Death by graft-versus-host disease associated with HLA mismatch, high recipient age, low marrow cell dose, and splenectomy.
In 65 recipients of marrow from HLA-identical siblings, the death rate from graft-versus-host disease (GVHD) at 1 year was 13%, which was significantly less when compared with 50% among 10 recipients of marrow from HLA-non-identical donors (P less than 0.001 log-rank test). Among recipients of HLA-matched marrow the following was found: patients below 17 years of age had a death rate from GVHD of 4% compared with 32% in elder patients (P less than 0.01). In patients who received greater than or equal to 3 X 10(8) marrow cells/kg 3% died of GVHD compared with 31% in those receiving fewer marrow cells (P less than 0.02). Furthermore, death by GVHD was 11% among nonsplenectomized patients compared with 60% in splenectomized patients (P less than 0.001). Among all children, and among nonsplenectomized patients, those receiving less than 3 X 10(8) marrow cells/kg had a significantly increased death rate by GVHD. The number of T cells or T cell subsets in the marrow graft was not correlated with GVHD or death by GVHD.


A new evaluation method for quantifying PI3K activity by HTRF assay.
PIK3CA, coding a catalytic subunit of PI3K p110alpha, is frequently mutated in cancer. In previous studies, p110alpha with hotspot mutations such as E545K and H1047R were shown to be gain-of-function mutations. However, quantitative evaluation of these mutants was not well established. Recently, a new method for measuring PI3K activity using homogeneous time-resolved fluorescence (HTRF) has been developed. Using this method, we constructed a quantitative evaluation system for PI3K activity. Serial dilutions of standard PIP3 were subjected to the PI3K-HTRF assay in order to establish a regression line for calibration. The recombinant FLAG-tagged p110alpha proteins were engineered together with a regulatory subunit p85alpha in human embryonic kidney 293T cells. Anti-FLAG-Ig immunoprecipitates were then subjected to the assay, which enabled us to quantitatively evaluate the activities of hotspot mutants of p110alpha. We believe this method will also be applicable to the evaluation of p110alpha having uncharacterized mutations found in cancer.


Ontogeny and the effect of aging on pancreatic polypeptide and peptide YY.
Pancreatic polypeptide (PP) and peptide YY (PYY) are related neuroendocrine peptides that are expressed in specialized cells. PP is found around the time of birth in different species. PYY in mice and rats has been extensively studied. PYY is the first peptide hormone to appear in both the pancreas and the colon and is initially expressed together with all other pancreatic islet and gut hormones. This suggests that there is a PYY-producing endocrine progenitor cell, at least in rodents. Whether the same is true for other species is unknown. In chickens, however, pancreatic insulin and glucagon cells appear before PYY. After birth, PYY levels in rats and humans reflect adaptation to enteral feeding. Whereas PYY cells increase with age in rodents, no such changes have been found in humans.


The grounding of higher order concepts in action and language: a cognitive robotics model.
In this paper we present a neuro-robotic model that uses artificial neural networks for investigating the relations between the development of symbol manipulation capabilities and of sensorimotor knowledge in the humanoid robot iCub. We describe a cognitive robotics model in which the linguistic input provided by the experimenter guides the autonomous organization of the robot's knowledge. In this model, sequences of linguistic inputs lead to the development of higher-order concepts grounded on basic concepts and actions. In particular, we show that higher-order symbolic representations can be indirectly grounded in action primitives directly grounded in sensorimotor experiences. The use of recurrent neural network also permits the learning of higher-order concepts based on temporal sequences of action primitives. Hence, the meaning of a higher-order concept is obtained through the combination of basic sensorimotor knowledge. We argue that such a hierarchical organization of concepts can be a possible account for the acquisition of abstract words in cognitive robots.


An inhibitor of cyclic AMP-dependent protein kinase enhances the superoxide production of human neutrophils stimulated by N-formyl-methionyl-leucyl-phenylalanine.
Intact human neutrophils produced superoxide (O2-) by the stimulation with N-formyl-methionyl-leucyl-phenylalanine (fMLP) even when the extracellular Ca2+ was absent (0.56 +/- 0.13 nmol/min per 10(6) cells). The production by fMLP was enhanced more than twice in the presence of the extracellular Ca2+. Moreover, the O2- production by fMLP in the presence of extracellular Ca2+ was enhanced nearly three times by the treatment of cells with H-89, an inhibitor of cyclic AMP-dependent protein kinase (PKA). The enhancement was not observed when the extracellular Ca2+ was depleted from the reaction mixture. In addition, H-89 did not enhance fMLP-induced O2- production of electropermeabilized neutrophils in which the intracellular Ca2+ concentration was fixed to about 100 nM. These observations suggest that not only Ca2+ influx but the inhibition of PKA is necessary for the maximum O2- production by fMLP and that the O2- production is partially suppressed by the activation of PKA induced by fMLP.


Comparison of the time course of the anorectic effect of fenfluramine and amphetamine with drug levels in blood.
Time courses of the suppressive effects on food intake of (+)-amphetamine and (plus or minus)-fenfluramine in deprived rats were found to be different. Amphetamine displayed a potent initial action which rapidly decayed, and this behavioural effect was consistent with the measured blood concentration of amphetamine which showed a peak at 1 h followed by rapid clearance. For fenfluramine, the initial suppression of eating was maintained over several hours and was, for the first hour, related to the blood concentration of fenfluramine but later to an active metabolite, norfenfluramine. The study shows how drug-induced changes in feeding behaviour fluctuate over time and illustrate how single measures of food intake may overlook information about the effectiveness of anorectic drugs.


Quantitative imaging of Na/I symporter transgene expression using positron emission tomography in the living animal.
Transgene expression can be measured in living animals by positron emission tomography (PET) using reporter genes associated with radiolabeled substrates or ligands. We examined here whether PET images obtained with a new reporter gene system (sodium/iodide symporter (NIS) and [124I]iodide) could provide quantitative information on gene expression in mice. Mice received various doses of recombinant adenovirus in which the expression of the NIS cDNA was driven by the CMV promoter and subsequently [124I]iodide. Postmortem gamma counting of liver biopsies was correlated to the adenovirus dose and with NIS mRNA concentration. In addition, immunohistochemically NIS-positive cells increased with higher tissue activities. Finally, a linear relationship existed between the postmortem gamma counting in liver tissues and that calculated from images obtained through small animal PET scanning (r = 0.9581), although there was a bias at high and low specific values. This systematic study on 35 animals demonstrates that quantitative information on gene expression can be obtained from PET images using the NIS reporter system. This new methodology of quantitative imaging of gene expression presents the advantage of avoiding extensive radiochemistry, an important step for more disseminated use of this emerging technology. In addition, this work supports further development of the NIS system for noninvasive assessment of gene delivery in preclinical and clinical studies.


Influencing factors on women's attitudes toward hormone therapy acceptance for menopause treatment: a systematic review.
There is a paucity of data on recent attitudes and perceptions toward hormone therapy use, especially subsequent reanalysis and follow-up of Women's Health Initiative data. The aim of this systematic review was to assess the factors influencing women's attitudes and perceptions toward hormone therapy use for menopausal symptoms. We conducted a comprehensive search of several medical databases including PubMed, Web of Science, Google Scholar, and Scopus. Quality assessment was performed using the Strengthening the Reporting of Observational Studies in Epidemiology Statement for cross-sectional studies. A search was conducted for cross-sectional articles published from January 2012 to March 2023 in English medical databases (PubMed, Web of Science, Scopus, and Google Scholar). Search keywords included "hormone therapy," "acceptance," "menopause," "attitudes," "influence," "factor," "estrogen," "perimenopause," "postmenopause," and "climacteric." Studies evaluating factors that influenced women's attitudes toward hormone therapy were identified. A total of 1,280 articles were initially identified. Twenty-one articles were ultimately included in the review after screening studies based on inclusion and exclusion criteria. The studies were conducted between 2012 and 2023 and included a total of 40,226 participants. The most common positive factor included awareness of the existence and efficacy of hormone therapy. The most common negative factors included concern for general adverse effects and negative perception of hormone therapy from family and friends. The factors assessed in this review on women's attitudes toward hormone therapy acceptance for menopause treatment were categorized into three main themes: (1) demographic factors, (2) environmental/contextual factors, and (3) health care-related factors. Hormone therapy can be a safe and effective tool to improve the quality of life in perimenopausal and postmenopausal women with vasomotor and genitourinary symptoms. However, there are many complex factors that shape women's perceptions of the efficacy, safety, and accessibility of hormone therapy. Healthcare providers should seek to understand these factors to better discuss the benefits and risks with women and assist with decision making based on cultural, personal, and environmental factors.


Recurrent spontaneous abortion: histocompatibility between partners, response to immune therapy, and subsequent reproductive performance.
Immunological factors may account for previously unexplained cases of recurrent abortion. After screening 76 couples for causes of recurrent spontaneous abortion and measuring maternal antipaternal immunity, 23 primary spontaneous recurrent aborters were immunized once with their husbands' leukocytes. Testing for antipaternal cytotoxicity was repeated in 21 couples. Seroconversion was significantly less frequent in couples who shared more than one human leukocyte antigen [one of five (20%) versus 13 of 16 (81%), P < .02]. Twelve of 16 women (75%) who became pregnant had live children and five of those have had a second live child. All 12 women who achieved successful pregnancies had become antipaternal cytotoxic antibody-positive after immunization, whereas all four patients who had repeat abortions had failed to seroconvert (P < .001). However, this relationship is not necessarily causative, as the successful group also tended to have fewer previous abortions and less human lymphocyte antigen sharing. Except for transient illness after immunization, one moderately small for gestational age baby and one premature labor at 32 wk, no complications were observed after immunization.


Isometric fatigue induced by different levels of rhythmic exercise.
Three subjects were trained in leg extensor isometric contractions and in cycling. They then cycled for three consecutive bouts, each of 2.75 min at a constant level of VO2, from 20 to 80% VO2 max. Fifteen seconds after each bout of cycling the subjects exerted an isometric contraction of the right leg at 40% of the maximum voluntary contraction. In each experiment, the duration of the three successive isometric contractions decreased as in hand-grip contractions. There was also a linear reduction in isometric endurance as the severity of the preceding rhythmic exercise increased. In other experiments, after three bouts of rhythmic exercise at 20% VO2 max (each followed by a fatiguing contraction at 40% MVC), further bouts of cycling at increasing levels of severity up to 60% VO2 max resulted in a linear fall in isometric endurance which could be reversed by interposing a lighter level of cycling. The heart rates during these experiments showed a steady increase during the isometric exercise, to about 150 beats X min-1, as the bouts of preceding rhythmic exercise became progressively more severe. The isometric contractions had little influence on the heart rate during cycling. But the rhythmic cycling exercise markedly increased the heart rate achieved at the end of the isometric contractions while decreasing the increment in heart rate during the contraction.


