Can Antidepressant Drug Impact on Blood Pressure Level in Patients with Psychiatric Disorder and Hypertension? A Randomized Trial.
High blood pressure (BP) has been known as a major risk factor for many chronic diseases. It should be noted, a psychiatric disorder which is common in the people living modern lifestyle may be one of the leading causes of hypertension, and many people are prescribed antidepressant each year. Hence, the purpose of this study was to evaluate the effect of selective serotonin reuptake inhibitors (SSRIs) and alprazolam which defined as antidepressant on the BP levels, and to compare the BP levels between the group of users and nonusers. This randomized clinical trial study was conducted at the Nohom Dey Hospital in the Torbat-e Heydarieh, Iran between December 2011 and March 2012. Participants comprised 101 psychiatric patients with hypertension that randomly separated into users and nonusers of antidepressant. The period of intervention lasted for 3 months. The mean of BP calculated by this formula (systolic BP [SBP] +2 diastolic BP [DBP])/3 which was the main outcome of the study. Users of antidepressant drugs did not have any significant changes in BP levels, except in patients who received SSRIs alone, significant improvement was observed in DBP (P = 0.04) and mean of BP (P = 0.03). While, in nonusers of antidepressant, significant development was observed in DBP, and mean of BP. Comparing the users and nonusers did not show any significant differences in SBP, DBP, and Mean of BP; even, when outcomes were adjusted for risk factors and antihypertensive drugs. Three months treatment with SSRIs and alprazolam did not have any effect on lowering BP level in patients with the psychiatric disorder.


A 52-Year-Old Man With Chest Pain and Dyspnea.
A 52-year-old man came to the cardiac surgery clinic for pulmonary thromboendarterectomy (PTE) evaluation. He had initially appeared at an outside hospital 1 year earlier, with chest pain and shortness of breath. He had no known chronic conditions. A CT pulmonary angiogram (CTPA) at that time showed a filling defect at the bifurcation of the main pulmonary artery. A transthoracic echocardiogram revealed mild mitral valve regurgitation, but otherwise the results were normal. As he was hemodynamically stable and not hypoxemic, he was treated solely by anticoagulation. Despite adhering to prescribed apixaban, he developed progressive dyspnea and reduced exercise tolerance over the subsequent year. A repeat CTPA performed 12 months after the initial presentation showed a persistent filling defect at the level of the pulmonary artery bifurcation, with a new extension now completely occluding the right main pulmonary artery. A pulmonary angiogram confirmed this complete occlusion, and right heart catheterization revealed precapillary pulmonary hypertension, with a mean pulmonary artery pressure of 50 mm Hg. His anticoagulation was transitioned to enoxaparin for presumed apixaban treatment failure, and an investigation for hypercoagulable conditions was initiated. His lupus anticoagulant test result was positive, but he did not meet the criteria for antiphospholipid syndrome because he was negative for anticardiolipin and β2-glycoprotein antibodies. Assays for antithrombin III, protein C, prothrombin gene, and factor V Leiden mutations produced normal results.


Biomedical and biophysical limits to mathematical modeling of pulmonary system mechanics: a scoping review on aerosol and drug delivery.
Undoubtedly, the construction of the biomechanical geometry systems with the help of computer tomography (CT) and magnetic resonance imaging (MRI) has made a significant advancement in studying in vitro numerical models as accurately as possible. However, some simplifying assumptions in the computational studies of the respiratory system have caused errors and deviations from the in vivo actual state. The most important of these hypotheses is how to generate volume from the point cloud exported from CT or MRI images, not paying attention to the wall thickness and its effect in computational fluid dynamic method, statistical logic of aerosol trap in software; and most importantly, the viscoelastic effect of respiratory tract wall in living tissue pointed in the fluid-structure interaction method. So that applying the viscoelastic dynamic mesh effect in the form of the moving deforming mesh can be very effective in achieving more appropriate response quality. Also, changing the volume fraction of the pulmonary extracellular matrix constituents leads to changes in elastic modulus (storage modulus) and the viscous modulus (loss modulus) of lung tissue. Therefore, in the biomedical computational methods where the model wall is considered flexible, the viscoelastic properties of the texture must be considered correctly.


Deletion of b1/b3 shows risk for expanse of Yq microdeletion in male offspring: Case report of novel Y chromosome variations.
This study aimed to report 1 family case with novel Y chromosome structural variations by an established next-generation sequencing (NGS) method using unique STSs. The case studied was from a family with a father and son (the proband). G-band staining was used for karyotype analysis. Y chromosome microdeletions were detected by sequence-tagged site (STS)-PCR analysis and a new NGS screening strategy. Semen analysis showed that the proband was azoospermic. The patient had an abnormal karyotype (45,X[48%]/46,XY[52%]). His father exhibited a normal karyotype. STS-PCR analysis showed that the proband had a deletion of the AZFb+c region, and his father had no deletion of STS markers examined. The sequencing method revealed that the patient had DNA sequence deletions from nt 20099846 to nt 28365090 (8.3 Mb), including the region from yel4 to the Yq terminal, and his father exhibited a deletion of b1/b3 and duplication of gr/gr. The proband was advised to undergo genetic counseling, and consider the use of sperm from a sperm bank or adoption to become a father. The proband was azoospermic. AZFc partial deletions may produce a potential risk for large AZFb+c deletions or abnormal karyotypes causing spermatogenic failure in men. The NGS method can be considered a clinical diagnostic tool to detect Y chromosome microdeletions. The partial AZFc deletions and/or duplications can be a risk of extensive deletions in offspring.


Mind the gap: the role of time between sex with two consecutive partners on the transmission dynamics of gonorrhea.
Both the duration of sexual partnerships and the time between two consecutive partnerships (gap length) varies between populations. We use a mathematical model with multiple partnership durations and gap lengths to identify the types of relationship cycles that sustain gonorrhea transmission in the United Kingdom. A mathematical model for gonorrhea transmission was constructed which tracks the duration of partnerships and their preceding gap lengths. The National Survey of Sexual Attitudes and Lifestyles was used to parameterize the model population into 5 different partnership lengths (mean of 1 day, 2 weeks, 8 weeks, 30 weeks, and 10 years) and 3 preceding gap lengths (14 days, 8 weeks, and 1.5 years). The model was able to reproduce patterns of gonococcal infection in the United Kingdom. Assortative (like-with-like) mixing of individuals with short gaps between partnerships was required for gonorrhea infection to persist. Prevalence was highest in individuals with short (>1 day-<1 month) and midterm partnership durations (>1 month-<3 months). Interventions (such as increased condom use) targeted at those with medium-term partnerships were most effective at reducing prevalence; in contrast targeting interventions at those with short partnerships but longer gap lengths (i.e., the group with the highest number of sexual partners) had relatively less impact. Our model suggests that gonorrhea is sustained by the presence of a small group of individuals with short gap lengths and medium length partnerships. Interventions targeted at this group are more effective than those targeted at individuals with high numbers of sexual partners but longer gap lengths.


Performance of single and multi-atlas based automated landmarking methods compared to expert annotations in volumetric microCT datasets of mouse mandibles.
Here we present an application of advanced registration and atlas building framework DRAMMS to the automated annotation of mouse mandibles through a series of tests using single and multi-atlas segmentation paradigms and compare the outcomes to the current gold standard, manual annotation. Our results showed multi-atlas annotation procedure yields landmark precisions within the human observer error range. The mean shape estimates from gold standard and multi-atlas annotation procedure were statistically indistinguishable for both Euclidean Distance Matrix Analysis (mean form matrix) and Generalized Procrustes Analysis (Goodall F-test). Further research needs to be done to validate the consistency of variance-covariance matrix estimates from both methods with larger sample sizes. Multi-atlas annotation procedure shows promise as a framework to facilitate truly high-throughput phenomic analyses by channeling investigators efforts to annotate only a small portion of their datasets.


Evaluation of a novel powered hip orthosis for walking by a spinal cord injury patient: a single case study.
The aim of this case study was to identify the effect of a powered hip orthosis on the kinematics and temporal-spatial parameters of walking by a patient with spinal cord injury (SCI). Two orthoses were evaluated while worn by an incomplete SCI subject with a T-8level of injury. Gait evaluation was performed when walking with an Isocentric Reciprocating Gait Orthosis (IRGO) and compared to that demonstrated by a newly powered version of the orthosis; based on the IRGO superstructure but incorporating powered hip joints using an electrically motorized actuator that produced active hip joint extension and flexion. The powered hip orthosis, when compared to the IRGO, increased the speed of walking, the step length and also the cadence demonstrated by this subject. Vertical and horizontal compensatory motions with new orthosis decreased. Hip angles when walking with this orthosis were comparative to those demonstrated by normal walking patterns. The hip actuator produced positive effects on the kinematics and temporal-spatial parameters of gait during level-ground walking trials, resulting in an alternative approach to walking by SCI patients.


Biological detectors in liquid chromatography.
The applicability of isolated organ preparations as chromatographic detectors was demonstrated. An appropriately designed detector cell (biological detector) applicable in both on-line and off-line modes was developed. Deproteinized sera from healthy volunteers and schizophrenic patients and human amniotic fluid were fractionated by gel-permeation, ion-exchange and reversed-phase liquid chromatography. Ultraviolet absorption and biological activity were compared. The results show that isolated organ preparations selected according to the needs of particular experiments meet the essential criteria of conventional chromatographic detectors. The use of isolated organs allows the detection of biologically active substances in a matrix of physicochemically closely related, but biologically distinct, fluid components. Biological detectors may also provide valuable additional information concerning the chemical structure of biologically active agents in an early stage of isolation.


Technical requirements for the licensing of pseudorabies (Aujeszky's disease) vaccines in the European Union.
Under the light of current scientific knowledge, particularly with the progress of molecular biology and of the definition of assays to be performed, it is possible to know, as accurately as possible, the biological properties of a vaccine. Most requirements of EP monographs and Directive 92/18 are founded on that concept. It is clear that there is a balance between safety and efficacy in the case of a live attenuated viral strain that means the more efficient a strain, the less safe it can be. Nevertheless, the problem is more complex; considerable progress has been done to set up new finished products and particularly with the adjuvants which are used now even in combination with live attenuated AD strains. The efficacy of a vaccine can be greatly enhanced, maintaining good local and general safety. But a debate always occurs when it is necessary to determine the acceptability threshold of a vaccine with regard to its safety and efficacy. The points of view are often very divergent. But, in any case, this threshold depends on the local conditions in the different countries. It is clear that objectives of a vaccination program and the requirements about a vaccine cannot be the same in heavily infected countries with a compulsory vaccination program as in countries or regions with a low prevalence of AD infection or with an absence of any infection. Moreover, it must also be considered that vaccines constitute only one element of a control or eradication program targeted against Aujeszky's disease virus.


