Nature and nurture in the differentiation of retinal photoreceptors and neurons.
This article reviews recent studies using a novel experimental system in which undifferentiated precursor cells from the 8-day chick embryo retina are grown in low density, clump-free, dissociated cell culture. The cultures initially consist of a morphologically homogeneous population of isolated process-free, round cells. Analysis of the cultures by phase contrast light microscopy, scanning and transmission electron microscopy, immunocytochemistry and autoradiography, shows that during the first week in vitro some precursor cells acquire a well differentiated photoreceptor phenotype, while others develop as neurons. Given that these divergent differentiation pathways are followed by cells developing in a homogeneous microenvironment in the absence of intercellular contacts, the evidence suggests that precursor cells present in the 8-day chick embryo retina are already preprogrammed to undergo an extensive series of chemical and structural modifications necessary to differentiate as either neurons or photoreceptors.


Evidence for shared susceptibility to epilepsy and psychosis: a population-based family study.
There is emerging evidence of an etiological overlap between a range of neurodevelopmental disorders, including schizophrenia and epilepsy. Here we investigate shared familial vulnerability to psychotic illness and epilepsy in a family-based study. The study population consisted of parents and their children born in Helsinki between 1947 and 1990. The Finnish Hospital Discharge Register was used to determine psychiatric and neurological outcomes in adulthood for all offspring. Parental history of psychosis and epilepsy was determined by linking the Hospital Discharge Register and the Finnish Population Register. Our total sample comprised 9653 families and 23,404 offspring. Individuals with epilepsy had a 5.5-fold increase in the risk of having a broadly defined psychotic disorder, an almost 8.5-fold increase in the risk of having schizophrenia, and a 6.3-fold increase in the risk of having bipolar disorder. There was strong evidence of clustering of the association between epilepsy and psychosis within families. Individuals with a parental history of epilepsy had a 2-fold increase in the risk of developing psychosis, compared with individuals without a parental history of epilepsy. Individuals with a parental history of psychosis had, reciprocally, a 2.7-fold increase in the risk of having a diagnosis of generalized epilepsy, compared with individuals without a parental history of psychosis. Post hoc analyses showed that these associations were not driven by the comorbidity of epilepsy and psychosis in the parents. These findings support recent evidence of overlapping etiological factors between epilepsy and schizophrenia, especially recent evidence of a genetic overlap between these disorders.


Relative insensitivity to glucagon of sterol synthesis in cultured rat aortic smooth muscle cells. Effect of dibutyryl cyclic AMP.
The smooth muscle cell plays an important role in the process of atherogenesis. In these experiments the effect of glucagon and dibutyryl cyclic AMP on sterol synthesis in cultured rat arterial smooth muscle cells was studied. Glucagon in concentrations of 1 X 10(-9) mol/l inhibited the incorporation of sodium (2(-14)C)acetate into non-saponifiable lipids and digitonin precipitable sterols but lower concentrations of glucagon had no effect. In cells which were exposed to serum, dibutyryl cyclic AMP also resulted in a decrease in the incorporation of labelled acetate into sterols but when the cells were grown in serum free medium, dibutyryl cyclic AMP had no inhibitory effect on sterol synthesis. These results provide further evidence that sterol metabolism in arterial smooth cells may be influenced by hormones but suggest that glucagon is relatively less important than insulin in this respect.


Mediator release in cerebrospinal fluid of human immunodeficiency virus-positive patients with central nervous system involvement.
In this study we evaluated the release of some mediators of inflammatory reactions such as histamine (H), leukotriene B4 (LTB4), leukotriene C4 (LTC4) and prostaglandin D2 (PGD2) in the cerebrospinal fluid (CSF) of 15 patients with acquired immunodeficiency syndrome (AIDS), eight with opportunistic infections of the central nervous system (CNS) and seven without HIV-related neurological pathology, and of 25 HIV-negative control subjects with other neurological diseases. The cerebrospinal LTB4 level was increased in all the AIDS patients (mean 348 pg/ml); the control group revealed normal levels of LTB4 in the CSF (mean 63.2 pg/ml). The PGD2 level in the HIV-positive (mean 264 pg/ml) patients was higher than of the control subjects (mean 50 pg/ml), while low LTC4 levels were found both in the HIV-positive and control groups. We did not find any significant concentration of H in the CSF of either the HIV-positive or the control subjects. These findings may be due to the presence of chronic HIV infection or to the opportunistic infections of the CNS that so often occur in the latest stages of the disease.


