Pituitary MRI in Cushing's disease - an update.
Pituitary MRI is essential in the diagnosis of ACTH-dependent Cushing's syndrome, but its results are inconsistent. The demonstration of a sellar image compatible with the diagnosis of corticotropinoma varies from 40% to 90%, depending on the centre where the imaging is performed. In fact, the expertise of the neuroradiologist, use of a Tesla 3.0 MRI and choice of sequences are fundamental. The T2 and 3D gradient echo sequences after gadolinium injection are the most informative and today allow the detection of macro- and microadenomas in almost all cases. The diagnosis of numerous picoadenomas (<3-4 mm) is more challenging. The 2D and 3D spin echo or delayed T1 SE or FLAIR sequences after gadolinium can be used as a complement or to confirm a suspicious image. Characterization of corticotropinomas remains problematic. However, the correct assessment of so-called incidentalomas by recognizing artifacts, anatomical variants and frequent Rathke's cleft cysts eliminates around 90% of the incidentalomas that mimic pituitary adenomas, as repetitively reported in the literature. For the time being, there is reason to believe that hybrid imaging combining PET and MRI such as 11C-methionine PET coregistered with volumetric MRI will solve the diagnosis of corticotropinomas in the near future.


Differential regulation and transcriptional control of immediate early gene expression in forskolin-treated WEHI7.2 thymoma cells.
Agents that increase intracellular cAMP are frequently growth inhibitory for lymphocytes and induce apoptosis in cortical thymocytes by regulating gene expression. In the present study, immediate early gene expression was examined in WEHI7.2 thymoma cells undergoing cAMP-mediated apoptosis. Temporal differences in c-fos, junB, and inducible cAMP early repressor (ICER) steady-state mRNA levels were observed after forskolin exposure. Maximal induction of c-fos and junB occurred within 1 h, returning to basal levels by 3.5 h. In contrast, a 1.5-h time lag was observed before ICER transcript levels increased, reaching maximal levels after 3.5 h. This rise in expression, correlating with the decrease in c-fos and junB levels, preceded apoptotic DNA fragmentation by 1.5 h. Transient expression of ICER promoter constructs demonstrated that cAMP responsiveness occurred through cAMP-autoregulatory response element (CARE)3/4, two of the four proposed response elements in the ICER promoter. In contrast to the cAMP-responsive cell line JEG-3, CARE1/2 was not functional for cAMP-activated transcription in WEHI7.2 cells. An observed differential binding pattern of WEHI and JEG nuclear extracts to these elements may account for the cell-specific differences in expression patterns. To determine the role of endogenous ICER in regulating gene expression, cells were treated with two sequential doses of forskolin after which ICER and c-fos mRNA levels were measured. The high levels of cAMP-induced ICER expression dramatically reduced a second induction of c-fos. These data suggest that ICER expression may function as an antioncogene to attenuate the expression of certain protooncogenes, thereby preventing transformation and oncogenesis due to continuous overexpression. Moreover, inhibition of growth-stimulatory genes may be required for the activation of the cell death machinery in specific cells.


Application of artificial intelligence neural network modeling to predict the generation of domestic, commercial and construction wastes.
Reliable prediction of municipal solid waste (MSW) generation rates is a significant element of planning and implementation of sustainable solid waste management strategies. In this study, the multi-layer perceptron artificial neural network (MLP-ANN) is applied to verify the prediction of annual generation rates of domestic, commercial and construction and demolition (C&D) wastes from the year 1997 to 2016 in Askar Landfill site in the Kingdom of Bahrain. The proposed robust predictive models incorporated selected explanatory variables to reflect the influence of social, demographical, economic, geographical and touristic factors upon waste generation rates (WGRs). The Mean Squared Error (MSE) and coefficient of determination (R2) are used as performance indicators to evaluate effectiveness of the developed models. MLP-ANN models exhibited strong accuracy in predictions with high R2 and low MSE values. The R2 values for domestic, commercial and C&D wastes are 0.95, 0.99 and 0.91, respectively. Our results show that the developed MLP-ANN models are effective for the prediction of WGRs from different sources and could be considered as a cost-effective approach for planning integrated MSW management systems.


LDBio Aspergillus immunochromatographic test lateral flow assay for IgG/IgM antibody detection in chronic pulmonary aspergillosis: Single-centre evaluation and meta-analysis.
Chronic pulmonary aspergillosis (CPA) is an infection of the lung usually caused by Aspergillus fumigatus in patients with pre-existing pulmonary diseases. Its diagnosis hinges on demonstrating IgG antibodies against A. fumigatus. Herein, we evaluated the performance of a newly introduced point of care test (POCT) kit, the LDBio Aspergillus IgG/IgM lateral flow assay (LFA) in India with the standard ImmunoCAP kit for diagnosing CPA. A total of 60 serum samples (30 CPA cases and 30 controls) were evaluated by the Aspergillus immunochromatographic test (ICT) IgG/IgM LFA. Fluorescent-enzyme immunoassay was used to determine specific A. fumigatus-IgG concentrations (positive >27 mgA/L). Further, a systematic review and meta-analysis of studies (up to August 26, 2021) reporting the performance of LDBio ICT for the diagnosis of CPA was performed. A sensitivity of 86.7%, specificity of 90%, negative predictive value of 87.1%, positive predictive value of 89.7%, negative likelihood ratio of 0.15, positive likelihood ratio of 8.67, and was observed for the LDBio IC. There was good agreement between LDBio ICT and ImmunoCAP (88.3%) with a Cohen's Kappa score of 0.77. Our systematic review identified four studies and the pooled sensitivity of 90%, specificity of 91%, area under the curve of 0.94 and diagnostic odds ratio of 57.2, for CPA diagnosis by LDBio ICT. Aspergillus LDBio ICT assay exhibits good sensitivity and can be used to screen CPA cases.


Plaque echolucency and stroke risk in asymptomatic carotid stenosis: a systematic review and meta-analysis.
Ultrasonographic plaque echolucency has been studied as a stroke risk marker in carotid atherosclerotic disease. We performed a systematic review and meta-analysis to summarize the association between ultrasound-determined carotid plaque echolucency and future ipsilateral stroke risk. We searched the medical literature for studies evaluating the association between carotid plaque echolucency and future stroke in asymptomatic patients. We included prospective observational studies with stroke outcome ascertainment after baseline carotid plaque echolucency assessment. We performed a meta-analysis and assessed study heterogeneity and publication bias. We also performed subgroup analyses limited to patients with stenosis ≥50%, studies in which plaque echolucency was determined via subjective visual interpretation, studies with a relatively lower risk of bias, and studies published after the year 2000. We analyzed data from 7 studies on 7557 subjects with a mean follow-up of 37.2 months. We found a significant positive relationship between predominantly echolucent (compared with predominantly echogenic) plaques and the risk of future ipsilateral stroke across all stenosis severities (0% to 99%; relative risk, 2.31; 95% confidence interval, 1.58-3.39; P<0.001) and in subjects with ≥50% stenosis (relative risk, 2.61; 95% confidence interval, 1.47-4.63; P=0.001). A statistically significant increased relative risk for future stroke was preserved in all additional subgroup analyses. No statistically significant heterogeneity or publication bias was present in any of the meta-analyses. The presence of ultrasound-determined carotid plaque echolucency provides predictive information in asymptomatic carotid artery stenosis beyond luminal stenosis. However, the magnitude of the increased risk is not sufficient on its own to iden tify patients likely to benefit from surgical revascularization.


Isotopic ecology ten years after a call for more laboratory experiments.
About 10 years ago, reviews of the use of stable isotopes in animal ecology predicted explosive growth in this field and called for laboratory experiments to provide a mechanistic foundation to this growth. They identified four major areas of inquiry: (1) the dynamics of isotopic incorporation, (2) mixing models, (3) the problem of routing, and (4) trophic discrimination factors. Because these areas remain central to isotopic ecology, we use them as organising foci to review the experimental results that isotopic ecologists have collected in the intervening 10 years since the call for laboratory experiments. We also review the models that have been built to explain and organise experimental results in these areas.


[Macrophage phenotype in induced sputum in asthma subjects].
Macrophages represent the most predominant immune effector cells in the alveolar spaces and conducting airways and are known to express activated phenotype. The study was aimed at assessing the differences in cellular profile and the expression of selected surface markers on sputum macrophages in asthma and healthy subjects. 17 healthy subjects (never smoked) and 10 mild asthma subjects treated with glucocorticosteroids were enrolled into the study. For macrophage phenotyping a immunocytochemistry method was used with commercially available antibodies anti: CD14, CD71, CD11b and CD54. The nonparametric Mann Whitney U test was applied for data comparison, p value <0.05 being regarded as significant. The total number of cells were increased in asthma patients 4.81+/-5.27x 10(6) /ml vs healthy 2.8+/-2.15 x 10(6)/ml and it was statistically significant. Statistically significant increase in the percentage of eosinophils was observed in mild asthma subjects. No differences were found between the proportion in macrophages and lymphocytes. The macrophage phenothype in induced sputum differed in both groups. The expression of CD11b was higher in asthma group and the difference was statistically significant. The proportion of macrophages with the expression of CD 14, CD 71 and CD54 was comparable in both groups. Macrophage phenotyping during glucocorticosteroid therapy is useful in the assessment of inflammatory process in asthma subject.


"Ab initio" synthesis of zeolites for preestablished catalytic reactions.
Unlike homogeneous catalysts that are often designed for particular reactions, zeolites are heterogeneous catalysts that are explored and optimized in a heuristic fashion. We present a methodology for synthesizing active and selective zeolites by using organic structure-directing agents that mimic the transition state (TS) of preestablished reactions to be catalyzed. In these zeolites, the pores and cavities could be generated approaching a molecular-recognition pattern. For disproportionation of toluene and isomerization of ethylbenzene into xylenes, the TSs are larger than the reaction products. Zeolite ITQ-27 showed high disproportionation activity, and ITQ-64 showed high selectivity for the desired para and ortho isomers. For the case of a product and TS of similar size, we synthesized a catalyst, MIT-1, for the isomerization of endo-dicyclopentane into adamantane.


