Tolerance and efficacy of targeted therapies prescribed for off-label indications in refractory systemic autoimmune diseases: data of the first 100 patients enrolled in the TATA registry (TArgeted Therapy in Autoimmune Diseases).
To assess the tolerance and efficacy of targeted therapies prescribed off-label in refractory low-prevalence autoimmune and inflammatory systemic diseases. The TATA registry (TArgeted Therapy in Autoimmune Diseases) is a prospective, observational, national and independent cohort follow-up. The inclusion criteria in the registry are as follows: age >18 years; low-prevalence autoimmune and inflammatory systemic disease treated with off-label drugs started after 1 January 2019. Hundred (100) patients (79 women) were enrolled. The median age was 52.5 years (95% CI 49 to 56) and the median disease duration before enrolment was 5 years (3 to 7). The targeted therapies at enrolment were as follows: Janus kinase/signal transducers and activators of transcription inhibitors (44%), anti-interleukin (IL)-6R (22%), anti-IL-12/23, anti-IL-23 and anti-IL-17 (9%), anti-B cell activating factor of the tumour necrosis factor family (5%), abatacept (5%), other targeted treatments (9%) and combination of targeted treatments (6%). 73% of patients were receiving corticosteroid therapy at enrolment (median dose 10 mg/day). The current median follow-up time is 9 months (8 to 10).Safety: 11 serious infections (incidence rate of 14.8/100 patient-years) and 1 cancer (1.3 cancers/100 patient-years) were observed. Two patients died from severe COVID-19 (2.7 deaths/100 patient-years).Efficacy: the targeted treatment was considered effective by the clinician in 56% of patients and allowed, in responders, a median reduction of oral corticosteroids of 15 (9 to 21) mg/day, below 7.5 mg/day in 76% of patients, while 28% discontinued. These initial results of the TATA registry confirm the diversity of targeted treatments prescribed off-label in refractory autoimmune diseases and their corticosteroid-sparing effect when effective. Tolerance was acceptable in these refractory patients with a long history of treatment with immunosuppressive drugs.


What is the functional relevance of reorganization in primary motor cortex after spinal cord injury?
Motor output maps within primary motor cortex are widely distributed and modified by motor skill learning and neurological injury. Functions that these maps represent after spinal cord injury remain debatable. Moreover, the pattern of reorganization and whether it supports recovery of compromised motor function is not well understood. A deeper understanding of the pathophysiological mechanisms of motor dysfunction after spinal cord injury is necessary to develop and optimize repair strategies. There are three purposes for this review. The first is to synthesize available research on spontaneous reorganization with primary motor cortex following spinal cord injury. The second is to draw on existing evidence from the motor skill learning and brain injury literature to interpret the form and purpose of motor maps. The third purpose is to account for the existing research on intervention-induced reorganization of primary motor cortex following spinal cord injury. We conclude with directions for future work, emphasizing the need for multi-modal investigations that construct maps with both neuroimaging and non-invasive stimulation methods to derive a cohesive understanding of the effects of spinal cord injury on reorganization within primary motor cortex.


Wafer embedding: specimen selction in electron microscopic cytochemistry with osmiophilic polymers.
A new wafer embedding procedure is described that permits light microscopic screening of embedded tissue prior to ultrathin sectioning. It is particularly valuable when used on specimens obtained with an automatic sectioner and treated cytochemically to obtain visible intermediate or visible and electron opaque final reaction products. Aldehyde-fixed tissues are cut into sections with an automatic sectioner, incubated cytochemically osmication if required, then embedded in epoxy resin between fluorocarbon coverglasses which are supported by a platform specially designed for this purpose. The resultant wafter, less than 0.2 mm thick, is examined by light microscopy for optimal areas of cytochemical reaction and desirable structural features. Such areas are cut out and glued to blank blocks with fast curing cyanoacrylate cement for subsequent ultrathin sectioning. The usefulness of this technique is demonstrated by the location of: (1) esterase-positive lysosomes in kidney and trigeminal ganglia; (2) palatal sensory endings stained for acetylcholinesterase; and (3) phagosomes arising from the resorption of horseradish peroxidase tracer by the cuboidal parietal epithelial cells of Bowman's capsule in the male mouse.


PLA2R and membranous nephropathy: A 3 year prospective Australian study.
The phospholipase A2 receptor (PLA2R) is the major target antigen in idiopathic membranous nephropathy (iMN). The aim of this prospective study was to determine the prevalence of anti-PLA2R in iMN in an Australian cohort. Serum anti-PLA2R was measured using two techniques, an enzyme-linked immunosorbent assay (ELISA) and a cell-based indirect immunofluorescence test. Kidney biopsies were also examined for the presence of PLA2R using a polyclonal antibody. A group of 21 patients with iMN were compared with a group of 19 patients with secondary MN and other glomerular diseases. Seventeen of 21 patients with iMN were positive for anti-PLA2R on both ELISA and indirect immunofluorescence test, and 14 of these patients also had positive staining for PLA2R in the biopsy (tissue was unavailable in two patients). Three patients with iMN had positive staining in the biopsy only, and one patient was negative in both the serum and the biopsy. None of the patients with secondary MN or other glomerular diseases had anti-PLA2R antibodies or PLA2R in the biopsy. There was wide inter-individual variation in titre on ELISA, but serial levels within an individual patient enabled monitoring of disease, and a fall in titre correlated with clinical remission. This is the first Australian series to examine the incidence of anti-PLA2R in iMN. It is also unique in examining sera by two separate techniques in conjunction with tissue localization of PLA2R. We have shown 100% specificity of both serum anti-PLA2R and glomerular PLA2R in iMN, with a sensitivity of 81.0%. When serum testing is combined with tissue localization of PLA2R, the sensitivity increases to 95.2%.


Understanding the Effect of Compound Probiotics on the Health of Rabbits and Its Mechanisms Through Metagenomics.
In this study, we investigated the effects of probiotics on growth performance, immunity, intestinal flora, and antioxidant capacity of rabbits. Three hundred New Zealand white rabbits were randomly divided into four groups. Groups A, B, C, and D were the lactobacillus group, compound probiotic group, control group, and antibiotic group, respectively. The results showed compared with the control group, the average weight of groups A, B, and D increased by 14.88%, 12.33%, and 11.97%, respectively. Moreover, the index of immune organs and the IgG and IgM in serum of group B were significantly increased (P < 0.05). Meanwhile, the activities of superoxide dismutase (SOD) in group B and catalase (CAT) in group A were significantly increased (P < 0.05). At week 5, the contents of rabbit cecum were taken for metagenome sequencing, and the results showed probiotics increased the relative abundance of Akkermansia, and decreased the relative abundance of Bacteroides. According to the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, we found probiotics could enrich metabolic pathways such as carbohydrates, amino acids, and lipids. According to the Comprehensive Antibiotic Resistance Database (CARD), we found antibiotic resistance ontology (ARO) in cecum mainly included β-lactamases, macrolide 2'-phosphotransferase II, and plasmid-mediated quinolone resistance protein. Among them, there were 1964, 2105, and 1982 types of ARO in group B, group D, and groups A and C, respectively. These results showed probiotics played a beneficial role in maintaining or enhancing the health and growth of rabbits and could replace antibiotics under certain feeding conditions.


Lipoprotein lipase and hepatic lipase activity after heparin administration in abetalipoproteinemia and hypobetalipoproteinemia.
The purpose of this study was to examine whether an absence of triglyceride-rich lipoproteins (chylomicrons and very-low-density lipoproteins) in plasma is associated with any changes in the enzyme activity of lipoprotein lipase or hepatic lipase after heparin administration. To study this, the activities of hepatic lipase and lipoprotein lipase were determined in control subjects, in two patients with heterozygous hypobetalipoproteinemia, and in three patients with phenotypic abetalipoproteinemia after administration of heparin. Both enzymes showed normal activity in the patients with hypobetalipoproteinemia, but showed consistently reduced activity in the patients with abetalipoproteinemia. Hepatic lipase activity in plasma samples from these three patients obtained 15 minutes after intravenous injection of heparin was 55%, 87%, and 46% of that of the controls, whereas corresponding values in plasma samples obtained 30 minutes after heparin were 47%, 70%, and 57%, respectively. Lipoprotein lipase activity in the three patients with abetalipoproteinemia was 46%, 29%, and 34% of that of the controls in the samples obtained 15 minutes after heparin injection, whereas the values obtained after 30 minutes were 53%, 64%, and 47% of that of the controls. We conclude that an inherent absence of triglyceride-rich lipoproteins, as occurs in abetalipoproteinemia, is associated with reduced enzyme activity of both hepatic lipase and lipoprotein lipase in plasma after heparin administration.


[Primary mediastinal seminoma. Value of the assay of tumor markers before any surgery. Study of a case].
An excessive surgical excision of pulmonary parenchyme preceded the histological diagnosis of a mediastinal seminoma, concerning a 43 year-old man. Absence of all tumoral tracer during surgery did not permit to establish the difference between radiosensitive pure seminoma and impure seminoma of which repeated dosages should have improved medical strategy. In order to avoid, in the future, a similar error, in case of an anterior mediastinal tumor, the authors formally recommended, before all surgery, a dosage of HCG and AFP.


Skin-to-skin contact after birth: Developing a research and practice guideline.
Skin-to-skin contact immediately after birth is recognised as an evidence-based best practice and an acknowledged contributor to improved short- and long-term health outcomes including decreased infant mortality. However, the implementation and definition of skin-to-skin contact is inconsistent in both practice and research studies. This project utilised the World Health Organization guideline process to clarify best practice and improve the consistency of application. The rigorous guideline development process combines a systematic review with acumen and judgement of experts with a wide range of credentials and experience. The developed guideline received a strong recommendation from the Expert Panel. The result concluded that there was a high level of confidence in the evidence and that the practice is not resource intensive. Research gaps were identified and areas for continued work were delineated. The World Health Organization guideline development process reached the conclusion immediate, continuous, uninterrupted skin-to-skin contact should be the standard of care for all mothers and all babies (from 1000 g with experienced staff if assistance is needed), after all modes of birth. Delaying non-essential routine care in favour of uninterrupted skin-to-skin contact after birth has been shown to be safe and allows for the progression of newborns through their instinctive behaviours.


The pattern of antiganglioside antibody reactivities producing myelinated nerve conduction block in vitro.
We studied the pattern of human antiganglioside antibody reactivities causing an acute conduction block in rat myelinated nerve fibers, using an in vitro preparation of the sciatic-tibial nerve. With the aid of complements, IgM antibodies reacting with the terminal disaccharide of galactose (beta1-3)N-acetylgalactosamine produced the block. These findings may help us to understand the mechanism in which the conduction block occurs in neuropathies associated with antiganglioside antibodies.