The evolution of symptoms in the early course of non-affective psychosis.
Most previous studies investigating the factor structure of psychosis have focussed on chronic samples. First episode samples with longitudinal follow up are few. To investigate the stability and validity of symptom factors, a sample of 257 patients with DSM IV nonaffective psychoses were assessed using the PANSS during the acute first episode and at 3- and 18-month follow up. Exploratory factor analysis of the changes in PANSS item scores over time gave a five-factor solution. This was consistent with the solutions to factor analyses at the initial assessment and each of the follow-ups. However, there was progression over follow-up. Confirmatory factor analysis demonstrated that symptom ratings at 18-month follow-up fitted the models from existing research, in relatively chronic samples, better than the ratings at the initial assessment. A psychomotor poverty factor showed most stability over time and a positive symptom factor most change. Factors showed different associations with demographic and external variables, further supporting their validity.


Palliative radiation and fractionation in medicare patients with incurable non-small cell lung cancer.
Palliative radiation therapy (RT) can improve quality of life but also incurs time and financial costs. The aim of this study was to evaluate factors associated with use and intensity of palliative RT for incurable non-small cell lung cancer (NSCLC). This was a retrospective analysis of Medicare's Surveillance, Epidemiology and End Results data. We identified patients who were diagnosed with incurable (American Joint Committee on Cancer 6th edition stage IIIB with malignant effusion or stage IV) NSCLC between 2004 and 2011. Univariable and multivariable logistic regressions were used to identify factors associated with the receipt of palliative RT and the use of >10 fractions during the first course of radiation. Among patients who were treated with radiation, freestanding versus hospital-based center information was collected on the basis of the location of the RT delivery claim. Among 55,258 patients with incurable NSCLC, 38% (21,053 patients) received palliative RT during the first year after diagnosis. Among patients who received RT, 56% (11,717 patients) received >10 fractions. On multivariable analysis, factors associated with greater RT use included younger age group (overall P < .01), lower modified Charlson comorbidity score (overall P < .01), female sex (odds ratio [OR]: 1.1; P < .01), marital status (OR: 1.1; P < .01), and chemotherapy use (OR: 3.6; P < .01). Predictors for >10 fractions were chemotherapy use (OR: 1.7; P < .01) and treatment at a freestanding versus hospital-based facility (58% vs 43%; OR: 1.7; P < .01). More than a third of patients diagnosed with incurable lung cancer receive palliative RT and 56% received >10 fractions. The use of RT varied by region and patient characteristics, and patients treated at freestanding RT centers were more likely to receive >10 fractions. Further research into factors that influence treatment decisions including potential financial incentives may contribute to the high value and strategic utilization of palliative RT.


Tumor immunogenicity dictates reliance on TCF1 in CD8+ T cells for response to immunotherapy.
Stem-like CD8+ T cells are regulated by T cell factor 1 (TCF1) and are considered requisite for immune checkpoint blockade (ICB) response. However, recent findings indicate that reliance on TCF1+CD8+ T cells for ICB efficacy may differ across tumor contexts. We find that TCF1 is essential for optimal priming of tumor antigen-specific CD8+ T cells and ICB response in poorly immunogenic tumors that accumulate TOX+ dysfunctional T cells, but is dispensable for T cell priming and therapy response in highly immunogenic tumors that efficiently expand transitory effectors. Importantly, improving T cell priming by vaccination or by enhancing antigen presentation on tumors rescues the defective responses of TCF1-deficient CD8+ T cells upon ICB in poorly immunogenic tumors. Our study highlights TCF1's role during the early stages of anti-tumor CD8+ T cell responses with important implications for guiding optimal therapeutic interventions in cancers with low TCF1+CD8+ T cells and low-neo-antigen expression.


Rebamipide significantly inhibits indomethacin-induced mitochondrial damage, lipid peroxidation, and apoptosis in gastric epithelial RGM-1 cells.
Nonsteroidal antiinflammatory drugs (NSAIDs) cause complications such as gastrointestinal injury. NSAIDs were recently reported to cause mitochondrial injury: to dissipate the mitochondrial transmembrane potential (MTP), and to induce mitochondrial permeability transition pore (PTP), which liberates cytochrome c. This enzyme generates reactive oxygen species (ROS) thereby triggers caspase cascade and cellular lipid peroxidation, resulting in cellular apoptosis. However, the mechanism of this NSAID-induced MTP's role in cellular apoptosis remains unknown. Rebamipide, an antiulcer drug, is reported to scavenge ROS and to show the protective effects on indomethacin-induced tissue peroxidations. Since cytochrome c and its generation of ROS are involved in indomethacin-induced cellular apoptosis, rebamipide may attenuate mitochondrial damage. The aim of this study was to elucidate whether indomethacin induces both the MTP decrease and cellular apoptosis, and the effect of rebamipide on these phenomena. We examined the effect of rebamipide on 1) MTP change, 2) lipid peroxidation, 3) apoptosis, and 4) caspase activation using gastric mucosal epithelial cell-line treated with indomethacin. With a specially designed fluorescence analyzing microscope system, MTP change, cellular lipid peroxidation, and cellular apoptosis were investigated with the small star, filled following fluorescent dyes, MitoRed, DPPP, and Hoechst 33,258, respectively. Indomethacin treatment decreased MTP but increased both cellular lipid peroxidation and cellular apoptosis via caspase 3 and 9 activation. Rebamipide clearly inhibited these phenomena {in vitro}. We demonstrated that fluorescent dyes such as MitoRed, DPPP, and Hoechst 33,258 are useful indicators for detecting oxidative cellular injuries in living cells. Rebamipide exerts a protective effect on mitochondrial membrane stability in gastric epithelial cells.


Formation of monoclonal antibody against a major ginseng component, ginsenoside Rb1 and its characterization.
The ratio of hapten and bovine serum albumin in an antigen conjugate was determined by matrix-assisted laser desorption/ionization mass spectrometry. A hybridoma secreting monoclonal antibody against ginsenoside Rb1 was produced by fusing splenocytes immunized with a ginsenoside Rb1- bovine serum albumin conjugate with HAT-sensitive mouse myeloma cell line, P3-X63-Ag8-653. A very small cross-reaction appeared with ginsenoside Rc and ginsenoside Rd. The full measuring range of the assay extends from 20 ngml-1 to 400 ngml-1 of ginsenoside Rb1.


Peptide-based radiopharmaceuticals: future tools for diagnostic imaging of cancers and other diseases.
Small synthetic receptor-binding peptides are the agents of choice for diagnostic imaging and radiotherapy of cancers due to their favorable pharmacokinetics. Molecular modification techniques permit the synthesis of a variety of bioactive peptides with chelating groups, without compromising biological properties. Various techniques have been developed that allow efficient and site-specific labeling of peptides with clinically useful radionuclides such as (99m)Tc, (123)I, (111)In, and (18)F. Among them, (99m)Tc is the radionuclide of choice because of its excellent chemical and imaging characteristics. Recently, many (99m)Tc-labeled peptides have proven to be useful imaging agents. Beside (99m)Tc-labeled peptides, several peptides radiolabeled with (111)In and (123)I have been prepared and characterized. In addition, (18)F-labeled peptides hold clinical potential due to their ability to quantitatively detect and characterize a variety of human diseases using positron-emission tomography. The availability of this wide range of peptides labeled with different radionuclides offers multiple diagnostic and therapeutic applications. Various receptors are over-expressed in particular tumor types and peptides binding to these receptors can be used to visualize tumor lesions scintigraphically. Thus, radiolabeled peptides have potential use as carriers for the delivery of radionuclides to tumors, infarcts, and infected tissues for diagnostic imaging and radiotherapy. Many radiolabeled peptides are currently under investigation to determine their potential as imaging agents. These peptides are designed mainly for thrombus, tumor, and infection/inflammation imaging. This article presents recent developments in small synthetic peptides for imaging of thrombosis, tumors, and infection/inflammation.


Select strengths and biases of models in representing the Arctic winter boundary layer over sea ice: the Larcform 1 single column model intercomparison.
Weather and climate models struggle to represent lower tropospheric temperature and moisture profiles and surface fluxes in Arctic winter, partly because they lack or misrepresent physical processes that are specific to high latitudes. Observations have revealed two preferred states of the Arctic winter boundary layer. In the cloudy state, cloud liquid water limits surface radiative cooling, and temperature inversions are weak and elevated. In the radiatively clear state, strong surface radiative cooling leads to the build-up of surface-based temperature inversions. Many large-scale models lack the cloudy state, and some substantially underestimate inversion strength in the clear state. Here, the transformation from a moist to a cold dry air mass is modelled using an idealized Lagrangian perspective. The trajectory includes both boundary layer states, and the single-column experiment is the first Lagrangian Arctic air formation experiment (Larcform 1) organized within GEWEX GASS (Global atmospheric system studies). The intercomparison reproduces the typical biases of large-scale models: Some models lack the cloudy state of the boundary layer due to the representation of mixed-phase micro-physics or to the interaction between micro-and macrophysics. In some models, high emissivities of ice clouds or the lack of an insulating snow layer prevent the build-up of surface-based inversions in the radiatively clear state. Models substantially disagree on the amount of cloud liquid water in the cloudy state and on turbulent heat fluxes under clear skies. Observations of air mass transformations including both boundary layer states would allow for a tighter constraint of model behaviour.