Technology in body composition: considerations for a traditional, elderly Indonesian population.
Body composition has been measured in a group of elderly people living in nursing home care in West Sumatra, Indonesia. Anthropometric techniques were used to measure height, weight, waist and hip circumference, and skinfolds at four sites (triceps, biceps, suprailiac and subscapula). Body fat was determined with the equations of Durnin and Womersley, although difficulties were encountered because of the age and leanness of some of the subjects. The average age of the subjects was 73.0± 7.5 years (n=20) and 73.4± 5.4 (n= 15) for males and females respectively. The average body mass index (BMI) was 18.2 kg/m2 for both groups. The mean total body fat and waist/hip ratio for the males was 8.8 kg and 0.86; corresponding results for the females were 12.3 kg and 0.77. The results demonstrate the limitations of these techniques, when they are applied to an elderly population for which appropriate standards are not available.


Purification and properties of the membrane form of variant surface glycoproteins (VSGs) from Trypanosoma brucei.
Variant surface glycoproteins (VSG) of Trypanosoma brucei are released in a water soluble form on impairment of membrane integrity. We have previously shown that this release is the result of an enzyme-mediated event which converts the hydrophobic membrane form VSG into the hydrophilic water-soluble form. We now present further details of the methods by which membrane form VSG ( mfVSG ) may be isolated, uncontaminated by water-soluble VSG ( sVSG ). The sensitivity to different metal ions of the enzyme that mediated the conversion event is discussed, and some biochemical characteristics of different mfVSG preparations are presented.


Drug resistance in epilepsy: the role of the blood-brain barrier.
The blood-brain barrier (BBB) is formed by the endothelial cells lining the brain microvessels. Complex tight junctions linking adjacent endothelial cells make brain capillaries around 100 times tighter than peripheral capillaries to small hydrophilic molecules. As a result, drugs required to act in the brain, including anti-epileptic drugs (AEDs), have generally been made lipophilic, and are thus able to cross the brain endothelium via the lipid membranes. However, such lipophilic drugs are potential substrates for efflux carriers of the BBB, particularly P glycoprotein (Pgp), predominantly located on the endothelial luminal membrane. It is estimated that up to 50% of drug candidates may be substrates for Pgp. The barrier phenotype of the brain endothelium is induced and maintained by chemical factors released by brain cells, particularly perivascular astrocytic end feet. In several neuropathological conditions, the BBB is disturbed, either as a result of pathology of the endothelium, or of the cells responsible for barrier induction and maintenance. During epileptic attacks, there may be transient BBB opening in the epileptogenic focus. There is evidence that under such pathological conditions, 'second line defence' mechanisms in perivascular glia may be up-regulated, including expression of Pgp and other drug efflux transporters. This complicates interpretation of drug resistance in epilepsy, and therapeutic strategies.


Ion transport through confined ion channels in the presence of immobile charges.
We study charge transport in an ionic solution in a confined nanoscale geometry in the presence of an externally applied electric field and immobile background charges. For a range of parameters, the ion current shows nonmonotonic behavior as a function of the external ion concentration. For small applied electric field, the ion transport can be understood from simple analytic arguments, which are supported by Monte Carlo simulations. The results qualitatively explain measurements of ion current seen in a recent experiment on ion transport through a DNA-threaded nanopore [D. J. Bonthuis, Phys. Rev. Lett, 97, 128104 (2006)].


Phylogenetic placement of plant pathogenic Sclerotium species among teleomorph genera.
Phylogenetic analyses and morphological characteristics were used to assess the taxonomic placement of eight plant-pathogenic Sclerotium species. Members of this genus produce only sclerotia and no fruiting bodies or spores, so Sclerotium species have been difficult to place taxonomically. Sequences of rDNA large subunit (LSU) and internal transcribed spacer (ITS) regions were determined for isolates of Sclerotium cepivorum, S. coffeicola, S. denigrans, S. hydrophilum, Ceratorhiza oryzae-sativae, S. perniciosum, S. rhizodes, S. rolfsii and S. rolfsii var. delphinii. Parsimony analysis grouped two species previously thought to be in the Basidiomycota, S. denigrans and S. perniciosum, within the Ascomycota; these species were found to have affinities with the teleomorph genera Sclerotinia and Stromatinia and the asexual Sclerotium cepivorum, which was known earlier to be related to Sclerotinia species. The other Sclerotium species were placed in one of two basidiomycetous groups, genera Athelia or Ceratobasidium. Based on rDNA analysis and morphology the basidiomycetous Sclerotium hydrophilum and S. rhizodes were transferred to genus Ceratorhiza, the anamorph of Ceratobasidium species. Sclerotium coffeicola was found to be close to S. rolfsii var. delphinii and S. rolfsii var. rolfsii, which was shown earlier to have an Athelia teleomorph.


Predicting the accuracy of ligand overlay methods with Random Forest models.
The accuracy of binding mode prediction using standard molecular overlay methods (ROCS, FlexS, Phase, and FieldCompare) is studied. Previous work has shown that simple decision tree modeling can be used to improve accuracy by selection of the best overlay template. This concept is extended to the use of Random Forest (RF) modeling for template and algorithm selection. An extensive data set of 815 ligand-bound X-ray structures representing 5 gene families was used for generating ca. 70,000 overlays using four programs. RF models, trained using standard measures of ligand and protein similarity and Lipinski-related descriptors, are used for automatically selecting the reference ligand and overlay method maximizing the probability of reproducing the overlay deduced from X-ray structures (i.e., using rmsd < or = 2 A as the criteria for success). RF model scores are highly predictive of overlay accuracy, and their use in template and method selection produces correct overlays in 57% of cases for 349 overlay ligands not used for training RF models. The inclusion in the models of protein sequence similarity enables the use of templates bound to related protein structures, yielding useful results even for proteins having no available X-ray structures.


Biosynthetic pathways of ergot alkaloids.
Ergot alkaloids are nitrogen-containing natural products belonging to indole alkaloids. The best known producers are fungi of the phylum Ascomycota, e.g., Claviceps, Epichloë, Penicillium and Aspergillus species. According to their structures, ergot alkaloids can be divided into three groups: clavines, lysergic acid amides and peptides (ergopeptines). All of them share the first biosynthetic steps, which lead to the formation of the tetracyclic ergoline ring system (except the simplest, tricyclic compound: chanoclavine). Different modifications on the ergoline ring by specific enzymes result in an abundance of bioactive natural products, which are used as pharmaceutical drugs or precursors thereof. From the 1950s through to recent years, most of the biosynthetic pathways have been elucidated. Gene clusters from several ergot alkaloid producers have been identified by genome mining and the functions of many of those genes have been demonstrated by knock-out experiments or biochemical investigations of the overproduced enzymes.


How severe is depression in low back pain patients?
The aim of the present study was to determine the prevalence of depression among low back pain (LBP) patients and to investigate the sociodemographic characteristics of pa- tients with LBP and relationship between depression and pain intensity in LBP patients. The study was conducted on 99 patients treated at Clinical Department of Neurology, Split University Hospital Center. There were 36 (36%) men and 63 (64%) women. Some degree of depression was present in 73 (74%) study patients, including all patients with severe LBP. In the group of patients with severe LBP, the rate of moderate, severe and very severe depression was 1.36-fold that recorded in the gro- up of patients with moderate LBP and 2.58-fold that found in the group of patients with mild LBP (χ2 = 16.2; p = 0.003). The most common symptoms were general physical symptoms 70 (71%), psychic anxiety 69 (70%) and depressed mood 66 (67%). It is concluded that depression was more severe in LBP patients with severe disease compared to patients with mild or moderate LBP.


[Molecular analysis on non-O1 and non-O139 Vibrio cholerae isolates].
According to results from the two-month consecutive surveillance program in Maanshan, six suspected cases of non-O1 non-O139 Vibrio (V.) cholerae infection, were found that called for identification of pathogens as well as molecular-epidemiological analysis to determine the aggregation of the epidemic situation. Biochemical and serotype identification, hemolysis test, and drug sensitive test were used to detect the drug resistance spectrum. Real-time PCR and conventional PCR were used to detect the presence of V. cholerae specific genes, virulent genes and its related genes, including ompW, ctx, tcpA, toxR, hlyA, zot, ace, rstR and gIII(CTX). Pulsed-field gel electrophoresis (PFGE) was used to analyze the molecular type of strains. All the six isolates of non-O1 non-O139 V. cholerae were identified by biochemical and serologic tests, and appeared to be β hemolytic. Twelve out of the 14 kinds of drugs showed 100% sensitive. All isolates were positive of ompW gene by real-time PCR, but negative for ctx, tcpA, zot, ace, rstR and gIII(CTX). Five of the six isolates were positive for toxR and hlyA, except for strain 1001434446. All strains had different PFGE types, but two strains had similar types. All strains had a low similarity compared to the toxigenic V. cholerae. Six cases of non-O1 and non-O139 nontoxigenic V. cholerae infection appeared in the same period. Along with epidemiological information, we noticed that these cases had a sporadic nature, but frequently appeared in the same area. We got the impression that public health measurements should be strengthened, with special attention paid to those diarrhea outbreaks caused by non-O1/non-O139 strains since V. cholerae had appeared in low incidence.


Generalizability of Cardiovascular Disease Clinical Prediction Models: 158 Independent External Validations of 104 Unique Models.
While clinical prediction models (CPMs) are used increasingly commonly to guide patient care, the performance and clinical utility of these CPMs in new patient cohorts is poorly understood. We performed 158 external validations of 104 unique CPMs across 3 domains of cardiovascular disease (primary prevention, acute coronary syndrome, and heart failure). Validations were performed in publicly available clinical trial cohorts and model performance was assessed using measures of discrimination, calibration, and net benefit. To explore potential reasons for poor model performance, CPM-clinical trial cohort pairs were stratified based on relatedness, a domain-specific set of characteristics to qualitatively grade the similarity of derivation and validation patient populations. We also examined the model-based C-statistic to assess whether changes in discrimination were because of differences in case-mix between the derivation and validation samples. The impact of model updating on model performance was also assessed. Discrimination decreased significantly between model derivation (0.76 [interquartile range 0.73-0.78]) and validation (0.64 [interquartile range 0.60-0.67], P<0.001), but approximately half of this decrease was because of narrower case-mix in the validation samples. CPMs had better discrimination when tested in related compared with distantly related trial cohorts. Calibration slope was also significantly higher in related trial cohorts (0.77 [interquartile range, 0.59-0.90]) than distantly related cohorts (0.59 [interquartile range 0.43-0.73], P=0.001). When considering the full range of possible decision thresholds between half and twice the outcome incidence, 91% of models had a risk of harm (net benefit below default strategy) at some threshold; this risk could be reduced substantially via updating model intercept, calibration slope, or complete re-estimation. There are significant decreases in model performance when applying cardiovascular disease CPMs to new patient populations, resulting in substantial risk of harm. Model updating can mitigate these risks. Care should be taken when using CPMs to guide clinical decision-making.


