patients with ARDS were included. The crude incidence of ARDS was 24.6 per 100,000 person-years, varying with age from 6.7 per 100,000 person-years for those 18 through 40 years of age to 51.9 per 100,000 person-years for those 68 through 76 years of age. The in-hospital mortality rate was 51.1%. Day-90 mortality (day-1 being the ICU admission) was 51.2% and increased with age from 29.0% for patients 18 through 40 years of age to 69.3% for patients 77 years of age or older (p < 0.001). Only 53.9% of the survivors were transferred home directly after hospital discharge. The incidence and mortality of ARDS in adults in France are higher than that generally reported in other countries.


Contact dermatitis: Clinical practice findings from a single tertiary referral hospital, a 4-Year retrospective study.
It is estimated that 20% of the general population is sensitized to some kind of contact allergen. Contact dermatitis is one of the major occupational diseases worldwide. This disease has a higher prevalence in the female gender and is more frequently observed in the third or fourth decade of life. The main objective of this study was to describe the main sociodemographic and clinical characteristics of patients with contact dermatitis treated in the Allergy Unit of the San Juan De Dios Hospital - Caja Costarricense de Seguro Social. Clinical records of contact dermatitis outpatients from a single hospital were analyzed, in a 4-year retrospective observational study. At the time of the patch testing, patients showed a mean age of 42.2 years. Disease frequency was higher in the female population (female/male ratio of 4.2:1) and in patients mostly dedicated to household workchores. Most patients presented several years of disease history, and the hands were the highest affected body part. Patch testing revealed that nickel sulfate, Cl+Me-Isothiazolinone (Kathon CG), and thimerosal were allergens regularly associated with contact dermatitis in the analyzed population. To a great extent, sociodemographic and clinical characteristics identified in these patients resemble what is reported in other regions, including the Americas and worldwide. It is worth highlighting a high female proportion rate probably related to cultural aspects, a smaller percentage of irritant contact dermatitis that may be associated to institutional patient management, and a slight difference in the most common allergens when compared to other published studies.


Capsaicin treatment in adult Wistar-Kyoto and spontaneously hypertensive rats: neurochemical effects in the spinal cord.
The effects of s.c. capsaicin treatment on the thoracic spinal cord contents of immunoreactive substance P (ISP), norepinephrine (NE) and serotonin (5-HT) were investigated in adult male Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats. Capsaicin administered s.c. significantly reduced the concentration of ISP in the thoracic spinal cords from rats of both the WKY and SHR strains. The s.c. administration of capsaicin significantly increased the NE contents of the thoracic spinal cords in rats of both the WKY and SHR strains, and both vehicle- and capsaicin-treated SHR animals exhibited significantly greater thoracic spinal cord NE concentrations than did rats from the corresponding WKY treatment groups. In contrast, s.c. capsaicin treatment significantly increased the concentration of 5-HT only in the thoracic spinal cords of SHR subjects. These results strongly suggest that the neurochemical effects of s.c. capsaicin administration on the spinal cord were not specific to ISP-containing neurons since significant changes in the concentrations of NE and 5-HT were also produced by capsaicin treatment. These capsaicin induced changes in the concentrations of putative neurotransmitter substances in the spinal cord are related to previously reported alterations in nociception and cardiovascular regulation produced by s.c. capsaicin administration. Physiological and pharmacological mechanisms possibly relating the neurochemical changes produced by capsaicin to the behavioral and cardiovascular effects of the drug previously reported are advanced and discussed.


Evaluation of the genotoxic activity of 2-nitroanthrafurans.
We measured the genotoxic activities in two bacterial tests, the Salmonella/histidine assay (a reverse mutation assay) and the SOS chromotest (an assay for SOS induction in E. coli), of three 2-nitroanthrafurans: 2-nitroanthra[1,2-b]furan (R-7688), the isomeric compound 2-nitroanthra[2,1-b]furan (R-7686) and its 8-methoxylated derivative (R-7707). Their genotoxic activities were compared to that of 7-methoxy-2-nitronaphtho[2,1-b]furan (R-7000) which has been studied in previous works (Arnaise et al., 1986). We found that: (1) for all three 2-nitroanthrafurans, as generally observed for other 2-nitrofuran derivatives, the responses were correlated in the 2 tests and were decreased in the presence of an 'activating mixture' and in nitroreductase-deficient strains; (2) in contrast to what is usually observed with other 2-nitrofuran derivatives for which methoxylation increases genotoxic activity, the genotoxic activity of the methoxylated 2-nitroanthrafuran (R-7707) was comparable and may be even lower than that of the unsubstituted 2-nitroanthrafuran (R-7686); (3) the addition of a third ring that leads from 2-nitronaphthofurans to 2-nitroanthrafurans increased slightly the genotoxic activity of these compounds; (4) compounds with the oxygen heteroatom outside the 'bay region', R-7686 and R-7707, gave higher responses than their isomers with the oxygen heteroatom within the 'bay region', R-7688.


Roles of SIRT6 in kidney disease: a novel therapeutic target.
SIRT6 is an NAD+ dependent deacetylase that belongs to the mammalian sirtuin family. SIRT6 is mainly located in the nucleus and regulates chromatin remodeling, genome stability, and gene transcription. SIRT6 extensively participates in various physiological activities such as DNA repair, energy metabolism, oxidative stress, inflammation, and fibrosis. In recent years, the role of epigenetics such as acetylation modification in renal disease has gradually received widespread attention. SIRT6 reduces oxidative stress, inflammation, and renal fibrosis, which is of great importance in maintaining cellular homeostasis and delaying the chronic progression of kidney disease. Here, we review the structure and biological function of SIRT6 and summarize the regulatory mechanisms of SIRT6 in kidney disease. Moreover, the role of SIRT6 as a potential therapeutic target for the progression of kidney disease will be discussed. SIRT6 plays an important role in kidney disease. SIRT6 regulates mitochondrial dynamics and mitochondrial biogenesis, induces G2/M cycle arrest, and plays an antioxidant role in nephrotoxicity, IR, obstructive nephropathy, and sepsis-induced AKI. SIRT6 prevents and delays progressive CKD induced by hyperglycemia, kidney senescence, hypertension, and lipid accumulation by regulating mitochondrial biogenesis, and has antioxidant, anti-inflammatory, and antifibrosis effects. Additionally, hypoxia, inflammation, and fibrosis are the main mechanisms of the AKI-to-CKD transition. SIRT6 plays a critical role in the AKI-to-CKD transition and kidney repair through anti-inflammatory, antifibrotic, and mitochondrial quality control mechanisms. AKI Acute kidney injury, CKD Chronic kidney disease.