Role of Ca(2+)-dependent regulator protein in intestinal secretion.
AFTER exposure to secretagogues the small intestine changes from a tissue that absorbs fluid and electrolyte from lumen to blood into a tissue that secretes electrolyte and fluid into the lumen(1-4). It has been shown that this secretion results from an increase in the passive Cl(-) permeability of the mucosal border, which permits Nad to leak passively from the lateral intercellular spaces, where it is present at hypertonic concentrations(5), into the mucosal bathing solution. Na(+) and water, electroosmotically coupled to Na(+) movement, leak through the tight junctions(1,2), and Cl(-) leaks through relatively anhydrous anion-selective channels, induced withira the mucosal border by secretagogues. The increased reflux of NaCl from the lateral intercellular space accounts for both the apparent decrease in electroneutral NaCl uptake across the mucosal border induced by secretagogues and the apparent increase in active CP secretion and short-circuit current(3,6,7). We have investigated the mechanism by which intestinal secretagogues increase passive Cl(-) permeability and thereby cause secretion. Cl(-) permeability is increased by several secretagogues, some of which, such as theophylline and choleragen, increase intracellular cyclic AMP concentration, and others, such as A23187, the Ca(2+) ionophore, or carbachol, do not(8). Thus there has been no known common mode of secretory induction. To investigate this problem we used two drugs that prevent intestinal secretion in vitro, RMI 12330A (Richardson Merrell), and the antipsychotic pheno-thiazine trifluoperazine (Stelazine, Smith, Kline and French). RMI 12330A prevents secretion by inhibiting choleragen-induced adenylyl cyclase activity(9). Stelazine inhibits phosphodiesterase in tissues(11,12) by preventing the activation of the enzyme by Ca(2+)-dependent regulator protein, CDR. We report here that it also inhibits Cl(-) secretion and binds to CDR.


Relationship between DLK1 gene promoter region DNA methylation and non-small cell lung cancer biological behavior.
[This retracts the article DOI: 10.3892/ol.2017.6019.].


[Non-surgical method of treatment of dislocation of the acromial end of the clavicle].
An apparatus for reposition and fixation of the clavicle in case of the dislocation, in the acromioclavicular joint is described. The method was used in the treatment of 60 patients. There were 57 good results, and in 3 cases the results were fair.


Vaginal colonization by bacteria and yeast.
A number of different factors have been found to influence the microflora of the vagina. Studies showing an increased rate of colonization associated with pregnancy, menses, oral contraceptive use, and estrogen replacement therapy illustrate the influence of hormones, glycogen content, and pH on vaginal colonization. The microorganisms found in the vagina may also be dependent on the existence of specific attachment sites, which may differ in the various areas of the vagina. Vaginal colonization appears to be altered in patients with diabetes mellitus, those receiving steroid therapy, and immunosuppressed individuals. Surgical manipulation of the vagina and the use of broad-spectrum antibiotics may also contribute to the growth of organisms in the vaginal tract.


Return to Work Experience of Young and Middle-Aged Patients With Acute Myocardial Infarction: A Longitudinal Qualitative Study.
Return to work (RTW) is a critical component of rehabilitation for most young and middle-aged patients after an acute myocardial infarction (AMI). Its success is related to the quality of life and social psychological function of patients, and their social economic growth. However, healthcare professionals often do not deeply understand the patients' experience and their difficulties and coping methods during this process, which limits their ability to institute effective management and support. In this study, we aimed to explore the lived experiences and change processes of young and middle-aged patients with AMI at the different stages of RTW. A descriptive qualitative approach was used. Patients aged 20 to 59 years with AMI were recruited from the Department of Cardiology of 3 general hospitals. Data were collected via semistructured interviews. Data analysis was performed by conventional content analysis methods. In total, 18 participants were included. Five main themes emerged: (1) "chaos," (2) "rebuilding," (3) "conflict," (4) "coping," and (5) "benefits." Patients may be more concerned about physical recovery during the initial clinical event. They then begin to plan and adjust for an RTW. Patients in the maintenance phase need strategies to prevent, identify, and respond to conflicts and challenges to maintain long-term stable work. We identified several post-AMI stages spanning from the initial illness event to the maintenance of stable work. We described their perceived barriers, coping strategies, and support needs at these various stages. These data are crucial for healthcare professionals to develop improved vocational rehabilitation strategies for patients with AMI.


Non responders to interferon therapy among chronic hepatitis patients infected with hepatitis C virus.
We studied a series of 268 chronic hepatitis C patients (31 chronic persistent hepatitis CPH, 69 mild chronic active hepatitis CAH, 125 severe CAH, and 43 active cirrhosis) enrolled from 1988 to 1991 in different therapeutic protocols using lymphoblastoid or recombinant interferon (IFN) at a dosage of 3 mega units (M.U.), three times a week for 12 months. Of these patients 54.8% showed a complete response (normalization of aminotransferases), 14.2% a partial response (decrease in aminotransferases of over 50%), 27.6% no response, and 3.4% a substantial progressive increase in the liver enzymes during IFN (becoming worse). The prevalence of non responders was lower in CPH (9.7%) than in CAH patients (31.9% in the mild form and 20.8% in the severe), and significantly higher in patients with cirrhosis (53.5%). No correlation was observed between non response and the baseline aminotransferase level or the patient's sex. Patients under 35 had a better response to IFN when compared with patients 36-50 years. This is probably due to the higher prevalence of CPH patients with a good response to IFN in the youngest group. No effect was gained in non responders by increasing the dose or shifting from recombinant to lymphoblastoid IFN; three patients were then treated with steroids, but only one benefitted. For 5 of the 9 patients who became worse, steroids were started after discontinuation of IFN therapy, and they induced a favorable response only for the 3 who had developed autoantibodies during IFN treatment.


Different association of hypertension and insulin-related metabolic syndrome between men and women in 8437 nondiabetic Chinese.
Insulin resistance may cause a metabolic syndrome but whether insulin resistance causes hypertension is very controversial. Furthermore, it remains unclear whether the link between the insulin-resistance-related metabolic syndrome and hypertension is different between men and women. We examined fasting insulin, glucose, triglyceride and high-density lipoprotein (HDL)-cholesterol levels, systolic blood pressure, body mass index, and waist-to-hip ratio in a dataset from 8437 nondiabetic residents (age range, 30 to 89 years) in Kinmen. Factor analysis, a multivariate correlation statistical technique, was used to investigate the clustering and interdependence of these risk variables. Factor analysis identified two factors for men (n = 3659) and three factors for women (n = 4778, respectively. In men, a cluster of insulin, triglyceride, HDL-cholesterol, body mass index, and waist-to-hip ratio (metabolic syndrome) accounted for 29.7%, and a cluster of systolic blood pressure and glucose (hyperglycemia plus hypertension) accounted for 18.1% of the total variance in all variables considered. In women, a cluster of insulin, triglyceride, body mass index, waist-to-hip ratio, and systolic blood pressure (metabolic syndrome plus hypertension) accounted for 29.4%, a cluster of systolic blood pressure, glucose, and triglyceride (hyperglycemia plus hypertension plus dyslipidemia) accounted for 14.0%, and a cluster of triglyceride and HDL-cholesterol (dyslipidemia) accounted for 16.2% of the total variance. In conclusion, a distinct insulin-resistance-related metabolic syndrome characterized by hyperinsulinemia, dyslipidemia, and obesity was observed for both men and women in this Chinese population. However, hypertension was linked to the metabolic syndrome in women only.


Alarm substance in Gyrinus aeratus (Coleoptera, Gyrinidae).
Gyrinid beetles are common in ponds and lakes in Sweden, where they aggregate in open areas of the surface. Gyrinid beetles have pygidial glands which produce compounds rendering them unpalatable to fish. This study examines whether the pygidial secretion can be used for alarm purposes in addition to other functions. Experiments showed that gyrinid beetles responded to water prepared with the pygidial compounds by evasive behaviour. The beetles did not respond when the compound was mediated by air. One component of the defense system of gyrinids is how they advertise their presence. The aggregation of dark beetles with their typical motion pattern when alerted is very conspicuous and easily identified by an experienced predator. We suggest that this aspect of gyrinid defence can be characterized as aposematic.


What does my neighbourhood have to do with my weight? A protocol for systematic review and meta-analysis of the association between neighbourhood socioeconomic status and body weight.
Individuals living in poor neighbourhoods are at a higher risk of overweight/obesity. There is no systematic review and meta-analysis study on the association of neighbourhood socioeconomic status (NSES) with overweight/obesity. We aimed to systematically review and meta-analyse the existing evidence on the association of NSES with overweight/obesity. Cross-sectional, case-control and cohort studies published in English from inception to 15 May 2017 will be systematically searched using the following databases: PubMed, EMBASE, Web of Sciences and Google Scholar. Selection, screening, reviewing and data extraction will be done by two reviewers, independently and in duplicate. The Newcastle-Ottawa Scale (NOS) will be used to assess the quality of evidence. Publication bias will be checked by visual inspection of funnel plots and Egger's regression test. Heterogeneity will be checked by Higgins's method (I2 statistics). Meta-analysis will be done to estimate the pooled OR. Narrative synthesis will be performed if meta-analysis is not feasible due to high heterogeneity of studies. Ethical clearance is not required as we will be using data from published articles. Findings will be communicated through a publication in a peer-reviewed journal and presentations at professional conferences. CRD42017063889.


Validating MARK2 Gene Polymorphism as a Predictor of Response to Lithium Treatment in Bipolar Patients
Lithium is a therapeutic option for the treatment of the acute phase of the bipolar disorder and long-term management of this disorder. However, it is estimated that 10 to 60% of patients do not properly response to this medication. To investigate the role of MARK2 gene in response to lithium, we genotyped the MARK2 rs10792421 polymorphism in Iranian bipolar patients using amplification Refractory Mutation System-PCR. Results of this study showed a significant association of this polymorphism with response to lithium. The A allele was more frequent in the responder than the non-responder group and also in the semi- responder group compared to the non-responder group in the codominant model of analysis. AA and AG genotypes were more frequent in both the responder and semi-responder groups compared to the non-responder group in dominant model of analysis. Based on the findings of the current study, the rs10792421 variant of MARK2 gene could be considered as a potential biomarker for predicting the treatment outcome of bipolar disorder type 1 in Iranian population.