Role of Wnt/β-catenin signaling regulatory microRNAs in the pathogenesis of colorectal cancer.
Colorectal cancer (CRC) is one of the leading causes of cancer death worldwide. In more than 90% of all CRC patients, the master oncogenic Ras-Wnt signaling axis is over-activated. MicroRNAs (miRNAs) are potential novel diagnostic and prognostic biomarkers as well as therapeutic targets for several cancers including lung, breast, gastric, and colorectal cancers. Oncogenic or tumor suppressor miRNAs modulate tumor cells proliferation, cell cycle progression, angiogenesis, invasion, and metastasis through regulating oncogenic pathways including Wnt/β-catenin signaling. This review summarizes the current knowledge about the role of Wnt/β-catenin signaling regulatory miRNAs in the pathogenesis of colorectal cancer for a better understanding and hence a better management of this disease.


Primary Epstein-Barr virus infection with polyradiculitis: a case report.
Nervous system complications of primary Epstein-Barr virus (EBV) infection in adults are rare, but may occur with encephalitis, meningitis, myelitis, cranial and peripheral neuropathies, or radiculitis. We describe an immune competent adult with a primary EBV infection complicated by lumbosacral polyradiculitis with pure radicular pain. Prior to the onset of radicular pain the 35-year-old woman had been suffering from infectious mononucleosis misdiagnosed for streptococcal tonsillitis. The diagnosis of primary EBV infection associated polyradiculitis was proven by serology and PCR in serum and CSF. Under initially started empiric therapy with intravenous acyclovir and analgesics the patient completely recovered within a few days. This case report highlights that EBV should be taken into consideration in the diagnostic work up of radicular pain syndromes, even in immune competent adults. There is no approved causal therapy for EBV infections. In accordance with our case, observations based on a few patients with EBV and nervous system involvement suggest, that acyclovir treatment might be associated a with better course. However, prospective randomized controlled trials addressing the question of the effectiveness of acyclovir in patients with primary EBV infection and neurological complications are lacking.


Do characteristics associated with nursing home residents vary by race/ethnicity?
This study identifies differences in the predisposing, enabling, and need characteristics of racial/ethnic minorities and non-Hispanic white men and women upon nursing home admission. The data come from the 1999 National Nursing Home Survey of Current Residents and contain 3,798 women of color, 3,787 men of color, 18,719 non-Hispanic white men, and 36,900 non-Hispanic white women. We estimated prevalence differences and 95% confidence intervals for the absolute differences in prevalence. Women of color in nursing homes are more likely than non-Hispanic white women in nursing homes to be bedfast and require assistance with dressing and money management. Men of color in nursing homes are more likely than non-Hispanic white men in nursing homes to require assistance with eating, care of possessions, managing money, securing personal items, and using the telephone. The overall finding suggests that people of color in nursing homes have greater impairments than non-Hispanic whites in nursing homes, and that men of color in nursing homes have greater impairment than any other race or gender categories.


Pathways from childhood sexual abuse to sexual aggression victimization and perpetration in adolescence and young adulthood: a three-wave longitudinal study.
Childhood sexual abuse (CSA) has been identified as a risk factor for later sexual aggression perpetration and vulnerability factor for sexual victimization. However, the use of cross-sectional designs, the focus on female victimization and male perpetration, and the lack of evidence from outside North America limit the existing knowledge base. The study was designed to examine pathways from CSA to sexual revictimization and sexual aggression perpetration after the age of consent. A total of 588 university students in Germany (308 female) took part in a three-wave longitudinal study covering 23 months. At each wave (T1-T3), all participants completed measures of sexual aggression victimization and perpetration. Experiences of CSA were measured at T1. The rate of CSA was significantly higher for women (20.8%) than for men (12.4%). Rates of sexual victimization for women were 60.9% at Time 1 (since age 14), 22.3% at Time 2 (since T1), and 17.4% at Time 3 (since T2). For men, the rates were 39.2% at Time 1, 15.9% at Time 2, and 14.1% at Time 3. Rates of sexual aggression perpetration for women were 10.6% at Time 1 (since age 14), 3.5% at Time 2 (since T1), and 3.6% at Time 3 (since T2). For men, the rates were 18.0% at Time 1, 6.2% at Time 2, and 3.8% at Time 3. The gender differences in victimization and perpetration were significant only at T1. CSA predicted higher odds of sexual aggression victimization and perpetration cross-sectionally at T1 and indirectly at T2 and T3 via T1. Gender did not moderate the associations. The results confirm previous findings of elevated rates of sexual aggression victimization and perpetration in adolescence and young adulthood in victims of CSA. The implications for understanding and preventing adverse sexuality-related outcomes of CSA are discussed.


Pain and dyspnea control during awake fiberoptic bronchoscopy in critically ill patients: safety and efficacy of remifentanil target-controlled infusion.
Flexible fiberoptic bronchoscopy is frequently used in intensive care unit, but is a source of discomfort, dyspnea and anxiety for patients. Our objective was to assess the feasibility and tolerance of a sedation using remifentanil target-controlled infusion, to perform fiberoptic bronchoscopy in awake ICU patients. This monocentric, prospective observational study was conducted in awake patients requiring fiberoptic bronchoscopy. In accordance with usual practices in our center, remifentanil target-controlled infusion was used under close monitoring and adapted to the patient's reactions. The primary objective was the rate of successful procedures without additional analgesia or anesthesia. The secondary objectives were clinical tolerance and the comfort of patients (graded from "very uncomfortable" to "very comfortable") and operators (numeric scale from 0 to 10) during the procedure. From May 2014 to December 2015, 72 patients were included. Most of them (69%) were hypoxemic and admitted for acute respiratory failure. No additional medication was needed in 96% of the patients. No severe side-effects occurred. Seventy-eight percent of patients described the procedure as "comfortable or very comfortable". Physicians rated their comfort with a median [IQR] score of 9 [8-10]. Remifentanil target-controlled infusion administered to perform awake fiberoptic bronchoscopy in critically ill patients is feasible without requirement of additional analgesics or sedative drugs. Clinical tolerance as well as patients' and operators' comfort were good to excellent. This technique could benefit patients' experience.


Effectiveness of personal protective equipment: relevance of dermal and inhalation exposure to chlorpyrifos among pest control operators.
This study assessed the effectiveness of a custom fit personal protective equipment (PPE) program aimed at reducing occupational exposure to pesticides. The intervention study was carried out on 15 pest control operators (PCOs) during mixing/loading and application of chlorpyrifos. Each worker was measured twice; first while the worker used PPE as normal (baseline measurement), and second after making some adjustments to the PPE (postintervention measurement). The applied intervention consisted of a tight-fitting, full-face respirator, fit-testing, long gloves, chemical-proof boots, a Tyvek hood, and an instruction video that was shown prior to putting on the PPE. A comprehensive evaluation program was used for the within-subject comparisons, including assessment of potential dermal exposure, actual dermal exposure, inhalation exposure, and internal dose as measured by the urinary metabolite 3,5,6-trichloro-2-pyridinol (TCP). The PPE program resulted in a significant increase in fit factors from a mean of 670 to 132,000. Actual dermal exposure levels decreased on average by fourfold after implementation of the PPE program (baseline AM = 132.1 microg; postintervention AM = 32.6 microg). The TCP levels in urine collected 24-32 hours after spray activities were lower in the postintervention data set (AM = 21.2 microg TCP/g creatinine vs. AM = 13.9 microg TCP/g creatinine). However, it is impossible to attribute these differences totally to the PPE program since workers had significant and varying urinary TCP levels before onset of spraying activities. Linear regression models showed that dermal exposure was only a predictive parameter for TCP levels in urine in the baseline data set. Although the results should be interpreted cautiously this study suggests a protective effect of the evaluated PPE program.


Firing properties of head direction cells in the rat anterior thalamic nucleus: dependence on vestibular input.
Vestibular information influences spatial orientation and navigation in laboratory animals and humans. Neurons within the rat anterior thalamus encode the directional heading of the animal in absolute space. These neurons, referred to as head direction (HD) cells, fire selectively when the rat points its head in a specific direction in the horizontal plane with respect to the external laboratory reference frame. HD cells are thought to represent an essential component of a neural network that processes allocentric spatial information. The functional properties of HD cells may be dependent on vestibular input. Here, anterior thalamic HD cells were recorded before and after sodium arsanilate-induced vestibular system lesion. Vestibular lesions abolished the directional firing properties of HD cells. The time course of disruption in the directional firing properties paralleled the loss of vestibular function. Arsanilate-treated rats exhibited only minor changes in locomotor behavior, which were unlikely to account for the loss of direction-specific firing. Vestibular lesions also disrupted the influence of angular head velocity on anterior thalamic single-unit firing rates. Finally, a subset of anterior thalamic neurons recorded from vestibular-lesioned rats exhibited a pattern of intermittent firing bursts that were distinctly unrelated to HD. This novel anterior thalamic firing pattern has not been encountered in any vestibular-intact rat. These data suggest that: (1) the neural code for directional bearing is critically dependent on vestibular information; and (2) this loss of HD cell information may represent a neurobiological mechanism to account for the orientation and navigational deficits observed after vestibular dysfunction.


Targeted construction of a high-resolution, integrated, comprehensive, and comparative map for a region specific to bovine chromosome 6 based on radiation hybrid mapping.
To resolve a candidate chromosome region on the middle part of bovine chromosome 6 (BTA6) containing several different quantitative trait locus (QTL) intervals, we constructed a high-resolution, integrated, comprehensive, and comparative map using a 12,000-rad, whole-genome, cattle-hamster radiation hybrid (RH) panel. The RH map includes a total of 71 loci either selected from bovine and comparative maps or targeted directly from a microdissection library specific for the BTA6 region. All loci typed were placed in one linkage group at a lod score threshold of 4.0. The length of the comprehensive RH map, which is the first high-resolution RH map in cattle, spans 2568.8 cR(12,000). The order of markers obtained principally agrees with the order on published bovine genetic maps. Our RH map integrates markers as well as genes and ESTs available from several physical and genetic maps of BTA6 and the orthologous ovine chromosome 6, human chromosome 4, and mouse chromosomes 5/3. Comparative analysis confirms and refines current knowledge about conservation and rearrangements in corresponding chromosomal regions on BTA6. We identified and localized two new breakpoints for intrachromosomal rearrangements between human chromosome 4 and BTA6. This RH map is a powerful tool in all aspects of genetic, physical, transcript, and comparative mapping. Due to its links to the gene-dense maps of human and mouse, it can serve as a prerequisite to identify possible candidate genes for quantitative trait loci localized in the targeted BTA6 region.