Function of the C. elegans T-box factor TBX-2 depends on interaction with the UNC-37/Groucho corepressor.
T-box transcription factors are important regulators of development in all animals, and altered expression of T-box factors has been identified in an increasing number of diseases and cancers. Despite these important roles, the mechanism of T-box factor activity is not well understood. We have previously shown that the Caenorhabditis elegans Tbx2 subfamily member TBX-2 functions as a transcriptional repressor to specify ABa-derived pharyngeal muscle, and that this function depends on SUMOylation. Here we show that TBX-2 function also depends on interaction with the Groucho-family corepressor UNC-37. TBX-2 interacts with UNC-37 in yeast two-hybrid assays via a highly conserved engrailed homology 1 (eh1) motif located near the TBX-2 C-terminus. Reducing unc-37 phenocopies tbx-2 mutants, resulting in a specific loss of anterior ABa-derived pharyngeal muscles and derepression of the tbx-2 promoter. Moreover, double mutants containing hypomorphic alleles of unc-37 and tbx-2 exhibit enhanced phenotypes, providing strong genetic evidence that unc-37 and tbx-2 share common functions in vivo. To test whether interaction with UNC-37 is necessary for TBX-2 activity, we developed a transgene rescue assay using a tbx-2 containing fosmid and found that mutating the tbx-2 eh1 motif reduced rescue of a tbx-2 null mutant. These results indicate that TBX-2 function in vivo depends on interaction with UNC-37. As many T-box factors contain eh1 motifs, we suggest that interaction with Groucho-family corepressors is a common mechanism contributing to their activity.


[Prevalence and severity of pulmonary embolism are dependent on clinical and paraclinical parameters : Analysis of 1,943 consecutive patients with CT pulmonary angiography].
Patients with pulmonary embolism (PE) have heterogeneous symptoms. Clinical scores and age-adjusted D‑dimer should help clinicians to establish the correct diagnosis. A cohort of 1,943 consecutive patients with positive D‑dimer levels who were referred for CT pulmonary angiography (CTPA) over a period of 5 years to rule PE in or out were retrospectively analyzed. On CTPA n = 362 (19 %) had PE. The prevalence of PE increased stepwise with increasing D‑dimer levels (prevalence of PE with 10 percentiles of D‑dimers was: 3 %, 4 %, 7 %, 8 %, 8 %, 21 %, 20 %, 27 %, 37 %, 52 %; p < 0.001). D‑dimers > 2.0 were significantly associated with PE (OR 7.17 95 % CI 5.27-9.76, p < 0.001). Chest discomfort and tachypnea showed no association with PE. Dyspnoea, pleuritic pain, and general fatigue showed significant associations with age: pleuritic chest pain was more frequent in patients aged < 76 years than in patients aged > 76 years (15 % vs 3 %; p < 0.001) and was highly significantly associated with PE (OR 4.99 95 % CI 2.83-8.81; p < 0.001). General fatigue was more prevalent in patients aged > 76 years (44 % vs 24 %; p < 0.001). PE patients with D‑dimers > 6.0 mg/l were hemodynamically more compromised than patients with D‑dimers < 6.0 mg/l: tachycardia 32 % vs 20 %, p = 0.015; right ventricular strain on echocardiography: 38 % vs 23 %, p = 0.003; right ventricular strain on ECG: 27 % vs 13 %; p = 0.001; resuscitation 4 % vs 0 %, p = 0.003; lytic therapy 6 % vs 1 %, p = 0.014. The symptoms of PE patients are often vague. Particularly in older patients, fatigue may be the only symptom. The absolute level of D‑dimers, particularly > 2.0 mg/l, is a strong predictor of PE. A D‑dimer level > 6.0 mg/l is associated with more severe hemodynamic impairment in patients with PE.


Detection of human Enterovirus 71 reverse transcription loop-mediated isothermal amplification (RT-LAMP).
In this study, a one-step, single-tube reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay was developed and validated for the detection of human Enterovirus 71 (EV71), the major aetiological agent of hand, foot and mouth disease (HFMD). Reverse transcription loop-mediated isothermal amplification assay was optimized to amplify VP1 gene in the presence of a specific primer set and Bst DNA polymerase at an isothermal temperature of 63°C for 1 h. Amplified products were evaluated by visual inspection and agarose gel electrophoresis. The detection limit of RT-LAMP assay was 10(-5) 100 TCID50 or 160 copies in samples after RNA extraction, which was 10-fold higher in sensitivity than traditional reverse transcription polymerase chain reaction (RT-PCR). The specific positive amplification was only observed in EV71 strains, while no amplification was detected in other tested viruses. Digestion with a specific Escherichia coli restriction enzymes V (EcoR V) demonstrated that the amplified product was unique. A good correlation between RT-LAMP and real-time RT-PCR was observed on the basis of the analysis of 33 clinical samples. Reverse transcription loop-mediated isothermal amplification is a novel, alternative microbiological approach for rapid, sensitive and specific detection of EV71 in HFMD. Reverse transcription loop-mediated isothermal amplification assay is suitable for the diagnosis of EV71 infection as a routine diagnostic tool for HFMD because of fewer requirements of experimental conditions such as private clinics, field applications as well as an epidemiological survey in epidemic areas. RT-LAMP can also be used as an alternative method for EV71 detection.


Evaluation of standardized triple intrathecal therapy toxicity in oncohematological pediatric patients.
Background The administration of triple intrathecal therapy with methotrexate, cytarabine and a corticosteroid for the prophylaxis and treatment of neoplastic cell infiltration in the central nervous system in hematological malignancies is a widespread practice. There is limited information available about its toxicity profile. Several factors related to intrathecal preparation can affect toxicity. Thus, it was decided to standardize intrathecal chemotherapy, trying to obtain the best toxicity profile. Objective To assess the toxicity of a standardized triple intrathecal chemotherapy in oncohematological pediatric patients and to establish risk factors of toxicity. Setting Oncohematological pediatric unit from a tertiary hospital in Spain. Methods Prospective, descriptive and observational study in which all the administrations of standardized triple intrathecal chemotherapy in pediatric patients were registered. Main outcome measure Toxicity of the intrathecal therapy was recorded and possible risk factors were assessed. Results A total of 269 administrations of triple intrathecal chemotherapy were registered in 41 patients (mean age = 6.6 ± 3.9 years). In 16.7% of the procedures, an adverse event was reported (total number of adverse events = 61). 47.5% were grade 1, 47.5% grade 2 and 4.9% grade 3. The administration of intrathecal chemotherapy inpatient and patient age ≥3 years were risk factors of toxicity in the multivariate analysis. Conclusions The administration of standardized triple intrathecal chemotherapy is related to a low frequency of toxicity and most of the adverse events registered were mild/moderate. The detection of adverse effects was significantly greater in children with age greater than or equal to three years and in hospitalized patients.


Behaviour and stability of thermodilution signals in a closed extracorporeal circuit: a bench study.
Thermodilution is the gold standard for cardiac output measurement in critically ill patients. Its application in extracorporeal therapy is limited, as a portion of the thermal indicator is drawn into the extracorporeal circuit. The behaviour of thermodilution signals in extracorporeal circuits is unknown. We investigated thermodilution curves within a closed-circuit and assessed the impact of injection volume, flow and distance on the behaviour of the thermodilution signals and catheter constants. We injected 3, 5, 7 and 10 ml of thermal indicator into a heated closed circuit. Thermistors at distances of 40, 60, 80, and 100 cm from the injection port recorded the thermodilution signals (at flow settings of 0.5, 1, 1.5, and 2 L/min). Area under the curve (AUC), rise time, exponential decay and catheter constants were analysed. Linear mixed-effects models were used to evaluate the impact of circuit flow, distance and injection volume. Catheter positioning did not influence AUC (78 injections). Catheter constants were independent of flow, injection volume or distance to the injection port. The distance to the injection port increased peak temperature and rise time and decreased exponential time constant significantly. The distance to the injection port did not influence catheter constants, but the properties of the thermodilution signal itself. This may influence measurements that depend on the exponential decay of the thermodilution signal such as right ventricular ejection fraction.


Information extraction from electronic medical documents: state of the art and future research directions.
In the medical field, a doctor must have a comprehensive knowledge by reading and writing narrative documents, and he is responsible for every decision he takes for patients. Unfortunately, it is very tiring to read all necessary information about drugs, diseases and patients due to the large amount of documents that are increasing every day. Consequently, so many medical errors can happen and even kill people. Likewise, there is such an important field that can handle this problem, which is the information extraction. There are several important tasks in this field to extract the important and desired information from unstructured text written in natural language. The main principal tasks are named entity recognition and relation extraction since they can structure the text by extracting the relevant information. However, in order to treat the narrative text we should use natural language processing techniques to extract useful information and features. In our paper, we introduce and discuss the several techniques and solutions used in these tasks. Furthermore, we outline the challenges in information extraction from medical documents. In our knowledge, this is the most comprehensive survey in the literature with an experimental analysis and a suggestion for some uncovered directions.


Regulation of Pol II Pausing during Daily Gene Transcription in Mouse Liver.
Cell autonomous circadian oscillation is present in central and various peripheral tissues. The intrinsic tissue clock and various extrinsic cues drive gene expression rhythms. Transcription regulation is thought to be the main driving force for gene rhythms. However, how transcription rhythms arise remains to be fully characterized due to the fact that transcription is regulated at multiple steps. In particular, Pol II recruitment, pause release, and premature transcription termination are critical regulatory steps that determine the status of Pol II pausing and transcription output near the transcription start site (TSS) of the promoter. Recently, we showed that Pol II pausing exhibits genome-wide changes during daily transcription in mouse liver. In this article, we review historical as well as recent findings on the regulation of transcription rhythms by the circadian clock and other transcription factors, and the potential limitations of those results in explaining rhythmic transcription at the TSS. We then discuss our results on the genome-wide characteristics of daily changes in Pol II pausing, the possible regulatory mechanisms involved, and their relevance to future research on circadian transcription regulation.


Effect of glycosaminoglycans and divalent cations on the thermal properties of dipalmitoylphosphatidylcholine.
The effect of glycosaminoglycans (GAG) and divalent cations on the thermal properties of dipalmitoyl-phosphatidylcholine (DPPC)-water systems was examined in order to model some interactions taking place on low density lipoprotein (LDL) surfaces. The thermal properties of these systems were measured by differential scanning calorimetry (DSC). According to the results, all three glycosaminoglycans used (chondroitin-4-sulfate, chondroitin-6-sulfate and heparin) were effective but to a different extent. Calcium ions enhance the interaction more than magnesium ions, probably because divalent cations form bridges between the negatively charged groups of GAGs and the headgroups of lipids. It is conceivable that similar processes might occur in the case of LDL.