Regulation of insulin-like peptide expression in adult Blattella germanica females.
The insulin-IGF-signalling (IIS) pathway regulates key processes in metazoans. The pathway is activated through the binding of the ligands, which in insects are usually referred to as insulin-like peptides (ILPs), to a class of receptor tyrosine kinases, the insect insulin receptor. To study the pathway regulation, it is therefore essential to understand how ILPs are produced and released. In this study we analysed the factors that regulate the expression of the seven ILPs (BgILPs) expressed in adult females of the German cockroach, Blattella germanica. The results showed that the starvation-induced expression reduction of brain BgILP3, 5 and 6 and fat body BgILP7 is not due to reduced juvenile hormone (JH) or decreased TOR pathway activity. In addition, depletion of FoxO in starved females did not correct the low levels of these BgILPs, but even reduced further BgILP5 expression, indicating the need to maintain certain basal levels of BgILP5 even during starvation. Furthermore, JH promoted increased BgILP5 and decreased BgILP3 expression in the brain, an effect that required Methoprene-tolerant (Met), the JH receptor, but not Krüppel homolog 1 (Kr-h1), the main JH transducer. On the other hand, JH inhibited the expression of BgILP7 in the fat body, although in this case, the action required both Met and Kr-h1. In addition, JH reduction treatments produced a decrease in the expression of the insulin receptor in the fat body, which suggests an increase in IIS. The results show a peculiar regulation of ILP expression in adult B. germanica females, which is clearly different than that seen in other species. This is understandable given that gene duplications in recent clades have resulted in different sets of ILP genes, involving substantial changes in gene regulatory networks.


[Allergen specific immunotherapy for rhinitis allergica : New applications].
Allergic diseases are among the most common diseases of humans. The immune response towards allergens is regulated by T-lymphozytes and characterized by an interleukin (IL)-4, IL-5 and IL-13 dominated Th2 cytokine profile. Allergen-specific immunotherapy (AIT) is the only causative treatment option and able to change the course of disease, e. g. to prevent the development of asthma and new sensitizations. The intralymphatic delivery of allergenes named intralymphatic immunotherapy (ILIT) has been evaluated in clinical trials and was demonstrated to be a highly potent application route with low effort and side effects while having equal efficacy if compared with current standard AIT forms. However, studies that verify important questions like optimal dose, new allergen forms, use of adjuvants etc. are still missing. Moreover, it has to be evaluated, whether different indications like rhinitis, or atopic dermatitis are suitable for ILIT and whether it is useful in children. Epicutaneous immunotherapy (EPIT) is a possible alternative application form. It is minimally invasive and basically consists of the affixation of allergen containing patches to the epidermis over 6 weeks. From the studies performed so far, the authors concluded, that epicutaneous immunotherapy is safe and efficacious in a dose-dependent manner after 6 patches only. AIT is accepted to be the only causative treatment option for allergies. New application routes in ILIT and EPIT may become more important and allow for different delivery methods in the future, however further clinical studies are required and in preparation.


Halohydrin analogues of cryptophycin 1: synthesis and biological activity.
The chloro-, bromo-, and iodo-derivatives 2-4 of the antimitotic drug cryptophycin 1 were synthesized by opening the epoxide ring. The biological activities of the compounds were tested in an in vitro microtubule assembly and a cell proliferation assay. The chloro-derivative 2 showed lower activity in the tubulin assay compared to 3 and 4, but they all showed similar inhibition in the proliferation assay.


Estrogen-induced alterations of hematoside of rat small intestinal mucosa.
Prior studies have suggested that sex hormones could influence the ganglioside and/or neutral glycosphingolipid composition of various organs. To date, the effects of sex hormones on the glycosphingolipid composition of the rat small intestinal mucosa, however, have not been examined. In the present studies, male albino rats of the Sherman strain were subcutaneously administered the synthetic estrogen, ethinylestradiol (5 mg/kg body wt. per day), or diluent for 5 days, and the ganglioside, neutral glycosphingolipid and ceramide composition of the small intestinal mucosa of these animals were analyzed and compared. The results of these experiments demonstrate that estrogen administration: increased the ganglioside concentration of this tissue, including hematoside (Gm3); increased the percentage of the long-chain base phytosphingosine of hematoside; and did not appear to significantly influence the concentration or composition of the neutral glycosphingolipids or ceramide in this tissue. These data, therefore, indicate that estrogen administration induces quantitative and qualitative alterations in the gangliosides but not in the neutral glycosphingolipids or ceramide of rat small intestinal mucosa.


Studies on acute and chronic toxicity of cadmium to freshwater snail Lymnaea acuminata (Lamarck) with special reference to behavioral and hematological changes.
Molluscs have long been regarded as promising bioindicator and biomonitoring subjects for heavy metals as molluscs are highly tolerant to heavy metals and exhibit high accumulation in their body. In spite of several previous studies about the impact of cadmium on molluscs, little information exists in literatures concerning the toxic effects of cadmium on Lymnaea acuminata, especially pertaining to behavioral and hematological changes as these are considered effective bioindicators and biomonitoring variables for detecting heavy metals in polluted water bodies. In the present study, the median lethal concentrations of cadmium chloride to snail, Lymnaea acuminata, were estimated to be 9.66, 7.69, 6.26, and 5.54 mg/L at 24, 48, 72, and 96 h, respectively. For behavioral studies, variable test concentrations of cadmium from 0.00 to 10 mg/L were used. The clumping tendency, crawling activity, and touch reflex in the exposed snails were gradually decreased with higher concentrations at 72 and 96 h. For measuring the hemocyte numbers in the circulating hemolymph of snail during chronic cadmium exposure, two sublethal doses of cadmium (10 and 20% 96-h LC50-0.55 and 1.11 mg/L, respectively) were used. A significant variation (p < 0.05) from the control at all exposure times (7, 14, 21, and 28 days) was recorded at 1.11 mg/L concentration. The total count of circulating hemocytes was significantly reduced (p < 0.05) compared to the controls at both concentrations of cadmium exposure at all time periods except 14 and 21 days exposure at 0.55 mg/L where values were non-significantly increased. In comparison between two sublethal doses, blood cells were significantly (p < 0.05) lowered at 1.11 mg/L cadmium treatment. Considering the behavioral and hematological data, it seems possible to forecast the physiological state of snails in cadmium-contaminated water bodies and these findings can be used in determining the safe disposal level of cadmium in aquatic ecosystem.


The DREAM Dataset: Supporting a data-driven study of autism spectrum disorder and robot enhanced therapy.
We present a dataset of behavioral data recorded from 61 children diagnosed with Autism Spectrum Disorder (ASD). The data was collected during a large-scale evaluation of Robot Enhanced Therapy (RET). The dataset covers over 3000 therapy sessions and more than 300 hours of therapy. Half of the children interacted with the social robot NAO supervised by a therapist. The other half, constituting a control group, interacted directly with a therapist. Both groups followed the Applied Behavior Analysis (ABA) protocol. Each session was recorded with three RGB cameras and two RGBD (Kinect) cameras, providing detailed information of children's behavior during therapy. This public release of the dataset comprises body motion, head position and orientation, and eye gaze variables, all specified as 3D data in a joint frame of reference. In addition, metadata including participant age, gender, and autism diagnosis (ADOS) variables are included. We release this data with the hope of supporting further data-driven studies towards improved therapy methods as well as a better understanding of ASD in general.


Modeling an active conformation for linear peptides and design of a competitive inhibitor for HMG-CoA reductase.
This study presents an approach that can be used to search for lead peptide candidates, including unconstrained structures in a recognized sequence. This approach was performed using the design of a competitive inhibitor for 3-hydroxy-3-methylglutaryl CoA reductase (HMGR). In a previous design for constrained peptides, a head-to-tail cyclic structure of peptide was used as a model of linear analog in searches for lead peptides with a structure close to an active conformation. Analysis of the conformational space occupied by the peptides suggests that an analogical approach can be applied for finding a lead peptide with an unconstrained structure in a recognized sequence via modeling a cycle using fixed residues of the peptide backbone. Using the space obtained by an analysis of the bioactive conformations of statins, eight cyclic peptides were selected for a peptide library based on the YVAE sequence as a recognized motif. For each cycle, the four models were assessed according to the design criterion ("V" parameter) applied for constrained peptides. Three cyclic peptides (FGYVAE, FPYVAE, and FFYVAE) were selected as lead cycles from the library. The linear FGYVAE peptide (IC(50) = 0.4 microM) showed a 1200-fold increase the inhibitory activity compared to the first isolated LPYP peptide (IC(50) = 484 microM) from soybean. Experimental analysis of the modeled peptide structures confirms the appropriateness of the proposed approach for the modeling of active conformations of peptides.


Mesobuthus gibbosus (Scorpiones: Buthidae) on the island of Rhodes -- hybridization between Ulysses' stowaways and native scorpions?
Allozyme data suggest that the Rhodes population of Mesobuthus gibbosus is a hybrid population of recent origin. Namely, it is a mixture between an autochthonous population and an artificially introduced population probably from the Greek mainland. All samples were mainly composed of F1 hybrid genotypes and genotypes either fixed for autochthonous or introduced alleles. Back-cross hybrid genotypes were very rare. Mitochondrial DNA analysis, in contrast, revealed only one group of closely related haplotypes that are unique for the Rhodes populations, thus suggesting asymmetric introgression of the two marker classes.


Studying Plant Stress Reactions In Vivo by PAM Chlorophyll Fluorescence Imaging.
Plant photosynthetic and mitochondrial electron transfer chains (ETCs) are delicate environmental sensors and active players in stress acclimation. The performance of photosynthetic ETC can be deduced from chlorophyll a fluorescence. This makes chlorophyll fluorescence imaging a powerful tool to study plant stress in vivo. Many stress treatments enhance production of reactive oxygen species (ROS) by photosynthetic or mitochondrial ETCs. These ROS affect cellular metabolism and signalling. Generation of ROS can be manipulated in planta by specific pharmacological treatments with methyl viologen (MV), antimycin A (AA), myxothiazol (myx), and salicylhydroxamic acid (SHAM). This chapter describes how chlorophyll fluorescence imaging together with pharmacological treatments can be employed to probe ROS-dependent plant stress reactions in vivo.


Life-threatening Hypercalcemia as the First Manifestation of Acute Lymphoblastic Leukemia.
Hypercalcemia of malignancy, usually reported in adults in advanced stages, is rare in children. A 4-year-old boy presented with intermittent episodes of severe hypercalcemia, which improved with intravenous hydration therapy, furosemide and bisphosphonates as the initial manifestation of occult acute lymphoblastic leukemia. Pediatricians should rule out hematological malignancy in patients with severe hypercalcemia.