Focusing management in implementing a smoking ban in a university hospital in Sweden.
To explore the impact of various steps when introducing a smoking ban at the Karolinska Hospital (1000 beds; 6000 employees) in Stockholm, Sweden, a multiple evaluation strategy was performed over 5 years. All heads of clinical departments (N = 41) and a random sample of employees (n = 517) and a convenience sample of hospital labour managers (n = 17) were separately addressed through questionnaire surveys at different time intervals after the introduction of the ban in 1992. An observational and interview study completed the follow-up. The implementation process was supplemented by a comprehensive information strategy over 5 years. The two most important steps during implementation were management support and focus on environmental tobacco. The ban was well known at introduction. Heads of clinical departments reported a third of staff to be satisfied with the restrictions. In contrast, the staff survey revealed 62% to be positive. A shift in favour of a radical tobacco-free hospital was perceived during follow-up. Co-operation between hospital board, heads of clinical departments and local labour managers proved successful. The consecutive evaluations served as tools in labour management and contributed to staff compliance. A total ban, including the selling of tobacco and smoking in the hospital grounds is still to be achieved.


[Children and tuberculosis--diagnosis, treatment and follow-up].
Since the 1980s, there has been an increase in the incidence of tuberculosis (TB) world-wide. Mainly due to immigration, the number of new TB cases in the Norwegian child population is also increasing. In March 2000, a selected group of Norwegian paediatricians interested in infectious diseases held a meeting to discuss the clinical management of tuberculosis in children, and develop recommendations. The recommendations are based on current British, European and American recommendations. Two recent Norwegian recommendations on the management of tuberculosis in the general population were also reviewed. Epidemiological data from Norway and the clinical characteristics of tuberculosis in children are briefly presented, followed by recommendations regarding diagnostic procedures, chemoprophylaxis, treatment of latent tuberculosis and disease. Local health services play a crucial role in the follow-up of children with tuberculosis, and the importance of co-operation between the hospital paediatrician and the primary health care service is emphasised. Early diagnosis and adequate treatment of tuberculosis is necessary to reduce mortality and morbidity from tuberculosis. Clinical guidelines may aid in management.


Managing Formaldehyde indoor pollution in anatomy pathology departments.
Nearly eleven years have passed since the International Agency for Research on Cancer classified Formaldehyde (FA) as a known human carcinogen (group 1), yet the safety of anatomy pathology workers who are currently exposed to FA is still a matter of concern. The purpose of this study was to evaluate the literature to discover which topics have been focused on and what the latest developments are in managing FA indoor pollution in anatomy pathology departments. which topics have been focused on and what the latest developments in managing FA indoor pollution in anatomy pathology departments. For the purpose of this review, we searched for publications in PubMed and Web of Science using selected keywords. The articles were reviewed and categorized into one or more of the following three categories based on subject matter: exposure levels exposure controls and alternatives. Our search resulted in a total of 31 publications that matched our inclusion criteria. The topics discussed, in order of frequency (from highest to lowest), were: "exposure controls", "exposure levels" and "alternatives". The most frequently suggested intervention was to improve local exhaust ventilation systems to minimize FA levels in gross anatomy laboratories. We found a lack of evidence-based improvement interventions that aimed to control exposure to FA. According to this finding, and pending a valid chemical substitute for FA, we suggest the need for more in-depth studies targeting measures to minimize exposures to FA in pathology departments.


Asthma and allergic rhinitis in Swedish conscripts.
The computer records of Swedish conscript examinations in 1971 and 1981 were analysed regarding the prevalence of asthma and allergic rhinitis. The material comprised approximately 55,000 18-year-old males in each cohort. During the 10-year period the prevalence of asthma increased from 1.9 to 2.8% and of allergic rhinitis from 4.4 to 8.4%. The prevalence of allergic rhinitis was already higher in the northern than in the southern part of the country in 1971. The increase in both diseases was higher in the northern parts of Sweden, giving double prevalence figures in the northern part of the country compared to the southern part in 1981. The distribution of the prevalence was similar to the temperature pattern in the country, the higher prevalence being associated with a colder outdoor climate. Both diseases were more prevalent in urban than in rural areas.


Does radioiodine therapy have an equal effect on substernal and cervical goiter volumes? Evaluation by magnetic resonance imaging.
Most often thyroidectomy is recommended in patients with large goiters. However, high-dose (131)I therapy may be used in case of contraindications to surgery. Large goiters are often partially located in the mediastinum. The aim of this study was to evaluate the impact of (131)I therapy on the cervical and the substernal goiter volume, separately. Fourteen patients (median age, 69 years; range, 52-86 years) with a large multinodular goiter (three hyperthyroid) and with a substernal extension greater than 15 mL were included. T1-weighted magnetic resonance (MR) estimates of the thyroid volume in the cervical and substernal compartments were obtained before and 1 year after high-dose (131)I therapy. The total goiter volumes ranged from 182 to 685 mL. The median substernal volume was 66 mL (fraction of total volume, 17.6%; range, 8.0%-78.9%). One year after treatment, the median substernal goiter volume was reduced by 29.2% (range, -6.1%-59.4%, mean: 26.1% +/- 6.0%), and the cervical goiter volume by 30.3% (range, 6.0%-75.4%, mean, 35.6 +/- 5.6%) compared to baseline values; p = 0.25 for difference in a regional effect. The volume reduction was unrelated to initial substernal goiter size. Likewise, deterioration of the inspiratory capacity did not correlate with the magnitude of the substernal goiter extension. In conclusion, high-dose (131)I therapy seems as effective in reducing the substernal as the cervical goiter volume. However, because the overall effect is modest, this therapy should primarily be considered for the patient with a high surgical risk.


Adult respiratory distress syndrome in Thai medical patients.
Adult respiratory distress syndrome (ARDS) has been a well recognized severe form of acute respiratory failure of multiple causes, which is characterized by intractable hypoxemia and an extremely high mortality rate. Forty-six cases of ARDS admitted to the Department of Medicine, Ramathibodi Hospital during a 39 months period were studied prospectively to explore the etiologic risk, positive end-expiratory pressure (PEEP) profiles, complications and outcome of treatment. There were 19 females and 27 males with the mean age of 40 years. Risks of ARDS included intra- and extra-pulmonary disease conditions and also tropical diseases such as malaria and leptospirosis. At the time of diagnosis, patients in this group were extremely hypoxic with a mean arterial/alveolar oxygen tension (PaO2/PAO2) of 0.125 +/- 0.04. After the application of appropriate PEEP, the mean PaO2/PAO2 ratios increased significantly in both survivor and non-survivor groups (0.277 and 0.199). The levels of PEEP used were below 16 and 11 cmH2O in 93.46% and 67.38% of cases, respectively. Complications of PEEP which included barotrauma and hypotension were found in 11 cases (23.9%) with a very high mortality rate (81.8%). There were 28 deaths of patients in this study, giving an overall 60.8% group mortality rate. Despite the similarities in most clinical profiles, the survivors, when compared to the non-survivors, showed a greater extent of improved oxygenation in response to the application of PEEP, with fewer PEEP complications. The present study would, hopefully, provide the Thai clinicians with valuable informations in the management of ARDS.


Rab coupling protein (RCP): a novel target of progesterone action in primate endometrium.
Acquisition of functional receptivity by the endometrium is assumed to be effected by progesterone-dependent expression and repression of several genes during the implantation window in a menstrual cycle. In the present study, we employed differential display (DD) reverse transcription-polymerase chain reaction (RT-PCR) to identify progesterone-dependent gene/gene fragments that are differentially expressed during the peri-implantation phase in receptive and nonreceptive endometria, obtained from fertile and infertile bonnet monkeys respectively. Receptive endometria were obtained from regularly cycling (n=5) fertile female bonnet monkeys. Endometrial nonreceptivity was induced by treating bonnet monkeys with either 2.5 mg (n=5) or 5.0 mg (n=5) onapristone (ZK 98.299), an antiprogestin, on every third day for one cycle. Ovulation, levels of circulatory hormones (estradiol and progesterone) and menstrual cycle length did not change in treated animals; however, endometrial growth was retarded. DD2, one of the differentially expressed cDNA fragments, showed higher representation in nonreceptive endometria than in receptive endometria. The DD2 sequence was found to be homologous to the sequence of the carboxyl terminal region of Rab coupling protein (RCP), a recently discovered protein involved in intracellular vesicular trafficking. To confirm the identity of DD2 as RCP, RT-PCR studies were carried out with a forward primer deduced from the RCP sequence and a reverse primer from the DD2 sequence. The product (DDRCP) obtained, when sequenced, revealed 95% homology with the nucleotide number 1196-1757 of human RCP cDNA. Furthermore, the pattern of DDRCP expression at transcript level was found to be similar to that shown by DD2; that is, it was higher in nonreceptive endometrium. Northern analysis using labeled DD2 or DDRCP cDNA fragments identified two transcripts of 6.0 and 4.0 kb in human endometrium. In situ hybridization studies using digoxigenin-labeled DD2 revealed significantly higher (P < 0.05) localization of endometrial RCP transcripts in the proliferative phase than in the peri-implantation phase in control animals. The localization was also significantly (P < 0.01) higher in peri-implantation-phase endometria from antiprogestin-treated animals than in control animals. These antiprogestin-treated animals, however, did not demonstrate any concomitant increase in the levels of immunoreactive endometrial Rab4 and Rab11 during the peri-implantation phase. A similar pattern of cycle-dependent RCP expression was observed in human endometrial biopsies. Furthermore, significantly higher (P < 0.05) levels of RCP transcripts were detected during the peri-implantation phase in women with unexplained infertility (n=3) than in fertile women (n=3). This is the first report indicating the endometrial expression of RCP and its hormonal regulation.