Synergistic targeting tenascin C and neuropilin-1 for specific penetration of nanoparticles for anti-glioblastoma treatment.
The pathological and physiological barriers of glioblastoma multiforme (GBM) lead to insufficient extravasation and penetration of nano-sized therapeutics. As the main driver of interstitial fluid pressure-related drug efflux, the aberrant extracellular matrix (ECM) appears to be a valuable target that plays a crucial role in forming pathological barriers of GBM. Herein, a new Ft peptide was synthesized by coupling FHK and tLyp-1 sequence together via a cysteine to synergistically target glioma-associated tenascin C (extracellular matrix component) and neuropilin-1 on neovasculature and glioma cells to enable specific penetration of nanoparticles for anti-glioblastoma treatment. In vitro, Ft peptide-functionalization not only enabled the internalization of poly (ethyleneglycol)-poly (lactic acid) nanoparticulate system in 2D U87 MG cells and HUVEC cells but also facilitated its deep penetration in 3D glioma spheroids. Similarly, in vivo real-time 2D and 3D imaging clearly showed a substantial accumulation of the Ft-functionalized nanoparticles (Ft-NP) in the glioma foci of intracranial U87 glioma-bearing mice. Glioma distribution assay demonstrated a tenascin C-mediated accumulation in glioma foci and neuropilin-1-mediated transportation through glioma cells. Paclitaxel-loaded Ft-NP (Ft-NP-PTX) induced higher cytotoxic effect and apoptosis rate compared with FHK or tLyp-1-modified ones. The highest anti-glioma efficacy was also achieved following the i.v. administration of Ft-NP-PTX, with a median survival promotion of 269% than that of the saline-treated mice, while only limited life span promotion was obtained after the treatment of other formulations (31.3%, 59.4%, 134.4% and 109.3% respectively for Taxol(®), NP-PTX, tLyp-1-NP-PTX and FHK-NP-PTX). In conclusion, all these evidences together verified the improved therapeutic effect of Ft-NP-PTX for anti-glioma drug delivery via neuropilin-1- and tenascin C-mediated specific penetration of nanoparticles in to glioma parenchyma.


[Clinicopathologic study of 8 cases of poorly differentiated cutaneous angiosarcoma of scalp].
To study the clinical and pathologic characteristics of poorly differentiated cutaneous angiosarcoma of scalp. Eight cases of poorly differentiated cutaneous angiosarcoma of scalp were enrolled into this study. The clinical manifestations and histopathologic features were analyzed. Immunohistochemical study for CD31, CD34, factor VIII-related antigen, vimentin, AE1/AE3, CAM5. 2, epithelial membrane antigen and carcinoembryonic antigen was performed. The mean age of the patients was 69 years. The male-to-female ratio was 5 : 3. The tumor manifested clinically as bruise-like lesion in early phase, indurated erythematous plaque accompanied by nodules, ulcerations and bleeding in advanced phase. Histologically, the tumor was composed of solid sheets of undifferentiated spindle cells which were not easily recognizable as vascular in origin. Nuclear atypia was always present. The tumor cells in all of the 8 cases strongly expressed CD31, factor VIII-related antigen and vimentin. Weak expression of CD34, AE1/AE3 and CAMS. 2 was noted in 2, 4 and 4 cases, respectively. The staining for epithelial membrane antigen, carcinoembryonic antigen and S-100 was negative. Conclusions Angiosarcoma needs to be excluded by histologic examination whenever bruise-like and erythematous lesions occurring on scalp skin of elderly patients. The endothelial origin of the tumor cells can be confirmed with immunostaining for CD31, CD34 and factor VIII-related antigen.


Apoptotic abnormalities in differential gene expression in peripheral blood mononuclear cells from children with Fabry disease.
This study was designed to examine the effect of enzyme replacement therapy (ERT) on differential gene expression in peripheral blood mononuclear cells (PBMCs) of children with Fabry disease who had not previously been exposed to ERT. Thirteen children with Fabry disease (age range, 6.5-17.0 years) were studied as part of a 6-month, open-label study of ERT with agalsidase alfa. Paired blood samples were taken at the start of the study and after 6 months of ERT. Further blood samples were also taken from 16 age-matched control subjects. PBMCs were isolated and, following RNA extraction, differential gene expression analysis was performed using the Human Genome U133 Plus 2.0 microarray. Twenty-one genes were determined to be differentially expressed in PBMCs of ERT-naïve children with Fabry disease compared with healthy controls; neuronal apoptosis inhibitory protein ranked as the most significantly differentially expressed gene. Comparison of gene expression in children with Fabry disease prior to and after ERT showed that two genes were significantly differentially expressed (p < or = 0.05) following treatment; the expressed sequence tag (probe set ID, 243259_at) was downregulated, while expression of apoptosis-inducing factor was increased, possibly as an antioxidant counter-regulatory response. This study identifies a number of genes that are differentially expressed in a small cohort of children with Fabry disease relative to healthy controls. These genes may relate to the underlying biological abnormalities in Fabry disease.


Synthesis and biological activity of tricyclic aryloimidazo-, pyrimido-, and diazepinopurinediones.
Syntheses and physicochemical properties of N-aryl-substituted imidazo-, pyrimido-, and 1,3-diazepino[2,1-f]purinediones are described. These derivatives were synthesized by the cyclization of 7-haloalkyl-8-bromo-1,3-dimethyl- or 1,3-dipropyl-xanthine derivatives with corresponding arylamines. The obtained compounds (1-40), which can be envisaged as sterically fixed and configurationally stable analogs of 8-styrylxanthines, were evaluated for their affinity to adenosine A(1) and A(2A) receptors, the receptor subtypes that are predominant in the brain. Selected compounds were additionally investigated for affinity to the A(2B) and A(3) receptor subtypes. Many of the compounds showed adenosine A(2A) receptor affinity at micromolar or submicromolar concentrations and were A(2A)-selective, for example, compound 23 with p-fluoro substituent displayed K(i) value of 0.147 microM at the rat A(2A) receptor and more than 170-fold-A(2A) selectivity, compound 17 with naphthyl substituent had K(i) value of 0.219 microM and a more than 114-fold-A(2A) selectivity. The compounds were somewhat weaker and less selective at the human receptor subtypes. Elongation of the dimethyl substituent to dipropyl in xanthine moiety improved affinity but reduced selectivity. 1,3-Dimethylimidazo-, pyrimido-, and diazepinopurinediones were evaluated in vivo as anticonvulsants in MES, ScMet, TTE tests and examined for neurotoxicity in mice (ip). Substances with pyrimido ring displayed protective activity in ScMet or in MES and ScMet tests, showing also neurotoxicity. The pyrimidine annelated ring is beneficial for both receptor affinity and anticonvulsant activity.


Trajectories of depressive symptoms and their predictors in Chinese older population: Growth Mixture model.
Given the rapidly rising proportion of the older population in China and the relatively high prevalence of depressive symptoms among this population, this study aimed to identify the trajectories of depressive symptoms and the factors associated with the trajectory class to gain a better understanding of the long-term course of depressive symptoms in this population. Data were obtained from four wave's survey of the China Health and Retirement Longitudinal Study (CHARLS). A total of 3646 participants who aged 60 years or older during baseline survey, and completed all follow-ups were retained in this study. Depressive symptoms were measured using the 10-item version of the Center for Epidemiologic Studies Depression Scale (CES-D-10). Growth mixture modelling (GMM) was adopted to identify the trajectory classes of depressive symptoms, and both linear and quadratic functions were considered. A multivariate logistic regression model was used to calculate the adjusted odds ratios (ORs) of the associated factors to predict the trajectory class of participants. A four-class quadratic function model was the best-fitting model for the trajectories of depressive symptoms in the older Chinese population. The four trajectories were labelled as increasing (16.70%), decreasing (12.31%), high and stable (7.30%), and low and stable (63.69%), according to their trends. Except for the low and stable trajectory, the other trajectories were almost above the threshold for depressive symptoms. The multivariate logistic regression model suggested that the trajectories of chronic depressive symptoms could be predicted by being female, living in a village (rural area), having a lower educational level, and having chronic diseases. This study identified four depressive symptom trajectories in the older Chinese population and analysed the factors associated with the trajectory class. These findings can provide references for prevention and intervention to reduce the chronic course of depressive symptoms in the older Chinese population.


Inhibition of the tumor necrosis factor-alpha pathway is radioprotective for the lung.
Radiation-induced lung toxicity limits the delivery of high-dose radiation to thoracic tumors. Here, we investigated the potential of inhibiting the tumor necrosis factor-alpha (TNF-alpha) pathway as a novel radioprotection strategy. Mouse lungs were irradiated with various doses and assessed at varying times for TNF-alpha production. Lung toxicity was measured by apoptosis and pulmonary function testing. TNF receptor 1 (TNFR1) inhibition, achieved by genetic knockout or antisense oligonucleotide (ASO) silencing, was tested for selective lung protection in a mouse lung metastasis model of colon cancer. Lung radiation induced local production of TNF-alpha by macrophages in BALB/c mice 3 to 24 hours after radiation (15 Gy). A similar maximal induction was found 1 week after the start of radiation when 15 Gy was divided into five daily fractions. Cell apoptosis in the lung, measured by terminal deoxyribonucleotide transferase-mediated nick-end labeling staining (mostly epithelial cells) and Western blot for caspase-3, was induced by radiation in a dose- and time-dependent manner. Specific ASO inhibited lung TNFR1 expression and reduced radiation-induced apoptosis. Radiation decreased lung function in BALB/c and C57BL mice 4 to 8 weeks after completion of fractionated radiation (40 Gy). Inhibition of TNFR1 by genetic deficiency (C57BL mice) or therapeutic silencing with ASO (BALB/c mice) tended to preserve lung function without compromising lung tumor sensitivity to radiation. Radiation-induced lung TNF-alpha production correlates with early cell apoptosis and latent lung function damage. Inhibition of lung TNFR1 is selectively radioprotective for the lung without compromising tumor response. These findings support the development of a novel radioprotection strategy using inhibition of the TNF-alpha pathway.