Association between the percent tissue altered and post-laser in situ keratomileusis ectasia in eyes with normal preoperative topography.
To investigate the association of a novel metric, percent tissue altered, with the occurrence of ectasia after laser in situ keratomileusis (LASIK) in eyes with normal corneal topography and to compare this metric with other recognized risk factors. Retrospective case-control study. The study included 30 eyes from 16 patients with bilateral normal preoperative Placido-based corneal topography that developed ectasia after LASIK (ectasia group) and 174 eyes from 88 consecutive patients with uncomplicated LASIK and at least 3 years of postoperative follow-up. The following metrics were evaluated: age, preoperative central corneal thickness, residual stromal bed, Ectasia Risk Score System scores, and percent tissue altered, derived from [PTA = (FT + AD)/CCT], where FT = flap thickness, AD = ablation depth, and CCT = preoperative central corneal thickness. In the ectasia group, percent tissue altered ≥40 was the most prevalent factor (97%), followed by age <30 years (63%), residual stromal bed ≤300 μm (57%), and ectasia risk score ≥ 3 (43%) (P < .001 for all). Percent tissue altered ≥ 40 had the highest odds ratio (223), followed by residual stromal bed ≤ 300 μm (74) and ectasia risk score ≥ 4 (8). Stepwise logistic regression revealed percent tissue altered ≥ 40 as the single most significant independent variable (P < .0001). Percent tissue altered at the time of LASIK was significantly associated with the development of ectasia in eyes with normal preoperative topography and was a more robust indicator of risk than all other variables in this patient population.


Bikaverin production by Fusarium species.
Production of bikaverin has been examined in 130Fusarium isolates belonging to 21 species. The highest yield of bikaverin was produced on autoclaved rice - up to 2.5g/kg of dry culture. Bikaverin was produced by the following species:F verticillioides, F sacchari varsubglutinans, F proliferatum, F anthophilum, F oxysporum, F dlamini, F nygamai, F napiforme, andF solani. SpeciesF coeruleum, F poae, F sporotrichioides, F tricinctum, F chlamydosporum, F culmorum, F graminearum, F cerealis (F crookwellense), F avenaceum, F acuminatum, andF equiseti did not produce bikaverin.The production of bikaverin determines the colour of the mentionedFusarium species cultures on agar media and on rice. The pigment has indicator properties and changes colour from red in acidic solution to violet-blue in alkaline. The role it plays in fungus metabolism is not elucidated.


Professional self-concept of nurses: a comparative study of four strata of nursing students in a Canadian university.
This study represents an effort to refine our understanding of measurement of professional self-concept by testing a tool across various strata of nursing students. The Professional Self Concept of Nurses Instrument, developed in studies of Australian nursing students, was applied to samples of basic undergraduate, post-basic and graduate students in a Canadian university nursing programme. The findings suggest that the tool is sensitive to the predictable development of professional self-concept as students advance through professional education, especially in the dimensions of professional practice and satisfaction. The authors propose that the instrument may have specific applications in evaluating the effects of traditional and innovative educational strategies upon the evolution of professional self-concept in nurses.


Impact of the 7-Day Disabled List Rule Change on Economics and Performance After Reported Concussion Injuries in Major League Baseball.
The incidence of concussions is increasing in Major League Baseball (MLB), and the cost of these injuries in 2008 was reportedly as high as US$423 million. Team officials are more aware of concussion injuries, and one measure to address this issue was the creation of a concussion-specific 7-day disabled list (DL) in 2011. To evaluate concussion trends among MLB players and the impact of concussion-specific 7-day DL status on postinjury player performance and team financials. Descriptive epidemiology study. From 2005 to 2016, a total of 112 players placed on the DL because of a concussion were identified using the MLB website and were verified using established news databases. Salary information for players was collected using MLB published data, and cost was calculated with a previously published formula utilizing the injured player's salary per game and adding the cost of his replacement. Performance metrics were compared before and after the rule change. The mean number of days on the DL decreased from 38.8 before 2011 to 29.2 after 2011. The mean annual cost per player before 2011 was $1.1 million and decreased to $565,000 after the rule change. Regression analyses demonstrated a downward trend in the mean cost (R = -0.61, P < .001). A comparison of postinjury performance metrics showed no significant differences with decreased time on the DL. The minimum 7-day DL change has not had a negative impact on reporting; instead, it has demonstrated decreased time on the DL and lower associated team costs. Performance metrics demonstrated no differences compared with before the rule change, suggesting that players are not negatively affected by decreased time on the DL.


Genotyping of human Echinococcus granulosus cyst in Morocco.
Echinococcus granulosus is the etiological agent of cystic echinococcosis (CE), also commonly called hydatidosis. This is a zoonotic infection endemic worldwide, including the Mediterranean basin and Morocco. The genetic variability of Echinococcus granulosus is known to influence development of parasitic cysts in different intermediate hosts, and therefore the epidemiology of infection. Molecular studies have identified nine genotypes of Echinococcus granulosus, eight of them affect humans, grouped today in four distinct species. In Morocco, molecular studies on CE cysts from animals showed the presence, for the large majority of cases, of the G1 genotype (« sheep strain » or Echinococcus granulosus sensu stricto), which is also the cause of the majority of human infections worldwide, and to a lesser extent of the other genotypes (G2 and G3) within Echinococcus granulosus sensu stricto complex. However, so far no genotyping of echinococcal cysts in Morocco has been carried out. We collected CE cysts material from 15 patients diagnosed with abdominal CE in the Meknès-Tafilalt region, Middle Atlas of Morocco, and an endemic area and genotyped by multiplex PCR. The only five cysts from which it was possible to successfully amplify the DNA were all belonging to the G1-G3 genotype, in line with the epidemiology of CE in animals in the same area. Our results add new information, on the human side, to the epidemiological picture of CE in the region, which are important in the context of any control plan for the infection.