Awareness and willingness to participate in clinical trials in Togo.
Clinical Trials (CTs) are the key when it comes to informing clinical decision-making processes. There is a very low number of CTs conducted in Togo, and there is no study that assessed the willingness of Togolese to participate in CTs. The aim of this study was to assess public awareness and willingness to participate in CTs in Togo. We designed a cross-sectional study, using an online survey with Google Form in the general population, carried out from December 2019 to March 2020. An Excel sheet was generated from the Google Form, and we performed a descriptive analysis using IBM SPSS Statistics 21. All variables were presented as frequencies and percentages. This study involved 210 participants. The findings of this study are showing that Togolese are reasonably aware about CTs, and they have a positive intention to participate, but they are ignorant of national CTs regulations. Although unawareness and unwillingness may be universally common, one challenge in Togo is the lack of communication. The findings of this study are encouraging. The National Bioethics Committee for Health needs to be better communicative, and providing training in clinical research is essential.


[Neurogenic spinal deformities. II. Sitting and seating devices: principles and indications].
Sitting is a dynamic process regulated by motor reactions due to endogenic and exogenic influences. Patients with neuromuscular disorders may not continuously adapt their sitting posture but seating devices may improve their quality of life. Prerequisites for the indication of high quality and cost effective seating devices are guidelines for planning and fitting which consider both pathomorphologic mechanisms and the patient's personality. In order to avoid functional problems and pain caused by an insufficient seating device it is necessary to pay attention to the exact indication, time, and combination of technical options. Planning within a seating clinic needs teamwork. First the goal of treatment is defined; it depends on the functional deficit, on the daily living activities of the patient, and on the social environmental factors. Second fitting of the devices follows defined treatment guidelines. By examination of the sensoric and statomotoric system it is possible to classify the patient's sitting or seating ability for simplifying indication: three groups of active sitters who are able to change position of trunk and pelvis actively are differentiated from three groups of passive sitters who have to be seated.


Phylogenetic relationships of the macaques (Cercopithecidae: Macaca), inferred from mitochondrial DNA sequences.
To study the phylogenetic relationships of the macaques, five gene fragments were sequenced from 40 individuals of eight species: Macaca mulatta, M. cyclopis, M. fascicularis, M. arctoides, M. assamensis, M. thibetana, M. silenus, and M. leonina. In addition, sequences of M. sylvanus were obtained from Genbank. A baboon was used as the outgroup. The phylogenetic trees were constructed using maximum-parsimony and Bayesian methods. Because five gene fragments were from the mitochondrial genome and were inherited as a single entity without recombination, we combined the five genes into a single analysis. The parsimony bootstrap proportions we obtained were higher than those from earlier studies based on the combined mtDNA dataset. Excluding M. arctoides, our results are generally consistent with the classification of Delson (1980). Our phylogenetic analyses agree with earlier studies suggesting that the mitochondrial lineages of M. arctoides share a close evolutionary relationship with the mitochondrial lineages of the fascicularis group of macaques (and M. fascicularis, specifically). M. mulatta (with respect to M. cyclopis), M. assamensis assamensis (with respect to M. thibetana), and M. leonina (with respect to M. silenus) are paraphyletic based on our analysis of mitochondrial genes.


Atrophy of hand muscles associated with gastric cancer: coincidence or paraneoplastic manifestation?
A case of a stage IB gastric cancer associated with spontaneous muscle atrophy of both hands is reported. The cause of this atrophy was not apparent with current neurologic diagnostic modalities. Although the association of gastric cancer with muscle atrophy may be coincidental, it may be part of a paraneoplastic syndrome.


Nutritional deficiencies in morbidly obese patients: a new form of malnutrition? Part B: minerals.
Even though in the Western world there is almost no limitation to a wide variety of food supply, nutritional deficiencies can be found in both normal-weight population and in the obese population. In this review, we examine the prevalence and manifestations of various mineral deficiencies in obese patients.


A comparison of two assessments of high level cognitive communication disorders in mild traumatic brain injury.
Individuals with traumatic brain injury (TBI) frequently encounter cognitive communication disorders. Deficits can be subtle but can seriously influence an individual's ability to achieve life goals. Feedback from rehabilitation facilities indicated that high level cognitive communication disorders are not consistently identified in the acute setting. This study aimed to compare the cognitive communication results from two screening assessments, the Cognistat and the Cognitive Linguistic Quick Test (CLQT), in participants with a mild traumatic brain injury and to relate these findings to a range of prognostic indicators. Eighty-three adults post-TBI (16-81 years; 79.5% males) were recruited at an acute trauma centre. The language components of the two tests were analysed. The CLQT identified more participants with an impairment in language than the Cognistat, 19.3% compared to 1.2% (p < 0.001). No clinical variables relating to the participants' brain injury were found to be associated with language impairment. This study found that the CLQT identified more individuals with high level cognitive communication deficits than the Cognistat in the acute setting.


Renal sympathetic baroreflex during normoxia and during hypoxia in conscious and in anesthetized rabbits.
The responses of renal sympathetic nerve activity (RSNA) to changes in mean arterial pressure (MAP) during normoxia and hypoxia was studied in conscious rabbits and during anesthesia with pentobarbitone (PB) by determining the RSNA baroreflex curves. In conscious rabbits, the gain in RSNA response was greater and the range of MAP between minimum and maximum levels of RSNA was narrower than in anesthetized rabbits. The renal sympathetic baroreflex was augmented by hypoxia, indicating a central excitatory interaction between the effects of baro- and chemoreceptor stimulation. However, hypoxia produced no significant change in median blood pressure. During anesthesia with PB, resting MAP was decreased, median blood pressure was lowered, and renal sympathetic baroreflexes were less pronounced. Renal sympathetic baroreflex was augmented by hypoxia, and there was a significant increase in median blood pressure. These results provide direct evidence of an inhibitory effect of PB on the response of RSNA to baro- and chemoreceptor stimulation.


NAIP expression increases in a rat model of liver mass restoration.
The neuronal apoptosis inhibitory protein (NAIP) is a constituent of the NLRC4 inflammasome, which plays a key role in innate immunity, and an antiapoptotic protein. Recently, we reported the previously undescribed role of NAIP in cell division. The liver is one of the body's most actively regenerative organs. Given the novel mitotic role of NAIP, we examined its expression in hepatic mass restoration. The major liver lobe of Wistar rats was removed, and samples from both newly formed liver tissue, assessed by positive Ki67 immunostaining, and the remnant, intact liver lobes from hepatectomized rats were taken 3 and 7 days after surgery. Naip5 and Naip6 mRNA levels were significantly higher in regenerating hepatic tissue than in intact liver lobe tissue, and this increase was also observed at the protein level. Naip5 and Naip6 mRNA in situ hybridization showed that this increase occurred in the hepatic parenchyma. The histology of the regenerated liver tissue was normal, with the exception of a noticeable deficiency of hepatic lobule central veins. The results of this study suggest the involvement of NAIP in liver mass restoration following partial hepatectomy.


A phase II study of doxifluridine in elderly patients with advanced gastric cancer: the Japan Clinical Oncology Group Study (JCOG 9410).
A previous phase II study of doxifluridine in non-elderly patients with advanced gastric cancer demonstrated a favorable survival with mild toxicity, despite a low response rate. The objectives of this study were to evaluate efficacy and feasibility of this agent for elderly patients. This study protocol required elderly patients, aged 76-80 years, with advanced gastric cancer and having no prior chemotherapy. Doxifluridine, at a dose of 1400 mg/m(2)/day, was administered for four consecutive days followed by a 10-day rest. Between October 1994 and March 1998, 18 patients were registered. The study was then closed because of poor accrual. Toxicity was moderate; three patients suffered from grade 3 anemia and one patient each had grade 3 thrombocytopenia, nausea/vomiting and grade 4 diarrhea. There was one partial response, seven with no change and 10 with progressive disease, yielding a response rate of 5.6%. The median progression-free survival and median survival time for the 18 patients were 55 and 164 days, respectively, with a 1-year survival rate of 5.6%. Although the number of patients was too small to draw any definitive conclusions, this study failed to demonstrate the survival advantage of doxifluridine.


Diagnostic efficacy of the optical flow ratio in patients with coronary heart disease: A meta-analysis.
Coronary atherosclerotic heart disease (CAD) remains one of the most serious diseases threatening human health and life. PCI (Percutaneous Coronary Intervention) is the most common treatment for patients with CAD. A rigorous and comprehensive assessment of coronary artery lesions is now needed before PCI, however, there is no consensus on how best evaluate the combination of various intracavitary imaging techniques. By merging the benefits of physiological assessment and high-definition imaging, the optical flow ratio (OFR) has emerged as a novel technology with promising prospects for application. A systematic review of the literature was conducted. Studies that met the criteria of the meta-analysis were considered to assess OFR and FFR (fractional flow reserve). And the summary values of sensitivity and specificity of diagnostic tests and summary receiver operating curves (SROC) were calculated. A total of 5 studies were included. The sensitivity and specificity of OFR in the diagnosis of coronary artery lesions were 0.83 (95% CI: 0.75-0.88) and 0.94 (95% CI: 0.91-0.96), respectively; the positive likelihood ratio and the negative likelihood ratio were 14 (95% CI: 9.3, 21.3) and 0.18 (95% CI:0.13, 0.27), respectively. OFR showed good correlation and consistency with FFR. The new OFR technique achieve an encouraging diagnostic performance, which also showed good correlation and consistency with FFR.


Transcriptomic analysis reveals differentially expressed genes and key immune pathways in the spleen of the yak (Bos grunniens) at different growth stage.
Yak is one of the rare and unique cattle species on the Qinghai-Tibetan Plateau, which has strong adaptability to the extreme environment of the plateau. The spleens are important functional organs that enable animals to adapt to their external environment and are vital in the growth and development process. To further investigate changes in immune function during yak development, we compared the transcriptome profiles of spleen tissues among juvenile (1-day old), youth (15-months old), and prime (5-years old) yaks. Immunology of spleen development was evaluated based on histological analyses and global gene expression was examined by using RNA-sequencing (RNA-seq) technology. In this work, we found 6378 genes with significant differences between the spleen of juvenile yak and youth yak, with the largest difference between groups. There were 3144 genes with significant differences between the spleen of young yak and prime yak, with the smallest differences between groups. Further, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were conducted for the functional annotation of these genes. GO and KEGG analysis showed that some of them were related to growth, disease, immune, and metabolism. However, the genetic mechanism underlying the adaptability of yak spleens at different ages to harsh plateau environments remains unknown. These findings are important for studying the mechanisms of spleen development in yaks of different age groups.