Classical discrimination conditioning of the rabbit's eyelid response using pontine stimulation as a conditioned stimulus.
Classical discrimination conditioning of the nictitating membrane/eyelid response was performed on seven rabbits using stimulation of the pontine nuclei or middle cerebellar peduncle as the conditioned stimulus (CS) and an air puff as the unconditioned stimulus (US). The rabbits learned to discriminate between a CS paired with a US and delivered to one pontine nucleus (the CS+) and a CS presented alone and delivered to the contralateral pontine nucleus (the CS-). Subsequent reversal of the discrimination was also achieved when the CS+ and CS- stimulation sites were interchanged. The results are interpreted as support for the idea that essential plasticity for classical eyelid conditioning occurs efferent to the pontine nuclei, possibly in regions of the cerebellum.


Falls in the inpatient rehabilitation facility.
Older adults are rehabilitated for a variety of conditions in an inpatient rehabilitation facility (IRF), and they are often at an increased risk for falling during their stay. This article (1) provides an overview of the incidence, prevalence, and impact of falls in facilities that provide inpatient rehabilitation; (2) provides some key factors to be considered in the assessment of the patient admitted to the IRF for risk factors associated with falling; and (3) identifies strategies that can help reduce the risk of falling in patients admitted to an IRF.


Decreased expression of the thyroid hormone-inactivating enzyme type 3 deiodinase is associated with lower survival rates in breast cancer.
Thyroid hormones (THs) are critical regulators of cellular processes, while changes in their levels impact all the hallmarks of cancer. Disturbed expression of type 3 deiodinase (DIO3), the main TH-inactivating enzyme, occurs in several human neoplasms and has been associated with adverse outcomes. Here, we investigated the patterns of DIO3 expression and its prognostic significance in breast cancer. DIO3 expression was evaluated by immunohistochemistry in a primary cohort of patients with breast cancer and validated in a second cohort using RNA sequencing data from the TCGA database. DNA methylation data were obtained from the same database. DIO3 expression was present in normal and tumoral breast tissue. Low levels of DIO3 expression were associated with increased mortality in the primary cohort. Accordingly, low DIO3 mRNA levels were associated with an increased risk of death in a multivariate model in the validation cohort. DNA methylation analysis revealed that the DIO3 gene promoter is hypermethylated in tumors when compared to normal tissue. In conclusion, DIO3 is expressed in normal and tumoral breast tissue, while decreased expression relates to poor overall survival in breast cancer patients. Finally, loss of DIO3 expression is associated with hypermethylation of the gene promoter and might have therapeutic implications.


Effects of occupational cobalt exposure on the heart in the production of cobalt and cobalt compounds: a 6-year follow-up.
It has been suspected that cobalt is toxic to the heart. It can cause cardiotoxicity in heavily exposed humans and in experimental systems. The issue of interest for this study is whether cobalt also affects the myocardium at occupational exposure levels. To study the effect of occupational cobalt exposure on the heart, we conducted a follow-up of workers at a cobalt production plant. The workers' hearts had been examined by echocardiography in 1999-2000. Altogether 93 exposed and 49 non-exposed workers examined in 1999-2000 were re-examined in 2006. Occupational history and health data were collected with a questionnaire. Blood pressure was measured, and electrocardiography (ECG), laboratory tests, Holter registration, and echocardiography were conducted for all participants. Analysis of covariance (ANCOVA) was used to analyse the data. No differences were found between the exposed and unexposed groups for any of the echocardiographic parameters in 2006. There were no differences in the laboratory values, the ECG parameters, or the results of the Holter registration of the exposed and unexposed workers. Although the previous results in 2000 suggested an association between cumulative exposure to cobalt and echocardiographic findings, the results of this new cross-sectional study with a tissue Doppler 6 years later did not confirm the association in the present cohort. If cobalt exposure affects heart muscle functions at this exposure level, the effects are smaller than those caused by physiological changes due to ageing, medication, and traditional cardiovascular risk factors, such as elevated blood pressure.


[Oligozoospermia in Klinefelter's syndrome].
Case report of a 31 year old male with a 47-XXY-Klinefelter-syndrome which showed a maximum of 4,0 million spermatozoa/ml with a motility of up to 51% in his ejaculate. No rise of spermatozoa counts could be observed after 3x25 mg mesterolone/day over 8 weeks.


Sympathetic hypertensive syndrome: a possible surgically curable type of hypertension.
Poorly controlled hypertension was incidentally cured after performing an endoscopic sympathetic block (ESB) in a patient with hyperhidrosis craniofacialis (HHC). A survey of the literature indicated that 30% to 40% of essential hypertension is of sympathetic origin. Patients with facial sweating associated with hypertension were then studied to determine whether blood pressure is lowered after performing ESB. Between November 2002 and July 2003, 17 hypertensive patients (13 males and 4 females) ranging in age from 22 to 62 years underwent ESB solely for HHC at the Department of Surgery of Kaohsiung Medical University, Taiwan. Their preoperative systolic blood pressure (SBP) values ranged from 170 +/- 6 to 200.7 +/- 7.6 mmHg, and their diastolic blood pressure (DBP) values ranged from 94.7 +/- 6.1 to 120.3 +/- 5.7 mmHg. Their heart rates were between 92.67 +/- 2.28 and 119.67 +/- 5.13 beats per minute (bpm). They were refractory to aggressive medical treatment, including lifestyle modifications and antihypertensive medications. Their postoperative blood pressure, heart rate and surgical outcomes were recorded. After performing ESB, HHC was cured in all 17 patients. Based on the reductions in blood pressure and heart rate, the patients could be divided into two groups, one showing high-level reductions (Group T) and one showing low-level reductions (Group S). The blood pressure of Group T (ten patients) was reduced to the range of 120.2 +/- 6.9 to 131.6 +/- 3.5 mmHg SBP and 74.8 +/- 3.1 to 85.4 +/- 4.5 DBP, and the heart rate of this group was reduced to the range of 65.36 +/- 4.63 to 85 +/- 3.60 bpm, while the blood pressure and heart rate of Group S (seven other patients) were reduced to the ranges of 145.9 +/- 5.7 to 160.5 +/- 5.5 mmHg SBP, 90 +/- 4 to 100.7 +/- 3.2 mmHg DBP, and 80 +/- 4 to 90.83 +/- 3.53 bpm, respectively. The patients in Group S were well controlled at 119.8 +/- 5.5 to 130.6 +/- 8.0 mmHg SBP and 70.1 +/- 3.8 to 84.5 +/- 5.7 mmHg DBP with a daily low-dose of calcium channel blocker. The average follow-up periods of the two groups were 17.00 +/- 2.906 and 17.43 +/- 2.37 months, respectively. We named this surgically curable form of hypertension "Sympathetic Hypertensive Syndrome" (SHS), which we define by the presence of all three of the following: 1) stage II hypertension; 2) HHC or other sympathetic disorders; and 3) heart rate > or = 100 bpm. If the patient is male the reductions of blood pressure after the surgery will be better, which might be due to the link with Y chromosome. Finally, we recommend that ESB should be performed in patients with SHS, although the female would respond less satisfactorily in terms of the blood pressure.


Crumley's Classification of Laryngeal Synkinesis: A Comparison of Laryngoscopy and Electromyography.
Applying the principles of misdirected nerve regeneration to the larynx, Roger Crumley in 1989 coined the term laryngeal synkinesis (LS) which he later (2000) classified into 4 types (type I - good voice, type II - involuntary twitches and poor voice, type III - adduction during inspiration, type IV - abduction during phonation). Neurophysiological data were not available for all LS patients at that time. The current study was undertaken to utilize and test the Crumley classification for a clinical interrater comparison and, secondly, compare predicted with actual laryngeal electromyography (LEMG) results. Descriptive study. Laryngoscopic and LEMG data of patients with unilateral vocal fold paralysis (VFP) of 6 months duration or longer were combined for retrospective evaluation. Forty-five data sets were available for laryngoscopic classification by two local laryngologists and by Roger Crumley. Twenty-three data sets with complete thyroarytenoid (TA) and posterior cricoarytenoid (PCA) - EMG data were used to compare predicted with actual LEMG results. Local laryngologists were able to classify 24 of 45, Crumley 30 of 45 cases into one of the 4 synkinesis types. There was substantial agreement between examiners (Cohens Kappa 0.66 [P < .001]). Comparison of predicted and actual LEMG data showed only moderate agreement. EMG sykinesis rates were lower in TA than in PCA and highest in Crumley type I cases. The Crumley classification is helpful in describing and understanding synkinesis. It does not always correlate predictably with actual LEMG data. A complete LEMG mapping of all intrinsic muscles may improve understanding of chronic VFP. 4. Laryngoscope, 131:E1605-E1610, 2021.


Situational changes in self-awareness influence 3- and 4-year-olds' self-regulation.
In adults, heightened self-awareness leads to adherence to socially valued norms, whereas lowered self-awareness is associated with antinormative behavior. Levels of self-awareness are influenced by environmental cues such as mirrors. Do situational changes in self-awareness also have an impact on preschoolers' self-regulation? Adherence to a socially valued standard was observed under different conditions of self-focus. In Experiment 1 the standard was prescribed ("don't look in the box"), and in Experiment 2 children had the opportunity to be altruistic. Heightened self-focus was induced using a large mirror. In a neutral condition, the nonreflective side of the mirror was shown. To lower self-focus, children wore a disguise. Preschoolers peeked less and showed more altruism when the mirror image was present. As found for adults, it appears that self-awareness leads 3- and 4-year-olds to adhere to salient social standards. These results suggest that self-focus has a socially adaptive regulatory function from an early age.


A survey of members of the European Surveillance System on Contact Allergy and the EU project "StanDerm" to identify allergens tested in cosmetic series across Europe.
There is currently no agreed cosmetic series for use across Europe. To establish allergens currently tested in local and national cosmetic series. Members of the European Surveillance System on Contact Allergy and the European Cooperation in Science and Technology project TD1206 ("StanDerm") were surveyed to establish their current practice. A wide range of allergens was tested but there was significant variation between centres on the allergens considered to be important in screening for allergy to cosmetics. The number of allergens tested in addition to the baseline series varied between 2 and 50. There is a need for further investigation to establish the frequency and relevance of reactions to cosmetic allergens to enable an agreed evidence-based cosmetic series to be produced. Criteria for inclusion need to be established.