Intermittent versus continuous electronic monitoring in labour: a randomised study.
To compare the efficacy in detecting signs of fetal hypoxia in labour of intermittent (I-group) versus continuous (C-group) electronic fetal monitoring in women with low or moderate risk factors for fetal distress. A prospective, randomised study. A tertiary referral centre. Four thousand and forty-four parturients at low risk for obstetric complications with a reactive fetal heart rate admission test at arrival in labour. During the study period (October 5 1989 to May 31 1991), 5647 women were delivered in the labour ward. Of these, 1178 women (20.9%) were excluded because of high risk factors in pregnancy or at admission for labour, including women undergoing elective caesarean section. Of the remaining 4469 women 4044 (90.5%) were randomised to either intermittent (n = 2015) or continuous monitoring (n = 2029) during the first stage of labour. In the C-group the fetal heart rate was recorded continuously with electronic fetal monitoring during the first stage of labour. In the I-group the fetal heart rate was recorded with electronic fetal monitoring for 10 to 30 min every 2 to 2.5 h during the first stage of labour, and the fetal heart rate was auscultated every 15 to 30 min in between recording periods. If complications occurred, recording was changed to continuous. In the second stage of labour all the women were monitored continuously. Umbilical cord artery acid-base status was assessed at birth. Duration of electronic fetal monitoring, rates of abnormal fetal heart rate patterns, caesarean section for fetal distress, acidosis in umbilical cord arterial blood at birth, Apgar scores of less than 7 at 1 or 5 min, and referrals to the neonatal intensive care unit. There were no significant differences between the study groups in the incidence of ominous fetal heart rate recordings: 6.3% (I-group) versus 6.6% (C-group), or the interval from arrival to first detected abnormal fetal heart rate, although the number of suspicious fetal heart rate patterns was higher in the C-group (28.6%) than in the I-group (24.6%). In the I-group electronic fetal monitoring was performed for (median monitoring time) 38.8% of the first stage of labour as compared with 78.6% in the C-group. The incidence of caesarean section for fetal distress was similarly low in both groups: 1.2% versus 1.0%. There were no significant differences in the immediate neonatal outcome in terms of umbilical artery pH, Apgar scores, or admissions to the neonatal care unit. Intermittent use of electronic fetal monitoring at regular intervals (with stethoscopic auscultation in between) appears to be as safe as continuous electronic fetal monitoring in low risk labours.


Benefit of neoadjuvant concurrent chemoradiotherapy for locally advanced perihilar cholangiocarcinoma.
To clarify the role of neoadjuvant concurrent chemoradiotherapy (NACCRT) followed by surgical resection for localized or locally advanced perihilar cholangiocarcinoma (CCA). We retrospectively reviewed 57 patients who underwent surgical resection with or without NACCRT for perihilar CCA; 12 patients received NACCRT and 45 patients did not received NACCRT. Patients with locally advanced perihilar CCA requiring NACCRT were defined as follows: (1) a mass involving unilateral branches of the portal vein or hepatic artery with insufficient volume of the anticipated remnant lobe; or (2) an infiltrating mass in the main portal vein that was too long for reconstruction, identified at preoperative staging. The median disease-free survival (DFS) durations of the neoadjuvant and non-neoadjuvant CCRT groups were 26.0 and 15.1 mo, respectively (P = 0.91). The median overall survival (OS) durations of the neoadjuvant and non-neoadjuvant CCRT groups were 32.9 and 27.1 mo, respectively (P = 0.26). The NACCRT group showed a downstaging tendency compared to the non-NACCRT group as compared with the tumor stage confirmed by histological examination after surgery and the tumor stage confirmed by imaging test at the time of diagnosis (P = 0.01). NACCRT does not prolong DFS and OS in localized or locally advanced perihilar CCA. However, NACCRT may allow tumor downstaging and improve tumor resectability.


The Effect of Amantadine on Agitation in the Pediatric Traumatic Brain Injury Population: A Case Series.
In this report, we present a case series involving four pediatric patients who sustained a traumatic brain injury (TBI) and required intensive care unit admission immediately after the injury. In each of the four cases, amantadine was started during the acute care hospital admission to address agitation. Cases were retrieved from the electronic medical record at the Children's Hospital of Philadelphia between July 1, 2020, and October 31, 2022. This case series describes clinical data on TBI presentation, amantadine administration, patient behavior, and hospital course relating to agitation. This is the first publication that reports the effect of amantadine on agitation in the acute phase of recovery in the pediatric TBI population. Improvement in agitation was observed within 48 hours of amantadine initiation in all four cases based on the primary team progress notes, as well as the quantity of pro re nata medications given for agitation. Resolution of agitation was also observed in all cases, though the time scale varied. No adverse events were reported in relation to amantadine use, supporting other reports that the medication may be well tolerated in the pediatric population. More research is needed to determine the optimal dose of amantadine for the pediatric population and whether amantadine hastens agitation resolution compared to the current standard of care.


Development of a hydrophilic interaction liquid chromatography coupled with matrix-assisted laser desorption/ionization-mass spectrometric imaging platform for N-glycan relative quantitation using stable-isotope labeled hydrazide reagents.
In this work, the capability of newly developed hydrophilic interaction liquid chromatography (HILIC) coupled with matrix-assisted laser desorption/ionization-mass spectrometric imaging (MALDI-MSI) platform for quantitative analysis of N-glycans has been demonstrated. As a proof-of-principle experiment, heavy and light stable-isotope labeled hydrazide reagents labeled maltodextrin ladder were used to demonstrate the feasibility of the HILIC-MALDI-MSI platform for reliable quantitative analysis of N-glycans. MALDI-MSI analysis by an Orbitrap mass spectrometer enabled high-resolution and high-sensitivity detection of N-glycans eluted from HILIC column, allowing the re-construction of LC chromatograms as well as accurate mass measurements for structural inference. MALDI-MSI analysis of the collected LC traces showed that the chromatographic resolution was preserved. The N-glycans released from human serum was used to demonstrate the utility of this novel platform in quantitative analysis of N-glycans from a complex sample. Benefiting from the minimized ion suppression provided by HILIC separation, comparison between MALDI-MS and the newly developed platform HILIC-MALDI-MSI revealed that HILIC-MALDI-MSI provided higher N-glycan coverage as well as better quantitation accuracy in the quantitative analysis of N-glycans released from human serum. Graphical abstract Reconstructed chromatograms based on HILIC-MALDI-MSI results of heavy and light labeled maltodextrin enabling quantitative glycan analysis.


Shape evolution of ooids: a geometric model.
Striking shapes in nature have been documented to result from chemical precipitation - such as terraced hot springs and stromatolites - which often proceeds via surface-normal growth. Another studied class of objects is those whose shape evolves by physical abrasion - the primary example being river and beach pebbles - which results in shape-dependent surface erosion. While shapes may evolve in a self-similar manner, in neither growth nor erosion can a surface remain invariant. Here we investigate a rare and beautiful geophysical problem that combines both of these processes; the shape evolution of carbonate particles known as ooids. We hypothesize that mineral precipitation, and erosion due to wave-current transport, compete to give rise to novel and invariant geometric forms. We show that a planar (2D) mathematical model built on this premise predicts time-invariant (equilibrium) shapes that result from a balance between precipitation and abrasion. These model results produce nontrivial shapes that are consistent with mature ooids found in nature.


[Khat: from traditional usage to risk of drug addiction].
In much of East Africa and the Arabian Peninsula, the leaves of the qat tree (Catha edulis Forsk) are highly prized for their euphoric effects. Use is deeply anchored in regional customs and traditions. Once controversial, the chemical properties of qat are now well-documented; the active agent responsible for the physical and mental effects observed when the leaves are chewed is cathinone or alpha-aminopropiophenone. According to the definition of the World Health Organization, qat is not classified as an inevitably addictive drug. However recent reports of psychosis related to qat abuse in Great Britain and the United States have raised new alarm in the Narcotics Commission of the United Nations. Should qat be prohibited? International law on this issue is currently highly ambiguous. Importation of qat is illegal in France as in Switzerland, but legal in the United States and Great Britain as in most African countries.


A novel leukocyte adhesion deficiency type III mutation manifests functional importance of the compact FERM domain in kindlin-3.
Leukocyte adhesion deficiency III (LAD-III) is a rare autosomal recessive syndrome characterized by functional deficiencies of platelets and leukocytes that occurs due to mutations in the FERMT3 gene encoding kindlin-3. Kindlin-3 is a FERM domain-containing adaptor protein that is essential in integrin activation. We have previously demonstrated that the FERM domain of kindlin-3 is structurally compact and plays an important role in supporting integrin activation in a mouse model. The impact of destabilizing the compact FERM domain in kindlin-3 on the development of LAD-III in humans remains uncertain. To use primary cells from a patient with LAD-III to validate the role of the compact FERM domain in kindlin-3 function in platelets and leukocytes. The patient is a 4-year-old girl who since infancy has displayed clinical features of LAD-III. Patient platelets and leukocytes were functionally analyzed, and structural analysis of the kindlin-3 variant was conducted. We identified a novel homozygous missense mutation in the FERMT3 (c.412G>A, p.E138K) FERM domain. Substantially reduced levels of kindlin-3 were detected in the proband's platelets and leukocytes. Functional evaluation verified that integrin αIIbβ3-mediated platelet activation, spreading, and aggregation and β2-integrin-mediated neutrophil adhesion and spreading were significantly compromised. Structural analysis revealed that this newly identified E138K substitution in kindlin-3 destabilizes the compacted FERM domain, resulting in poor expression of kindlin-3 in blood cells and subsequent LAD-III. We have identified a novel missense mutation and verified the functional significance of the compact kindlin-3 FERM domain in supporting integrin functions in platelets and leukocytes.


The ICRP working party on bioassay interpretation.
In recent years there have been many developments in modelling the behaviour of radionuclides in the human body. The current generation of models is designed to be more 'realistic' than the previous generation of simple compartment models. The International Commission on Radiological Protection (ICRP) uses these models to produce dose coefficients and recognises that there is a need to give more guidance on how these models can be used to interpret bioassay data. A working party has been set up to address the issue. This paper describes some of the problems, some approaches to solving the problems and the progress of the ICRP working party.