Characterization of adverse drug events identified by trigger in Brazilian pediatric inpatients.
To describe the frequency and characteristics of adverse drug events in pediatric inpatients in a Brazilian tertiary teaching hospital. A cross-sectional study was conducted by retrospective and manual chart review of 240 pediatric admissions to identify adverse drug events using 17 triggers. When triggers were detected in the chart, reviewers investigated the chart in depth to decide whether an event occurred. Consensus about the occurrence of the event was obtained in meeting with a healthcare team. Events were classified by harm category and drugs were classified according to the Anatomical Therapeutic Chemical Classification. Patients who had suffered were compared to those who had not experienced events using the chi-squared test and the Mann-Whitney U test. A total of 62 adverse events were found, and 18.8% of the patients had at least one event. Adverse events rates were 25.83 per 100 admissions, 20.27 per 1000 patient-days, 25.94 per 1000 drugs, and 2.12 per 1000 drug doses. All events found were classified as temporary harm, and cardiovascular drugs were most frequently related to events. Groups of patients with and without event were segregated (p<0.05) by the length of stay, number of drugs, and drug doses. The use of triggers demonstrated its utility in a pediatric setting by identifying harm. Adverse events rates were found to be higher than those of previous studies, but the harm rate was lower than other studies. This study enables the measurement of adverse events in order to define strategies to mitigate or reduce harm.


Social work influence on interdisciplinary ethical decision making in health care settings.
Because of structural and philosophical changes in health care, social work practitioners are having to interact more with other practitioners in health care settings. Many of those interactions are interdisciplinary and often involve an understanding of the application of professional values and ethics. The authors have suggested that social workers' influence on ethical decision making is correlated directly to their ability to contribute to those decisions. In their study, the authors tested five independent variables and one dependent variable to show the factors that are related significantly to social workers' influence on ethical decision-making processes in multidisciplinary health care settings.


Extracephalic tenderness and pressure pain threshold in children with headache.
Sensitisation of the pain detection system has been suggested to be involved in the pathogenesis of recurrent headache. In adults, increased sensitivity to pain has been found in patients with chronic tension type headache. Children with migraine or with unspecific headache report non-headache pains and interictal pericranial muscular tenderness more often than headache-free children. To study if children with different types of headache report non-headache pain more often than children with no headache and if extracephalic muscular tenderness is different in children with headache in comparison to headache-free children. To find out if interval to the headache episode has influence on the extracranial muscular tenderness. A population-based sample of 13-year-old children with migraine (n=48), episodic tension type headache (61) or no headache (59) were interviewed for the occurrence and characteristics of headache and fulfilled a questionnaire on non-headache pain. A structured manual palpation test on muscular tenderness and a pain threshold measurement were done on seven cephalic and three extracephalic points. Children with migraine reported other pains, especially stomach pain and limb pain more often than children with episodic tension type or no headache. There were no significant differences in the extracephalic muscular tenderness or in the pressure pain thresholds between the three groups. Children with migraine experience more non-headache pains than children with episodic tension type headache and with no headache. However, neither children with migraine nor children with episodic tension type headache show increased interictal extracephalic muscular sensitivity for palpation.


Comparative efficacy of 24 exercise types on postural instability in adults with Parkinson's disease: a systematic review and network meta-analysis.
To compare, rank and evaluate the 24 exercise types that improve postural instability in patients with Parkinson's disease (PD). We searched the data in PubMed, MEDLINE, Embase, PsycINFO, Cochrane library, and Web of Science from their inception date to January 23, 2023. Randomized controlled trials (RCTs) that aimed at determining the effectiveness of physical activity interventions on postural instability in adults with PD. This review focused on different balance outcome categories: (a) balance test batteries (BBS); (b) static steady-state balance (sSSB); (c) dynamic steady-state balance (dSSB); (d) proactive balance (PB); (e) reactive balance (RB). Among 10,474 records, 199 studies (patients = 9523) were eligible for qualitative synthesis. The random-effects NMA model revealed that the following exercise training modalities had the highest p score of being best when compared with control group: body-weight support treadmill training (BWS_TT) for BBS (p score = 0.97; pooled standardised mean difference (95% CI): 1.56 (0.72 to 2.39)) and dSSB (1.00; 1.53 (1.07 to 2.00)), aquatic exercise (AQE) for sSSB (0.85; 0.94 (0.33 to 1.54)), Pilates for PB (0.95; 1.42 (0.59 to 2.26)). Balance and gait training with the external cue or attention (BGT_ECA) and robotic assisted gait balance (RA_GT) had similar superior effects in improving RB. The confidence in evidence was often low according to Confidence in Network Meta-Analysis. There is low quality evidence that BWS_TT, AQE, Pilates, BGT_ECA and RA_GT are possibly the most effective treatments, pending outcome of interest, for adults with PD.


Evaluation of performance of hearing aid users using Acoustic Change Complex (ACC) and behavioral measures.
To validate the clinical use of Acoustic Change Complex (ACC) as an objective tool in children who use hearing Aids and explore how far ACC response parameters could be correlated to behavioral tests. Sixty Arabic speaking children, using binaural Hearing Aids (H.As), participated in the present study. Their age ranged from 6 to 12 years. Evaluation of Hearing aid device performance was performed through questionnaire, speech in noise tests and aided/unaided ACC recordings. Two stimuli '' vowel/o/with SNR (0 &+8) ''were developed and standardized to elicit ACC response. The replicated ACC waveforms were collected and analyzed and the aided ACC responses were compared with unaided ACC and correlated to behavioral tests. The ACC percent identification in children using H.As using vowel/o/with SNR (+8 & 0) stimuli was 75% and 45% respectively in aided condition, the percent decreased to 40% and 15% in unaided condition. Speech in noise stimuli showed significant difference of ACC-N1 latency between the aided and unaided groups being longer in the unaided condition. The correlations between behavioral tests and ACC response (latency and amplitude) were irrelevant. Hearing-impaired subjects can process speech stimulus at the level of the auditory cortex, and in a more effective manner when they used their H.As. ACC can be used as an objective measure for selective auditory attention ability using vowel-in-noise. However, it couldn't replace Behavioral measures.


Training in cardiac surgery using human cadavers: Effectiveness of "Silent Teachers".
Surgical skills acquisition in cardiac surgery requires consistent and hard practice. Furthermore, training using cadaver is advocated as a means of transferring learned skills to the operating room and recreate surgical situations for trainees to practice and hone their skills. We expose our experience in training for cardiac surgical procedures using human cadavers. From June 2013 to November 2016, we performed 302 cardiac surgical procedures on 50 human cadavers obtained according to the Ivorian laws in force. Cadavers were preserved in 10% formaldehyde and by cryopreservation. In open heart, cardiac surgical techniques were achieved via sternotomy (n = 24) or via "lid-anterolateral thoracotomy" (n = 2). Pericardotomy (n = 26) and/or pericardiectomy (n = 26) were systematic. Aortic and caval canulations and pulmonary artery control (n = 30) were performed. After cardiotomy and arterial incisions (n = 34), 18 atrial and ventricular septal defects repair, 1 Fontan operation, 1 arterial switch, 11 enlargement procedures of the whole right ventricular outlet and 15 acquired valve heart diseases corrections were performed. In closed-heart surgery, procedures were achieved via sternotomy (n = 7), posterolateral thoracotomy (n = 12), or Marfan retroxiphoid approach (n = 3). Pericardotomy (n = 7) or pericardiectomy (n = 7) were performed. Great vessels dissections and expositions (n = 21) were achieved to perform 4 pulmonary artery bandings, 12 patent ductus arteriosus closures, 3 Waldhausen procedures, 7 Brock Operations, and 2 Blalock-Taussig shunts. In both situations, 29 direct pulmonary arterial, auricular, and ventricular sutures were achieved. Surgical simulation in cadaver models offer an opportunity for trainees to practice their surgical skills before entering operating room.


Effects of different grains on bacterial diversity and enzyme activity associated with digestion of starch in the foal stomach.
Compared with the stomach of ruminant cattle, the stomach of horse is small and mainly for chemical digestion, but the microorganisms in the stomach play an important role in maintaining the homeostasis of the internal environment. Due to the complexity of the microbes in the stomach, little is known about the diversity and structure of bacteria in the equine stomach. Grains are the main energy source for plant-eating livestock and energy is derived through enzymatic hydrolysis of grains into glucose or their microbial fermentation into Volatile fatty acids (VFA). However, the mechanism through which these ingested grains are chemically digested as well as the effect of these grains on the stomach remains elusive. This study explored the effects of feeding different grains (corn, oats, and barley) on bacterial diversity, structure, and composition in the foal's stomach content. Furthermore, the effects of different grains on the vitality of starch digestion-related stomach enzymes were investigated. No significant differences were observed (P > 0.05) in the bacterial rarefaction curves of Operational Taxonomic Units (OTUs) and diversity of the stomach microbiota in all foals. This study also revealed the statistical differences for Firmicutes, Cyanobacteria, Actinobacteria, Fibrobacteres, Lactobacillaceae, Streptococcaceae, Unidentified_Clostridiales, Prevotellaceae, Lactobacillus, Streptococcus, Unidentified_Cyanobacteria, Unidentified_Clostridiales, Lactococcus, Sphingomonas, Lactobacillus_hayakitensis, Lactobacillus_equigenerosi, and Clostridium_perfringens. The linear discriminant analysis effect size analysis revealed 9 bacteria at each classification level. The functional analysis of species information by using FAPROTAX software was able to predict 35 functions, and the top 5 functions were chemoheterotrophy, fermentation, animal_parasites_or_symbionts, nitrate_reduction, and aerobic_chemoheterotrophy. The study also revealed statistical differences for pH, glucose concentration, β-amylase, maltase, and amylase. The different grains had no significant effect on the microbial diversity of the stomach content of the foal. However, the relative bacterial abundances differed significantly in response to different diets. Particularly, oats fed to the foals significantly increased the relative abundance of Firmicutes, Lactobacillaceae, Lactobacillus, and Lactobacillus_hayakitensis. The grain had no significant effect on the pH of the stomach content, glucose concentration, and enzyme viability in the foal.