Neuromodulation of the prefrontal cortex facilitates diet-induced weight loss in midlife women: a randomized, proof-of-concept clinical trial.
High body mass index (BMI) is associated with neurocognitive impairments that contribute to overeating and interfere with weight loss efforts. Overweight and obesity at midlife can accelerate neurodegenerative changes and increase the risk of late-life dementia. Noninvasive neuromodulation represents a novel, affordable and scalable approach to improve neurocognitive function in this context. The purpose of this proof-of-concept study was to examine whether transcranial direct current stimulation (tDCS) aimed at enhancing prefrontal cortex activity could enhance weight loss, in combination with a hypocaloric diet, and study underlying mechanisms. Overall, 38 women with BMI 25-35 kg/m2 underwent a 4 week randomized, double-blinded, sham-controlled, and parallel-design intervention, during which they received eight sessions of tDCS (n = 18 sham, n = 20 active) in combination with a diet (caloric goal of 20 kcal/kg/day). We evaluated longitudinal changes in body weight, appetite and food craving. In addition, we examined the contribution of cognitive-executive processes via food-modified computerized tasks. We found that the active group had more reduction in body weight than the sham group throughout the study (p = 0.020) and significant weekly weight loss. At 4 weeks, the active group lost 2.32% of initial body weight (sham: 1.29%). Components of subjective appetite and food craving showed a trend toward more reduction in the active group. These changes were paralleled by significant improvements in task performance in the active group, particularly in a dual task that required inhibitory control and working memory (p = 0.007-0.031). Improvement in inhibitory control performance predicted reduction in lack of control overeating, explaining 43.5% of its variance at the end of the study (p = 0.003). No significant adverse effects were observed. Our results provide proof-of-concept validation of prefrontal-targeted tDCS, combined with a diet, in midlife women with excess body weight, paving the way for larger studies evaluating clinical efficacy and long-term effects of this intervention.


The assembly process and co-occurrence patterns of soil microbial communities at a lead smelting site.
The potential toxic elements of the site are diverse and complex, seriously threatening the land utilization potential and soil ecological function. Microbial community is critical to maintaining ecosystem function, their assembly processes and diversity play an essential role in predicting changes in soil ecological function. However, our understanding of the mechanisms that shape community composition and successional direction in complex polluted environments is very limited. In this study, to explore the mechanisms driving community assembly and symbiosis in different contaminated regional environments, the biological characteristics of bacterial and fungal communities in four different polluted areas of a typical lead smelting site were studied. Contamination by PTEs appears to increase microbial networks, as well as altering microbial community composition, with relative abundance of dominant phyla such as Actinomycetes and Acidobacteria decreasing, whilst Proteobacteria and Ascomycota increased, this indicated that communities may shift from K-strategy to r-strategy and become opportunistic. Dispersal limitation (DL, 42 %-86 %), drift (Dr, 8 %-37 %) and homogeneous selection (HoS, 1 %-31 %) proved to be the important community assembly process. The top ten bins controlling the contribution of different biological processes were identified, and the relative abundance of these bacterial and fungal taxa varied with CPI. Collectively, our results suggest that CPI and nutrient availability regulate soil bacterial and fungal community assembly processes. The results of this study provide potential guidance for community regulation in the process of ecological restoration and mitigating degraded soils at smelting sites.


Prevalence and determinants of diabetic retinopathy in Al hasa region of saudi arabia: primary health care centre based cross-sectional survey, 2007-2009.
To evaluate the prevalence of diabetic retinopathy (DR) in the urban and rural areas of Al Hasa region of Saudi Arabia and to determine risk factors related to DR. This study was conducted on patient attending primary health care centers between July 2007 and June 2009. A retrospective chart review was conducted on subjects with diabetes mellitus greater than 18 years old. Ophthalmologists examined DR status through dilated pupils by using direct, indirect, and slit lamp bio-microscopy. Frequencies, percentage, and their 95% confidence intervals (CIs) were calculated. Odd's ratio was used to associate DR with possible risk factors. A P value less than 0.05 was considered statistically significant. The prevalence of DR among 473 diabetic subjects was 30% (95% CI: 25.80-34.20). The odd ratios (ORs) of DR among diabetic residing in an urban area was significantly higher than diabetics residing in rural areas [OR = 1.94 (95% CI of OR 0.82-2.89)]. DR was associated to the duration of diabetes (adjusted OR = 1.70), uncontrolled blood sugar level (adjusted OR = 1.96), hyperlipidemia (adjusted OR = 2.04), and hypercholesterolemia (adjusted OR = 2.80). DR appears to be a public health problem in the Al Hasa district of Saudi Arabia, and a planned approach is required to avoid severe visual impairment in patients with diabetes mellitus. Primary prevention and early detection could be implemented through primary health centers and non-ophthalmologists.


An innovative solid-phase biosensor for rapid on-site detection of N-nitrosodimethylamine incorporating zein film and upconversion nanoparticles.
Pickled frequently contains nitrosodimethylamine (NDMA), a mutagenic and carcinogenic substance that is dangerous for the general public's health. This study reports on the fabrication of a fluorescent biosensor using zein film and aptamer functionalized upconversion nanoparticles (UCNPs) for on-site monitoring of NDMA in meat. UCNPs were first prepared followed by aptamer binding and mixing with zein film, which was further conjugated with cDNA of dabcyl modified at 5'. The fluorescence resonance energy transfer (FRET) mechanism between the UCNPs and dabcyl was exploited. The fluorescence signals of the zein film recovered when NDMA was present because it was selectively collected by the particular aptamer and damaged the cDNA structure. The designed functionalized zein film was used for on-site and portable determination of NDMA with a lower limit of detection of 0.017 ng/mL, and possessed a satisfactory recovery ranging from 95.8% to 100.2% with no significant difference compared with the GC-MS method.


Identification of a highly reactive substrate peptide for transglutaminase 6 and its use in detecting transglutaminase activity in the skin epidermis.
Mammalian transglutaminases (TGs) are a family of enzymes that catalyze the formation of covalent crosslinks between glutamine and lysine residues in proteins. These catalytic reactions play roles in several essential biological processes, including blood coagulation, skin formation, and stabilization of the extracellular matrix. Among the members of this family, factor XIII and TGs 1-5 have been characterized well, but very little is known about the novel members TG6 and TG7. Recently, however, autoantibodies against TG6 were found in a patient with gluten ataxia, a disease caused by enzymatically modified gluten-derived peptides in neuronal cells. To characterize the possible physiological functions of TG6, in this study we screened a phage-displayed random peptide library to find highly reactive glutamine donor substrate peptides. From several candidate peptides, one sequence, designated Y25, appeared to have the highest reactivity. The Y25 sequence also has apparent isozyme specificity when evaluated by incorporation of the labeled glutamine acceptor substrate as a fusion protein with glutathione-S-transferase. Also, the sequence retained high reactivity as well as the isozyme specificity in the peptide form. Analyses with the biotin-labeled and fluorescence-labeled peptides showed TG6 to be an active enzyme and react to specific substrates in the skin, which is consistent with the results of the expression pattern of its transcripts.


Nickel(II) inhibits the repair of O6-methylguanine in mammalian cells.
Nickel compounds are widespread carcinogens, and although only weakly mutagenic, interfere with nucleotide excision repair and with the repair of oxidative DNA base modifications. In the present study we investigated the effect of nickel(II) on the induction and repair of O6-methylguanine and N7-methylguanine after treatment with N-methyl-N-nitrosourea (MNU). We applied Chinese hamster ovary cells stably transfected with human O6-methylguanine-DNA methyltransferase (MGMT) cDNA (CHO-AT), and compared the results with the MGMT-deficient parental cell line. As determined by high-performance liquid chromatography/electrochemical detection (HPLC/ECD), there was a slight but mostly not significant reduction in the formation of both types of DNA lesions by MNU in the presence of nickel(II). Although nickel(II) did not markedly affect the repair of N7-methylguanine, it decreased the repair of O6-methylguanine in a dose-dependent manner, starting at concentrations as low as 50 microM. While the MGMT protein level was not altered in the presence of nickel(II), the MGMT activity was diminished as demonstrated in cell extracts form nickel-treated cells. This repair inhibition was accompanied by an increase in MNU-induced cytotoxicity in nickel-treated CHO-AT cells but not in MGMT-deficient control cells. There is strong evidence that O6-methylguanine is involved in tumour formation after exposure to alkylating agents. Thus, the finding that nickel(II) inhibits the repair of this lesion could be of major importance for risk assessment in case of combined exposures at work places and in the general environment.


Regulation of several androgen-induced genes through the repression of the miR-99a/let-7c/miR-125b-2 miRNA cluster in prostate cancer cells.
The androgen receptor (AR) stimulates and represses gene expression to promote the initiation and progression of prostate cancer. Here, we report that androgen represses the miR-99a/let7c/125b-2 cluster through AR and anti-androgen drugs block the androgen-repression of the miRNA cluster. AR directly binds to the host gene of the miR-99a/let7c/125b-2 cluster, LINC00478. Expression of the cluster is repressed or activated by chromatin remodelers EZH2 or JMJD3 in the presence or absence of androgen, respectively. Bioinformatics analysis reveals a significant enrichment of targets of miR-99a, let-7c and miR-125b in androgen-induced gene sets, suggesting that downregulation of the miR-99a/let7c/125b-2 cluster by androgen protects many of their target mRNAs from degradation and indirectly assists in the gene induction. We validated the hypothesis with 12 potential targets of the miR-99a/let7c/125b-2 cluster induced by androgen: 9 out of the 12 mRNAs are downregulated by the microRNA cluster. To ascertain the biological significance of this hypothesis, we focused on IGF1R, a known prostate cancer growth factor that is induced by androgen and directly targeted by the miR-99a/let7c/125b-2 cluster. The androgen-induced cell proliferation is ameliorated to a similar extent as anti-androgen drugs by preventing the repression of the microRNAs or induction of IGF1R in androgen-dependent prostate cancer cells. Expression of a microRNA-resistant form of IGF1R protects these cells from inhibition by the miR-99a/let7c/125b-2 cluster. These results indicate that a thorough understanding of how androgen stimulates prostate cancer growth requires not only an understanding of genes directly induced/repressed by AR, but also of genes indirectly induced by AR through the repression of key microRNAs.


Neuroendocrine control of pheromone biosynthesis in moths.
Prevalent among the Lepidoptera, as in many other insect orders, species-specific pheromones are synchronously produced and released for mate finding. Pheromone biosynthesis activating neuropeptide (PBAN) is a neuropeptide widespread throughout the class Insecta. Although its role in the several different orders of insects has not been fully elucidated, its regulatory role in Lepidopteran pheromone biosynthesis has been strongly implicated. The biosynthesis, gene expression, distribution, and release of PBAN have been studied in several moth species. This review discusses PBAN's mode of action as a pheromonotropic neurohormone at the organism, tissue, and cellular levels. The discussion includes an overview on PBAN structure-activity relationships, its target tissue identification, its putative receptor proteins, and the second messengers involved in signal transduction and the key regulatory enzymes in the pheromone biosynthetic pathway that may be influenced by PBAN. Finally, the review includes a discussion of various mediators and inhibitors of the pheromonotropic action due to PBAN.