Microvascular injection studies in rubeosis iridis and neovascular glaucoma.
Microvascular silicone injection, tissue clearing, and histologic examination were used to demonstrate the origin, distribution, and interconnections of newly formed iris and chamber angle blood vessels in four eyes with rubeosis iridis and neovascular glaucoma associated with diabetic retinopathy and central retinal vessel occlusion. The newly formed iris vessels that formed either a tight, evenly distributed (diabetic) or loose, irregularly distributed (central vessel occlusion) network in the iris originated from the normal iris arteries that were branches of either the major arterial circle or of the perforating branches of the anterior ciliary arteries, and drained into the normal iris and ciliary body veins and occasionally into the paralimbal episcleral veins. These newly formed iris vessels appeared to shunt intravascular fluid from arteries to veins. The newly formed anterior chamber angle vessels that formed tufts and arcades at the trabecular meshwork also originated from the roots of the iris arteries and the ciliary body arteries and connected with the peripheral neovascular iris network. In addition, the circumferentially running angle vessels that coursed within the trabecular meshwork branched into and coursed within a fibrosed Schlemm's canal and into two of its intrascleral collector channels. No open communication between these newly formed vessels and the Schlemm's canal-aqueous outflow system was seen.


Hippocampal-medial prefrontal cortex network dynamics predict performance during retrieval in a context-guided object memory task.
Remembering life episodes is a complex process that requires interaction among multiple brain areas. It is thought that contextual information provided by the hippocampus (HPC) can trigger the recall of a past event through the activation of medial prefrontal cortex (mPFC) neuronal ensembles, but the underlying mechanisms remain poorly understood. However, little is known about the coordinated activity between these structures during recall. We performed electrophysiological recordings in behaving rats during the retrieval phase of the object-in-context (OIC) memory task. Context-guided recognition of objects in this task requires the activity of both the mPFC and the ventral HPC (vHPC). Coherence, phase locking, and theta amplitude correlation analysis showed an increase in vHPC-mPFC LFP synchronization in the theta range when animals explore contextually mismatched objects. Moreover, we identified ensembles of putative pyramidal cells in the mPFC that encode specific object–context associations. Interestingly, the increase of vHPC-mPFC synchronization during exploration of the contextually mismatched object and the preference of mPFC incongruent object neurons predicts the animals' performance during the resolution of the OIC task. Altogether, these results identify changes in vHPC-mPFC synchronization and mPFC ensembles encoding specific object–context associations likely involved in the recall of past events.


Extraperitoneal laparoscopic radical prostatectomy: early experience in Thailand.
The transperitoneal approach is the conventional technique for laparoscopic radical prostatectomy. There are, however, several disadvantages of the approach, such as damage to intraperitoneal organs and long-term ileus. To prevent these complications, we propose an extraperitoneal approach that has been successfully used for open radical prostatectomy in treating patients with localized prostate cancer. The aim of this study was to evaluate the feasibility of extraperitoneal laparoscopic radical prostatectomy (ELRP). The outcomes of ELRP and open radical prostatectomy were also assessed and compared. There were two groups of patients with localized prostate cancer confirmed by transrectal ultrasound biopsy. Patients were included if they had no previous hormonal treatment and no previous transurethral prostatectomy. Group I comprised patients in whom open radical prostatectomy was performed between February 2001 and August 2005 ( n = 55). Group II comprised patients in whom ELRP was performed between December 2005 and October 2006 (n = 41). Early postoperative results, clinical outcomes and complications were analysed among the two groups using Chi-squared, t and Mann-Whitney tests. Group I and Group II did not show significant differences regarding age, clinical staging, hospitalization time, or pathological stage. Group II had a longer mean operative time than Group I (t test, p< 0.001). Median blood loss was significantly less in Group I (Mann-Whitney test, p < 0.001). Group II also demonstrated shorter catheter removal time (Mann-Whitney test, p = 0.003). In Group II, there were two rectal complications, including rectal injury and rectal necrosis, which were treated laparoscopically and conservatively without long-term problems. With experience, ELRP is feasible with equal oncological outcomes to open radical prostatectomy. Although a certain disadvantage was presented by ELRP, the less invasive surgery and reduction in operative blood loss were major advantages. It is suggested that a large and longitudinal trial be conducted to investigate the effectiveness of such an approach in managing functional outcomes.


Intracochlear schwannoma presenting as diffuse cochlear enhancement: diagnostic challenges of a rare cause of deafness.
Intracochlear schwannoma is a rare, treatable, cause of unilateral hearing loss. Due to the small size, position, and variable clinical and imaging features, diagnosis presents a significant challenge and is often delayed. We present a case of a patient with an intracochlear schwannoma presenting as a diffuse enhancement of the cochlea, mimicking an infectious or inflammatory process. The absence of focal nodularity in this lesion on multiple high-resolution MRI examinations led to a delay of over 3 years from the patient's initial presentation to surgical diagnosis. Clinical history and examination, imaging features, pathologic findings, and surgical management options are described.


Genetic variation in the histoarchitecture of the hippocampal region of mice.
Timm's sulphide-silver method and the histochemical procedures for the demonstration of AChE, MAO and SDH were applied to the brains of three strains of adult mice of either sex: C57/BL/6J, DBA/2J and NMRI. Differences between strains were found 1) in the sulphide-silver pattern of the molecular layer of area dentata, probably reflecting differences in entorhinal, ipsilateral and/or commissural connections, 2) in the distribution of the mossy fibers, 3) in the AChE-staining of a suprapyramidal zone of regio inferior, probably reflecting differences in septal connections, 4) in the AChE-staining of the induseum griseum. The staining patterns for MAO and SDH did not vary, at least not qualitatively, between the strains investigated. Variation in adult age and sex did not influence the results. Since the differences observed seemed to reflect a pattern of genetic differentiation, five more inbred mice (A/J, AKR/A, BALB/c/A, C3H/Tif, St/6Fi) were included to strengthen the hypothesis that different genetic systems are operating at separate septo-temporal levels in the same areas during the development of the hippocampal formation.