Influence of Apolipoprotein E on the Lipid Profile and Postprandial Triglyceride Levels in Brazilian Postmenopausal Women With Artery Disease.
This study confirms the association of risk factors for coronary artery disease (CAD) and the apoE polymorphisms, specifically related to the APOE*4 allele, with coronary disease in postmenopausal women. Significantly altered values of the lipid profile were found in patients when compared with controls, independent of the presence of the APOE*4 allele. However, the controls showed higher high-density lipoprotein cholesterol (HDL-C) levels and reduced triglyceride (TG) levels, differing significantly from patients. In this case, the study of subgroups, considering the APOE*3/3 and APOE*3/4 genotypes, suggests that the APOE*4 allele is not implicated in the variations of the lipid profile of patients and determined an increase in the production levels of HDL-C and a reduction in TG highly benefiting the control group compared with APOE*3/3 genotype. The metabolic kinetics of TG, although with the same pattern between groups, and the presence of the APOE*4 allele are suggested to be associated with accelerated clearance compared with APOE*3 allele in non-CAD group.


Myocardial contractile dysfunction associated with increased 3-month and 1-year mortality in hospitalized patients with heart failure and preserved ejection fraction.
There is a clinical need for a contractility index that reflects myocardial contractile dysfunction even when ejection fraction (EF) is preserved. We used novel relative load-independent global and regional contractility indices to compare left ventricular (LV) contractile function in three groups: heart failure (HF) with preserved ejection fraction (HFPEF), HF with reduced ejection fraction (HFREF) and normal subjects. Also, we determined the associations of these parameters with 3-month and 1-year mortality in HFPEF patients. 199 HFPEF patients [median age (IQR): 75 (67-80) years] and 327 HFREF patients [69 (59-76) years] were recruited following hospitalization for HF; 22 normal control subjects [65 (54-71) years] were recruited for comparison. All patients underwent standard two-dimensional Doppler and tissue Doppler echocardiography to characterize LV dimension, structure, global and regional contractile function. The median (IQR) global LV contractility index, dσ*/dtmax was 4.30s(-1) (3.51-4.57s(-1)) in normal subjects but reduced in HFPEF [2.57 (2.08-3.64)] and HFREF patients [1.77 (1.34-2.30)]. Similarly, median (IQR) regional LV contractility index was 99% (88-104%) in normal subjects and reduced in HFPEF [81% (66-96%)] and HFREF [56% (41-71%)] patients. Multi-variable logistic regression analysis on HFPEF identified sc-mFS <76% as the most consistent predictor of both 3-month (OR=7.15, p<0.05) and 1-year (OR=2.57, p<0.05) mortality after adjusting for medical conditions and other echocardiographic measurements. Patients with HFPEF exhibited decreased LV global and regional contractility. This population-based study demonstrated that depressed regional contractility index was associated with higher 3-month and 1-year mortality in HFPEF patients.


Branchial-like cysts of the thyroid associated with solid cell nests.
Presented herein is the case of a 65-year-old man with a 20 year history of thyroid hypofunction. On sonography a cystic lesion 4 x 4 x 5 cm in largest diameter was found, replacing most of the right lobe of the thyroid gland. Microscopically, the lesion was composed of labyrinth-like cystic structures (LCS) lined by a few layers of benign-appearing squamous cells and filled by mucinous material. Adjacent to the cyst walls were discontinuous patches of a lymphoid tissue, composed of haloed centrocyte-like cells or germinal centers mostly depleted of germinal cells. Additionally, there were numerous squamous cell nests equivalent to solid cell nests (SCN), all of which were surrounded by a similar-looking lymphoid tissue. Rare SCN were thus cystically changed and contained a small amount of mucus. The SCN communicated with the LCS: the former represented the most distal outpouchings of the latter. The epithelial structures were surrounded by a loose collagenous adipocytic stroma with plump fibroblasts, which resembled the stroma often seen in lateral neck cysts associated with structures such as cartilage, accessory salivary gland tissues, cysts and accessory thyroid and thymus. Immunohistochemically, all lesional elements were negative for calcitonin and thyroglobulin. The results of the paper suggest that branchial cleft-like cyst have an origin in the ultimobranchial body.


RNA helicase MOV10 functions as a co-factor of HIV-1 Rev to facilitate Rev/RRE-dependent nuclear export of viral mRNAs.
Human immunodeficiency virus type 1 (HIV-1) exploits multiple host factors during its replication. The REV/RRE-dependent nuclear export of unspliced/partially spliced viral transcripts needs the assistance of host proteins. Recent studies have shown that MOV10 overexpression inhibited HIV-1 replication at various steps. However, the endogenous MOV10 was required in certain step(s) of HIV-1 replication. In this report, we found that MOV10 potently enhances the nuclear export of viral mRNAs and subsequently increases the expression of Gag protein and other late products through affecting the Rev/RRE axis. The co-immunoprecipitation analysis indicated that MOV10 interacts with Rev in an RNA-independent manner. The DEAG-box of MOV10 was required for the enhancement of Rev/RRE-dependent nuclear export and the DEAG-box mutant showed a dominant-negative activity. Our data propose that HIV-1 utilizes the anti-viral factor MOV10 to function as a co-factor of Rev and demonstrate the complicated effects of MOV10 on HIV-1 life cycle.


Comment on "On the regulation of populations of mammals, birds, fish, and insects" I.
Sibly et al. (Reports, 22 July 2005, p. 607) concluded that density dependence acts far below the carrying capacity in most animal populations. We argue that the authors confused discrete and continuous models, that their best-fit models cannot explain observed oscillations, and that their estimation procedures appear biased. They also neglected trophic and migratory processes, which we demonstrate could underlie their empirical findings.


A perinatal coparenting intervention: Effects of a randomized trial on parent cardiometabolic risk and self-reported health.
The transition to parenthood is a common yet stressful experience faced by many young and midlife adults, and the risk of cardiometabolic conditions also begins to rise at this time. Consequently, parenthood represents an opportune time to intervene with adults to support their psychological and physical health. We examined whether the benefits of the Family Foundations program, a perinatal preventative intervention promoting positive coparenting, extend beyond documented mental health and family relationship outcomes to better cardiometabolic risk factors among parents. We analyzed data from 183 couples (n = 366 participants) who, eight years prior, were randomly assigned to the 9-session perinatal preventative intervention program or a control condition. We collected dried blood spots to measure C-reactive protein (CRP), interleukin-6 (IL-6), and cholesterol; parents also reported on their self-rated health. Randomization to the intervention condition was associated with lower cholesterol (B=-.081, p = .049). Among parents who demonstrated more negative communication styles at pretest (during pregnancy), the intervention was further associated with better self-rated health (B=.181, p = .018). Participation in the intervention program was also marginally associated with lower CRP (B=-.261, p = .077), particularly among mothers (B=-.428, p = .076). These findings indicate that coparenting-focused interventions, such as Family Foundations, can lead to benefits beyond psychosocial and behavioral outcomes, and suggest that Family Foundations may improve parents' longer-term physical health, with potentially more benefits among couples who demonstrated more negative communication styles during pregnancy.


Isolation of a beta 2-glycoprotein from human serum after precipitation with dextran sulfate and manganese chloride.
A new procedure was developed which affords isolation from among the euglobulins of human serum a beta 2-glycoprotein with a high degree of immunological and electrophoretic homogeneity. The isolated protein displays specific binding affinity for the activated form of the C4 component (C4b), and was identified by immunological and physico-chemical criteria as the C4 binding protein. The isolation procedure comprises the following steps: precipitation of euglobulins from serum at pH 5.5 and low ionic strength; precipitation of beta-lipoproteins from the redissolved precipitate with dextran sulfate and CaCl2; precipitation of a fraction of the lipoprotein-free euglobulins with dextran sulfate and MnCl2; redissolution of the precipitate and eventually chromatography on Sepharose 4B. The overall yield was between 15 and 20 per cent. The final product, devoid of immunologically detectable protein contaminants, was a homogeneous proline-rich monomeric beta 2-glycoprotein made up of eight disulfide-bonded polypeptide chains of the same molecular weight 63,000 +/- 3,000. Under non-reducing conditions, the molecular weight of both the native and the SDS-treated protein was 490,000 +/- 25,000. A monospecific antiserum to the isolated protein was raised in rabbits and used for the quantitation of the protein in sera of normal fasting donors; a mean concentration of 25 mg per 100 ml of serum (1 SD: 5) was established.


Calcaneus radiograph as a diagnostic tool for sexual dimorphism in Egyptians.
Measurements of calcaneus have been shown to be sexually dimorphic in American whites and blacks, Italians and South African whites and blacks. Since the validity of discriminant function equation in sex determination is population specific, the aim of the present study was to derive similar equations for the calcanei of Egyptians. Lateral radiographs of the ankles of 204 Egyptians aged 20-70 were analyzed with regards to sexual dimorphism, consisting of 104 males and 100 females. X-ray films were obtained from Minia Forensic Department. Six measurements were taken for every calcaneal X-ray film, three linear and three angular measurements. Data were analyzed by SPSS version 17, An independent samples t-test and discriminant function analysis were done. All linear measurements, but not angular, showed significant sexual differences. Maximum length was found to be the most sexually dimorphic (90.2%). Combination of maximum length with minimum height gave the same result of all linear measurements (92.6%) which was more than given by individual variables (81.4-90.2%).


Synthetic vitamin K analogs inhibit inflammation by targeting the NLRP3 inflammasome.
Vitamin K refers to a group of structurally similar vitamins that are essential for proper blood coagulation, as well as bone and cardiovascular health. Previous studies have indicated that vitamin K may also have anti-inflammatory properties, although the underlying mechanisms of its anti-inflammatory effects remain unclear. The NLRP3 inflammasome is a multiprotein complex, and its activation leads to IL-1β and IL-18 secretion and contributes to the pathogenesis of various human inflammatory diseases. Here, we show that synthetic vitamins K3 and K4 are selective, potent inhibitors of the NLRP3 inflammasome and specifically block the interaction between NLRP3 and ASC, thereby inhibiting NLRP3 inflammasome assembly. Moreover, we show that treatment with vitamin K3 or K4 attenuates the severity of inflammation in a mouse model of peritonitis. Our results demonstrate that vitamins K3 and K4 exert their anti-inflammatory effects by inhibiting NLRP3 inflammasome activation and indicate that vitamin K supplementation may be a treatment option for NLRP3-associated inflammatory diseases.