Effect of Helicobacter pylori eradication on antral somatostatin cell density in humans.
As Helicobacter pylori infection is associated with an elevation in plasma gastrin with normal antral gastrin cell counts, an abnormality in antral somatostatin cells may be associated with the infection. We evaluated the effect of eradication of H. pylori on antral somatostatin cell density in the light of antral gastrin cell density and plasma gastrin levels. Prospective study. Of 25 dyspeptic patients with H. pylori infection, nine had H. pylori successfully eradicated and the rest remained infected. Antral biopsies were immunostained for somatostatin cells and plasma gastrin measured before and 4 weeks after H. pylori eradication therapy. Ten other dyspeptic patients without H. pylori infection had their somatostatin cell density evaluated as controls. Somatostatin cell density in the patients without H. pylori infection at the outset was significantly higher than that in the patients with H. pylori infection at the outset (median 57 [18-83] vs. 37 [6-80] cells/mm) respectively (P <0.05). Somatostatin cell density increased after H. pylori eradication (before treatment, median 50 [15-72]; after treatment 71 [39-107] cells/mm) (P < 0.05) but was unchanged with persistent H. pylori infection. Plasma gastrin decreased after H. pylori eradication (before treatment, median 70 [45-100]; after treatment 30 [10-100] ng/l) (P < 0.05) but was unchanged with persistent H. pylori infection. Following eradication of H. pylori, there is an increase in somatostatin cell density with a fall in plasma gastrin. This supports the theory that H. pylori infection results in a decrease in somatostatin cell density and, as the latter is an inhibitor of gastrin cells, this results in an increased plasma gastrin.


An imperfect refuge: life in an 'old folk's home' for younger residents with psychiatric disorders.
Residents under age 65 comprise a small, but not insignificant, segment of the US nursing home population--a segment about which very little is known. This article explores the meaningful constitution of nursing home experience among younger, psychiatrically disabled residents of an urban nursing home. Residents' "behavior problems", the difficulties imposed by institutional life, and American age norms emerged as key dynamics in residents' understandings of nursing home life. In addition to these factors, the nursing home was evaluated in relation to previous life experiences, perceived alternatives, and expectations of personal freedom. Ultimately, most younger residents found the nursing home to be a refuge, albeit an imperfect one.


The importance of the reproducibility of oropharyngeal swallowing in amyotrophic lateral sclerosis. An electrophysiological study.
To investigate electrophysiologically the reproducibility of oropharyngeal swallowing in patients with ALS. We enrolled 26 ALS patients, both with and without clinical signs of dysphagia, and 30 age-matched controls. The reproducibility of the electrophysiological signals related to the oral phase (electromyographic activity of the submental/suprahyoid muscles) and the pharyngeal phase (laryngeal-pharyngeal mechanogram) of swallowing across repeated swallows was assessed. To do this we computed two similarity indexes (SI) by using previously described mathematical algorithms. The reproducibility of oropharyngeal swallowing was significantly reduced both in patients with and in those without clinical signs of dysphagia, with more marked alterations being detected in the dysphagic group. The SI of both phases of swallowing, oral and pharyngeal, correlated significantly with dysphagia severity and disease severity. In ALS different pathophysiological mechanisms can alter the stereotyped motor behaviors underlying normal swallowing, thus reducing the reproducibility of the swallowing act. A decrease in swallowing reproducibility could be a preclinical sign of dysphagia and, beyond a certain threshold, a pathological hallmark of oropharyngeal dysphagia. Electrophysiological assessment is a simple and useful tool for the early detection of swallowing abnormalities, and for the management of overt dysphagia in ALS.


Quasi-spherical silver nanoparticles: aqueous synthesis and size control by the seed-mediated Lee-Meisel method.
Silver nanoparticles (AgNPs) are attracting tremendous attention in biomedicine, and their related performances are shape and size-dependent. For biomedical applications, water-soluble AgNPs are necessary. However, aqueous syntheses of AgNPs with controlled shape and size are relatively difficult as the balance between nucleation and growth is hard to regulate. This paper describes a robust method for controllable synthesis of quasi-spherical AgNPs based on the combination of the seed-mediated growth and the Lee-Meisel method by thermal reduction of AgNO(3) with citrate. In the presented method, citrate-stabilized AgNPs with tunable sizes up to 80 nm were achieved through one-step or stepwise growth process using qualified spherical 4 nm AgNPs as starter seeds. Specially, the two main difficulties (formation of nanorods and secondary nucleation during the growth stage) in the previous studies have been effectively overcome by tailoring the experimental parameters such as the reaction temperature and the seed amount, without extra additives, pH adjustment, and laser treatment. The crucial factors that affect the uniformity of the resulting AgNPs are discussed.