A general method for the synthesis of aryl [11C]methylsulfones: potential PET probes for imaging cyclooxygenase-2 expression.
A general one-pot method has been developed for the conversion of an aryl thiol moiety masked as the butyrate ester to the corresponding 11C-labeled methylsulfone group. The potential of this methodology has been demonstrated by the successful radiosynthesis of carbon-11 analogues of several highly selective cyclooxygenase-2 (COX-2) inhibitors such as Rofecoxib, Etoricoxib, and 3-(4-methylsulfonylphenyl)-4-phenyl-5-trifluoromethyl isoxazole in high yield. The chemical and radiochemical purities obtained for the 11C-labeled COX-2 inhibitors are >99% with a specific activity >1000 Ci/mmol.


AMPK governs lineage specification through Tfeb-dependent regulation of lysosomes.
Faithful execution of developmental programs relies on the acquisition of unique cell identities from pluripotent progenitors, a process governed by combinatorial inputs from numerous signaling cascades that ultimately dictate lineage-specific transcriptional outputs. Despite growing evidence that metabolism is integrated with many molecular networks, how pathways that control energy homeostasis may affect cell fate decisions is largely unknown. Here, we show that AMP-activated protein kinase (AMPK), a central metabolic regulator, plays critical roles in lineage specification. Although AMPK-deficient embryonic stem cells (ESCs) were normal in the pluripotent state, these cells displayed profound defects upon differentiation, failing to generate chimeric embryos and preferentially adopting an ectodermal fate at the expense of the endoderm during embryoid body (EB) formation. AMPK(-/-) EBs exhibited reduced levels of Tfeb, a master transcriptional regulator of lysosomes, leading to diminished endolysosomal function. Remarkably, genetic loss of Tfeb also yielded endodermal defects, while AMPK-null ESCs overexpressing this transcription factor normalized their differential potential, revealing an intimate connection between Tfeb/lysosomes and germ layer specification. The compromised endolysosomal system resulting from AMPK or Tfeb inactivation blunted Wnt signaling, while up-regulating this pathway restored expression of endodermal markers. Collectively, these results uncover the AMPK pathway as a novel regulator of cell fate determination during differentiation.


Bullying Interrupted: Victimized Students in Remote Schooling During the COVID-19 Pandemic.
We investigated how the transition to remote schooling during the COVID-19 pandemic affected the rates of bullying victimization among students in primary and lower secondary education and analyzed how a specific group of students, namely previously victimized students experienced remote schooling. The 2-month school lockdown offered a unique setting to explore the association between increasing Internet use and cyberbullying and reflect on the overlap between traditional bullying and cyberbullying in a new context. The main sample (n = 34 771) consisted of 10-16-year-old Finnish students who responded to an online survey during the remote schooling period in spring 2020. The sample was supplemented with data from two previous surveys conducted in the same schools in 2019 (n = 43,216) and in 2017 (n = 24,727). The prevalence of bullying victimization decreased substantially in all grade levels during the school lockdown. Physical isolation and surge in students' Internet use did not seem to lead to an increase in cyberbullying. Before-lockdown victimized students evaluated the time in remote schooling more positively than expected: they reported relatively high school liking and more teacher support than other students. The pre-existing gap in school adjustment between victimized and non-victimized students did not increase, but surprisingly, decreased. Our results highlight the notion that the main arena to fight bullying is within in-person interactions in schools.


Examining predictive factors of nursing students' self-confidence in multiple simulation sessions: A randomized controlled study.
The aim of this study was to examine and describe predictors of self-confidence among nursing students attending multiple simulation-based education sessions during a bachelor program. This was a randomized controlled longitudinal study. Participants (n = 146) were randomly assigned to a single or double set of acute care scenarios in each session. Participants attended 4 days of simulation sessions throughout a 3-year bachelor program. At four separate time points, both groups answered a survey including the Self-confidence scale and The Kolb Learning Style Inventory version 3.1. Descriptive statistics, cross-tabulations and linear models were employed to analyze the data. No significant interaction effects were found between the students' self-confidence at the end of the educational program and predictive factors favoring a double set of simulation scenarios. Most third-year students (n = 52, 85%) preferred a concrete learning mode at baseline. No significant predictive factors increasing self-confidence in favor of a double set of simulation scenarios could be demonstrated in this study. Hence, the continuous search for how to effectively implement SBE is of major importance for the development of SBE as a pedagogical method and remains a challenge.


Differential mitogenic effects of methyl isobutyl xanthine and a tumor growth factor on G1-arrested 3T3 T proadipocytes at the predifferentiation GD state and the growth-factor deficiency GS state.
Two growth-states exist in the G1 phase of the 3T3 T proadipocyte cell cycle. GD is the arrest state at which proadipocytes must growth-arrest prior to differentiation. GS is the arrest state at which proadipocytes growth-arrest following deprivation of serum or growth factors. In an attempt to further distinguish these arrest states, we have compared the relative ability of a variety of mitogens to induce GD- and GS-arrested cells to initiate DNA synthesis. The data show that GD-arrested cells at both high and low densities can be induced to proliferate by methyl-isobutyl-xanthine (MIX), whereas high and low density GS-arrested cells are not. The data also show that a tumor growth factor can stimulate the proliferation of both high and low density GD- and GS-arrested cells, whereas other agents are poor mitogens for high density GD-arrested cells. We conclude that MIX and a tumor growth factor (TUGF) can serve as probes to study the characteristics of the GD arrest state.


Effect of vitamin D on regression to normal glucose regulation and individual glycemic measures: A secondary analysis among participants adherent to the trial protocol in the randomized clinical trial vitamin D and type 2 diabetes (D2d) study.
To examine the effect of vitamin D on regression to normal glucose regulation (NGR) and individual glycemic measures in the D2d study. In per-protocol analyses, we examined time to new-onset diabetes; time to new-onset NGR defined as first occurrence of: 2-or-3 glycemic criteria in the normal range (NGR-1) or fasting plasma glucose (FPG) and 2-hour post-load-glucose (2hPG) in the normal range (NGR-2); proportion meeting NGR at the last study visit; and change in FPG, 2hPG, and HbA1c. Among 2423 participants, hazard ratio [HR] for diabetes was 0.84 [95%CI, 0.71, 0.99]). HR (95%CI) was 1.16 (0.99, 1.36) for new-onset NGR-1 and 1.06 (0.87, 1.30) for NGR-2. At the last visit, NGR-1 occurred in 12.4% vs. 9.5% participants in the vitamin D vs. placebo group (rate ratio for vitamin D 1.31 [1.02, 1.70]); whereas, NGR-2 occurred in 8.7% vs. 6.0% (rate ratio for vitamin D 1.45 [1.05, 2.00]). During follow-up, FPG, HbA1c, and 2hPG increased in both groups. Mean difference in FPG favored vitamin D (-0.80 mg/dL; 95%CI, -1.26, -0.33). In secondary analyses among participants adherent to the trial protocol, vitamin D lowered risk of developing diabetes and increased likelihood of NGR at the end of the study.