Implementing a health labour market analysis to address health workforce gaps in a rural region of India.
Human Resources for Health (HRH) are essential for making meaningful progress towards universal health coverage (UHC), but health systems in most of the developing countries continue to suffer from serious gaps in health workforce. The Global Strategy on Human Resources for Health-Workforce 2030, adopted in 2016, includes Health Labor Market Analysis (HLMA) as a tool for evidence based health workforce improvements. HLMA offers certain advantages over the traditional approach of workforce planning. In 2018, WHO supported a HLMA exercise in Chhattisgarh, one of the predominantly rural states of India. The HLMA included a stakeholder consultation for identifying policy questions relevant to the context. The HLMA focused on state HRH at district-level and below. Mixed methods were used for data collection and analysis. Detailed district-wise data on HRH availability were collected from state's health department. Data were also collected on policies implemented on HRH during the 3 year period after the start of HLMA and changes in health workforce. The state had increased the production of doctors but vacancies persisted until 2018. The availability of doctors and other qualified health workers was uneven with severe shortages of private as well as public HRH in rural areas. In case of nurses, there was a substantial production of nurses, particularly from private schools, however there was a lack of trusted accreditation mechanism and vacancies in public sector persisted alongside unemployment among nurses. Based on the HLMA, pragmatic recommendations were decided and followed up. Over the past 3 years since the HLMA began an additional 4547 health workers including 1141 doctors have been absorbed by the public sector. The vacancies in most of the clinical cadres were brought below 20%. The HLMA played an important role in identifying the key HRH gaps and clarifying the underlying issues. The HLMA and the pursuant recommendations were instrumental in development and implementation of appropriate policies to improve rural HRH in Chhattisgarh. This demonstrates important progress on key 2030 Global Strategy milestones of reducing inequalities in access to health workers and improving financing, retention and training of HRH.


Skin infections in Egyptian renal transplant recipients.
The risk of skin infections in renal transplant recipients (RTRs) has been described previously; however, it differs markedly by ethnic groups, skin type, and geographical location. We investigated the prevalence and nature of skin infections in a large series of RTRs in our locality in Egypt. A total 302 RTRs (216 males and 86 females) were included in this study. They were screened for the presence of bacterial, fungal, and viral skin infections depending on clinical signs, Woods lamp examinations, culture, and biopsy if indicated. The patients were compared with 300 healthy controls matched for age and sex (200 males and 100 females). We found 191 (63.25%) RTRs had some kind of skin infection. Folliculitis (10.3%), tinea versicolor (30.1%), dermatophytosis (19.5%), and onychomycosis (7.6%) were statistically significantly more common in RTRs compared with control subjects. Our RTRs have higher prevalence rates of folliculitis and superficial fungal infections than the healthy population and they should be searched for in every patient with renal transplantation to ensure early treatment and avoid complications. Low-dose ketoconazole should be considered in renal transplant populations with high rates of superficial fungal infections, as it may reduce risk of such infections.


Evidence of body size and shape stasis driven by selection in Patagonian lizards of the Phymaturus patagonicus clade (Squamata: Liolaemini).
During the speciation process sibling lineages accumulate differences in time (e.g. genetic, morphological, and/or ecological). Phenotypic traits such as size or shape, however, could experience rapid changes or show stasis depending on their role in survival and reproduction. The clade Phymaturus patagonicus includes 26 species characterized by a conservative morphology, and all inhabit rock crevice microhabitats in arid environments. In this study we quantify levels of morphological divergence (size and shape) among the multiple species relative to interspecific molecular divergence, and show that most species have not diverged significantly in size and/or shape to permit unambiguous species diagnosis with morphological data alone. The influence of stabilizing selection for an adaptive optimum in body size and head shape was detected for 13 of the 16 variables analyzed in an Ornstein-Uhlenbeck model. The strict dependence of these species to rock-crevice microenvironments likely explains the observed morphological stasis across the many species of the Phymaturus patagonicus group.


Hydrogels based on poly(ethylene oxide) and poly(tetramethylene oxide) or poly(dimethyl siloxane): synthesis, characterization, in vitro protein adsorption and platelet adhesion.
In vitro protein adsorption, platelet adhesion and activation on new hydrogel surfaces, composed of poly(ethylene oxide) (PEO) and poly(tetramethylene oxide) (PTMO) or poly(dimethyl siloxane) (PDMS), were investigated. By varying PEO length (MW = 2000 or 3400), hydrophobic components (PTMO or PDMS) or polymer topology (block or graft copolymers), various physical hydrogels were produced. Their structures were verified by 1H NMR and ATR-IR and the molecular weights were determined by gel permeation chromatography. The hydrogels were soluble in a variety of organic solvents, while absorbed a significant amount of water with preserved three-dimensional structure by physical crosslinking. The dynamic contact angle measurement revealed that the surface hydrophilicity increased by incorporating longer PEO, PEO grafting, and adopting PDMS as a hydrophobic segment instead of PTMO. It was observed from in vitro protein adsorption study that the hydrogels exhibited significantly lower adsorption of human serum albumin (HSA), human fibrinogen (HFg), and IgG, when compared with Pellethane, a commercial polyurethane taken as a control. The hydrogels were attractive for HSA but not sensitive to HFg and IgG. And more than 65% of the proteins detected on the surfaces of the hydrogels were reversibly detached by being treated with an SDS solution. It was evident that the hydrogels synthesized in this study were much more resistant to platelet adhesion than the control, which might depend on the composition of proteins adsorbed on the surfaces and their degree of denaturation. Among the hydrogels tested, PEO3,4kPDMS exhibited albumin-rich and platelet-resistant surfaces, implying a potential candidate for biomaterial.


Seasonal variation in responsiveness of human eccrine sweat glands to phenylephrine.
The responses of eccrine sweat glands to intradermally injected phenylephrine were studied in six healthy male volunteers in two experiments carried out in February and June. Phenylephrine (10(-7)-10(-2) M, 50 microliters) had no consistent effect on sweat gland activity during February, but evoked dose-related increases in sweat gland activity during June. Responsiveness to phenylephrine could be antagonized by prazosin (10(-5) and 10(-4) M) added to the injection solution.


Preparation, characterization, and in vitro cytotoxicity of COM and COD crystals with various sizes.
Calcium oxalate crystals in urine often differ in size and crystal phase between healthy humans and patients with kidney stones. In this work, calcium oxalate monohydrate (COM) and dihydrate (COD) with sizes of about 50 nm, 100 nm, 1 μm, 3 μm, and 10 μm were prepared by varying reactant concentration, reaction temperature, solvent, mixing manner, and stirring speed. These crystals mainly had a smooth surface and no obvious pore structure, except COM-1 μm. In cell culture medium, the zeta potential of crystals became increasingly negative with increasing size, and the absolute value of zeta potential of COD was greater than the same-sized COM. Results of cell viability and PI staining assays showed that the order of injury degree in African green monkey renal epithelial (Vero) cells caused by different sizes of COD was COD-50 nm>COD-100 nm>COD-1 μm>COD-3 μm>COD-10 μm, and that of different sizes of COM was COM-1 μm>COM-50~COM-100 nm>COM-3 μm>COM-10 μm. COM-1 μm presented the highest cytotoxicity in Vero cells, which was associated with its rougher surface, larger specific surface area (SBET), and larger pore volume. Overall, these findings indicated that the physical properties of crystals play an important role in their cytotoxicity.


Association of personality disorders with Type A and Type B alcoholics.
Personality disorders frequently occur as comorbid disorder in alcohol-dependent subjects. Antisocial personality was described as an important characteristic in Cloninger's Type 2 and Babor's Type B subjects. The impact of other personality disorders on these alcoholism typologies, their pathogenesis and prognosis is, however, still unclear. The present study investigated the prevalence of personality disorders in 237 (194 males) detoxified alcohol-dependent patients after subtyping this sample according to Babor's Type A/B following the criteria suggested by Schuckit et al. (1995). Personality disorders were assessed with the SCID-II (DSM-IV). In all, 160 patients (68 %) could be classified as Type A, and 77 (32 %) as Type B. Type B subjects were younger, had an earlier onset,more alcohol intake and a more severe course of alcohol dependence. Type B patients had significantly more often any cluster A and B personality disorder, and significantly specifically more often a borderline, antisocial and avoidant personality disorder. There were no statistical differences concerning the other personality disorders. In summary, the Type A/B dichotomy using the criteria of Schuckit et al. (1995) was replicated successfully. Differences concerning cluster B personality disorder prevalence of Type B subjects demonstrated that these subjects are significantly more often affected from borderline and antisocial personality disorder. The impact of other personality disorders does not play a substantial role in subtyping alcoholics.


Chlorocholine chloride induced testosterone secretion inhibition mediated by endoplasmic reticulum stress in primary rat Leydig cells.
Chlorocholine chloride (CCC) is well acknowledged as a plant growth regulator and may be considered as a potential environmental endocrine disrupting chemical. In our previous studies, it was found that CCC exposure at a pubertal stage reduced the serum and testicular levels of testosterone, decreased the sperm motility and delayed the puberty onset. However, the molecular mechanisms of CCC-induced testosterone secretion disorders remain unclear. In this study, we found that CCC exposure above 20 μg/mL inhibited the secretion of testosterone in Sprague-Dawley rats Leydig cells. Proteomic and pathway enrichment analysis indicated that CCC might induce endoplasmic reticulum (ER) stress. Western blot detection showed CCC exposure at 100, 200 μg/mL increased the protein level of glucose-regulated protein 78 (GPR78), C/EBP-homologous protein (CHOP), the ubiquitin-conjugating enzyme E2 D1 (UBE2D1) and the ring finger protein (RNF185) in the Leydig cells. The Leydig cells treated with 4-phenyl butyric acid (4-PBA), an ER stress inhibitor, rescued the testosterone secretion disorders and alleviated CCC-induced increase in the ER stress related protein levels at 200 μg/mL CCC treatment. Overall, CCC in vitro exposure might disturb testosterone production of Leydig cells and endoplasmic reticulum stress was involved in it.