Pre-Hospital Management of Critically Ill Patients with SARS-CoV-2 Infection: A Retrospective Multicenter Study.
The COVID-19 outbreak had a major impact on healthcare systems worldwide. Our study aims to describe the characteristics and therapeutic emergency mobile service (EMS) management of patients with vital distress due to COVID-19, their in-hospital care pathway and their in-hospital outcome. This retrospective and multicentric study was conducted in the six main centers of the French Greater East region, an area heavily impacted by the pandemic. All patients requiring EMS dispatch and who were admitted straight to the intensive care unit (ICU) were included. Clinical data from their pre-hospital and hospital management were retrieved. We included a total of 103 patients (78.6% male, median age 68). In the initial stage, patients were in a critical condition (median oxygen saturation was 72% (60-80%)). In the field, 77.7% (CI 95%: 71.8-88.3%) were intubated. Almost half of our population (45.6%, CI 95%: 37.1-56.9%) had clinical Phenotype 1 (silent hypoxemia), while the remaining half presented Phenotype 2 (acute respiratory failure). In the ICU, a great number had ARDS (77.7%, CI 95% 71.8-88.3% with a PaO2/FiO2 < 200). In-hospital mortality was 33% (CI 95%: 24.6-43.3%). The two phenotypes showed clinical and radiological differences (respiratory rate, OR = 0.98, p = 0.02; CT scan lesion extension >50%, OR = 0.76, p < 0.03). However, no difference was found in terms of overall in-hospital mortality (OR = 1.07, p = 0.74). The clinical phenotypes appear to be very distinguishable in the pre-hospital field, yet no difference was found in terms of mortality. This leads us to recommend an identical management in the initial phase, despite the two distinct presentations.


Changes in Neuroendovascular Procedural Volume During the COVID-19 Pandemic: An International Multicenter Study.
The effect of coronavirus disease 2019 (COVID-19) pandemic on performance of neuroendovascular procedures has not been quantified. We performed an audit of performance of neuroendovascular procedures at 18 institutions (seven countries) for two periods; January-April 2019 and 2020, to identify changes in various core procedures. We divided the region where the hospital was located based on the median value of total number of COVID-19 cases per 100,00 population-into high and low prevalent regions. Between 2019 and 2020, there was a reduction in number of cerebral angiograms (30.9% reduction), mechanical thrombectomy (8% reduction), carotid artery stent placement for symptomatic (22.7% reduction) and asymptomatic (43.4% reduction) stenoses, intracranial angioplasty and/or stent placement (45% reduction), and endovascular treatment of unruptured intracranial aneurysms (44.6% reduction) and ruptured (22.9% reduction) and unruptured brain arteriovenous malformations (66.4% reduction). There was an increase in the treatment of ruptured intracranial aneurysms (10% increase) and other neuroendovascular procedures (34.9% increase). There was no relationship between procedural volume change and intuitional location in high or low COVID-19 prevalent regions. The procedural volume reduction was mainly observed in March-April 2020. We provided an international multicenter view of changes in neuroendovascular practices to better understand the gaps in provision of care and identify individual procedures, which are susceptible to change.


Theoretical Modeling on the Reaction Mechanism of p-Nitrophenylmethylphosphate Alkaline Hydrolysis and its Kinetic Isotope Effects.
We have studied the alkaline hydrolysis of p-nitrophenylmethylphosphate (p-NPmP) in aqueous solution by means of polarizable continuum models and by hybrid quantum-mechanical/molecular-mechanical (QM/MM) methods. The theoretical predictions of kinetic isotope effects (KIEs) are in very good agreement with the experimental data, confirming a concerted asynchronous molecular mechanism. In addition, comparison of high level DFT theory with semiempirical AM1/d Hamiltonian has allowed checking the reliability of the later to be used in modeling very large molecular models containing phosphorus atoms.


Intravitreal triamcinolone acetonide for diabetic macular edema.
Intravitreal injection of triamcinolone acetonide has been advocated to treat exudative diabetic macular edema. The purpose of the study was to evaluate the clinical outcome of an intravitreal injection of triamcinolone acetonide as treatment for diffuse diabetic macular edema. This study was a retrospective, interventional, clinical case series examining 210 eyes of 174 patients who received an intravitreal injection of 1 or 4 mg of triamcinolone acetonide for treatment of diffuse diabetic macular edema. Inclusion criteria were clinically significant macular edema, visual acuity loss, and leakage shown by fluorescein angiography. Main outcome measures were visual acuity and intraocular pressure. Mean follow-up time +/- SD was 6.6 +/- 3.1 months. In the study group, visual acuity improved significantly (P < 0.001) from a median of 20/200 (mean logMAR, 0.92) at baseline to 20/80 (mean logMAR, 0.82) at 6 months. Mean intraocular pressure +/- SD increased from 15.4 +/- 3.4 mmHg (median, 16 mmHg; range, 6-26 mmHg) to a maximal value of 20.4 +/- 6.2 mmHg (median, 19 mmHg; range, 12-51 mmHg) during the follow-up period. Complications included culture-negative sterile endophthalmitis in six cases and cataract extraction in five eyes. Intravitreal injection of 1 to 4 mg of triamcinolone acetonide may benefit patients by improving visual acuity in eyes with clinically significant diabetic macular edema. This study did not provide significant evidence to justify its routine use in clinical practice for all patients with diabetic macular edema. A randomized clinical trial on this issue would provide more conclusive evidence and help identify those patients most likely to benefit from intravitreal triamcinolone acetonide.


Glial proteins in canine distemper virus-induced demyelination. A sequential immunocytochemical study.
A temporal series of demyelinating lesions in experimental canine distemper virus (CDV) infection was examined with immunohistological techniques demonstrating myelin basic protein (MBP), myelin-associated glycoprotein (MAG), and glial fibrillary acidic protein (GFAP) on serial sections. The earliest lesions were characterized by decreased MBP and MAG and increased GFAP. During the further progression of the disease, MBP and MAG losses continued to match each other. There was no indication of MAG loss preceding the disappearance of MBP. In the more advanced lesions there was a marked decrease of GFAP positive cells. Since these findings differed considerably from similar immunohistochemical studies in progressive multifocal leukoencephalopathy (PML) where demyelination results from oligodendroglial infection, it was concluded that the oligodendroglial cell body is not the primary target of CDV. The marked astroglial changes were also considered to contribute to demyelination in CDV infection but the mechanism by which this happens remains unknown.


Cadaveric Classification of the Genicular Arteries, with Implications for the Interventional Radiologist.
To document and assess the genicular arterial variation in a large multicenter cadaveric sample and to generate an anatomical classification with implications for genicular artery embolization (GAE). A total of 212 dissected donor body lower limbs from 3 medical school institutions were included. The descending genicular artery (DGA), superior lateral genicular artery, superior medial genicular artery, middle genicular artery, inferior lateral genicular artery, inferior medial genicular artery, and anterior tibial recurrent artery were identified for gross anatomical appearance, location of origin, diameter of vessels, and variation in branching patterns. A total of 198 DGAs, 204 popliteal-origin genicular arteries, and 183 anterior tibial recurrent arteries were adequately preserved and reviewed. Three types (A: 26%, B: 71%, and C: 5%) of DGA branching patterns were proposed along with 6 types (I: 28%, II: 22%, III: 15%, IV: 15%, V: 10%, and VI: 6%) of popliteal-origin genicular artery branching variants. Right versus left comparisons did not reveal clinically significant differences in the vessel distance (P = .30 to .82). Despite the large number of possible anatomical variations of the genicular arteries, 6 main patterns corresponded to >96% of the cases. The description and classification of the genicular arterial anatomy may provide useful information to the interventional radiologist and add to the technical nuances of GAE.


Pervasive changes of mRNA splicing in upf1-deficient zebrafish identify rpl10a as a regulator of T cell development.
The transcriptome of eukaryotic cells is constantly monitored for errors to avoid the production of undesired protein variants. The evolutionarily conserved nonsense-mediated mRNA decay (NMD) pathway degrades aberrant mRNAs, but also functions in the regulation of transcript abundance in response to changed physiological states. Here, we describe a zebrafish mutant of upf1, encoding the central component of the NMD machinery. Fish homozygous for the upf1t20450 allele (Y163X) survive until day 10 after fertilization, presenting with impaired T cell development as one of the most conspicuous features of the mutant phenotype. Analysis of differentially expressed genes identified dysregulation of the pre-mRNA splicing pathway, accompanied by perturbed autoregulation of canonical splicing activators (SRSF) and repressors (HNRNP). In upf1-deficient mutants, NMD-susceptible transcripts of ribosomal proteins that are known for their role as noncanonical splicing regulators were greatly increased, most notably, rpl10a When the levels of NMD-susceptible rpl10a transcripts were artificially increased in zebrafish larvae, T cell development was significantly impaired, suggesting that perturbed autoregulation of rpl10a splicing contributes to failing T cell development in upf1 deficiency. Our results identify an extraribosomal tissue-specific function to rpl10a in the immune system, and thus exemplify the advantages of the zebrafish model to study the effects of upf1-deficiency in the context of a vertebrate organism.


Preservation of bowel and urinary continence in the management of locally recurrent rectal cancer.
The management of locally recurrent rectal cancer should achieve local tumor control and potentially improving disease-free and overall survival. Radical pelvic resection has traditionally been associated with permanent fecal and urinary diversion. However, as advanced techniques have evolved to allow restoration of intestinal and urinary continence, we reviewed the use of these techniques in patients with recurrent rectal cancer. Patients with recurrent rectal cancer who underwent a resection at Norris Comprehensive Cancer Center between 1993 and 1999 were retrospectively reviewed. Data collected included demographic data, surgical and oncological history, patterns of recurrence, treatment modalities, and outcome. Follow-up data was obtained from the last clinic visit and/or tumor registry. Sixty-seven patients with locally recurrent rectal cancer (male/female 45/22, age 32-81 years) were included in the analysis. Continence was re-established in 22 (33%) patients, urinary continence was restored in 12 patients, and intestinal continuity in 14 patients (both in 4 patients). A temporary diverting ostomy was necessary in 5 out of 14 (36%) patients. Mortality was zero and morbidity was low and included two urinary leaks and one fecal leak all of which could be managed non-operatively. At a median follow-up of 16 months (range 5-55), 11 (50%) patients were still alive, 7 (31%) without evidence of disease. Comparison of the groups of patients either with or without continence preservation showed no statistically significant difference in disease-free survival and overall survival rates. High quality of life was achieved with restoration of continuity, no patient with restored continuity expressed a desire for a diversion. If an oncologically adequate resection of the recurrent rectal cancer can be performed without impairment of the pelvic floor integrity, continence preservation is feasible and results in good functional and oncological outcome.