Levetiracetam in autistic children: an open-label study.
The objectives of this study were to determine whether autistic children taking levetiracetam (1) showed improvement in the areas of aggression, impulsivity, hyperkinesis, and mood instability, and (2) showed a nootropic response. Ten white autistic boys ranging from 4 to 10 years were compared pretreatment and while taking levetiracetam for an average of 4.1 weeks. Inattention, hyperkinesis, and impulsivity were evaluated using the Achenbach Attention Problems scale, Conners DSM-IV Total scale, and the Conners Attention-Deficit Hyperactivity Disorder Index scale, all of which showed statistically significant improvements. Mood instability was measured with the Conners Global Index (CGI) Emotional Lability and CGI Total scales, both of which showed statistically significant improvements. Aggressive behavior, as measured with the Achenbach Aggression scale, showed statistically significant improvement only for subjects who were not recently weaned from medications that reduce aggression (e.g., risperidone, carbamazepine, desipramine). Levetiracetam may reduce hyperactivity, impulsivity, mood instability, and aggression in autistic children with these problems. No nootropic effect was observed.


Using indocyanine green fluorescent imaging to successfully resect metachronous regional lymph node recurrence of rectosigmoid cancer.
A 39-year-old female patient underwent anterior resection with locoregional lymph node dissection for rectosigmoid cancer at another hospital. The procedure involved transection of the superior rectal artery just below the origin of the left colic artery. Postoperative diagnosis was stage III B. The patient received adjuvant chemotherapy with oxaliplatin plus capecitabine for 6 months. Sixteen months after the operation, PET-CT scans revealed regional lymph node metastases around the root of the inferior mesenteric artery. The patient was referred to our hospital with a recurrence of rectosigmoid cancer. We performed laparoscopic lymph node dissection with real-time indocyanine green fluorescent images superimposed on color images to prevent intraoperative vascular insufficiency. We were able to successfully observe the sufficient blood flow in the descending colon. Postoperative pathological findings showed lymph node recurrence after initial surgery. She was discharged 7 days after the operation. In the 8 months since the second operation, the patient has not had any indication of further recurrence.


Assessment of cervical elastography strain pattern and its association with preterm birth.
The aim of the study was to assess the cervical strain pattern by an ultrasound elastography cervix examination and to determine its association with preterm delivery. In this study, 30 cases resulting in preterm birth and 30 gestational age-matched controls were included. A vaginal ultrasound examination with cervical length and elastography measurement was performed. We calculated four strain ratios (SR1-SR4) of the regions of interest (ROIs) arranged in pairs in four different positions on the anterior cervical lip. The strain ratios were correlated to the outcome of spontaneous preterm delivery. The inter-observer and intra-observer variability of the strain measurement was evaluated. We observed an association between the value of the strain ratio that was calculated from the ROIs placed side by side in the middle of the anterior lip (SR4), and preterm delivery (P<0.001). The predictive values of cervical length and SR4 were comparable (AUC 0.7394; AUC 0.8322, respectively). The combination of cervical length and SR4 was superior in predicting preterm delivery compared to both parameters alone (AUC 0.8789). The inter-observer and intra-observer variability of data acquisition and measurement was excellent. Our study assesses the cervical elastography strain pattern and shows a correlation to a spontaneous preterm birth.


[Resistance to organophosphorus insecticides found in Aedes aegypti (Diptera: Culicidae) from Santiago de Cuba, 1997-2009].
resistance to organophosphorus insecticides was diagnosed in Aedes aegypti (Linnaeus, 1762) from Santiago de Cuba in 1997 and some of them are still used up to date; hence the need of ascertaining how the insecticidal resistance has changed in recent times, particularly in 2009. to evaluate the resistance to organophosporus insecticides in larvae from Santiago de Cuba collected in 2009, and its variation in comparison with that observed in 1997; and to determine the frequency of occurrence of resistance mechanisms on the basis of high esterase activity and its classification. resistance to organophosphorus insecticides such as malathion, pirimiphos, methyl, phenitrotion, phention, temephos and clorpiriphos in larvae by using the WHO recommended methodology. The esterase mechanism was identified through biochemical assays and polyacrylamide gel electrophoresis. larvae from the Santiago de Cuba strain were susceptible to malathion, pirimiphos, methyl and phenitrothion; there was no variation with the results achieved in a Santiago de Cuba strain in 1997, moderate resistance to phenthion and high resistance to temephos and chlorpiriphos were observed. When comparing these results with those of 1997, it was noted that resistance to the three insecticides increased in the 1997-2009 period. In the Santiago de Cuba strain 2009, it was shown that esterase activity was very high at a rate of 0.7. The presence of an amplified type B esterase with relative mobility of 0.95 cm was detected, which did not exist in the reference strain. resistance to insecticides and its mechanisms are highly variable, even in the same species subjected to various intensities in the insecticidal use, therefore, it is necessary to constantly monitor both aspects at local level in the course of time, with a view to an effective vector control program.


Genetic Tailors: CTCF and Cohesin Shape the Genome During Evolution.
Research into chromosome structure and organization is an old field that has seen some fascinating progress in recent years. Modern molecular methods that can describe the shape of chromosomes have begun to revolutionize our understanding of genome organization and the mechanisms that regulate gene activity. A picture is beginning to emerge of chromatin loops representing a widespread organizing principle of the chromatin fiber and the proteins cohesin and CCCTC-binding factor (CTCF) as key players anchoring such chromatin loops. Here we review our current understanding of the features of CTCF- and cohesin-mediated genome organization and how their evolution may have helped to shape genome structure.


Testing the construct validity of willingness to pay valuations using objective information about risk and health benefit.
This paper describes an experiment to test the construct validity of contingent valuation, by eliciting women's valuations for the NHS cervical cancer screening programme. It is known that, owing to low levels of knowledge of cancer and screening in the general population, women both over-estimate the risk of disease and the efficacy of screening. The study is constructed as a randomised experiment, in which one group is provided with accurate information about cervical cancer screening, whilst the other is not. The first hypothesis supporting construct validity, that controls who perceive greater benefits from screening will offer higher valuations, is substantiated. Both groups are then provided with objective information on an improvement to the screening programme, and are asked to value the improvement as an increment to their original valuations. The second hypothesis supporting construct validity, that controls who perceive the benefits of the programme to be high already will offer lower incremental valuations, is also substantiated.


Internet-Delivered Self-help for Adults With ADHD (MyADHD): Usability Study.
Although effective pharmacological treatment exists, many adults with attention-deficit/hyperactivity disorder (ADHD) prefer a nonpharmacological option for managing their symptoms. Internet-delivered self-help interventions have the potential to address this unmet supportive care need reported by adults with ADHD, at relatively low costs. However, if the intervention does not offer optimal functions, content, and layout, it could decrease adherence and engagement and potentially compromise the effectiveness of such interventions. Thus, there is a need for examining the usability and factors that enhance and impair the usability of internet-delivered self-help interventions. This study evaluates the usability of an internet-delivered self-help intervention for adults with ADHD (MyADHD). The main goals were to (1) collect qualitative and quantitative data on usability and (2) identify usability problems. Individual think-aloud interviews and staged usability testing (N=5) were conducted to evaluate the usability of the MyADHD intervention in terms of function, content, and design. MyADHD end users provided iterative feedback to maximize engagement and usability. They performed tasks involved in operating the intervention and provided "think-aloud" commentary and postsession usability ratings. The interviews were recorded, transcribed verbatim, and analyzed. Participants were satisfied with the overall usability of the program. The average perceived usability score out of 100 was 70 for the first round of testing and improved to 77.5 after applying modifications, with a mean score of 75.5 (SD 5.9) for all rounds of usability testing. The analysis of the interviews revealed 3 central themes: functionality, content, and layout. Optimizing the usability of internet-delivered self-guided interventions is a critical step in the design and development process. The usability testing in this study provided valuable information from users' perspectives on the content and platform of the intervention. Analysis revealed the need for intervention enhancement with regard to design, functionality, and content from the perspective of potential end users. Overall, participants saw value in the MyADHD intervention and were confident that they could use it for the self-management of symptoms and expressed the desire to use the entire intervention when it becomes available. Through this development process, we produced an intervention that is likely to be used successfully and is ready for deployment in a randomized controlled trial. ClinicalTrials.gov NCT04511169; https://clinicaltrials.gov/ct2/show/NCT04511169.


Prognostic value of lymph node metastasis in patients with T1-stage colorectal cancer from multiple centers in China.
To explore the features and prognostic value of lymph node metastasis in patients with T1-stage colorectal cancer (CRC). In all, 321 cases of T1-stage CRC were selected from 10132 patients with CRC who received surgical therapy in six large-scale hospitals in China and were retrospectively analyzed. Univariate and multivariate analyses were performed to analyze the risk factors for lymphatic metastasis. A survival analysis was then performed to analyze the prognostic value of lymph node metastasis. The occurrence rate of T1 stage was 3.17% (321/10132); of these patients, the lymph node metastasis rate was 8.41% (27/321), and the non-lymph node metastasis rate was 91.59% (294/321). Univariate analysis showed that preoperative serum CEA, preoperative serum CA199, preoperative serum CA724, vascular invasion, and degree of differentiation were associated with lymph node metastasis in T1-stage CRC (P < 0.05 for all). Multivariate analysis indicated that preoperative serum CA724, vascular invasion, and degree of differentiation were closely related to lymph node metastasis (P < 0.05 for all). Log-rank survival analysis showed that age, preoperative serum CEA, preoperative serum CA199, vascular invasion, degree of differentiation, and lymph node metastasis (χ2 = 24.180, P < 0.001) were predictors of 5-year overall survival (OS) (P < 0.05 for all). COX regression analysis demonstrated that preoperative serum CA199 and lymph node metastasis (HR = 5.117; P < 0.05; 95%CI: 0.058-0.815) were independent prognostic indicators of 5-year OS in patients with T1-stage CRC (P < 0.05 for both). The morbidity of T1-stage CRC was 3.17% for all CRC cases. Preoperative serum CA724, vascular invasion, and degree of differentiation are independent risk factors for lymph node metastasis. Lymph node metastasis is an independent prognostic factor for OS in patients with T1-stage CRC.