Detection of the schizont stage in experimentally infected cattle with Japanese Theileria sergenti.
Calves infected with a sporozoite suspension of the Ikeda strain of Theileria sergenti were examined in attempts to detect the schizont stage. A suspension equivalent to the contents of 70-200 ticks was inoculated subcutaneously into 10 splenectomized calves. Schizonts and micromerozoites were found in the prescapular lymph nodes of 5 calves about 8 days after the sporozoite inoculation. Schizonts detected at the time of nuclear division had large and diffuse nuclei, and many of the schizonts were very large and extracellular in lymph node smears. The schizonts were also detected by the direct fluorescent antibody staining.


Waterpipe smoking, internet addiction and depression: A public health problem trio?
Waterpipe smoking and Internet addiction may result in a new public health problem globally. This study aimed to explore waterpipe use among a large group of adolescents and its association with Internet use, mental health, primarily depression and their demographic characteristics. Using a stratified random sampling method, 2054 tertiary school students aged 14-18 years were recruited in 2019. Demographical information and use of tobacco products (eg, waterpipe) were explored and compared with severity of Internet addiction and mental status. A total of 288 (14.0%) adolescents had ever used waterpipe. Multivariate logistic regression analyses suggested that being male (OR = 2.55 and 95% CI = 1.98-3.30; P = .0001), being depressed (OR = 1.62 and 95% CI = 1.24-2.11) and excessive Internet use (OR = 1.94 and 95% CI = 1.50-2.52; P = .0001) were significantly associated with waterpipe use. Family income and parents' educational status showed no relationship with waterpipe smoking. We suggest that adolescents who are depressed and who use the Internet excessively are at an increased risk for waterpipe use, independent of income and parenteral education.


Combined hereditary factor XI (plasma thromboplastin antecedent) deficiency, von Willebrand's disease, and xeroderma pigmentosum in a Japanese family.
We report a 28-year-old-Japanese male who had a skin tumor derived from variant type xeroderma pigmentosum (XP), combined with factor XI (FXI) deficiency and type IIB von Willebrand's disease (vWd). The patient had abnormal bleeding history on tooth extraction. FXI clotting activity (FXI:C) and antigen (FXI:Ag) were remarkably decreased (< 0.01 U/ml, < 0.02 U/ml, respectively). Factor VIII (FVIII) clotting activity, von Willebrand factor antigen (vWf:Ag), and ristocetin cofactor (RCoF) were 0.43 U/ml, 45%, and 57%, respectively. Ristocetin-induced platelet agglutination (RIPA) revealed hyper-aggregation compared with a normal control. Multimeric composition of vWf in plasma showed a reduction in high molecular weight forms. The family study revealed two other subjects with homozygous hereditary FXI deficiency and vWd, and five subjects with heterozygous FXI deficiency. The relationship between FXI deficiency and vWd is discussed and previously reported cases are reviewed.


Correction: A method to quantify mechanobiologic forces during zebrafish cardiac development using 4-D light sheet imaging and computational modeling.
[This corrects the article DOI: 10.1371/journal.pcbi.1005828.].


Potassium ion channels and human disease: phenotypes to drug targets?
A significant difficulty faced by the pharmaceutical industry is the initial identification and selection of macromolecular targets upon which de novo drug discovery programs can be initiated. A drug target should have several characteristics: known biological function; robust assay systems for in vitro characterization and high-throughput screening; and be specifically modified by and accessible to small molecular weight compounds in vivo. Ion channels have many of these attributes and can be viewed as suitable targets for small molecule drugs. Potassium (K+) ion channels form a large and diverse gene family responsible for critical functions in numerous cell types, tissues and organs. Recent discoveries, facilitated by genomics technologies combined with advanced biophysical characterization methods, have identified novel K+ channels that are involved in important physiologic processes, or mutated in human inherited disease. These findings, coupled with a rapidly growing body of information regarding modulatory channel subunits and high resolution channel structures, are providing the critical information necessary for validation of K+ channels as drug targets.