[Assessment of tele-expertise among elderly subjects in retirement homes].
Chronic wounds (leg ulcers, pressure ulcers, diabetic foot ulcers, etc.) constitute a real public health problem and engender high economic and human costs. Due to the declining physical and mental conditions of our elderly subjects and their rural environment, we created a computer program to assist with chronic wound management in elderly subjects living in retirement homes and to reduce the amount of ambulance transportation. Each participating establishment was provided with a digital camera and its own secure e-mail address in order to allow photographs to be sent anonymously. Patients with chronic wounds entailing treatment difficulties were included. Details were recorded of the number of tele-expertise consultations given, the chronic wound type, the number of hospitalizations or medical consultations, and the number of ambulance trips avoided. The project was evaluated at 1 year. Of the 40 establishments invited to take part, 22 agreed to do so but only the first 10 respondents were accepted for participation in the pilot feasibility study. Funding ("Health and social prize" provided by the Haute-Vienne region Social Security Office - CPAM) was used to purchase the cameras. Beginning on 15 April 2010, 10 establishments for the elderly sent photographs of 34 patients presenting 26 chronic wounds and tele-expertise was provided for 10 pressure ulcers, two diabetic feet and 14 leg ulcers. Over a two-year period, this program helped avoid 20 trips for patients and enabled rapid hospitalization of nine patients by the university hospital by optimizing chronic wound management for patients residing in establishments for the elderly.


Gender-specific development of experimental autoimmune cholangitis induced by double-stranded RNA.
Here we investigated the gender difference in murine cholangitis resembling human primary biliary cholangitis (PBC) caused by synthetic double-stranded RNA, and underlying hepatic innate immune responses. Female C57Bl/6 mice given repeated injections of polyinosinic-polycytidylic acid (poly I:C) for 24 weeks developed overt cholangitis with positive serum anti-mitochondria-M2 antibody, whereas male mice showed minimal pathological changes without induction in autoantibody. Poly I:C induced hepatic inflammatory cytokines and type-I interferons predominantly in females. Hepatic expression levels of toll-like receptor (TLR) 3 and melanoma differentiation-associated protein (MDA) 5 were equivalent in both genders; however, both mRNA and protein levels of retinoic acid-inducible gene (RIG)-I were nearly doubled in female livers. Following 4-week injections of poly I:C, not only hepatic RIG-I, but also TLR3 and MDA5 showed female-predominance. Moreover, hepatic RIG-I levels were 25% lower in ovariectomized mice, whereas supplementation of 17 β-estradiol enhanced hepatic RIG-I expression, as well as cytokine induction. These results clearly indicate that hepatic RIG-I expression is potentiated by estrogen, and triggers gender-dependent hepatic innate immune response against double-stranded RNA, which most likely play a pivotal role in the pathogenesis of autoimmune cholangiopathies including PBC.


Cushing's syndrome, nodular adrenal hyperplasia and virilizing carcinoma.
A 48-year-old hypertensive diabetic woman rapidly became virilized. Urine 17-oxo-and oxogenic steroids and plasma testosterone, androstenedione, DHEA, DHEA-sulphate and androstenediol were greatly elevated. Plasma cortisol was constantly high and was not suppressed by dexamethasone. Circulating immunoreactive ACTH was consistently detectable at 18-24 ng/l. A 450 g carcinoma arising from a nodular hyperplastic right adrenal gland was resected. Production by the tumour of 17a-hydroxypregnenolone, 17a-hydroxyprogesterone and five C-19 steroids, but very little prenenolone, progesterone or cortisol, was shown by blood sampling, tumour culture and dramatic falls after operation. The plasma cortisol fell to half, with no diurnal variation, consistent with persistent Cushing's syndrome, and the plasma ACTH rose to 55 ng/l. She died 3 months later from a myocardial infarction. Autopsy revealed a pituitary basophil adenoma at a site where radiologically there had been an indentation in the fossa floor for at least 7 years. The left adrenal gland showed nodular hyperplasia. Therefore we conclude that mild pituitary-dependent Cushing's syndrome may have been present for many years before development of a virilizing carcinoma. This case demonstrates that adrenal carcinoma in man can sometimes develop as a consequence of nodular adrenal hyperplasia which may in turn be due to long-standing trophic hyper-stimulation.


Tilted trans-sinus implants for the treatment of maxillary atrophy: case series of 35 consecutive patients.
To evaluate tilted trans-sinus implants for rehabilitation of the atrophic maxilla. A case series of 35 patients (32 consecutive edentulous and 3 partially edentulous patients) treated with trans-sinus dental implants is presented. Edentulous patients received 4 or 6 implants depending on anatomic conditions and a 12-unit final restoration; partially edentulous patients received 2 implants supporting a 3-unit partial fixed bridge. Thirty-five patients (14 men, 21 women) underwent rehabilitation. Thirty-two patients with 190 implants placed received a full-arch fixed prosthesis supported by axial and trans-sinus tilted implants. Three patients each received 2 implants with a 3-unit fixed restoration. The mean age at surgery was 59.2 ± 9.5 years. The cumulative survival rate was calculated only for the full-arch fixed prosthesis group and was 98.42%. Crestal bone loss averaged 0.9 ± 0.4 and 0.8 ± 0.5 mm for the axial and tilted implants, respectively, at the 12-month evaluation. Biological complications at the implant level were 1 case of peri-implantitis and 3 cases of mucositis; no patient developed sinus infections. The prosthetic complications encountered were screw loosening in 17.5% of cases and chipping of the esthetic part in 30% of cases. These complications were easily resolved chairside and did not lead to prosthetic failure. Trans-sinus tilted implants and sinus membrane distal displacement appear to be a viable minimally invasive alternative for the treatment of maxillary atrophy.


Hyperpolarized relaxometry based nuclear T1 noise spectroscopy in diamond.
The origins of spin lifetimes in quantum systems is a matter of importance in several areas of quantum information. Spectrally mapping spin relaxation processes provides insight into their origin and motivates methods to mitigate them. In this paper, we map nuclear relaxation in a prototypical system of [Formula: see text] nuclei in diamond coupled to Nitrogen Vacancy (NV) centers over a wide field range (1 mT-7 T). Nuclear hyperpolarization through optically pumped NV electrons allows signal measurement savings exceeding million-fold over conventional methods. Through a systematic study with varying substitutional electron (P1 center) and [Formula: see text] concentrations, we identify the operational relaxation channels for the nuclei at different fields as well as the dominant role played by [Formula: see text] coupling to the interacting P1 electronic spin bath. These results motivate quantum control techniques for dissipation engineering to boost spin lifetimes in diamond, with applications including engineered quantum memories and hyperpolarized [Formula: see text] imaging.


Effective strategies to prepare infants and families for home tracheostomy care.
In neonates tracheostomies are most often indicated to provide a stable airway for infants with congenital or acquired airway obstructions and to provide long-term mechanical ventilation. Learning to care for an infant with a tracheostomy can be challenging for both professionals and families. This article provides an overview of tracheostomy care and the essential elements of family teaching. The surgical procedure and basic anatomical changes are reviewed. Complications such as accidental decannulation, mucus plugging, infection, bleeding, and granulation tissue formation are discussed. Humidification is critical for the infant with a tracheostomy and humidification delivery methods are discussed. Further, an overview of the impact of the tracheostomy on normal development, such as swallowing and language development, is provided. Teaching parents to safely care for the infant with a tracheostomy at home requires careful planning and systematic education. The parents must acquire a unique set of technical skills demonstrating competence and comfort in providing stoma care, suctioning, and tube changes. Parents must be prepared to initiate cardiopulmonary resuscitation (CPR) and need to understand alterations in CPR techniques in infants with a tracheostomy. They also need to develop critical thinking skills to handle emergency situations. A safe transition to the home can be accomplished by using a multidisciplinary approach to coordinate all facets of care.


Effects of maternal hyperoxia with and without normocapnia in uteroplacental and fetal Doppler studies.
One hundred percent oxygen is given in pregnancy to improve fetal oxygenation, yet has been shown in both animal and human studies ex utero to increase cerebral vascular resistance. Adjusting end-tidal pCO2 (ET-pCO2) levels to normocapnic levels during hyperoxygenation offsets this effect in non-pregnant individuals. We aimed to evaluate the effect of maternal hyperoxygenation with and without maintaining normocapnia on the fetal and uteroplacental circulations in healthy near-term human pregnancies. Eight healthy pregnant women, serving as their own controls, sequentially breathed room air, breathed 100% oxygen, and underwent normocapnic hyperoxygenation (NH) in a three-phase experiment involving a tight-fitting facemask. Each phase lasted 10-15 min. After steady state had been reached, peak velocities and pulsatility index (PI) values were obtained from the uterine, umbilical and fetal middle cerebral arteries (MCA) by color/pulsed Doppler. In addition, maternal ventilation and ET-pCO2 were monitored. One hundred percent oxygen induced maternal hyperventilation and hypocapnea. Uterine artery PI and peak systolic velocities were stable during 100% oxygen. In contrast, during NH uterine artery PI values decreased by 21% (P=0.04). Umbilical artery PI and peak velocities were stable during 100% oxygen; PI increased by 16% during NH (P=0.056), with no change in peak velocities. Peak MCA velocities decreased by 8% during 100% oxygen, and by 9.6% during NH, while MCA-PI decreased by 13% during 100% oxygen and by 21% during NH (P=0.06). Maternal and fetal circulations exhibit divergent responses to 100% oxygen and NH. While no change is observed in the uteroplacental circulation on 100% oxygen, decreased resistance and increased flow velocity are evident during NH. Increased umbilical artery PI during NH with no change in absolute velocities may suggest a reduction in fetoplacental blood flow. Maintaining normocapnia during hyperoxygenation does not appear to beneficially influence the circulation of the near-term human fetus as it does in non-pregnant individuals.


Childhood abuse and association with adult depressive symptoms among people with cardiovascular disease.
To study the association between the total/different types of childhood abuse and adult depressive symptoms in people with cardiovascular disease (CVD). The subjects were people with CVD who continuously participated in the China Health and Retirement Longitudinal Study (CHARLS) life history survey and the 2018 wave of the CHARLS national baseline Survey. Multi-level logistic regression models were used to analyze the relationship between emotional neglect, physical neglect, physical abuse and adult depressive symptoms. A total of 4,823 respondents were included in this study. The incidence of childhood abuse (existed emotional neglect, physical neglect or physical abuse) was 43.58% among people over 45 years old with CVD, which was higher than that of the general population (36.62%, p < 0.05). Adjusted model showed that overall childhood abuse was associated with adult depressive symptoms (OR = 1.230, 95%CI:1.094-1.383). Among different types of childhood abuse, only physical abuse was associated with depressive symptoms in adulthood (OR = 1.345, 95%CI:1.184-1.528). Compared with that of the general population, the incidence of childhood abuse in CVD population is higher. Physical abuse in childhood increased the risk of depressive symptoms in adulthood. It suggested that the occurrence of depressive symptoms was the result of related factors in the whole life course. In order to prevent the depressive symptoms, childhood abuse also needs to be considered. It is very important to identify and prevent the continuation of childhood abuse in time.