The hidden identity of faces: a case of lifelong prosopagnosia.
Not being able to recognize a person's face is a highly debilitating condition from which people with developmental prosopagnosia (DP) suffer their entire life. Here we describe the case of J, a 30 year old woman who reports being unable to recognize her parents, her husband, or herself in the mirror. We set out to assess the severity of J's prosopagnosia using tests with unfamiliar as well as familiar faces and investigated whether impaired configural processing explains her deficit. To assess the specificity of the impairment, we tested J's performance when evaluating emotions, intentions, and the attractiveness and likability of faces. Detailed testing revealed typical brain activity patterns for faces and normal object recognition skills, and no evidence of any brain injury. However, compared to a group of matched controls, J showed severe deficits in learning new faces, and in recognizing familiar faces when only inner features were available. Her recognition of uncropped faces with blurred features was within the normal range, indicating preserved configural processing when peripheral features are available. J was also unimpaired when evaluating intentions and emotions in faces. In line with healthy controls, J rated more average faces as more attractive. However, she was the only one to rate them as less likable, indicating a preference for more distinctive and easier to recognize faces. Taken together, the results illustrate both the severity and the specificity of DP in a single case. While DP is a heterogeneous disorder, an inability to integrate the inner features of the face into a whole might be the best explanation for the difficulties many individuals with prosopagnosia experience.


The blood count as a compass to navigate in the ever-changing landscape of the carrier state of hemoglobinopathies: a single-center Italian experience.
Approximately 7% of the worldwide population exhibits variations in the globin genes. The recent migration of populations from countries where hemoglobin disorders are endemic has resulted in important epidemiological changes with the diffusion of newly discovered or poorly characterized genetic variants and new combinations and very heterogeneous clinical phenotypes. The aim of our study is to assess the parameters that are more significant in predicting a positive genetic testing outcome for hemoglobinopathies in a pediatric population of patients presenting with anemia or microcythemia, without a definite diagnosis. This study included patients evaluated in our hematological outpatient clinic for anemia and/or microcythemia despite normal ferritin levels. A screening of pathological hemoglobins using high-performance liquid chromatography (HPLC) was performed for the entire population of the study. Subsequently, patients with hemoglobin (Hb) S trait and patients with an HPLC profile compatible with beta thalassemia trait were excluded from the study. Genetic screening tests for hemoglobinopathies were performed on the remaining patients, which involved measuring the red blood cell (RBC) counts, red blood cells distribution width (RDW), reticulocyte count, and mean corpuscular volume of reticulocytes (MCVr). This study evaluated a total of 65 patients, consisting of nine patients with negative genetic analysis results and 56 patients with positive genetic analysis results. The Hb and RDW values in these two groups did not demonstrate statistical significance. On the other hand, there were statistically significant differences observed in the mean corpuscular volume (MCV), RBC count, reticulocyte count, and MCVr between the two groups. Furthermore, in the group of patients with positive genetic test results, specific genetic findings associated with different HPLC results were observed. In particular, 13 patients with positive genetic test results had normal HPLC findings. This study has demonstrated that HPLC, while serving as a valuable first-level test, has some limitations. Specifically, it has been observed that some patients may exhibit a negative HPLC result despite a positive genetic analysis. In addition to the presence of low levels of Hb and HPLC alterations, other parameters could potentially indicate the underlying mutations in the globin genes. Therefore, we propose that the complete blood cell count be utilized as a widely available parameter for conducting targeted genetic analyses to avoid the risk of overlooking rare hemoglobinopathies.


Influences of dysfunctional respiratory mechanics on orofacial pain.
This article reviewed the anatomic issues of respiration and the active and passive mechanics of the thorax as related to dysfunctional breathing. Influences from respiratory dysfunction on forward head posture and temporomandibular dysfunction were offered. Discussion of inspiratory and expiratory muscle responsibilities, effects of diaphragmatic dystonia and abdominal weakness, and results of improper coordination and timing of respiratory muscle should all give the dentist and physical therapist an appreciation of the need for careful observation and appropriate treatment with the patient experiencing TMD and dysfunctional respiratory mechanics. Summaries of hyperinflation relationships and treatment considerations should help in the management of TMD.


Ultra-short echo-time 2D time-of-flight MR angiography using a half-pulse excitation.
Flow-related artifacts remain a significant concern for magnetic resonance (MR) angiography because their appearance in angiograms adversely impacts accuracy in evaluation of arterial stenoses. In this paper, a half-pulse excitation scheme for improved two-dimensional time-of-flight (2D TOF) angiography is described. The proposed method eliminates the need for gradient moment nulling (of all orders), providing significant reductions in spin dephasing and consequent artifactual signal loss. Furthermore, because the post-excitation refocusing and flow compensation gradients are obviated, the achievable echo time is dramatically shortened. The half-pulse excitation is employed in conjunction with a fast radial-line acquisition, allowing ultra-short echo times on the order of 250-300 microsec. Radial-line acquisition methods also provide additional benefits for flow imaging: effective mitigation of pulsatile flow artifacts, full k-space coverage, and decreased scan times. The half-pulse excitation/radial-line sequence demonstrated improved performance in initial clinical evaluations of the carotid bifurcation when compared with a conventional 2D TOF sequence.


[Autonomic dysfunction in patients with multiple sclerosis].
To optimize the early diagnosis of the autonomic dysfunction in patients with MS. The main group consisted of 46 patients: 15 men and 31 women with MS (McDonald, 2005), the average age was 33.35±9.9 years, the average score of the Expanded disability scale (EDSS) was 2.8±1.17 points. The control group consisted of 24 healthy subjects matched by age and sex with the main group. A study of the autonomic nervous system was carried out using the Scheme for detection of signs of autonomic disorders (A.M. Vein, 1998) and analysis of heart rate variability (HRV) at rest and after active orthostatic test (AOT). Autonomic dysfunction was found in 73% of the patients. The overall score of the Scheme was significantly higher in MS patients (31.32±9.43 points) compared to the comparison group (2.36±4.39 points, p<0.05). According to HRV, the contribution of brainstem autonomic centers in the regulation of stress-response during AOP was significantly reduced (p<0.05) and was characterized by the lack of activation of the sympathetic division of the ANS. In patients with MS, cerebral influences were dominating on HRV baseline records, evaluated by the domination of the VLF component in the spectrum. During AOP, VLF was almost leveled in both groups, and the VLF changes in patients before and after the AOP reached statistical significance (p<0.05). The use of the Scheme is preferable in outpatient clinics to screen the large numbers of patients with MS, and then selected patients could be referred to the instrumental methods of investigation.


The effects of music and visual stress on testosterone and cortisol in men and women.
The aims of the present study were to examine sex-related differences in testosterone (T) and cortisol (C) changes with music listening and visual stress. Saliva T and C concentrations were measured in 88 healthy college students (44 males and 44 females). These subjects were placed in one of 4 different conditions: (1) 30 min of listening to music, (2) 30 min of listening to music with visual stress (documentary film without sound including violent scenes), (3) 30 min of visual stress without music, and (4) 30 min of silence. All subjects provided two saliva samples, one collected before intervention and the other after intervention. T and C levels were assessed by radio immuno assay (RIA). There was a significant difference between the sexes in the way music affected T. Music decreased T in males, whereas it increased T in females. As for C, no sex-related differences were found under any of the conditions studied. C decreased with music and increased under other conditions. THE MAIN FINDINGS: Our data suggests that the effects of music and stress on T differ between males and females. Further investigation is necessary to evaluate the relationships between music and other substances, the effect of degree of preference and hormonal changes not only during music listening but also during music plays and creation.


Self-enhanced electrogenerated chemiluminescence of ruthenium(II) complexes conjugated with Schiff bases.
In this work, we obtain two ruthenium(ii) complexes with Schiff base cavities that exhibit significantly enhanced electrochemiluminescence (ECL) intensity and quantum efficiency due to Ru(bpy)3(2+) in aqueous solution, without the addition of tri-n-propylamine (TPrA). The great increase in ECL intensity is confirmed to be due to the electrochemical oxidation of phenolic hydroxyl groups and the resonant structure of imino radicals. Thus, the electrons are transferred intramolecularly to the Ru(iii) center, leading to efficient generation of the excited state of Ru(ii)*. Subsequently, we find that Co(2+) bonding with the salen cavity can selectively and quickly quench the ECL signal. Furthermore, we study the mechanism of the process by which Co(2+) hinders the oxidation of phenolic groups and blocks the electron transfer from imino radicals to the Ru center. Thus, a highly sensitive and selective ECL probe for the recognition of Co(2+) was developed with a stable response over a concentration range of 0.9 μM to 6.3 μM and a detection limit as low as 21 nM.


Efficacy of tranexamic acid for the prevention of bleeding in patients with von Willebrand disease and Glanzmann thrombasthenia: a controlled, before and after trial.
Reducing bleeding episodes is very important in haematology disorders like von Willebrand disease (VWD) and Glanzmann thrombasthenia (GT). Replacement factors are very expensive although prophylactic drugs are affordable. To study the prophylactic effects of tranexamic acid (TXA) for reduction of bleeding episodes in patients with VWD and GT in non-invasive conditions. A controlled, double-blind before and after single-centre trial was performed in Amir-Kabir Hospital (Arak, Iran). The study was done on 17 patients with VWD and three patients with GT with minimum age of 2 years. Patients were received placebo for 6 months to evaluate the frequency and severity of bleeding and also to record the frequency of use of factor concentrates and platelet transfusion. After that, patients were given oral single dose of TXA 25 mg kg(-1) day(-1) for 6 months. The mentioned outcomes were studied and compared between two phases of study. Safety assessment was done in all patients. Tranexamic acid caused a significant reduction in number of Grade 1 and Grade 2 bleeding episodes in VWD patients (P < 0.001 and P < 0.01 respectively). In addition, TXA therapy was associated with significant decrease in the use of factor concentrates (P < 0.05). Number of bleeding episodes decreased in GT patients who used TXA; however, difference between two phases of studies was not significant (P = 0.1). TXA had no effect in the frequency of platelet transfusions in GT patients. TXA therapy was associated with headache, back pain and musculoskeletal pain. No case of allergy or thromboembolic events was seen following treatment. The results suggest that TXA is safe and effective to reduce bleeding and use of factor concentrates in VWD patients. In addition, TXA therapy can decrease bleeding in GT patients.