Comparison of venous couplers versus hand-sewn technique in 4577 cases of DIEP-flap breast reconstructions - A multicenter study.
Venous anastomosis remains to be a challenging step in microsurgical tissue transfer and venous complications constitute to a common reason for free flap failure. While several studies have compared mechanical vs. hand-sewn venous anastomoses, there is no large-series study comparing the type of anastomosis exclusively in DIEP flap breast reconstructions. Between 2011 and 2019, 3926 female patients underwent 4577 free DIEP-flap breast reconstructions in 22 different breast cancer centers. Patient data was collected via an online database, files were screened and cases were divided into a hand- (HA) and a coupler-anastomosis (CA) group. Complications were accounted for and the two groups were then compared. Mean ischemia time was significantly shorter in the CA group (46.88 ± 26.17 vs. 55.48 ± 24.70 min; p < .001), whereas mean operative time was comparable (316 ± 134.01 vs. 320.77 ± 120.29 minutes; p = .294). We found no significant difference between both groups regarding the rate of partial (CA: 1.0% vs. HA: 1.3%) and total flap loss (CA: 2.2% vs. HA: 1.8%). However, revision rates were significantly higher in the CA group (CA: 10.5% vs. HA: 7.9%; p = .003), with higher numbers of arterial (2.3 vs. 0.9%; p < .001) and venous thromboses (3.4 vs. 1.8%; p = .001) accounting for this finding. All taken into account, our findings do support the feasibility of venous coupler anastomoses in principle, however the inflationary use of coupler devices should be evaluated critically.


[The Contractile Function of the Surviving Heart Muscle Following Coronary Occlusion (author's transl)].
Following acute myocardial infarction the functional load of the surviving heart muscle does increase considerably, leading to an increased release of adrenergic neurotransmitters with a consequent decrease in endogenous catecholamine stores. Within the first 24 h following infarction, a temporary decline in the high-energy phosphate content is observed in the surviving heart muscle; futhermore, a reduction in lactate extraction is noted. In the intact organism an increased shortening of the surviving heart muscle is noted as a consequence of the altered ventricular geometry and the increased release of catecholamines. If these effects are excluded by means of isolation and analysis in vitro, a decrease in contractile function could be demonstrated in the surviving heart muscle in the early phase following infarction; the response to positive inotropic interventions was depressed as well. These changes are reversible; six weeks following infarction a normal contractile behaviour is observed.


[Interactions of certain sapronotic infection pathogens in mixed cultures on a solid medium at different temperatures].
Under experimental conditions within the time limit of 21-35 days the causative agents of sapronotic infections in binary cultures, grown on a solid medium at 37 degrees C, 25-27 degrees C and 6-8 degrees C, interacted with one another transbiotically and through contact, their interactions having the character of amensalism, commensalisms-amensalism, competitive equilibrium, antibiosis. Irrespective of the initial density, a change in the species composition was observed, one of them playing the dominating role. At 37 degrees C mutual antagonism of Yersinia pseudotuberculosis and Pseudomonas aeruginosa killed both cultures. P. aeruginosa cells were also killed when cultivated at 37 degrees C jointly with Listeria monocytogenes, the most resistant species under experimental conditions. While studying the character of microorganisms interactions the method of contacting cultures on a solid medium was shown to give more information in comparison with the "cross-strip" method. Possible interspecific relationships between the causative agents of sapronotic infections under natural conditions are discussed.


Predictors of clinical and surgical characteristics of giant stones of the urinary bladder: a retrospective study.
Giant stones of the urinary bladder (GSBs) are rare and usually presented as case reports. We aimed to assess the clinical and surgical characteristics of GSBs and identify their predictors. A retrospective study of 74 patients with GSBs who presented between July, 2005 and June, 2020 was performed. Patients' demographics, clinical presentations, and surgical peculiarities were studied. Older age and male gender were risk factors for the occurrence of GSBs. The irritative lower urinary tract symptoms (iLUTS) were the main presenting symptoms (97.3%). Most patients were treated with cystolithotomy (90.1%). Univariate analyses showed that solitary (p < 0.001) and rough surface (P = 0.009) stones were significant factors for occurrence of iLUTS as the presenting symptoms. Also, the severity of symptoms (p = 0.021), rough surface (p = 0.010) and size (p < 0.001) of stones, and farmer occupation (p = 0.009) were significantly associated with adherence of the stone to the bladder mucosa at surgery. In multivariate analysis, the rough surface (p = 0.014) and solitary (p = 0.006) stones, and concomitant ureteral stones (p = 0.020) were independently associated with iLUTS as the main presentation. However, the stone size and severity of iLUTS were the independently associated factors for adherence of GSBs to the bladder mucosa. Solitary GSB, rough surface and the association with ureteral stones are independent risk factors for the occurrence of long-standing iLUTS. The stone size and severity of iLUTS were the independent predictors of adherence of GSBs to the bladder mucosa. Cystolithotomy is the main treatment, but it may be more difficult when there is bladder mucosa adherence.


Major craniomaxillofacial reconstruction aided by microsurgical tissue transfer.
The application of microsurgical tissue transplantation in craniomaxillofacial deformities is presented by regional anatomic examples and discussion.


Enquiries to the New Zealand National Poisons Centre in 2018.
A retrospective analysis of enquiries made to the New Zealand National Poisons Centre (NZNPC) in 2018; which includes direct contacts through telephone of caller, patient and exposure substance characteristics, and indirect contacts through the internet of page hits by New Zealand (NZ) healthcare professionals on the TOXINZ poisons information database. All calls made to the NZNPC, and TOXINZ page hits by NZ based healthcare professionals, from 1 January to 31 December 2018 were analysed. For calls, caller location and relationship to the patient, reason and site for the exposure, patient demographics and the management advice given by NZNPC were described. Substance classes and most frequently encountered individual agents were described for both call data and web page hits to TOXINZ. There were 25 330 calls to the NZNPC and 39 028 TOXINZ web page hits in 2018. Most callers were members of the public (79.4%), calling from residential settings (77.2%), reporting an exposure which had occurred in a residential setting (88.2%) because of child exploratory behaviour (50.3%), and which involved a person aged 0-4 years (50.3%) who could be managed at home (74.3%). TOXINZ searches mostly involved therapeutics, especially paracetamol. In 2018, the NZNPC provided assessment and/or advice in 64 358 enquiries, comprising 25 330 direct contacts and 39 028 indirect contacts. The NZNPC provides specialised services regularly used by both members of the public and healthcare professionals that contributes to the clinical management of poisoned and potentially poisoned patients in NZ.


Breaking Rotational Symmetry in Supertwisted WS2 Spirals via Moiré Magnification of Intrinsic Heterostrain.
Twisted stacking of van der Waals materials with moiré superlattices offers a new way to tailor their physical properties via engineering of the crystal symmetry. Unlike well-studied twisted bilayers, little is known about the overall symmetry and symmetry-driven physical properties of continuously supertwisted multilayer structures. Here, using polarization-resolved second harmonic generation (SHG) microscopy, we report threefold (C3) rotational symmetry breaking in supertwisted WS2 spirals grown on non-Euclidean surfaces, contrasting the intact symmetry of individual monolayers. This symmetry breaking is attributed to a geometrical magnifying effect in which small relative strain between adjacent twisted layers (heterostrain), verified by Raman spectroscopy and multiphysics simulations, generates significant distortion in the moiré pattern. Density-functional theory calculations can explain the C3 symmetry breaking and unusual SHG response by the interlayer wave function coupling. These findings thus pave the way for further developments in the so-called "3D twistronics".


Creativity, unique designs, and schizotypy in a nonclinical sample.
The present study examined whether creativity and novel design construction differ in 60 individuals who scored low and high (based on a median split) on a measure of schizotypy. Groups differed on one measure, total designs made, but not on creativity.


Quality Control of Personalized Drug Products - Identity and Quantity of Monoclonal Antibodies as Active Pharmaceutical Ingredient.
Deliberate underdosing occurred in personalized preparations of drugs such as monoclonal antibodies as the active pharmaceutical ingredient in the past. To ensure the required quality standard and to prevent future fraud attempts at an early stage, a HPLC-DAD-HRMS method was established. Thereby, identity and quantity of the active ingredients bevacizumab, rituximab and trastuzumab were determined. The analysis of ten samples from seven pharmacies fulfilled the quality criteria and were therefore not objectionable.


Diffusion-weighted MRI and ADC versus FET-PET and GdT1w-MRI for gross tumor volume (GTV) delineation in re-irradiation of recurrent glioblastoma.
GTV definition for re-irradiation treatment planning in recurrent glioblastoma (rGBM) is usually based on contrast-enhanced MRI (GdT1w-MRI) and, for an increased specificity, on amino acid PET. Diffusion-weighted (DWI) MRI and ADC maps can reveal regions of high cellularity as surrogate for active tumor. The objective of this study was to compare the localization and quality of diffusion restriction foci (GTV-ADClow) with FET-PET (GTV-PET) and GdT1w-MRI (GTV-GdT1w-MRI). We prospectively evaluated 41 patients, who received a fractionated stereotactic re-irradiation for rGBM. GTV-PET was generated automatically (tumor-to-background ratio 1.7-1.8) and manually customized. GTV-ADClow was manually defined based on DWI data (3D diffusion gradients, b = 0, 1000 s/mm2) and parametric ADC maps. The localization of recurrence was correlated with initial GdT1w-MRI and PET data. In 30/41 patients, DWI-MRI showed areas with restricted diffusion (mean ADC-value 0.74 ± 0.22 mm2/s). 66% of GTVs-ADClow were located outside the GdT1w-MRI volume and 76% outside increased FET uptake regions. Furthermore, GTVs-ADClow were only partially included in the high dose volume and received in mean 82% of the reference dose. An adjusted volume including GdT1w-MRI, PET-positive and restricted diffusion areas would imply a GTV increase of 48%. GTV-PET and GdT1w-MRI correlated better with the localization of re-recurrence in comparison to GTV-ADClow. Unexpectedly, GTV-ADClow overlapped only partially with FET-PET and GdT1w-MRI in rGBM. Moreover, GTV-ADClow correlated poorly with later rGBM-recurrences. Seeing as a restricted diffusion is known to correlate with hypercellularity, this imaging discrepancy could only be further explained in histopathological studies.