Minimally invasive repair for lateral ventral hernia: tailored approach from a hernia centre at a tertiary care institution.
Lateral ventral hernia (LVH) is rare and can be primary or secondary. Surgical treatment of this rare hernia type is challenging due the anatomic location and technical challenges in placement and secure anchoring of mesh. Patient demographic data, intra-operative data and post-operative outcomes on all LVH repairs performed with endo-laparoscopic and robotic approach between 2016 to 2018 were reviewed and analysed. 22 LVH were repaired in 21 patients. 9 had primary hernia and 13 had secondary hernia. All patients underwent minimally invasive surgery (MIS) for hernia repair with no conversion to open surgery. Fascial defect closure and placement of mesh were performed in all cases. Different approaches were utilized: 9 hernia repaired with laparoscopic intra-peritoneal on-lay mesh technique with defect closure (IPOM +), 4 had laparoscopic trans-abdominal pre-peritoneal repair (TAPP), another 4 had extended totally extra-peritoneal repair (eTEP), 3 had robotic TAPP (rTAPP) and 2 repaired with trans-abdominal partial extra-peritoneal (TAPE) approach. 4 (19%) of the patients developed post-operative seroma which were managed conservatively. No other significant complication was noted, and no chronic pain or recurrence reported within a minimum follow-up of 12 months. This case series gives a broad outline of possible MIS options available for LVH repair and recommendations for a tailored approach. The surgical technique needs to be individualized according to the size and anatomic location of the defect, other intra-operative findings and patient characteristics.


Parental co-exposure to bisphenol A and nano-TiO2 causes thyroid endocrine disruption and developmental neurotoxicity in zebrafish offspring.
The coexistence of organic toxicants and nanoparticles in the environment influences pollutant bioavailability and toxicity. Using chronic co-exposure to an adult zebrafish model, this study investigated the transfer kinetics and transgenerational effects of bisphenol A (BPA) and titanium dioxide nanoparticles (n-TiO2) exposure in F1 offspring. When single and combined exposure to BPA (0, 2, and 20 μg/L) and n-TiO2 (100 μg/L) were compared, combined exposure was found to reciprocally facilitate bioaccumulation in adult fish while enhancing maternal transfer to offspring. Thyroid endocrine disruption and developmental neurotoxicity were observed in larval offspring by parental exposure to BPA alone or in combination with n-TiO2. Exposure to 20 μg/L BPA significantly decreased the thyroxine (T4) concentration in adult plasma, leading to less transfer into the eggs. The presence of 20 μg/L BPA with n-TiO2 further decreased the level of T4 compared to BPA exposure alone. Additionally, offspring larvae derived from exposed parents exhibited lethargic swimming behavior. Overall, this study examined the interactions of BPA and n-TiO2 with regard to their bioaccumulation, maternal transfer, and developmental effects, which highlighted that co-exposure dynamics are important and need to be considered for accurate environmental risk assessment.


The effect of repeated firings on the color of an all-ceramic system with two different veneering porcelain shades.
Color matching between a restoration and natural teeth is a common clinical problem. Despite careful shade selection, color of the restoration may be affected by fabrication procedures. The purpose of this study was to determine the color changes of an all-ceramic restoration with 2 different veneering porcelain shades after repeated firings. Twenty disc-shaped ceramic specimens, 4 mm in diameter with a 1-mm core thickness and 2 different veneering porcelain shades (A1, A3), were fabricated from a zirconia-based porcelain (DC-Zirkon) (n=10). Repeated firings (3, 5, 7, or 9 firings) were performed for the specimens, and color differences (DeltaE) were determined using a spectrophotometer. Repeated measures ANOVA was used to analyze the data (number of firings, veneering porcelain color). The Tukey HSD test and paired 2-tailed tests were performed for multiple comparisons (alpha=.05). The L*a*b* values of the ceramic system were affected by the number of firings (3, 5, 7, or 9) (P<.001) and the veneering porcelain shade (P<.001). Significant interactions were present between the number of firings and veneering porcelain shade for L* (P=.003) and b* (P=.042) values, but not for the a* value (P=.82). An increase in the number of firings of the specimens with both A1 and A3 veneering porcelain shades produced an increase in the L* value, resulting in lighter specimens (P<.001). For both A1 and A3 veneering porcelain shades, the a* value decreased after repeated firings, which resulted in more green specimens (P=.002). The b* value did not change after repeated firings (P=.09) for the A1 veneering porcelain shade; however, it increased for the A3 veneering porcelain shade, which resulted in more yellow specimens (P=.001). The color of the all-ceramic specimens with different veneering porcelain shades is influenced by repeated firings. However, color changes that occurred are clinically acceptable.


Neuropsychiatric symptoms in dementia.
The prevalence of dementia is expected to rise with the aging of our population for decades to come. Neuropsychiatric symptoms of dementia, also known as behavioral and psychologic symptoms of dementia, are extremely common. Symptoms are most prevalent in the moderate stages of the disease, often increase with advancing disease stage, and often more than one symptom is present. These symptoms can cause a great deal of distress for patients and families, and take a toll on society as well. Evaluation and management can be challenging, with nonpharmacologic strategies recommended as first-line approach. There is growing evidence for specific pharmacologic strategies, but these come with significant risk, such that informed consent with the patient and surrogate decision maker is critical. In this chapter, we focus on general principles of etiology, assessment, and management, and then turn to individual symptoms of agitation, psychosis, apathy, sleep disturbance, and feeding and eating problems more specifically. Depression and anxiety are covered elsewhere in this text.


Do directional deep brain stimulation leads rotate after implantation?
The two middle contacts of directional leads (d-leads) for deep brain stimulation are split into three segments, allowing current steering toward desired axial directions. To facilitate programming, their final orientation needs to be reliably determined. However, it is currently unclear whether d-leads rotate after implantation. Our objective was to assess the degree of d-lead rotation after implantation. We retrospectively analyzed d-lead orientation on intraoperative X-rays, postoperative CT scans (latencies to surgery: 108-189 min postoperatively), and rotational fluoroscopies (4-9 days postoperatively) for a consecutive series of 32 implanted d-leads. For five d-leads, a CT scan with a mean follow-up of 57 days (range 28-182) was available. All d-leads were implanted with the marker facing anterior and the intention to hit an "iron sight" (ISi) on the X-ray, indicating anterior orientation (i.e., 0° ± 6°). In nine d-leads, an ISi was visible on the final X-ray; median orientation was 1.5° (range 0.5-6.0°) at the first follow-up CT, confirming anterior orientation. In d-leads without ISi or where ISi was not evaluable, the median rotation was 15.5° (9.5-35.0°) and 26.5° (5.5-62.0°), respectively. The orientation of the initial CT was comparable with the orientation determined by the postoperative rotational fluoroscopy and second CT in all d-lead groups. D-lead orientation does not change within the first week after implantation. We provide first indications that d-lead orientation remains stable for several weeks after surgery. Determination of lead orientation using marker-based X-ray alone seems too imprecise; adding the ISi method can increase determination of intraoperative orientation.


Maternal language disparities in neonatal intensive care unit outcomes.
To examine associations of maternal primary language with neonatal intensive care unit (NICU) outcomes (mother's milk at discharge, necrotizing enterocolitis [NEC], late-onset sepsis, weight gain) DESIGN: We performed a retrospective cohort study of mother-infant dyads (<34 weeks' gestation) in 9 NICUs (1/2016-12/2019), examining associations of maternal language (English [ref], Spanish, Other) with NICU outcomes, adjusting for birth weight for gestational age z-score, race/ethnicity, maternal age, and clustering by hospital. Among 1402 mothers, 85% spoke English, 7% spoke Spanish, and 7% spoke another language. Compared to English, infants with Spanish-speaking mothers had slower growth (-0.34 z-score units [-0.58, -0.10]). Infants with other non-English-speaking mothers had increased mother's milk at discharge (aOR 1.48 [1.18, 1.85]), NEC (aOR 1.43 [1.05, 1.95]), late-onset sepsis (aOR 2.84) [1.67, 4.83] and slower growth (-0.17 z-score units [-0.29, -0.05]). After adjustments, preterm infants with non-English-speaking mothers had worse outcomes than infants with English-speaking mothers.


Bradykinin-induced leukocyte- and platelet-endothelium interactions in the cerebral microcirculation.
Bradykinin is known for its pathophysiological role as mediator of inflammation. Following cerebral ischemia, bradykinin promotes the secondary brain damage through an increase of vascular permeability and brain edema formation, again hallmarks of inflammation. It is not clear, whether bradykinin also activates inflammatory cells and regulates microcirculatory blood flow in the brain. The purpose of the study is to investigate the reaction of bradykinin upon cerebral leukocyte- and thrombocyte-endothelium interactions as well as microvascular perfusion. Intravital fluorescence microscopy of pial blood vessels was performed in gerbils. Intracarotid injection of bradykinin resulted in increased numbers of rolling and adherent leukocytes as well as rolling platelets at the venular endothelium. This was reversed by administration of a bradykinin B2 receptor antagonist. In contrast, after additional administration of a B1 receptor antagonist, microvascular blood-flow and capillary density was decreased. We conclude that bradykinin initiates leukocyte- and platelet-endothelium interactions in the cerebral microcirculation via activation of B2 receptors. Activation of B1 receptors ensures regular cerebral perfusion. Thus, to attenuate secondary brain damage, inhibition of B2 but not B1 receptors might be of therapeutical benefit.


Nonfatal venous air embolism during cesarean section: a case report and review of the literature.
Venous air embolism occurs in more than half of all cesarean sections. Predisposing factors in pregnancy include uterine surgery and manipulation, hypovolemia, and maternal positioning. The presence of an intracardiac septal defect and use of certain anesthetic agents place the patient at greater risk of fatal air embolus. The sudden development of hypotension, hypoxia, and a drop in end-tidal CO2 are typical signs of this condition. Supportive therapy includes flooding the surgical field with normal saline, placing the patient in reverse Trendelenburg with a left-lateral tilt, and discontinuation of nitrous oxide anesthesia. We report a case that was diagnosed and successfully managed during a cesarean section and review the literature on prophylaxis, diagnosis, and therapy of this condition. A high index of suspicion and use of precordial Doppler studies in the future will permit earlier diagnosis and therapy and decreased mortality from this common condition. The phenomenon of venous air embolism in the intrapartum period has been well described in the anesthesia literature but there have been few case reports of patients having this complication in the recent obstetrical literature. We wish to describe the clinical course and successful management of a patient with this complication during cesarean section and provide a review of the literature on the phenomenon of venous air embolism in the obstetrical patient with particular emphasis on pathophysiology, detection, and treatment.