Neuroimaging-evident lesional pathology associated with REM sleep behavior disorder.
Rapid eye movement (REM) sleep behavior disorder (RBD) is a potentially injurious parasomnia characterized by dream enactment behavior and polysomnographic REM sleep without atonia (RSWA). Recently, RBD not only has been shown to be strongly associated with synucleinopathy neurodegeneration but has also been rarely reported to be associated with structural lesions involving the brainstem or limbic system. The aim of this study was to describe the clinical, neuroimaging, and outcome characteristics in a case series of patients with lesional RBD. This is a retrospective case series from a tertiary care referral center. A total of 10 patients with lesional RBD were identified. Seven (70%) were men, with an average age of sleep symptom onset of 53.7 ± 17.0 years. Structural pathology evident on neuroimaging included four extraaxial (three meningiomas and one basilar fusiform aneurysm with brainstem compression) and six intraaxial (encephalomalacia, multiple sclerosis, vasculitis, autoimmune limbic encephalitis, and leukodystrophy) lesions. No patient developed parkinsonian features or cognitive impairment suggestive of synucleinopathy over an average of 45.4 ± 35.2 months of follow-up. RBD is rarely associated with non-synuclein structural lesions affecting the pons, medulla, or limbic system. The spectrum of lesional RBD comprises tumors, aneurysms, leukodystrophy, and autoimmune/inflammatory/demyelinating brain lesions.


Biasing a Monte Carlo chain growth method with Ramachandran's plot: application to twenty-L-alanine.
In this paper, we explore the possibility of using experimental observations in the Monte Carlo chain growth method that we have previously developed. In this method, the macromolecule (peptide, protein, nuclei acid, etc.) is grown atom-by-atom (or residue-by-residue, etc.) and partial chains are replicated according to their Boltzmann weights. Once the molecule completed, we are left with a Boltzmann-distributed ensemble of configurations. For long molecules, an efficient sampling of the (extremely large) phase space is difficult for obvious reasons (existence of many local minima, limited computer memory, etc.). In the case in which one is mainly interested in the low energy conformations, we have incorporated in the growth scheme experimental observations taken from the Protein Data Banks. More precisely, we have considered the case of twenty-L-alanine and we have used the (experimental) Ramachandran's plot for this residue. The biased growth procedure goes as follows: (a) each time one adds along the main backbone chain, either a carbon atom belonging to a carbonyl group, or a nitrogen atom, its dihedral angle (theta) or (psi) is drawn with a probability law that reflects the experimental Ramachandran (theta, psi) plot; (b) the bias introduced in this way is canceled through an extra term in the energy (replication energy = true energy + bias energy); (c) the configurations, generated at T = 1000 K, are then energy minimized.(ABSTRACT TRUNCATED AT 250 WORDS)


Perception of risk from automobile safety defects.
Descriptions of safety engineering defects of the kind that compel automobile manufacturers to initiate a recall campaign were evaluated by individuals on a set of risk characteristic scales that included overall vehicle riskiness, manufacturer's ability to anticipate the defect, importance for vehicle operation, severity of consequences and likelihood of compliance with a recall notice. A factor analysis of the risk characteristics indicated that judgments could be summarized in terms of two composite scales, one representing the uncontrollability of the damage the safety defect might cause and the other representing the foreseeability of the defect by the manufacturer. Motor vehicle defects were found to be highly diverse in terms of the perceived qualities of their risks. Location of individual defects within the factor space was closely associated with perceived riskiness, perceived likelihood of purchasing another car from the same manufacturer, perceived likelihood of compliance with a recall notice, and actual compliance rates.


The efficacy of febantel on gastrointestinal nematodes in sheep.
Febantel (Bay h 5757, Rintal) is a broad-spectrum anthelmintic of a new type. A single oral dose of 5 mg/kg is fully effective against larval and adult stages of Haemonchus contortus, Trichostrongylus colubriformis, Oesophagostomum columbianum, Ostertagia circumcincta and Bunostomum trigonocephalum in sheep.


Demographic and behavioral factors associated with daily sugar-sweetened soda consumption in New York City adults.
The objective of the study was to assess the relations of socioeconomic and behavioral factors to frequent consumption of sugar-sweetened soda among New York City (NYC) adults and the relation of frequent consumption to body mass index (BMI; kg/m(2)). Data from the 2005 NYC Community Health Survey, a population-based telephone survey, were analyzed. Frequent consumption was defined as drinking one or more 12-oz servings of sugar-sweetened soda on an average day; 9,865 adults, aged 18 years and older, provided valid responses. Logistic regression was used to identify factors associated with frequent consumption, and linear regression models were used to assess the relation of frequent consumption to BMI. An estimated 27.5% of NYC adults are frequent sugar-sweetened soda consumers. Frequent consumption is independently associated with low household income (odds ratio [OR] = 1.7, 95% confidence interval [CI] 1.4-2.1 for <200% vs. > or =600% federal poverty level) and with ethnic group and nativity (e.g., OR = 3.1, 95% CI 2.6-3.7 for U.S.-born blacks vs. whites). Men report more consumption then women, but an association of less education with frequent consumption is stronger among women. Adjusting for demographics, frequent consumption is associated with more television viewing and with less physical activity. Adjusting for demographics and behaviors, frequent consumption was associated with higher BMI among women (0.7 BMI units, 95% CI 0.1-1.2) but not among men. Disparities in sugar-sweetened soda consumption mirror obesity disparities. Improved surveillance and interventions are needed to better quantify and reduce consumption of sugar-sweetened beverages, especially in groups most impacted by obesity.


An analysis of competitive interactions between 3 hermit crab species.
Competition for empty gastropod shells in a group of three sympatric hermit crabs (Pagurus hirsutiusculus, Pagurus granosimanus, and Pagurus beringanus) was studied in the San Juan Archipelago, Washington State. Estimates of the competitive effects of each species on the others' shell supplies were derived using field data on shell utilization and the results of laboratory experiments to determine rates of acquisition and exchange of shells and preferences for different shell species. Each species experienced approximately an order of magnitude more intraspecific competition than interspecific competition for empty shells. This resulted from differences in preference for shell shapes, shell size use, and habitat use between P. hirsutiusculus and P. granosimanus, and largely from differences in habitat use between P. beringanus and the other two species. Experiments involving the release and recensusing of marked empty shells were used to estimate competitive effects more directly for the interaction between P. hirsutiusculus and P. granosimanus. Results were consistent with the estimates derived from data on resource partitioning. Possible causes of the low levels of interspecific competition are discussed, and results are compared with studies of other organisms that estimated both inter- and intra-specific competition.


GRADE concept 4: rating the certainty of evidence when study interventions or comparators differ from PICO targets.
This Grading of Recommendations Assessment, Development and Evaluation (GRADE) concept article offers systematic reviewers, guideline authors, and other users of evidence assistance in addressing randomized trial situations in which interventions or comparators differ from those in the target people, interventions, comparators, and outcomes. To clarify what GRADE considers under indirectness of interventions and comparators, we focus on a particular example: when comparator arm participants receive some or all aspects of the intervention management strategy (treatment switching). An interdisciplinary panel of the GRADE working group members developed this concept article through an iterative review of examples in multiple teleconferences, small group sessions, and e-mail correspondence. After presentation at a GRADE working group meeting in November 2022, attendees approved the final concept paper, which we support with examples from systematic reviews and individual trials. In the presence of safeguards against risk of bias, trials provide unbiased estimates of the effect of an intervention on the people as enrolled, the interventions as implemented, the comparators as implemented, and the outcomes as measured. Within the GRADE framework, differences in the people, interventions, comparators, and outcomes elements between the review or guideline recommendation targets and the trials as implemented constitute issues of indirectness. The intervention or comparator group management strategy as implemented, when it differs from the target comparator, constitutes one potential source of indirectness: Indirectness of interventions and comparators-comparator group receipt of the intervention constitutes a specific subcategory of said indirectness. The proportion of comparator arm participants that received the intervention and the apparent magnitude of effect bear on whether one should rate down, and if one does, to what extent. Treatment switching and other differences between review or guideline recommendation target interventions and comparators vs. interventions and comparators as implemented in otherwise relevant trials are best considered issues of indirectness.


Endoscopic Intermetatarsal Ligament Decompression.
Morton neuroma is an entrapment of the intermetatarsal nerve by the deep intermetatarsal ligament. It is usually treated conservatively. Surgery is considered if there is recalcitrant pain that is resistant to conservative treatment. The surgical options include resection of the neuroma or decompression of the involved nerve. Decompression of the nerve by release of the intermetatarsal ligament can be performed by either an open or minimally invasive approach. We describe 2-portal endoscopic decompression of the intermetatarsal nerve. The ligament is released by a retrograde knife through the toe-web portal under arthroscopic guidance through the plantar portal.


Disseminated Cryptococcus neoformans infection diagnosed by endoscopic ultrasound guided fine needle aspiration (EUS-FNA).
A 34-year-old woman was admitted to the hospital because she had an intermittent fever for two months. The patient had a history of contact with pigeons. She had no human immunodeficiency virus (HIV) infection, and her physical examination was normal. Computed tomography of the abdomen revealed intrahepatic bile duct dilatation and multiple retroperitoneal lymphadenopathies, and the largest enlarged lymph node was in hepatic hilum.


Endoscopic total sphenoethmoidectomy.
Endoscopic total sphenoethmoidectomy is a procedure reserved for the patient with extensive paranasal sinus disease. Candidates for this operation should have radiographic evidence of pansinusitis and be refractory to medical and lesser surgical management. Given these criteria, total sphenoethmoidectomy with frontal sinusotomy and antrostomy offers an excellent treatment for this patient population.