Combinations of monoclonal antibodies distinguish mesenchymal, myogenic, and chondrogenic precursors of the developing chick embryo.
Monoclonal antibodies (MAbs) were used as probes for molecular differences in the surfaces of nonterminally differentiated cells of the developing chick limb. The specificity of the MAbs was determined by immunofluorescent localization performed on cultured breast muscle and limb bud cells and cryosections of a variety of embryonic (stages 15-37) and neonatal tissues. Subpopulations of MAb-positive and -negative cells were isolated by fluorescence-activated cell sorting and their developmental potential was assessed in vitro. Cells of the compacted somite, lateral plate mesoderm, and early limb bud were labeled with the CSAT MAb. Myogenic precursors of the dermatome and limb bud were labeled with the CSAT and L4 MAbs. Chondrogenic precursors of the sclerotome and limb bud were labeled with the CSAT, L4, and C5 MAbs. These precursors were distinguished from fibroblasts which were labeled with the CSAT and C1 MAbs. The differentiation and maturation of muscle and cartilage were accompanied by alterations in the labeling patterns of the MAbs. These results indicate that combinations of these MAbs can be used to distinguish mesenchymal, myogenic, and chondrogenic precursors, identify their site of origin during development, and isolate subpopulations of embryonic cells.


Strain and locomotor speed affect over-ground locomotion in intact rats.
A variety of animal models for neurological disease and injury exist and locomotor performance is an important outcome parameter in studies employing these models. The CatWalk, an automated quantitative gait analysis method is a method to study over-ground locomotor performance in large groups of animals. In the present study, we used the CatWalk which allowed us to investigate strain differences in over-ground locomotion in three commonly used strains of laboratory rat (i.e. Lewis, Wistar and Sprague-Dawley rats) based on objective data-analysis in a large number of animals. The present results revealed marked strain differences on the static paw parameters; base-of-support, and the relative paw position. Furthermore, strain differences were noted on the static parameter stride length and the dynamic parameters stance-, swing- and stepcycle duration, which are due logically to morphological differences between strains. The parameters related to coordination did not reveal any differences between the strains. Furthermore, the swing duration and the cruciate and alternate patterns i.e. regular step patterns Ca ("cruciate" pattern type a) and Ab ("alternate" pattern type b) were shown to be differentially affected by the locomotor speed. We conclude that differences in gait traits exist between the three laboratory rat strains investigated and several of the examined gait parameters showed strain dependent interdependency with locomotor speed.


A centralized resource for bacterial-fungal interactions research.
Research on bacterial-fungal interactions (BFIs) has revealed that fungi and bacteria frequently interact with one another within diverse ecosystems and microbiomes. Assessing the current state of knowledge within the field of BFI research, particularly with respect to what interactions between bacteria and fungi have been previously described, is very challenging and time consuming. This is largely due to a lack of any centralized resource, with reports of BFIs being spread across publications in numerous journals using non-standardized text to describe the relationships. To address this issue, we have developed the BFI Research Portal, a publicly accessible database of previously reported interactions between bacterial and fungal taxa to serve as a centralized resource for the field. Users can query bacterial or fungal taxa to see what members from the other kingdom have been observed as interaction partners. Search results are accompanied by interactive and intuitive visual outputs, and the database is a dynamic resource that will be updated as new BFIs are reported.


Primer: challenges in randomized and observational studies.
Randomized controlled trials (RCTs) are considered superior to observational studies, and both clinicians and researchers believe that conclusions that stem from observational research are flawed. RCTs, however, have important methodological and interpretational limitations, and particular clinical questions can only be addressed by observational research. This Review compares RCTs and observational studies with regard to particular limitations, and explains how the credibility of results from observational studies can be improved by making use of advanced analytical techniques.


Comparison of the anatomic crown width/length ratios of unworn and worn maxillary teeth in Asian and white subjects.
Various aspects of anatomic tooth dimensions have been examined in a number of studies where data are primarily based on the measurements obtained from white subjects. Additional factors such as ethnicity should be considered to produce a more comprehensive analysis. The purpose of this study is to compare the anatomic crown dimensions of extracted maxillary teeth in Asian and white populations. The width/length ratio (%) was calculated with standardized digital images of extracted maxillary anterior teeth from 157 Asian and 142 white subjects. Statistical analysis was performed to compare the 4 tooth groups (central incisiors, lateral incisiors, canines, and premolars) of the 2 ethnicities. The distribution of the outcome variables were examined for normality with the Kolmigorov-Smirnov test. Independent sample t tests were used to examine differences in outcomes in Asian and white subjects. There was a significant difference (P<.05) in the width/length ratios of all maxillary anterior teeth in Asian and white subjects. In addition, there was a significant difference in the width of unworn central incisors and the length of worn lateral incisors and canines. Ethnicity influences width/length ratios for all 4 anterior maxillary teeth. Anterior maxillary teeth in Asian subjects appear to be more slender when compared with those in white subjects.