Exploring Black-White Differences in the Relationship Between Inflammation and Timing of Menopause.
Understanding the biosocial context of menopausal timing offers insight into social and health inequalities. Prior research on inflammatory chronic conditions suggests that inflammation may predict how early women experience menopause. We explore the ability of black race to moderate the overall relationship between chronic inflammation and timing of menopause. We use data from the National Social Life, Health, and Aging Project on inflammation, age of last menstruation, and race as well as relevant social and medical covariates. We conduct event history modeling to predict age at menopause by inflammatory biomarker levels. Using interaction analysis, we investigate whether being black may shape the overall relationship between inflammation status and menopause timing. Our analyses find no significant statistical interactions between black race and inflammation in predicting menopausal onset. However, we do identify independent correlational relationships between inflammation and black race (r = 0.136) and between menopausal timing and black race (r = -0.129) as well as inflammation (r = -0.138) that emerge as significant in corresponding regression models. We conclude that race probably does not moderate associations between inflammation and menopause. Yet, we also note that the original parameter estimate for black race's impact on menopausal onset (HR = 1.29, p < 0.05) becomes non-significant in a model that includes inflammation (HR = 1.06, p < 0.01). To translate our findings into policy and practice implications, we present alternate conceptualizations of black-white disparity in the inflammation-menopause relationship and recommend future research using mediation modeling.


Recovery, viability and clinical toxicity of thawed and washed haematopoietic progenitor cells: analysis of 952 autologous peripheral blood stem cell transplantations.
Cryopreservation and thawing of haematopoietic stem cells are associated with cell loss and infusion-related toxicities. We analysed viability, total nucleated cell (TNC) and CD34+ cell recovery, and infusion-related toxicities of 952 thawed and washed products. Mean TNC and CD34+ viable cells recoveries were 55.9+/-18.6 and 98.0+/-36.5%, respectively. Mean cell viability was 68.25+/-18.9%. TNC recovery was correlated with viability but independent of the initial nucleated cell concentration. No difference in TNC recovery or viability was observed according to underlying diseases, except for myeloma, for which these variables were significantly lower (P<0.05). CD34+ cell recovery was not correlated with viability or CD34+ initial count and was similar for all diseases. Cryostorage duration was not associated with cell loss. Immediate adverse events occurred in 169 patients (19%) and were moderate (grade I or II) for the majority of patients. Clinical toxicity was associated with a higher infused cell number and the presence of clumps in infused bags. The washing procedure of cell products lead to a low rate of adverse events, but patients transplanted with high cell numbers or bags in which clumps were identified are predisposed to such complications.


CD43 expression is associated with inferior survival in the non-germinal centre B-cell subgroup of diffuse large B-cell lymphoma.
We evaluated the prognostic significance of CD43 (SPN), a membrane glycoprotein, in 140 patients with diffuse large B-cell lymphoma (DLBCL) by tissue microarray (TMA) immunostaining, and gene expression profiling (GEP) in 43 patients. CD43 protein was expressed in 19% of the cases and was strongly related to the non-germinal centre B-cell (non-GCB) subgroup by both TMA and GEP. Patients with CD43(+) DLBCL had an inferior 3-year overall survival (OS) compared to those with CD43(-) DLBCL (50% vs. 76%, P = 0·01). Within the non-GCB subgroup, patients with CD43(+) DLBCL had a particularly poor 3-year OS (32% vs. 71%, P < 0·001). Gene set enrichment analysis within the activated B-cell subgroup revealed significant enrichment in the stromal-1 signature in CD43(-) cases. We conclude that CD43 is an adverse prognostic marker in DLBCL, and is preferentially expressed in the non-GCB subgroup. The dismal outcome of CD43(+) cases in the non-GCB subgroup may be explained, at least in part, by a less favourable microenvironment.


Burden of fine air pollution on mortality in the desert climate of Kuwait.
Middle Eastern desert countries like Kuwait are known for intense dust storms and enormous petrochemical industries affecting ambient air pollution. However, local health authorities have not been able to assess the health impacts of air pollution due to limited monitoring networks and a lack of historical exposure data. To assess the burden of PM2.5 on mortality in the understudied dusty environment of Kuwait. We analyzed the acute impact of fine particulate matter (PM2.5) on daily mortality in Kuwait between 2001 and 2016. To do so, we used spatiotemporally resolved estimates of PM2.5 in the region. Our analysis explored factors such as cause of death, sex, age, and nationality. We fitted quasi-Poisson time-series regression for lagged PM2.5 adjusted for time trend, seasonality, day of the week, temperature, and relative humidity. There was a total of 70,321 deaths during the study period of 16 years. The average urban PM2.5 was estimated to be 46.2 ± 19.8 µg/m3. A 10 µg/m3 increase in a 3-day moving average of urban PM2.5 was associated with 1.19% (95% CI: 0.59, 1.80%) increase in all-cause mortality. For a 10 µg/m3 reduction in annual PM2.5 concentrations, a total of 52.3 (95% CI: 25.7, 79.1) deaths each year could be averted in Kuwait. That is, 28.6 (95% CI: 10.3, 47.0) Kuwaitis, 23.9 (95% CI: 6.4, 41.5) non-Kuwaitis, 9.4 (95% CI: 1.2, 17.8) children, and 20.9 (95% CI: 4.3, 37.6) elderly deaths each year. The overwhelming prevalence of devastating dust storms and enormous petrochemical industries in the Gulf and the Middle East has intensified the urgency to address air pollution and its detrimental health effects. Alarmingly, the region's epidemiological research lags behind, hindered by a paucity of ground monitoring networks and historical exposure data. In response, we are harnessing the power of big data to generate predictive models of air pollution across time and space, providing crucial insights into the mortality burden associated with air pollution in this under-researched yet critically impacted area.