[Not Available].
On the basis of relevant clinical studies performed so far, selective COX-2 inhibitors exhibit a therapeutic advantage over conventional NSAIDs with regard to the incidence of gastrointestinal (GI) damage such as perforation, ulceration, and bleeding (PUBs). The results prove that a risk reduction could be demonstrated during long-term treatment (6-9 months); nevertheless, PUBs cannot be ruled out under treatment with selective COX-2 inhibitors. In contrast to this, dyspeptic symptoms occur very frequently and their incidence is comparable to that of conventional NSAIDs. The increased incidence of thromboembolic, cardiovascular events documented in the VIGOR study for rofecoxib versus naproxen was not confirmed by comparison to placebo and other NSAIDs in additional clinical studies. In clinical studies no clear signs of thrombotic effects have been described for the therapeutic administration of celecoxib. Based on preclinical investigations as well as on the thromboembolic, cardiovascular events reported in connection with the therapeutic use of COX-2 inhibitors, safety measures are necessary and further investigations are recommended.


Differential regulation of osteoclastogenesis by Notch2/Delta-like 1 and Notch1/Jagged1 axes.
Osteoclastogenesis plays an important role in the bone erosion of rheumatoid arthritis (RA). Recently, Notch receptors have been implicated in the development of osteoclasts. However, the responsible Notch ligands have not been identified yet. This study was undertaken to determine the role of individual Notch receptors and ligands in osteoclastogenesis. Mouse bone marrow-derived macrophages or human peripheral blood monocytes were used as osteoclast precursors and cultured with receptor activator of nuclear factor-kappaB ligand (RANKL) and macrophage-colony stimulating factor (M-CSF) to induce osteoclasts. Osteoclasts were detected by tartrate-resistant acid phosphatase (TRAP) staining. K/BxN serum-induced arthritic mice and ovariectomized mice were treated with anti-mouse Delta-like 1 (Dll1) blocking monoclonal antibody (mAb). Blockade of a Notch ligand Dll1 with mAb inhibited osteoclastogenesis and, conversely, immobilized Dll1-Fc fusion protein enhanced it in both mice and humans. In contrast, blockade of a Notch ligand Jagged1 enhanced osteoclastogenesis and immobilized Jagged1-Fc suppressed it. Enhancement of osteoclastogenesis by agonistic anti-Notch2 mAb suggested that Dll1 promoted osteoclastogenesis via Notch2, while suppression by agonistic anti-Notch1 mAb suggested that Jagged1 suppressed osteoclastogenesis via Notch1. Inhibition of Notch signaling by a gamma-secretase inhibitor suppressed osteoclastogenesis, implying that Notch2/Dll1-mediated enhancement was dominant. Actually, blockade of Dll1 ameliorated arthritis induced by K/BxN serum transfer, reduced the number of osteoclasts in the affected joints and suppressed ovariectomy-induced bone loss. The differential regulation of osteoclastogenesis by Notch2/Dll1 and Notch1/Jagged1 axes may be a novel target for amelioration of bone erosion in RA patients.


Granular-cell tumors (myoblastomas) of the anal region.
Three cases of granular-cell tumor of the perianal region are reported. The clinical and pathologic features of these tumors are reviewed. Their precise histogenesis remains uncertain. The association with pseudoepitheliomatous hyperplasia of the overlying epithelium, which was well illustrated in two of the three cases, is discussed. The lesions are nearly always benign, and the treatment of choice is local excision.


Ocular response analyser to assess hysteresis and corneal resistance factor in low tension, open angle glaucoma and ocular hypertension.
The aim of this study is to compare the hysteresis and corneal resistance factor (CRF) in normal tension glaucoma (NTG), primary open angle glaucoma (POAG) and ocular hypertension (OHT) eyes measured by the ocular response analyser (ORA). This is a prospective, cross-sectional and comparative clinical trial. The setting was a teaching hospital in Birmingham, England. 216 eyes with POAG, 68 eyes with NTG and 199 eyes with OHT. Observational procedures: Goldmann applanation tonometry and intraocular pressure (IOP), hysteresis and CRF measured by ORA and central corneal thickness (CCT) by ultrasonic pachymetery. The main outcome measures were IOP, CCT, hysteresis and CRF. The hysteresis in NTG, POAG and OHT eyes was 9.0 +/- 1.9, 9.9 +/- 2.1 and 10.2 +/- 2.0 mmHg; CRF was 9.1 +/- 2.2, 10.6 +/- 2.0 and 12.0 +/- 2.0 mmHg; IOP by Goldmann applanation tonometry and ORA was 14.7 +/- 2.8 and 15.3 +/- 4.2 mmHg, 16.7 +/- 4.0 and 16.9 +/- 4.6 mmHg and 20.5 +/- 4.1 and 20.0 +/- 4.5 mmHg; CCT was 526.5 +/- 42.2, 537.0 +/- 36.0 and 563.4 +/- 35.9 microm, respectively. The difference for CRF, IOP and CCT for NTG, POAG and OHT eyes was statistically significant. Hysteresis and CRF were highest in OHT eyes. These factors may prove to be useful measurements of ocular rigidity and may help to understand role of the corneal rigidity in monitoring the progress of conditions such as NTG, POAG and OHT.


Recruitment patterns in multicentre randomised trials fit more closely to Price's Law than the Pareto Principle: A review of trials funded and published by the United Kingdom Health Technology Assessment Programme.
This review investigates whether the distribution of recruitment to multicentre randomised controlled trials (RCTs) fits the "Pareto Principle", i.e. 80% of participants are recruited by 20% of sites, or Price's Law, i.e. 50% of participants are recruited by the square root of the total number of sites. A review of HTA reports published between 2017 and 2019. 40 RCTs conducted face-to-face recruitment, five recruited via mail-outs and one used both methods. For face-to-face recruitment (n = 41 studies), 80% of participants were recruited by the top recruiting 42.6% of sites; for mail-out methods (n = 6 studies) this was 52.0%. From the square root of sites, 51.3% and 31.8% of participants were recruited for the two recruitment approaches, respectively. Specifically, 3 (7.3%, 95% CI 2.5% to 19.4%) and 20 (48.8%, 95% CI 34.3% to 63.5%) RCTs that recruited face-to-face followed Pareto Principle and Price's Law, respectively. One mail-out recruitment study followed one of these principles, Price's Law. Chief Investigator (CI) sites (n = 24) in face-to-face recruitment studies recruited 18.1% of participants. Face-to-face recruitment to HTA-funded RCTs fits more closely to Price's Law than the Pareto Principle, with the CI's site recruiting nearly a fifth of participants. Since we focussed on HTA-funded RCTs with ≥9 recruiting sites and for which the recruitment method and number recruited by site were known, our findings are limited in their generalisability. However, this trend could be used as a guide to aid in estimating how many sites RCTs need. More accurate estimation may prevent the need for recruitment extensions.


Interactions between heart rate, psychomotor performance and perceived effort during physical work as influenced by beta-adrenergic blockade.
Effects of a single intravenous dose of propranolol (0,25 mg/kg body weight) were examined in 15 healthy male subjects who performed three reaction-time tasks of different complexity, while pedalling at five work loads on a cycle ergometer. Comparisons between measurements after propranolol and after injection of a placebo solution showed a pronounced reduction of heart rate and an increase in catecholamine excretion following propranolol. Comparisons of psychomotor performance showed no significan difference between the propranolol and placebo conditions. Nor did self-estimates of perceived physical and task-induced efforts reveal any significant effects of propranolol. The results support the notion that heart rate is not a prominent cue for perceived effort.


Acceptance of mobile commerce in low-income consumers: evidence from an emerging economy.
This paper examines the intention to use m-commerce in low-income consumers in Ecuador by expanding the original unified theory of acceptance and use of technology (UTAUT2) model to include the trust and perceived security constructs. A total of 344 Ecuadorians were surveyed according to the following criteria: 1) had made at least one purchase through their mobile device in the last month and, 2) belonged to the low and medium-low socioeconomic segment of the selected country. The results showed that facilitating conditions, hedonic motivation, habit, and perceived trust significantly and positively predict the intention to use m-commerce. The best predictor was facilitating conditions followed by perceived trust. Contrary to expectations, performance expectancy, social influence, and perceived security did not significantly affect low-income consumers' intention to use m-commerce. This study produced diverging results in significant constructs used to validate the UTAUT2, highlighting the need to examine this model in different countries further. The relationships of the core constructs of UTAUT2 vary according to the country studied, possibly due to differences in national culture and economic development that could moderate the impact of explanatory constructs of technology adoption.


Distribution of somatostatin receptor subtypes in rat lumbar spinal cord examined with gold-labelled somatostatin and anti-receptor antibodies.
Using gold-labelled somatostatin, somatostatin binding sites were predominantly found in laminae I-III, X and on motorneurones of the rat lumbar spinal cord. A comparison with immunohistochemical staining using antisera against somatostatin receptor sequences revealed that the marked binding in laminae I-III coincided with the presence of somatostatin receptor-like immunoreactivity for the receptor subtypes 1, 2 and 3. Binding sites on motorneurones were only paralleled by an immunoreaction for subtype 3. In lamina X, however, the lack of a positive immunoreaction indicates that in this part other subtypes may be present.


Endoscopy in the management of choledocholithiasis.
Choledocholithiasis (bile duct stones) occurs in 10% to 15% of patients with cholelithiasis. Endoscopic retrograde cholangiopancreatography and biliary sphincterotomy, combined with the use of a variety of available accessories (eg, mechanical lithotriptors), are highly effective in managing most common bile duct stones. The combination of biliary sphincterotomy and papillary balloon dilation allows removal of many stones without the need for mechanical lithotripsy. Large stones may require additional expertise and the use of cholangioscopy with intraductal lithotripsy. Some patients, especially those with intrahepatic stones, require the help of an interventional radiologist or a biliary surgeon. The availability of endoscopists, radiologists, and surgeons interested in and experienced with biliary diseases will allow successful and safe therapy to be tailored to the individual patient.


Pharmacokinetics of calcium dobesilate in beagle dogs after a single administration.
A pharmacokinetic study was carried out in beagle dogs after a single intravenous infusion of 100 mg/kg of calcium dobesilate, a dose claimed to produce a cardiac lymphagogue effect. This effect on cardiac lymphatics is known to contribute to the reduction of myocardial infarct size after coronary artery occlusion. At the end of the intravenous infusion, which lasted about 30 minutes, the plasma level was 263 +/- 68 micrograms/ml, falling to 56 +/- 23 micrograms/ml by the third hour. This high plasma level of calcium dobesilate between the end of the infusion and the 3rd hour might explain the pharmacological effect of the drug on the cardiac lymphatic system.