Human resource development for a community-based health extension program: a case study from Ethiopia.
Ethiopia is one of the sub-Saharan countries most affected by high disease burden, aggravated by a shortage and imbalance of human resources, geographical distance, and socioeconomic factors. In 2004, the government introduced the Health Extension Program (HEP), a primary care delivery strategy, to address the challenges and achieve the World Health Organization Millennium Development Goals (MDGs) within a context of limited resources. The health system was reformed to create a platform for integration and institutionalization of the HEP with appropriate human capacity, infrastructure, and management structures. Human resources were developed through training of female health workers recruited from their prospective villages, designed to limit the high staff turnover and address gender, social and cultural factors in order to provide services acceptable to each community. The service delivery modalities include household, community and health facility care. Thus, the most basic health post infrastructure, designed to rapidly and cost-effectively scale up HEP, was built in each village. In line with the country's decentralized management system, the HEP service delivery is under the jurisdiction of the district authorities. The nationwide implementation of HEP progressed in line with its target goals. In all, 40 training institutions were established, and over 30,000 Health Extension Workers have been trained and deployed to approximately 15,000 villages. The potential health service coverage reached 92.1% in 2011, up from 64% in 2004. While most health indicators have improved, performance in skilled delivery and postnatal care has not been satisfactory. While HEP is considered the most important institutional framework for achieving the health MDGs in Ethiopia, quality of service, utilization rate, access and referral linkage to emergency obstetric care, management, and evaluation of the program are the key challenges that need immediate attention. This article describes the strategies, human resource developments, service delivery modalities, progress in service coverage, and the challenges in the implementation of the HEP. The Ethiopian approach of revitalization of primary care through innovative, locally appropriate and acceptable strategies will provide important lessons to other poorly resourced countries. It is hoped that the approaches and strategies described in this paper will aid in that process.


Diphenyldihydropentalenediones: Wide Singlet-Triplet Energy Gap Compounds Possessing the Planarly Fixed Diene Subunit.
2,2,5,5-Tetramethyl-3,6-diphenyl-2,5-dihydropentalene-1,4-dione (PD-H) and its dimethoxy (PD-OCH3) and bis(trifluoromethyl) derivatives (PD-CF3) were developed as a new class of compounds possessing a wide excited singlet-triplet energy gap. The PD derivatives would also have a high energy level of the triplet-excited state (E T) due to the planarity of the fused-diene subunit. The results of photophysical studies revealed that the energy level of the singlet-excited state (E S) and E T of PD-H are 2.88 and 1.43 eV, respectively. These values indicate that PD-H has the energy relationship, E S > 2E T, required for it to be a singlet fission (SF) material. Moreover, the introduction of electron-donating or -withdrawing groups on the benzene rings in PD-H enables fine-tuning of E S and E T. The results of transient absorption spectroscopic studies show that PD-H, PD-OCH3, and PD-CF3 in CH2Cl2 have respective T1 lifetimes of 71, 118, and 107 μs, which are long enough to utilize its triplet exciton in other optoelectronic systems. These findings suggest that the PDs are potential candidates for SF materials with high E T levels.


Serum alpha1-antitrypsin but not complement C3 and C4 predicts chronic inflammation in hemodialysis patients.
We studied whether predialysis serum levels of positive acute phase markers such as alpha1-antitrypsin (AT), and complement components C3 and C4 could identify the presence of chronic inflammation in maintenance hemodialysis (HD) patients. In 103 stable HD patients, AT directly correlated with C-reactive protein (CRP) (P < 0.005), alpha1 acid-glycoprotein (P < 0.005), fibrinogen ( P < 0.05), lipoprotein (a) (P < 0.01) and von Willebrand factor antigen (P < 0.05), while C3 and C4 were not related to any of these inflammatory markers. In the patients with elevated CRP and hypoalbuminemia, the mean AT value of 1.74 +/- 0.50 g/L was higher (P = 0.008) than that of 1.38 +/- 0.27g/L in the subjects with normal CRP and albumin. Using the above cut-off levels, the positive and negative predictive values of AT on the presence of severe inflammation were 0.86 and 0.62, respectively, and the sensitivity and specificity were 86% and 73%, respectively. Serum AT levels above 1.74 g/L and below 1.38 g/L may select the HD patients with severe inflammation from those without. Measurements of C3 and C4 are not helpful in this situation.