[Hyperekplexia -- a treatable neuropediatric disease].
Hyperekplexia (OMIM 138491) is primarily an autosomal dominant disease characterized by exaggerated startle reflex and neonatal hypertonia. If untreated it can be associated with sudden infant death from apnea or aspiration pneumonia and serious injuries. Different mutations of the alpha1-subunit of inhbitory glyzine receptor (GLRA1) could be found. Clonazepame, a gammaaminobutyric acid (GABA) receptor agonist is the therapy of choice. An early diagnose will lead to appropriate treatment and genetic counseling.


Predictors of noticing stroke educational campaign.
Long-term campaigns to improve stroke awareness, such as the campaign conducted in the Czech Republic since 2006, have not been effective. However, the small subpopulation that noticed the campaign had better stroke awareness than the population that did not. To better understand this awareness campaign responsiveness and to design more successful future campaigns, predictors of noticing campaigns were identified. This study is a secondary analysis of cross-sectional nationwide survey data of the Czech population older than 40 years, collected in 2009. The survey used a 3-stage random sampling method (area, household, and household member) and personal semistructured interview questionnaires concerning participants' stroke knowledge, demographic characteristics, medical history, and stroke information sources. To identify the association between these variables and whether the campaign was noticed (the primary outcome of the study), multivariate binary logistic regression analysis was used. A total of 601 participants were surveyed (90% response rate), 19% of them stated that they noticed the stroke awareness campaign. Primary independent predictors of campaign efficiency were heart disease (odds ratio [OR], 1.8; 95% confidence interval [CI], 1.0-3.2), obesity (OR, 2.4; 95% CI, 1.3-4.7), and current smoking (OR, .4; 95% CI, .3-.7). Tobacco smokers in particular should be targeted by stroke awareness campaigns, for example, through health warning labels on cigarette packs. People with some stroke risk factors, such as heart disease and obesity, are responsive to information about stroke. Therefore, educational campaigns should target the groups with increased risk of stroke.


Corneal sensitivity and vibratory perception in diabetes mellitus.
36 patients suffering from diabetes mellitus and 45 controls were subjected to blind studies for corneal sensitivity using Cochet & Bonnet's aesthesiometer and of vibratory perception of the left index finger and great toe by biothesiometer. 83% of the diabetics had a corneal sensitivity below 60 mm against 38% of the controls. Likewise a significantly reduced vibratory perception was noticed among the diabetics. Further, the reductions of corneal senstivity and vibratory perception were correlated in the diabetics. In both groups falling corneal sensitivity and vibratory perception were found with increasing age over and above 50 years. There is evidence to suggest that a reduced corneal sensitivity in relation to diabetes mellitus forms part of a polyneuropathy.


Adaptation and validation of a German version of the Multimorbidity Treatment Burden Questionnaire.
Patients with multiple long-term conditions often face a variety of challenges arising from the requirements of their health care. Knowledge of perceived treatment burden is crucial for optimizing treatment. In this study, we aimed to create a German version of the Multimorbidity Treatment Burden Questionnaire (MTBQ) and to evaluate its validity. The steps to translate the MTBQ included forward/back translation, cognitive interviews (n = 6) and a pilot test (n = 7). Psychometric properties of the scale were assessed in a cross-sectional survey with primary care patients aged 65 and older with at least 3 long-term conditions (n = 344). We examined the distribution of responses, dimensionality, internal reliability and construct validity. Cognitive interviewing and piloting led to minor modifications and showed overall good face validity and acceptability. As expected, we observed a positively skewed response distribution for all items. Reliability was acceptable with McDonald's omega = 0.71. Factor analysis suggested one common factor while model fit indices were inconclusive. Predefined hypotheses regarding the construct validity were supported by negative associations between treatment burden and health-related quality of life, self-rated health, social support, patient activation and medication adherence, and positive associations between treatment burden and number of comorbidities. Treatment burden was found to be higher in female participants (Mdn1 = 6.82, Mdn2 = 4.55; U = 11,729, p = 0.001) and participants with mental health diagnoses (Mdn1 = 9.10, Mdn2 = 4.55; U = 3172, p = 0.024). The German MTBQ exhibited good psychometric properties and can be used to assess the perceived treatment burden of patients with multimorbidity.


Hydatid disease of kidney.
A case of hydatid infestation of the kidney is presented. The natural history of the disease, the diagnostic workup including computerized tomography, and treatment are reviewed.


Effects of vagal blockade on neurohumoral systems in conscious dogs with heart failure.
It has been hypothesized that a decreased activity of vagal afferents might contribute to the activation of neurohumoral systems in congestive heart failure. Therefore, we studied the effects of vagal nerve blockade by local anesthesia on neurohormones in six conscious dogs before and after induction of heart failure by rapid right ventricular pacing (250 beats/min, 10 days). In healthy dogs, vagal blockade significantly increased plasma vasopressin levels (from 1.5 +/- .6 to 13.7 +/- 10.5 pg/ml, p less than 0.02), without significantly affecting plasma catecholamines and renin. After 10 days of pacing, mean arterial pressure and cardiac output were decreased, right atrial and pulmonary arterial pressures and plasma levels of norepinephrine, dopamine, and atrial natriuretic peptide were increased. In this state, vagal blockade significantly increased plasma renin activity (from 1.52 +/- .43 to 3.18 +/- .54 ngAI/ml/h, p less than 0.02) and plasma vasopressin (from 4.2 +/- 3.3 to 89.1 +/- 54.9 pg/ml, p less than 0.02), this increase being significantly higher than in healthy dogs. We conclude that in these dogs with low cardiac output state, which resembles early heart failure, vagal afferent activity is increased and effectively suppresses renin and vasopressin. This does not exclude the possibility that in later stages of heart failure vagal afferent dysfunction may develop, resulting in neurohumoral disinhibition.