Wound dressings - a review.
Wound healing is a dynamic and complex process which requires suitable environment to promote healing process. With the advancement in technology, more than 3000 products have been developed to treat different types of wounds by targeting various aspects of healing process. The present review traces the history of dressings from its earliest inception to the current status and also discusses the advantage and limitations of the dressing materials.


Treatment of idiopathic mixed cryoglobulinemia with alpha interferon.
Seven patients with type II idiopathic mixed cryoglobulinemia were treated with recombinant human leukocyte interferon (alpha interferon). In all of them, a conspicuous reduction of circulating cryoglobulins was noted, together with a definite, remarkable improvement of the clinical pattern. The immunologic parameters (natural killer cell activity and phagocytosis, among others) improved as well; side effects were usually mild and transient. Increases in the cryoglobulin level occurred in a few cases, but they were at least partly sensitive to readministration of alpha interferon treatment. The favorable results obtained in these cases of idiopathic cryoglobulinemia seem to be consistent and prolonged.


Ir d-band derived superconductivity in the lanthanum-iridium system LaIr3.
The electronic properties of the heavy metal superconductor [Formula: see text] are reported. The estimated superconducting parameters obtained from physical properties measurements indicate that [Formula: see text] is a BCS-type superconductor. Electronic band structure calculations show that Ir d-states dominate the Fermi level. A comparison of electronic band structures of [Formula: see text] and [Formula: see text] shows that the Ir-compound has a strong spin-orbit-coupling effect, which creates a complex Fermi surface.


Brewer's Yeast Improves Blood Pressure in Type 2 Diabetes Mellitus.
This study was conducted to investigate the effects of Brewer's yeast supplementation on serum lipoproteins and blood pressure in patients with Type 2 diabetes mellitus. In a randomized double blind clinical trial, 90 adults with type 2 diabetes mellitus were recruited, and divided randomly into 2 groups, trial group received brewer's yeast (1800 mg/day) and control group received placebo for 12 weeks. Weight, BMI, food consumption (based on 24 hour food recall), fasting serum lipoproteins (Cholesterol, Triglyceride, LDL-c, HDL-c), systolic and diastolic blood pressures were measured before and after the intervention. Data analyses were performed by Statistical Package for Social Sciences ver. 18.0, and the statistical tests included Independent t-test, Paired t-test, Kolmogorov-Smirnov and analysis of covariance. This trial was registered in Iranian Registry of Clinical Trials (IRCT), No.IRCT138807062513N1. Eighty-four subjects (21 men and 63 women) aged 46.3±6.1 years completed the study. After 12 weeks supplementation, systolic and diastolic blood pressures were decreased in the group receiving brewer's yeast (4.1±1.5, P=0.007 and 5.7±0.6, P=0.001 respectively). No-significant changes in LDL-c, HDL-c, Triglyceride and Cholesterol were shown. Supplementation with Brewer's yeast besides the usual treatment of type 2 diabetes mellitus can reduce systolic and diastolic blood pressures in diabetic patients.


Sex steroids and bone health in men.
The influence of sex steroids on bone in both men and women has long been recognized. In men, however, the relative contribution of androgens versus estrogens in the regulation of bone metabolism remains uncertain. Animal studies demonstrate that both estradiol (E2), via activation of estrogen receptor-α, and testosterone (T), via activation of the androgen receptor, regulate bone mass in male rodents. The main focus of this review is to summarize and discuss recent findings from the osteoporotic fractures in men (MrOS) cohorts regarding the impact of serum sex steroids on bone health in elderly men. Collectively, these data demonstrate that serum E2 is directly associated with bone mineral density (BMD) and that low serum E2 associates with higher rates of bone loss and fracture. In addition, they substantiate the concept of a threshold E2 level that determines fracture risk in elderly men. We propose that the effect of E2 on fracture risk is at least partly mediated by its effect on BMD, whereas the more modest effect of T on fracture risk mainly is mediated by effects on muscle strength and risk of falls. Findings from the MrOS cohorts also demonstrate that racial and genetic variations in aromatase activity influence serum E2 levels in men. In conclusion, there is compelling evidence that not only androgens, but also estrogens, are important regulators of bone health in men. Consequently, E2 should not exclusively be regarded as the 'female hormone' but as a sex steroid that is necessary for maintenance of bone health in men.


Dyadic parent-infant interaction patterns at 12 months: Exploring dyadic parent-infant gender compositions.
This study investigates differences in dyadic mother-infant and father-infant interaction patterns at infant age 12 months, and the relation between different parent-infant gender compositions and the dyadic interaction. Data were drawn from a large-scale, population-based Norwegian community sample comprising 671 mother-infant and 337 father-infant interactions. The Early Relational Health Screen (ERHS), a screening method for observing dyadic parent-infant interactions, was used to assess the parent-infant interactions. Scores on the ERHS were employed to investigate dyadic differences in the overall interaction scores, and dyadic interaction on seven sub-dimensions between mother-infant and father-infant pairs. The relation between different parent-infant gender compositions and the dyadic interaction scores was also examined. As expected in a normative sample, most parent-infant interactions received scores in the upper rating levels. Differences between mother-infant and father-infant patterns were generally small, but mother-infant dyads tended to obtain slightly higher scores. The mother-infant dyads received higher scores on the dimensions of engagement and enjoyment, but no other significant differences between the parent-infant pairs were found for the remaining dimensions. We did not find evidence for a moderation effect of child gender. However, parent-daughter dyads received somewhat higher scores than the parent-son dyads.


Cross-neutralizing activity of human anti-V3 monoclonal antibodies derived from non-B clade HIV-1 infected individuals.
One approach to the development of an HIV vaccine is to design a protein template which can present gp120 epitopes inducing cross-neutralizing antibodies. To select a V3 sequence for immunogen design, we compared the neutralizing activities of 18 anti-V3 monoclonal antibodies (mAbs) derived from Cameroonian and Indian individuals infected with clade AG and C, respectively. It was found that V3 mAbs from the Cameroonian patients were significantly more cross-neutralizing than those from India. Interestingly, superior neutralizing activity of Cameroonian mAbs was also observed among the nine VH5-51/VL lambda genes encoding V3 mAbs which mediate a similar mode of recognition. This correlated with higher relative binding affinity to a variety of gp120s and increased mutation rates in V3 mAbs from Cameroon. These results suggest that clade C V3 is probably weakly immunogenic and that the V3 sequence of CRF02_AG viruses can serve as a plausible template for vaccine immunogen design.


The mechanism of proteinuria in three different models of renovascular hypertension in the rat.
The proteinuria was measured in two-kidney hypertensive rats, in rats made hypertensive by aortic stenosis, in one-kidney hypertensive rats and in a group of control sham-operated animals. It was significantly increased in those of the first and second groups in direct correlation with the PRA which was elevated, while it was only slightly raised in those of the third group with a normal PRA. Following removal of the clip the proteinuria decreased in the two-kidney hypertensive rats, whilst it increased in the other two groups. It is suggested that in the latter cases the increase in protein excretion after removal of the clip could be due to an increase in the blood flow and filtration rate of the revascularized kidneys, whilst in the former this effect could be masked by the constant decreases in proteinuria from the intact kidney due to the fall in the PRA.


The effect of essential oils on work-related stress in intensive care unit nurses.
This small pilot study evaluated the effect of a topical application of the essential oils Lavandula angustifolia and Salvia sclaria on work-related stress of nurses in an ICU setting. Results demonstrated decreased perception of stress level in the intervention group during three 12-hour worked shifts.


Review of grey literature on Ayurveda wound healing formulations and procedures - A systematic review.
In the era of globalization and evidence-based medicines, a systematic documentation of information by compiling the studies carried out in different parts of India could be useful for the clinicians of Ayurveda and to the ailing community. In this review, an attempt has been made to compile all such clinical research works carried out on Vrana Ropana (wound healing). A grey literature of post graduate (PG) and Doctorate (PhD) researches on Vrana Ropana from various Ayurvedic institutes were collected in the form of soft or/and hard copy as per the availability. The studies were found to be a combination of drug/drug formulations and various procedures mentioned under Shashti Upakramas in Sushruta Samhitha. The use of the Lepa (topical application), Avachoornana (sprinkling of medicated powder), Raktamokshana (bloodletting) like Jalauokavacharana (medicinal leech application) and Kshalana (therapeutic procedure in which the wounds are cleansed with medicated liquids) were cross reviewed from various research works. All these works were mainly targeted to find the best Shodhana (cleaning) and Ropana (healing) drugs for the treatment of wound. On the basis of the clinical evidences on the same drug with positive outcomes, one should further try it in multi-centres and develop that drug for wound management. Hence this review study would help to know the previous research works carried out on wound healing and design further trials on specific parameters or treatment protocol as a whole with local as well systemic management of wounded patients.


The relationship between the serotonergic system and COVID-19 disease: A review.
COVID-19 is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which led to a pandemic started in Wuhan, China, in 2019. The rapid spread of the disease in the world, unprecedented mortality rate, and lack of definitive treatment for the disease have led to a global effort to develop effective vaccines as well as new therapeutic interventions. Immune cells activation with excessive inflammation is an important pathophysiological feature of COVID-19 that may impair the various organs functions. Accordingly, these could cause dysfunction in the brain with some symptoms such as respiratory failure, headache, impaired consciousness, olfactory and taste disorders, and severe neurological disorders such as encephalitis. It was found that there is a two-way communication between the immune system and the nervous system through classical neurotransmitters, hormones, and cytokines. Among neurotransmitters, serotonin plays important roles in the immune system and in regulating inflammatory responses by central and peripheral mechanisms. This article aimed to review the two-way relationship between the immune and the nervous systems by focusing on the serotonergic system and the emerging COVID-19 disease.


Smartphone Addiction and Checking Behaviors Predict Aggression: A Structural Equation Modeling Approach.
Despite the potential risks of excessive smartphone use for maladaptive outcomes, the link between smartphone use and aggression remains less understood. Furthermore, prior findings are inconclusive due to a narrow focus on limited aspects of smartphone use (e.g., screen time) and reliance on self-reported assessments of smartphone use. Therefore, using objective measures of smartphone use, we sought to examine the associations between several key indices of smartphone use-screen time, checking behaviors, and addictive tendency-and multifaceted aggression (i.e., confrontation, anger, and hostility). In a cross-sectional study, we administered a series of questionnaires assessing aggressive tendencies (i.e., The Aggression Questionnaire) and various aspects of smartphone use (N = 253, Mage = 21.8 years, female = 73.2%). Using structural equation modeling, we found that smartphone checking and addictive smartphone use predicted only hostility. In contrast, both objective and subjective measures of screen time did not predict any facets of aggression. These results highlight differing impacts of various indices of smartphone use on aggression and imply that excessive checking and addictive smartphone use are problematic smartphone-use behaviors that require more targeted interventions with respect to hostility.