Oral cancer and mouthwash use: evaluation of the epidemiologic evidence.
An association between mouthwash use and cancer of the oropharynx has been the focus of many epidemiologic studies. To critically review the methodology of studies of this association. Studies were identified through a computerized MEDLINE search of English-language publications from 1976 to 1994. Eligible studies were independently reviewed, and specific criteria were applied to assess issues in the design, analysis, and results of the studies. Methodologic criteria were used that define a case-control study of acceptable epidemiologic quality: (1) histologic confirmation of cancer; (2) use of incident cases; (3) population-based cases; (4) equal exclusions of controls; (5) population-based controls; (6) exposure to mouthwash use before the cancer diagnosis; and (7) adjustments or restrictions for tobacco, alcohol, or both. Seven case-control studies were identified. The odds ratios for these studies ranged from a protective effect (0.82 for any use of mouthwash) to an elevation in risk (2.5 at the highest exposure). Two studies had significant unadjusted odds ratios for the risk of oral cancer. Of the three studies with data on women adjusted for tobacco and alcohol use, one was statistically significant, and none of the three similar studies in men was significant (although one was close). The five studies with data on female nonsmokers, nondrinkers, or both had odds ratios ranging from 1.1 to 3.16 (only one study was significant at the p = 0.05 level), and the four studies with similar data on men were not significant. Two studies met only two of the methodologic criteria, three studies met three, one met four, and one met all seven. Few of the available studies on mouthwash use and risk of subsequent oropharynx cancer adhere to basic methodologic principles of case-control design. Neither the data for the overall association nor the analysis in patients without other clinical risk factors support a link between mouthwash use and oral cancer.


HAROW: the first comprehensive prospective observational study comparing treatment options in localized prostate cancer.
To collect data on primary treatment decision and follow-up in patients with diagnosed, histologically confirmed localized (T1a-T2c/N0/M0) prostate cancer (PCa) for up to 5 years in a prospective observational non-interventional study. Patients were non-randomly allocated to one of the five treatment strategies: hormone therapy, active surveillance, radiation, operation, or watchful waiting. A total of 3169 patients were included by 259 participating sites; 2957 patients had at least one follow-up visit. 54.8 % of tumors at baseline were staged as T1c, 38 % as T2a-T2c, and 7.1 % as T1a or T1b (missing: 0.2 %). 38.9, 32.6 and 26.6 % of patients were classified as low risk, intermediate risk, and high risk according to d'Amico, respectively (missing: 1.8 %). 56.6 % of patients underwent prostatectomy as primary therapy, 16.4 % received radiation, 6.9 % HT, 15.8 and 4.3 % decided for AS or WW. Mean follow-up was 28.4 months. Progression rates were between 8.6 % (RT) and 33.1 % (AS). Whereas RP remains the main treatment option of localized PCa, active surveillance appears to become an accepted and selectively employed treatment option. Careful selection of patients is documented by the highest proportion of patients with low risk (82.5 %), PSA density <0.2 ng/ml/ml (77.5 %), T1 staging (83.6 %), Gleason score ≤6 (92.5 %), ≤2 positive biopsies (79.4 %), and lowest mean PSA (5.8 ng/ml) in the AS group. The relatively high progression rate in the AS group has to be considered in the context of treatment changes; 71/155 patients had a documented change of treatment and 62 of them with a follow-up period of >3 months.


A putative role for TIP and PIP aquaporins in dynamics of leaf hydraulic and stomatal conductances in grapevine under water stress and re-watering.
We examined the role of aquaporins (AQPs) in regulating leaf hydraulic conductance (Kleaf ) in Vitis vinifera L. (cv Chardonnay) by studying effects of AQP inhibitors, and AQP gene expression during water stress (WS) and recovery (REC). Kleaf was measured after 3 h of petiole perfusion with different solutions and to introduce inhibitors. The addition of 0.1 mm HgCl2 to 15 mm KCl reduced Kleaf compared with perfusion in 15 mM KNO3 or KCl, and these solutions were used for leaves from control, WS and REC plants. Perfusion for 3 h did not significantly alter stomatal conductance (gs ) though expression of VvTIP1;1 was increased. WS decreased Kleaf by about 30% and was correlated with gs . The expression of VvTIP2;1 and VvPIP2;1 correlated with Kleaf , and VvTIP2;1 was highly correlated with gs . There was no association between the expression of particular AQPs during WS and REC and inhibition of Kleaf by HgCl2 ; however, HgCl2 treatment itself increased expression of VvPIP2;3 and decreased expression of VvPIP2;1. Inhibition by HgCl2 of Kleaf only at early stages of WS and then after REC suggested that apoplasmic pathways become more important during WS. This was confirmed using fluorescent dyes confined to apoplasm or preferentially accumulated in symplasm.


Power in college students' contraceptive decisions.
Excluding Hollerbach (1980), previous fertility researchers have paid little attention to contraceptive power bases, relationships that become the source of changes in birth control values and behavior. Eight contraceptive power bases, each evaluated as a direct or obvious strategy, were identified in a pilot study involving 25 college students as participants and 10 undergraduate raters. Two-hundred college students completed a questionnaire which included the Bem Sex Role Inventory, inquired into their sexual and contraceptive behavior, and asked about contraceptive power bases. There were highly significant main effects for both students' personal experiences with contraceptive power bases and for their opinions about the comfort and effectiveness of same. Coercion was the most popular and legitimate power was the least popular power base. Women were more likely than men to be the targets of contraceptive power bases, the majority of which were stereotyped as feminine by women in particular. Sex role identification was unrelated to students' experiences with contraceptive power bases. The implications of these findings for family-planning researchers and practioners are addressed.


Alterations of the basal serum insulin and blood glucose in brain-injured patients.
Serial fasting blood glucose and basal serum insulin were measured in brain-injured patients. The endocrine changes were compared with the level of consciousness. Evaluating the serial examinations of 92 brain-injured and 31 control patients we came to the following conclusions. There is a quantitative correlation between the alterations in the level of consciousness and the fasting blood-glucose and serum-insulin levels in brain-injured patients. Deep coma is connected with a high blood-sugar level, clear consciousness with a normal glucose level. The insulin level is, however, decreased in the comatose state and normal in the state of clear consciousness. According to the alterations in blood-glucose and insulin levels, brain-injured patients can be divided into four groups. The alterations in the insulin level cannot give a proper explanation of the blood-sugar changes. Some changes in the levels of both blood glucose and serum insulin may have prognostic significance. According to our results it can be supposed that certain cerebral structures take part in the regulation of the basal insulin secretion.


Safety and outcome of early enteral nutrition in patients receiving extracorporeal membrane oxygenation.
To explore the benefits and risks of early enteral nutrition (EN) in patients receiving extracorporeal membrane oxygenation (ECMO). A single center retrospective review was performed including patients receiving ECMO for more than 24 h from May 2014 to July 2021. A total of sixty-five patients were enrolled, of which thirty-six patients (55.4%) received early EN. On ECMO day 3rd, 7th and 14th, the median energy intake through EN in the early EN group was 500 kcal (IQR:300, 880), 1000 kcal (IQR: 500, 1500) and 1000 kcal (500, 1500), representing 29.7%, 66.7% and 66.7% of energy target, respectively. Thirteen (36.1%) patients had EN intolerance in the early EN group, which is significantly lower than that in the delayed EN group (82.8%, P < 0.001). The most common reasons for EN intolerance were abdominal distention (22.2%), followed by elevated gastric residual volume (8.3%) in the early EN group. Forty-three (66.1%) patients successfully weaned off ECMO, with higher rate in the early EN group than in the delayed EN group (80.6% vs 48.3%, p = 0.006). Nineteen patients (52.8%) survived in the early EN group, which is also significantly higher than that in the delayed EN group (20.7%, P = 0.008). Patients receiving early enteral nutrition significantly reduced the mortality rate and the adjusted mortality hazard ratio was 0.22 (95%CI:0.10, 0.47). Early EN was safe and well-tolerated and can reduce the in-hospital mortality of patients receiving ECMO. For patients receiving ECMO, EN started with hypocaloric doses within 48 h of ECMO initiation is recommend.


Ultrasonic vocalizations are elicited from rat pups in the home cage by pentylenetetrazol and U50,488, but not naltrexone.
Although isolated rat pups emit ultrasonic vocalizations (USVs), those kept warm and undisturbed in the home cage with their littermates seldom do. Drugs were administered to 10-day-old pups in the home cage to determine whether pharmacological agents can elicit USV in this familiar environment. Ten-day-old Wistar rats were injected with U50,488, a highly selective kappa opioid agonist; pentylenetetrazol (PTZ), an anxiogenic drug that binds at the GABA-benzodiazepine receptor complex; or naltrexone (NLX), an opiate receptor blocker, and then were returned to their littermates in the home cage. U50,488 increased USV and activity levels, lowered body temperature, and disrupted contact with littermates. PTZ raised activity levels but had a smaller effect on vocalization rates and did not alter temperature or contact with littermates. Behavioral measures and body temperature were unchanged by NLX.


8-Hydroxyquinoline functionalized covalent organic framework as a pH sensitive carrier for drug delivery.
A porous 8-hydroxyquinoline functionalized organic covalent framework (named COF-HQ) was synthesized. The as-prepared COF-HQ showed stable crystal structure, suitable pore size, excellent dispersibility in physiological solution and pH sensitivity, which would be employed as a potential nanocarrier for drug transport and controlled release. The drug loading experiment with 5-Fluorouracil (5-FU) as the model molecule proved that the drug loading capacity of COF-HQ was significantly improved due to the introduction of quinoline groups. The drug release profiles of 5-FU from 5-FU loaded COF-HQ (termed 5-FU@COF-HQ) under different pH showed that its release was controlled by pH owing to the pH sensitivity of conjugated nitrogen atoms from quinoline groups and CN. The in vitro hemolysis and in vivo biocompatibility experiments further verified the good biocompatibility of COF-HQ. Importantly, 5-FU@COF-HQ-treated B16F10 cell-induced tumor models showed that 5-FU@COF-HQ displayed enhanced anti-tumor efficacy than other groups. These results suggested that the drug-loading COF-HQ delivery system showed the potential for effective cancer therapy with advantages of high drug loading, good biocompatibility and the pH-sensitive release of the tumor microenvironment. Overall, our research provided a new functionalized COF-HQ drug delivery system, which further expanded the application of COFs as carriers in the field of cancer treatment.


Early developmental plasticity enables the induction of an intermediate extraembryonic cell state.
Two fundamental elements of pre-implantation embryogenesis are cells' intrinsic self-organization program and their developmental plasticity, which allows embryos to compensate for alterations in cell position and number; yet, these elements are still poorly understood. To be able to decipher these features, we established culture conditions that enable the two fates of blastocysts' extraembryonic lineages-the primitive endoderm and the trophectoderm-to coexist. This plasticity emerges following the mechanisms of the first lineage segregation in the mouse embryo, and it manifests as an extended potential for extraembryonic chimerism during the pre-implantation embryogenesis. Moreover, this shared state enables robust assembly into higher-order blastocyst-like structures, thus combining both the cell fate plasticity and self-organization features of the early extraembryonic lineages.