Solid-phase synthesis of an N-(phenylalkyl)cinnamide library via Horner-Wadsworth-Emmons reaction.
A readily automated solid-phase approach to the synthesis of diverse N-(phenylalkyl)cinnamides, analogues of the NR2B antagonist 2, is described. The procedure utilizes polymer supported N-(phenylalkyl)amines, (diethylphosphono)acetic acid and a wide range of commercially available hydroxybenzaldehydes. The key step, a Horner-Wadsworth-Emmons reaction is achieved under mild conditions and was found to be general for a large number of benzaldehydes. A 225-member focused library was synthesized using a Tecan Combitec synthesizer.


mRNAs for clozapine-sensitive receptors co-localize in rat prefrontal cortex neurons.
The clinical efficacy of clozapine in treating schizophrenia may stem from its lack of receptor selectivity. If true, several clozapine-sensitive receptors may be co-expressed by neurons dysfunctional in schizophrenia. To test this hypothesis, neurons from the rat medial prefrontal cortex were acutely isolated and subjected to single cell RT-PCR analysis. The co-ordinated expression of five clozapine-sensitive receptors (D4, m1, 5-HT2a, 5-HT2c, 5-HT7) was examined in interneurons and pyramidal neurons. Profiling of GABAergic interneurons commonly revealed the co-expression of two or more clozapine-sensitive receptor mRNAs. Although co-expression of these receptors was less extensive in pyramidal neurons, it was also commonly found. These results suggest that clozapine's therapeutic effects may be mediated by antagonism of dopaminergic, cholinergic and serotoninergic signaling pathways at the single cell level.


Treating depression in primary care practice. An application of decision analysis.
Decision analysis approaches complex treatment issues by considering alternative strategies in an explicit and logical manner, and examining their outcomes in the face of varied assumptions. Significant data gaps impede full application of this framework to the treatment of depressed primary care patients. Nevertheless, decision analysis already can be useful in emphasizing needed clinical information in treating these patients and highlighting future directions for research.


DNA repair gene deficiency does not predispose human bronchial epithelial cells to benzo(a)pyrene-induced cell transformation.
The development of cost and time-efficient in vitro assays to predict carcinogenicity of chemicals has become a very important direction for toxicological research. In this study, we generated a series of human bronchial epithelial (HBE) cells defect in DNA repair gene excision repair cross-completion 1 (ERCC1), excision repair cross-completion 2 (ERCC2), ataxia-telangiectasia mutated (ATM) and mutS homolog 2 (MSH2), respectively. The inhibition of gene expression was verified by detection of mRNA and protein levels of respective genes. The suppression of these DNA repair genes has no impact on cell proliferation or cell transformation. Although we found that the transgenic HBE cells were more sensitive in benzo(a)pyrene (BaP)-induced DNA damages measured by cytokinesis-block micronucleus (CBMN) assay and comet assay, we failed to observe enhanced effects on induction of cell transformation. HBE cells defect in DNA repair pathways did not exhibit malignantly transformed phenotype up to 20 weeks of BaP treatment, indicating that the deficiency of ERCC1, ERCC2, ATM, or MSH2 alone did not shorten the latency of cell transformation. In contrast, we found that HBE cells expressing H-Ras or c-Myc were transformed 8 or 12 weeks after BaP treatment. These findings demonstrate that silencing of a single DNA repair gene does not confer cells susceptible to chemical-induced cell transformation.


The Influence of histamine H1-receptor on liver functions in immunized rabbits.
This study was designed to investigate the functional roles of histamine and histamine H1-receptor agonist and antagonist in the development of liver function impairment in immunized rabbits. The study comprised of six groups containing 18 rabbits each. Group III-VI received histamine (100 μg/kg, s.c.), H1R-agonist (HTMT, 10 μg/kg, s.c.), H1R-antagonist (pheniramine, 10 mg/kg, i.m.), and H1R-antagonist (pheniramine, 10 mg/kg, i.m.) plus histamine (100 μg/kg, s.c.), respectively, b.i.d. for 10 days. Group I (negative control) and group II (positive control) received sterile distilled water intramuscularly b.i.d. for 10 days. Groups II-VI were immunized on day 3 with intravenous injection of SRBC (1 × 10(9) cells/ml). Blood samples were collected on pre-immunization day 0, as well as on days 7-, 14-, 21-, 28-, and 58-post-immunization. Biochemical parameters AST, ALT, alkaline phosphatase and bilirubin [total bilirubin (TB), direct bilirubin (DB), and indirect bilirubin (IB)] were determined. On each experimental day, the mean values of serum enzymes and bilirubin in group I and group II showed no significant changes while in group III, IV, V, and VI, these enzymes and bilirubin levels showed significant changes (p < 0.05), when compared with their experimental values within the group. The levels of serum enzymes and bilirubin showed significant difference (p < 0.05) in group III, IV, V, and VI on each experimental day, when compared with the corresponding values of each other, and also compared with the corresponding values of group I and II. Histamine, HTMT, pheniramine, and combination of histamine + pheniramine cause hepatic function impairment in terms of altered serum enzymes and bilirubin levels. The present findings suggest that HTMT causes moderate liver function impairment while others show mild impairment.


Big data and prediction: Four case studies.
Has the rise of data-intensive science, or 'big data', revolutionized our ability to predict? Does it imply a new priority for prediction over causal understanding, and a diminished role for theory and human experts? I examine four important cases where prediction is desirable: political elections, the weather, GDP, and the results of interventions suggested by economic experiments. These cases suggest caution. Although big data methods are indeed very useful sometimes, in this paper's cases they improve predictions either limitedly or not at all, and their prospects of doing so in the future are limited too.