Establishing the concurrent validity of a vocabulary checklist for young maltese children.
The current literature highlights the research and clinical applications of parental report in investigating the status of language skills in young children. Since language acquisition norms for Maltese have not yet been established, this study attempts to obtain preliminary indications of developmental trends in early lexical development by adapting an established parent-completed vocabulary checklist for use with Maltese children. The concurrent validity of this bilingual adaptation was examined relative to picture naming abilities and spontaneous vocabulary use in a cross-sectional cohort of 10 children aged between 12 and 30 months who were primarily exposed to Maltese. The results indicate a high and significant correlation between lexical production abilities as reported by parents completing the checklist and as measured through confrontation naming and conversational language use. Reported vocabulary measures indicate a steady increase in lexical production with age, with a sharp increment evident beyond the age of 24 months. These findings suggest that the preliminary version of the vocabulary checklist has potential for gauging early lexical growth and point towards the need for further research on a larger scale.


Rebound pain and postoperative pain profile following brachial plexus block compared to general anaesthesia-An observational study.
Regional anaesthesia has the benefit of reducing the need for systemic analgesia and therefore, potentially reducing undesired side effects. With the end of the sensory nerve block however, many patients report severe pain that requires therapy with opioids and often compromise the initial opioid sparing effect. This study aimed to characterise the postoperative pain profile and the phenomenon of rebound pain after axillary brachial plexus anaesthesia (RA) compared to general anaesthesia (GA). Single-centre observational, stratified cohort study. The study was conducted at University Hospital Marburg from May 2020 until September 2022. One hundred thirty-two patients receiving elective hand and forearm surgery were enrolled in this study. Group RA received ultrasound-guided brachial plexus anaesthesia via the axillary approach with 30 mL of prilocaine 1% and 10 mL ropivacaine 0.2%. Group GA received balanced or total intravenous general anaesthesia. Primary endpoint were integrated pain scores (IPS) within 24 h postoperatively. Secondary endpoints were pain scores (NRS 0-10), morphine equivalents, patient satisfaction, quality of recovery and opioid-related side effects. One hundred thirty-two patients were analysed of which 66 patients received brachial plexus block and 66 patients received general anaesthesia. Following RA significantly lower IPS were seen directly after surgery (p < .001) and during the post-anaesthesia care unit interval (p < .001) but equalised after 3 h at the ward. No overshoot in pain scores or increased opioid consumption could be detected. Patient satisfaction and postoperative recovery were comparable between both groups. The IPS and NRS was initially lower in the RA group, increased with fading of the block until equal to the GA group and equal thereafter. Although various definitions of rebound pain were met during this phase, the opioid sparing effect of regional anaesthesia was not counteracted by it. The incidence of episodes with uncontrolled, severe pain did not differ between groups. We found no clinical implications of rebound pain in this setting, since the RA group did not show higher pain scores than the GA group at any time point. German Clinical Trials Register (DRKS00021764).


The complete amino acid sequence of the catalytic domain of rat brain hexokinase, deduced from the cloned cDNA.
The complete amino acid sequence of the catalytic domain of rat brain hexokinase (ATP:D-hexose 6-phosphotransferase, EC 184.108.40.206) has been deduced from the nucleotide sequence of cloned cDNA. Extensive similarity in sequence, taken to indicate similarity in secondary and tertiary structure, is seen between the mammalian enzyme and yeast hexokinase isozymes A and B. All residues critical for binding glucose to the yeast enzyme are conserved in brain hexokinase. A location for the substrate ATP binding site is proposed based on relation of structural features in the yeast enzyme to characteristics commonly observed in other nucleotide binding enzymes; sequences in regions proposed to be important for binding of ATP to the yeast enzyme are highly conserved in brain hexokinase.


Fluid-solid coupling numerical simulation of trabecular bone under cyclic loading in different directions.
The structure of a bone tissue is capable of adapting to mechanical loading through the process of bone remodeling, which is regulated by osteoblasts and osteoclasts. Fluid flow within trabecular porosity under cyclic loading is one of the factors stimulating the biological response of osteoblasts and osteoclasts. However, the relation between loading directions and interstitial fluid flow was seldom studied. In the present study, a finite element model based on micro-computed tomographic reconstructions is built by using a mouse femur. Results from the fluid-solid coupling numerical simulation indicate that the loading in different directions generates a distinct distribution of von Mises stress in the bone matrix and a fluid shear stress (FSS) in the bone marrow. The loading along the physiological direction leads to a more uniform distribution of solid stress and produces an FSS level beneficial to the biological response of osteoblasts and osteoclasts compared with those along the non-physiological direction. There was a minimum threshold line of wall FSS with a specific solid stress at the bone surface, suggesting that the wall FSS is mainly induced by the solid strain. These results may offer fundamental data in understanding the mechanical environment around osteoblasts and osteoclasts and the cellular and molecular mechanisms of mechanical loading-induced bone remodeling.


Medical and lay attitudes towards genetic screening and testing in Finland.
The purpose of this study was to compare physicians', midwives' and lay people's attitudes towards genetic screening and testing to find out whether medical education and experience influence attitudes of genetic screening and testing. The study was based on comparison of answers to joint questions in three different cross-sectional postal surveys between October 1996 and April 1998 in Finland. Target groups were physicians (study base n=772, response rate 74%, including gynaecologists, paediatricians, general practitioners and clinical geneticists), midwives and public health nurses (collectively referred to as midwives in the following; n=800, response rate 79%), and lay people (n=2000, response rate 62%). Midwives were more worried about the consequences of genetic testing and stressed the autonomy of the customer more strongly than lay people did. Furthermore, professionals considered that lay peoples' expectations as regards to genetic testing are too high. Having more medical education was related to having less 'cannot say' and missing responses. Our results do not suggest that major conflicts about the direction of genetic testing and screening would arise in near future. However, different positions and interests should be considered. Reporting in public about new prospects and developments in medical genetics should pay more attention also to concerns for balancing promises and drawbacks.


Creatinine-to-bodyweight ratio is a predictor of incident non-alcoholic fatty liver disease: A population-based longitudinal study.
Serum creatinine (Cre) is used as a surrogate marker of muscle mass. We investigated the impact of the Cre-to-bodyweight (BW) ratio (Cre/BW) on incident non-alcoholic fatty liver disease (NAFLD). Fatty liver disease was diagnosed by abdominal ultrasonography. In this historical cohort study of 13 728 participants (6397 men and 7331 women), we divided the participants into two groups by sex and into quartiles according to Cre (mg/dL)/BW (kg; Q1-4). We carried out Cox proportional hazard models, adjusting for age, alanine aminotransferase, fasting plasma glucose, systolic blood pressure, alcohol consumption, smoking status, and exercise. During the 5.1-year follow up for men and 6.0-year follow up for women, 2497 participants (1696 men, 801 women) developed NAFLD. The 4000-days cumulative incidence rates of FLD for men and women were 29.6% and 16.6% in Q1, 28.2% and 10.6% in Q2, 25.5% and 8.8% in Q3, and 22.7% and 7.7% in Q4, respectively. The hazard ratios of incident NAFLD in Q1 (Cre/BW [×100]: men <1.28; women <1.17) were 1.89 (95% confidence interval 1.64-2.17, P < 0.001) in men and 2.96 (2.42-3.62, P < 0.001) in women, compared with Q4 (Cre/BW [×100]: men ≥1.61; women ≥1.51). A low Cre/BW is associated with an increased risk of NAFLD. Screening Cre/BW can be used to identify individuals who are at high risk of NAFLD.


Spontaneous bacterial peritonitis in hepatocellular carcinoma after PD-1 inhibitor therapy: two clinical cases.
With the recent advances in immunotherapy, especially programmed cell death protein 1 (PD-1) inhibitors, the treatment of hepatocellular carcinoma (HCC) patients has entered a new stage. However, few reports have focused on spontaneous bacterial peritonitis (SBP) after PD-1 inhibitor treatment of intermediate-to advanced-stage HCC. In this article, we report two clinical cases of SBP after successful PD-1 inhibitor therapy. The patient's condition was assessed as a complete response (CR) according to the mRECIST criteria. Based on these two cases, we found that patients with large or giant HCC who have large tumour diameter should be closely monitored for SBP after successful PD-1 inhibitor therapy, especially when the imaging shows the rapid development of marked necrosis and depression at the tumour site. Early and active treatment is necessary to reduce the suffering caused by SBP.


Enhanced diagnosis of coronary artery disease in women by dobutamine thallium-201 ST-segment/heart rate slope and thallium-201 myocardial SPECT.
The diagnosis of coronary artery disease (CAD) in women presents a great challenge because of poor exercise capacity and inadequate heart rate response during stress test. The clinical significance of stress-related ST-segment/heart rate slope (ST/HR slope) value for evaluating CAD in women remains controversial. Therefore, we conducted the present study to assess the diagnostic performance of dobutamine ST/HR slope in women, compared with myocardial perfusion study using thallium-201 single-photon emission computed tomography (Tl-201 SPECT). A total of 51 female patients with suspected CAD underwent simultaneous 12-lead electrocardiographic recording during 3-minute stages of dobutamine infusion as well as Tl-201 SPECT, and coronary angiography was performed within 2 weeks post Tl-201 SPECT. The sensitivity, specificity, positive predictive value and negative predictive value of dobutamine ST/HR slope and Tl-201 SPECT were assessed, and the results of coronary angiography were used as a gold standard. The sensitivity, specificity and accuracy of dobutamine ST/HR slope in detecting CAD were 43%, 83% and 61%, and those of Tl-201 SPECT were 71%, 87% and 78%, respectively. However, using both positive results of Tl-201 SPECT and ST/HR slope for detecting CAD, the diagnostic specificity increased from 87% to 96%. Using both negative results of Tl-201 SPECT and ST/HR slope to exclude CAD, the negative predictive value increased from 71% to 85%. The accuracy of dobutamine ST/HR slope in detecting CAD was not affected by the use of beta-blockers. Dobutamine ST/HR slope is less sensitive and less accurate than Tl-201 SPECT for detecting CAD in women. However, it adds diagnostic benefit to Tl-201 SPECT with only a little extra calculation.