Evidence for the spontaneous formation of interspecies hybrid molecules of human, rat and bovine serum albumins.
Utilizing electrophoretic and gel filtration techniques it was shown that a bovine C-terminal peptic fragment [residues 307-582] spontaneously forms interspecies hybrid molecules with three complementary N-terminal fragments derived from human [residues 1-308; 49-308] and rat [residues 1-308] albumins. The fragments associate with 1:1 stoichiometry to produce an albumin-like complex which has a molecular weight and electrophoretic mobility similar to intact albumin. These data demonstrate, for the first time, that albumin fragments derived from different species associate in a complementary fashion and provide direct evidence that the tertiary structure may be highly conserved.


Bioprosthetic mitral valve endocarditis after percutaneous device closure of severe paravalvular leak.
A large mitral paravalvular leak in a 63-year-old patient was closed by percutaneous placement of 2 Amplatzer Septal Occluder (AGA Medical Corporation, Plymouth, MN) devices. The patient had a residual paravalvular leak and subsequently developed infective endocarditis that was successfully treated by removal of all hardware and implantation of a new valve. Transcatheter treatment of paravalvular leaks may be useful in select patients who are poor candidates for open surgery; however, one must be aware of the potential complications. This report underscores the risk of device infection that may be increased if there is turbulence related to residual paravalvular leaks.


[Overview and evolving strategies of ventral hernia repair].
Incisional hernias occur in 5-10% of patients who have undergone laparotomy and are associated with high morbidity and significant socioeconomic costs. Techniques for reinforcing and/or replacing the abdominal wall with alloplastic meshes have reduced the recurrence rate in comparison to suture techniques from about 40% to less than 10%. A number of mesh types and surgical repair procedures are available, namely the onlay, inlay, sublay, underlay, and intraperitoneal onlay mesh (IPOM) techniques. Evolving strategies include precise criteria for incorporating patient body type, risk factors for recurrence, hernia morphology, and the available biomaterials into the planning of the surgical approach. The authors herein present an overview of the current surgical trends, focusing on mesh reinforcement (sublay technique) and mesh replacement (IPOM technique). Additionally, they review a classification of incisional hernias that is self-explanatory, practicable in routine clinical practice, and based on the cornerstones of morphology, hernia size, and risk factors for recurrence. Evidence for the indications and limitations of the main surgical repair techniques are illustrated and discussed.


Systemic inflammation induces anxiety disorder through CXCL12/CXCR4 pathway.
It is evidenced that inflammation is involved in the pathogenesis of anxiety disorder, as well as the dysfunction of glutamate neurotransmission in the central nervous system (CNS). Chemokine CXCL12 has been reported taking part in the regulation of neurotransmitter release, however, the roles of CXCL12 in the development of anxiety are still unclear. In this study, we found that intraperitoneal (i.p) injection of lipopolysaccharide (LPS) induced anxiety-like behaviors in adult mice as measured by elevated plus-maze test (EPM) and open field test (OFT). Astrocytes were responsible for CXCL12 induction upon LPS challenge in hippocampus and amygdala, and microinjection of CXCL12 into amygdala induced mice anxiety-like behaviors. AMD3100, which is an antagonist for CXCL12 receptor CXCR4, prevented the anxiety behaviors induced by microinjection of CXCL12 into amygdala as well as injection i.p of LPS. Knockdown of CXCR4 expression in neurons using short hairpin RNAs (shRNAs) significantly blocked anxiety behaviors mediated by CXCL12 i.c injection. Furthermore, AMD3100 or shCXCR4 prevented the impairment of nesting ability induced by CXCL12 in mice. Whole-cell patch-clamp recordings in the neurons of basolateral amygdala (BLA) revealed that CXCL12 enhanced glutamatergic transmission by increasing sEPSC frequency in the amygdala. AMD3100 inhibited the excitatory glutamatergic neural transmission and involved in the development of anxiety through CXCR4. These findings provide direct evidence that alterations of CXCL12 in BLA play critical roles in the development of anxiety induced by systemic inflammation and that CXCR4 may be a potential therapeutic target for inflammation-induced anxiety.


Options for Teens with No Options: A Self-Managed Second Trimester Abortion.
Several states have deemed abortions as nonessential services, effectively calling for a halt to abortion care during the COVID-19 pandemic. In response, women might elect for self-managed abortions by obtaining abortion medications online. A 15-year-old girl presented with abdominal cramping and vaginal discharge after taking misoprostol obtained from an online retailer for a self-managed abortion in her second trimester during the COVID-19 pandemic. Her exam showed products of conception protruding from the vagina. The patient was emergently evaluated for an incomplete and possible septic abortion and underwent a dilation and evacuation procedure.


[A method for quantitative dertermination of 20-keto steroids in urine during the use of a 3 alpha-, 20 beta-hydroxysteroid: NAD oxidoreductase (author's transl)].
A method is described for the quantitative determination of 20-ketosteroids in urine during the application of a 3alpha, 20beta-hydroxysteroid: NAD oxidoreductase. In the presence of NADH H+ the enzyme catalyses in an "equimolar" developing reaction the reduction of 20-keto groups of C-21 steroids giving 20 beta-alcohols. The measurable NADH H+ consumption is a measure for the quantity of those 20-ketosteroids present in the reaction mixture. The 3alpha-hydroxysteroid: NAD oxidoreductase activity of the enzyme does not influence the specificity of the method to determine the 20-ketosteroids because,-under the present extraction and purification conditions-those 3alpha-hydroxy-5alpha-androstan derivatives are not reaching the reaction mixture of determination. The demands towards the criterions of reliability (correctness and exactitude) come to be fulfilled by this method.


Surgical repositioning of dislocated capsular tension rings.
To present techniques and results of surgical repositioning of subluxed and dislocated capsular tension rings (CTRs). Retrospective interventional case series. Eleven patients with a previously implanted CTR in-the-bag for zonular weakness who presented with CTR-intraocular lens (IOL)-capsular bag decentration who underwent surgical repositioning. Data from 11 patients who underwent surgical repositioning were evaluated retrospectively for underlying diagnosis, interval between initial surgery and decentration, surgical technique, clinical results, and complications. Capsular tension ring-IOL-capsular bag centration, final best-corrected visual acuity (BCVA), and surgical complications. Of the 11 patients with CTR decentration, 3 had it early in the postoperative period, and 8 had it late. Mean (+/- standard deviation) durations from cataract extraction and CTR implantation to surgical repositioning were 6.1+/-7.9 months for those with decentration early and 49.6+/-15.3 months for late decentrations (overall range, 0.7-74.7). Of the 11 patients, 7 had pseudoexfoliation, and 4 of the 7 had associated glaucoma. Nine patients had subluxation of the CTR-IOL-capsular bag complex, which was managed by an anterior segment approach. A pars plana vitrectomy and levitation of the CTR was required in 2 patients due to complete dislocation of the CTR into the posterior vitreous. Surgical techniques for repositioning included single, double, or 3-point scleral suture loop fixation of the CTR through the capsular bag complex (8 eyes); use of the capsular tension segment (CTS) placed within the capsular bag for scleral suture fixation (2); or iris suture fixation of the IOL haptics (1). All patients achieved successful anatomical repositioning of the CTR-IOL-capsular bag complex. Mean preoperative BCVA improved from 20/100 to 20/40 postoperatively. After repositioning surgery, BCVA improved in 7 patients, was maintained in 2, and worsened in 2 (due to advanced glaucoma). Postoperative CTR subluxation or dislocation is a risk for patients with severe or progressive zonulopathy. Decentrations may be effectively managed with scleral suture fixation of the CTR through the capsular bag or the use of the CTS.


Molecular cloning and expression of murine homologue of semaphorin K1 gene.
We have cloned a mouse homologue of semaphorin K1 cDNA. Sequence analysis has predicted that the mouse semaphorin K1 encodes a 664 amino acid protein and contains a characteristic semaphorin domain in the N terminus followed by an immunoglobulin-like domain and a glycosylphosphatidylinositol anchoring sequence in the C terminus. In addition, this molecule has a RGD motif within the semaphorin domain. There is a high degree of amino acid identity between mouse and human semaphorin K1(89.5%). Northern blot analysis has revealed that the highest expression is detected in the nervous system and the expression level increases during neural development. Moreover, moderate expression is also detected in the immune system such as thymus and spleen. Thus, semaphorin K1 may play essential roles not only in the nervous system but also in the immune system.


Intestinal metabolism of T-2 toxin in the pig cecum model.
T-2 toxin, a toxic member of the group A trichothecenes, is produced by various Fusarium species that can potentially affect human health. As the intestine plays an important role in the metabolism of T-2 toxin for animals and humans, the degradation and metabolism of T-2 toxin was studied using the pig cecum in vitro model system developed in the author's group. In order to study the intestinal degradation of T-2 toxin by pig microbiota, incubation was performed with the cecal chyme from four different pigs in repeat determinations. A large variation in the intestinal degradation of T-2 toxin was observed for individual pigs. T-2 toxin was degraded almost completely in one out of four pigs, in which only 3.0 ± 0.1 % of T-2 toxin was left after 24 h incubation. However, in the other three incubations with pig cecal suspension, 54.1 ± 11.7-68.9 ± 16.1 % of T-2 toxin were still detectable after 24 h incubation time. The amount of HT-2 toxin was increased along with the incubation time, and HT-2 toxin accounted for 85.2 ± 0.7 % after 24 h in the most active cecum. HT-2 toxin was the only detectable metabolite formed by the intestinal bacteria. This study suggests that the toxicity of T-2 toxin for pigs is caused by the combination of T-2 and HT-2 toxins.


The effects of demethylsterigmatocystin and sterigmatin on ATP synthesis system in mitochondria: A comparison with sterigmatocystin.
The effects of demethylsterigmatocystin and its structural isomer, sterigmatin, on oxidative phosphorylation of mitochondria were studied by means of isolated rat liver mitochondria in comparison with sterigmatocystin. Both compounds were found to uncouple the oxidative phosphorylation in mitochondria, causing marked decreases in RC index and P/O ratio. Sterigmatin, in which dihydrobisfuran ring and xanthone nucleus are combined in a linear manner, was evidently more toxic to mitochondrial functions than demethylsterigmatocystin which was an angular molecular shape. Though their uncoupling concentrations were rather high for assessing theirin vivo toxicity, a good correspond was observed between their orders of potencies in the toxicity to mitochondrial functions and in the cytotoxicity to rat hepatocytes. The demethylation of sterigmatocystin resulted in an obvious decrease of uncoupling activity.