Hypo- and hyperresponders: individual differences in the response of serum cholesterol concentration to changes in diet.
The feeding of cholesterol-rich diets to random-bred animals results in marked interindividual differences in the response of serum cholesterol. Certain animals show only small responses (hyporesponders), whereas others develop high degrees of hypercholesterolemia (hyperresponders). Inbred strains of rabbits, rats, and mice differing in their sensitivity to dietary cholesterol are available. In these animals, and also in monkeys, the responsiveness to high-cholesterol diets has a strong genetic basis. The existence of hyper- and hyporesponders also holds in humans, though not as pronounced as in laboratory animals. Repeated trials with the same subjects have shown that persons exist with a consistently low or high response to increased intakes of cholesterol. However, "spontaneous," diet-independent within-person variations in the level of serum cholesterol markedly inflate the between-person variation in the response of serum cholesterol; both variations are of the same order of magnitude. Hypo- and hyperresponsiveness to dietary cholesterol extends to other hypercholesterolemic components of the diet. In humans and rabbits hyperresponsiveness to dietary cholesterol is associated with responsiveness to dietary saturated fatty acids. The mechanisms underlying hypo- and hyperresponsiveness to dietary cholesterol have not yet been unraveled. On the basis of available data, we propose that in hyperresponders, compared with hyporesponders, there is a higher hepatic efflux of cholesterol in low-density lipoproteins (LDL), or its precursors, after cholesterol consumption. This may be caused by insufficient inhibition of cholesterol biosynthesis and/or the high capacity of cholesterol absorption in the hyperresponders. The stimulation of LDL production accounts for the increase in LDL cholesterol in serum. The number of hepatic LDL receptors, which may be already decreased in hyperresponders, will decrease further through down-regulation. The receptor-mediated LDL clearance decreases, but the absolute amount of LDL cholesterol taken up by the cells via the receptor and by the receptor-independent pathway increases because of the increased level of LDL cholesterol. In this way a new equilibrium is reached in which LDL production equals LDL catabolism. The phenomenon of hypo- and hyperresponsiveness may have implications for counseling subjects who attempt to lower their serum cholesterol by diet. However, identification of true hyper- and hyporesponders is greatly hampered by within-person fluctuations of the level of serum cholesterol. No simple test is available to discriminate hypo- from hyperresponders.(ABSTRACT TRUNCATED AT 400 WORDS)


Apoptosis in fresh and cryopreserved cardiac valves of pig samples.
To analyse the influence of cold ischemic time (CIT) (2-24 h) and of cryopreservation (liquid phase) on the viability of the valvular fibroblasts and in the presence of apoptosis. Cardiac valves from 10 pigs were evaluated by anatomo-pathological study of the wall, muscle and leaflet. At the same time, the presence of cellular death due to apoptosis was investigated in two ways; directly on tissue by Apodetec system and by two-colour flow cytometry assay analyzing a suspension of fibroblast from valve leaflets using Anexina V and propidium iodure (PI). We established three groups of samples to compare different experimental conditions: 2 h of ischemia (group 1), 24 h of ischemia (group 2), and a programme of cryopreservation (-1 degrees C/min) after 2 h of ischemia, followed by storage in liquid nitrogen during a week and thawing was performed (group 3). The analysis of viabilities showed slight differences between all three groups. The results indicated CIT of 24 h undergoing more structural affectation than CIT of 2 h. Flow cytometry analysis did not show important differences between groups; however cryopreserved samples (group 3) slightly less viability and a higher percentage of death by apoptosis than group 1 and 2 using flow cytometry. Apoptosis was confirmed on tissue from all valves but mainly in samples of group 2 and group 3. In summary, the viability of the valves in the case of ischemic times of 2 h, 24 h or after cryopreservation/thawing differs slightly. The death of the cells is mainly mediated by necrosis and not by apoptosis.


Adverse childhood experiences and hallucinations.
Little information is available about the contribution of multiple adverse childhood experiences (ACEs) to the likelihood of reporting hallucinations. We used data from the ACE study to assess this relationship. We conducted a survey about childhood abuse and household dysfunction while growing up, with questions about health behaviors and outcomes in adulthood, which was completed by 17,337 adult HMO members in order to assess the independent relationship of 8 adverse childhood experiences and the total number of ACEs (ACE score) to experiencing hallucinations. We used logistic regression to assess the relationship of the ACE score to self-reported hallucinations. We found a statistically significant and graded relationship between histories of childhood trauma and histories of hallucinations that was independent of a history of substance abuse. Compared to persons with 0 ACEs, those with 7 or more ACEs had a five-fold increase in the risk of reporting hallucinations. These findings suggest that a history of childhood trauma should be looked for among persons with a history of hallucinations.


Use of Electronic Health Records to Characterize Patients with Uncontrolled Hypertension in Two Large Health System Networks.
Improving hypertension control is a public health priority. However, uncertainty remains regarding the optimal way to identify patients with uncontrolled hypertension using electronic health records (EHR) data. In this retrospective cohort study, we applied computable definitions to the EHR data to identify patients with controlled and uncontrolled hypertension and to evaluate differences in characteristics, treatment, and clinical outcomes between these patient populations. We included adult patients (≥18 years) with hypertension receiving ambulatory care within Yale-New Haven Health System (YNHHS; a large US health system) and OneFlorida Clinical Research Consortium (OneFlorida; a Clinical Research Network comprised of 16 health systems) between October 2015 and December 2018. We identified patients with controlled and uncontrolled hypertension based on either a single blood pressure (BP) measurement from a randomly selected visit or all BP measurements recorded between hypertension identification and the randomly selected visit). Overall, 253,207 and 182,827 adults at YNHHS and OneFlorida were identified as having hypertension. Of these patients, 83.1% at YNHHS and 76.8% at OneFlorida were identified using ICD-10-CM codes, whereas 16.9% and 23.2%, respectively, were identified using elevated BP measurements (≥ 140/90 mmHg). Uncontrolled hypertension was observed among 32.5% and 43.7% of patients at YNHHS and OneFlorida, respectively. Uncontrolled hypertension was disproportionately higher among Black patients when compared with White patients (38.9% versus 31.5% in YNHHS; p<0.001; 49.7% versus 41.2% in OneFlorida; p<0.001). Medication prescription for hypertension management was more common in patients with uncontrolled hypertension when compared with those with controlled hypertension (overall treatment rate: 39.3% versus 37.3% in YNHHS; p=0.04; 42.2% versus 34.8% in OneFlorida; p<0.001). Patients with controlled and uncontrolled hypertension had similar rates of short-term (at 3 and 6 months) and long-term (at 12 and 24 months) clinical outcomes. The two computable definitions generated consistent results. Computable definitions can be successfully applied to health system EHR data to conduct population surveillance for hypertension and identify patients with uncontrolled hypertension who may benefit from additional treatment.