Ultrastructural study of the mitochondria in the skeletal muscle fibers in the diabetic Chinese hamster.
An ultrastructural study of skeletal muscle fiber biopsies from the tongue and soleus muscle of diabetic Chinese hamsters revealed the presence of lipid droplets within the muscle fibers. These droplets often were found in the cyptoplasm near mitochondira, sometimes inside or surrounded by one or more mitochondria. Glycogen granules were found in great quantities in the cytoplasm of the tongue and soleus muscle. Granules which appeared to be glycogen were also found within the mitochondria of the tongue muscle.


Impact of Different Strategies for Delivering Supplemental Zinc on Selected Fecal Markers of Environmental Enteric Dysfunction among Young Laotian Children: A Randomized Controlled Trial.
The objective of this study was to assess the impact of different strategies for delivering supplemental zinc on fecal myeloperoxidase (MPO), neopterin (NEO), and calprotectin (CAL) among young Laotian children. In a double-blind controlled trial, children aged 6-23 months were randomized to receive either daily preventive zinc (PZ) tablets (7 mg/day), daily micronutrient powder (MNP; containing 10 mg zinc and 14 other micronutrients), therapeutic zinc (TZ) supplements for diarrhea treatment (20 mg/day for 10 days), or daily placebo powder and followed for ∼36 weeks. Stool samples were collected at baseline and endline. Fecal MPO, NEO, and CAL concentrations were determined in a randomly selected subsample of 720 children using commercially available ELISA kits. At baseline, the mean age was 14.1 ± 4.9 months and prevalence of stunting was 39%. The endline prevalence of stunting was 43%; there was no overall treatment effect on physical growth in the parent trial. At endline, the mean (95% CI) MPO in the PZ group was 1,590 [1,396; 1,811] ng/mL and did not differ from that in the MNP (1,633 [1,434; 1,859] ng/mL), TZ (1,749 [1,535; 1,992] ng/mL), and control (1,612 [1,415; 1,836] ng/mL) groups (P = 0.749). Similarly, there was no overall treatment effect on NEO and CAL concentrations (P = 0.226 and 0.229, respectively). In this population, the provision of PZ or TZ supplements or MNP had no impact on growth or environmental enteric dysfunction (EED) as assessed by fecal MPO, NEO, and CAL. Additional research is needed to better understand the etiology and proposed mechanisms of EED pathogenesis.


Estimates of heritabilities and of genetic and phenotypic correlations among growth and reproductive traits in yearling Angus bulls.
Data from Nichols Farm, Anita , Iowa, collected from 1975 through 1980, were used. Angus Herd Improvement Records with birth, weaning and yearling weights were obtained for 717 bulls by 80 sires. Also available, from Hawkeye Breeders Service, Des Moines , Iowa, were measures of sperm concentration and motility, percentage live sperm, number of sperm/ml, semen score and quality and scrotal circumference on the bulls as yearlings . Heritabilities and genetic and phenotypic correlations were estimated for the above traits from variance and covariance components calculated by restricted maximum likelihood. Estimates of heritability for birth, weaning and yearling weight were .70, .46 and .49, respectively. Heritability estimates for the semen traits were low (0 to .24); the estimate for scrotal circumference was .36. In general, genetic and phenotypic correlations among semen traits were high and favorable, with absolute values ranging between .49 and 1.11. Genetic correlations between semen traits and scrotal circumference were low; corresponding phenotypic correlations were moderate. Semen traits were lowly correlated phenotypically with growth traits (-.08 to .08) and genetic correlation estimates were variable. Estimates of phenotypic and genetic correlations suggested that yearling scrotal circumference was more closely related to yearling weight than to either birth or weaning weight. Estimates of phenotypic and genetic correlations between scrotal circumference and yearling weight were .26 and .68, respectively.


Increasing oxygen tension dilates fetal pulmonary circulation via endothelium-derived relaxing factor.
We examined the role of endothelium-derived relaxing factor (EDRF) in the increase in pulmonary blood flow caused by increasing oxygen tension in the lungs of the fetus. Fetal lambs at 133 days of gestation were instrumented for intrauterine measurement of pulmonary arterial, left atrial, and amniotic fluid pressure and pulmonary blood flow. Three days later oxygen tension in the pulmonary arterial blood of the fetus was doubled by having the ewe breathe 100% oxygen at 3 atm absolute pressure. In the control fetuses (n = 5), hyperbaric oxygenation increased pulmonary blood flow eightfold. Blocking EDRF production by infusing 45 mg of NG-monomethyl-L-arginine into the superior vena cava of the fetus over 5 min starting 30 min after the beginning of hyperbaric oxygen reversed the increase in pulmonary blood flow (n = 5). Blocking EDRF production by infusing NG-nitro-L-arginine at 1 mg/min for 60 min starting 30 min before hyperbaric oxygen blunted the initial increase in pulmonary blood flow and eliminated it by the end of the experiment (n = 5). As hyperbaric oxygen did not significantly alter pulmonary arterial or left atrial pressure, changes in pulmonary vascular conductance paralleled those in pulmonary blood flow. We conclude that the majority of the vasodilation of the fetal pulmonary circulation caused by increasing oxygen tension is mediated by EDRF. We speculate that EDRF is involved in maintaining low vascular tone at the relatively high oxygen tension of the postnatal lung.


Oxygen as an antibiotic. The effect of inspired oxygen on infection.
Granulocytes' in vitro bactericidal capacity for certain bacteria depends on an adequate environmental oxygen supply. Oxygen available to granulocytes in infected tissue is decreased by local conditions and can be altered significantly by small changes in its inspired concentration. We modified Burke's and Miles' bacteria-injection model in animals to test the effect of breathing 12%, 21%, and 45% oxygen on the size of lesions produced by intradermal injections of Escherichia coli. Moderately increased inspired oxygen concentrations (fraction of inspired oxygen [Flo2]) significantly decreased the size and number of necrotic lesions, whereas hypoxia increased both. Increasing Flo2 to 45% after three and 24 hours of hypoxia also significantly decreased lesion size. Suppression of infection by moderate hyperoxia is comparable with that reported by Burke after timely, adequate doses of type-specific antibiotics.


[Pregnancy in women with thyroid cancer treated with suppressive doses of L-thyroxine].
The aim of the study was to estimate the dose of thyroxine required by pregnant women who had undergone total thyreoidectomy and radioiodine treatment for thyroid cancer. Material consisted of 4 pregnant women, aged mean 30.8 years. One of patients was studied during 2 consecutive pregnancies. The daily mean dose of thyroxine was 175 micrograms. The control group consisted of 7 women with primary hypothyroidism aged mean 33.5 years, who were treated with replacement doses of thyroxine. One of them was pregnant twice. The mean daily dose of thyroxine was 106.3 micrograms. The estimation of TSH, fT4 were repeated every 4 weeks. In all cases natural deliveries took place. All infants were alive and had no congenital malformations and no clinical or biochemical thyroid dysfunction was found. Pregnant women treated for thyroid cancer needed to have optimized their suppressive therapy by increasing the dose of thyroxine by 26% at the first trimester, 27% at the second and 38% at the last one. Statistically significant increase was found at the 1st trimester of pregnancy and it remained at the same level till the delivery. Pregnant hypothyroid women needed to have optimized their replacement thyroxine therapy by increasing of the dose by 53% at the first trimester, by 49% at the second and by 53% at the last one. Similarly to the 1st group of patients, we noticed statistically significant increase at the 1st trimester of pregnancy. In pregnant women who have been previously treated for thyroid cancer the suppressive dose of thyroxine needs to be increased by 26-38% which is slightly less than the increase of the replacement dose in hypothyroid pregnant women.


Listening to Bedouin Women Who Were Affected by Intimate Partner Violence and Sought Help From a Doctor.
The purpose of this study was to examine how Bedouin women perceived and interpreted seeing a doctor for help in the aftermath of intimate partner violence. In the phenomenological study, 38 semi-structured interviews were conducted at two different points in time. The first interview took place before the first appointment with the doctor, and the second took place about 3 months after seeing the doctor. The findings revealed two main themes: an act of resistance against the prevailing social norms and empowerment out of crisis. The study found that doctors and other professionals working in the field of domestic violence in community clinics provide a reliable first source of support for women within a limiting social space. This brings into focus the centrality of the role of the doctor/health care professionals within the framework of the community clinic and is intended to direct, train, and deepen the insights of the medical staff that work with women affected by intimate partner violence and to create uniformity in the interventions for these women.


Utilisation of wartime nutrition survival experiences.
In protracted and recurrent conflict, Vietnamese people have learned to minimize food insecurity through governance, mutual social responsibility, infrastructure development, ecological sensitivity, agricultural diversification and emphasis on family needs and traditional food patterns. Drawing on this experience, in 1992 a National Plan of Action for Nutrition was devised. Its goals include increasing energy intake and reducing childhood malnutrition.


[Use of miocamycin in infections of the oral cavity].
The results of clinical experimental with a new antibiotic, Miocamycin (Macroral Zambeletti), are reported. 300 patients suffering from the most varied infections of the oral cavity were treated. In view of its utility and the lack of side-effects, it is concluded that this antibiotic may be used with peace of mind in odontostomatological pathology.


CRISPR/Cas9 Genetic Modification of CYP3A5 *3 in HuH-7 Human Hepatocyte Cell Line Leads to Cell Lines with Increased Midazolam and Tacrolimus Metabolism.
Clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 engineering of the CYP3A5 *3 locus (rs776746) in human liver cell line HuH-7 (CYP3A5 *3/*3) has led to three CYP3A5 *1 cell lines by deletion of the exon 3B splice junction or point mutation. Cell lines CYP3A5 *1/*3 sd (single deletion), CYP3A5 *1/*1 dd (double deletion), or CYP3A5 *1/*3 pm (point mutation) expressed the CYP3A5 *1 mRNA and had elevated CYP3A5 mRNA (P < 0.0005 for all engineered cell lines) and protein expression compared with HuH-7. In metabolism assays, HuH-7 had less tacrolimus (all P < 0.05) or midazolam (MDZ) (all P < 0.005) disappearance than all engineered cell lines. HuH-7 had less 1-OH MDZ (all P < 0.0005) or 4-OH (all P < 0.005) production in metabolism assays than all bioengineered cell lines. We confirmed CYP3A5 metabolic activity with the CYP3A4 selective inhibitor CYP3CIDE. This is the first report of genomic CYP3A5 bioengineering in human cell lines with drug metabolism analysis.