Characterization of rice endo-beta-glucanase genes (Gns2-Gns14) defines a new subgroup within the gene family.
Thirteen new beta-glucanase-encoding genes have been identified in the rice genome. These genes, together with other monocot beta-glucanases, have now been classified into four subfamilies based on the structure and function of the genes. Two tandem gene clusters, Gns2-Gns3-Gns4 and Gns5-Gns6, were classified in the defense-related Subfamily A. Growth-related 1,3;1,4-beta-glucanase Gns1 was classified in Subfamily B. Gns7 and Gns8, together with the barley genes GVI and Hv34, represent Subfamily C. Gns9 and a beta-glucanase gene from wheat were grouped in Subfamily D. Genes in Subfamilies C and D have structures that are distinct from those of the other subfamilies, but there are very little data available on the biochemical or physiological roles of these genes. Gene expression in growing tissues and lack of gene induction in response to disease-related treatments suggest that Subfamilies C and D may function in control of plant growth.


A size-invariant convolutional network with dense connectivity applied to retinal vessel segmentation measured by a unique index.
Retinal vessel segmentation (RVS) helps in diagnosing diseases such as hypertension, cardiovascular diseases, and others. Convolutional neural networks are widely used in RVS tasks. However, how to comprehensively evaluate the segmentation results and how to improve the networks' learning ability are two great challenges. In this paper, we proposed an ingenious index: fusion score (FS), which provides an overall measure for those binary images. The FS converts multiple metrics into a single target, and therefore facilitates the optimal threshold's selection and models' comparison. In addition, We simultaneously combined size-invariant feature maps and dense connectivity together to improve the traditional CNN's learning ability. Therefore, a size-invariant convolutional network with dense connectivity is designed for RVS. The size-invariant skill helps the deep layers create feature maps with high resolution. The dense connectivity technique is utilized to integrate those hierarchical features and reuse characteristic maps to enhance the network's learning ability. Finally, an optimized threshold is used on the output image to obtain a binary image. The results of experiments conducted on two shared retinal image databases, DRIVE and STARE, demonstrate that our approach outperforms other techniques when evaluated in terms of F1-score, Matthews correlation coefficient (MCC), G-mean and FS. In addition, the cross training reveals that our method has stronger robustness with respect to training sets. Segmenting a 565 × 584 image only takes 39 ms with a single GPU (graphics processing unit). Compared with those traditional metrics, the FS is a better indicator to measure the results of RVS tasks. The experimental results revealed that the proposed method is more suitable for real-world applications.


Redescription of two parasitic feather mites sampled from the last two Crested Ibises, Nipponia nippon (Temminck, 1835) (Pelecaniformes: Threskiornithidae), lived in Japan.
The objective of this paper is to redescribe two feather mites, Compressalges nipponiae Dubinin, 1950 (Caudiferidae) and Freyanopterolichus nipponiae Dubinin, 1953 (Kramerellidae), based on samples collected from the last two individuals of the Crested Ibis Nipponia nippon (Temminck, 1835) from the native Japanese populations, which had been extirpated in 2003. Our study provides detailed description of the leg and idiosomal chaetotaxy, and many morphological structures, which were missed or misinterpreted in the original publications.


The Business of Health Care: Virtual Nursing, a Postpandemic Plan for Efficiency and Cost Savings.
Nurse leaders need to continue to think innovatively and help improve the bottom line at their organizations and at the same time be concerned with nurse retention. Virtual nursing is one such approach that will help achieve both results. Nurse leaders must also know how to bring forth a return on investment in order to receive the funding to try innovative approaches to staffing.


NAV-003, a bispecific antibody targeting a unique mesothelin epitope and CD3ε with improved cytotoxicity against humoral immunosuppressed tumors.
Mesothelin (MSLN) is a cell surface protein overexpressed in a number of cancer types. Several antibody- and cellular-based MSLN targeting agents have been tested in clinical trials where their therapeutic efficacy has been moderate at best. Previous studies using antibody and Chimeric Antigen Receptor-T cells (CAR-T) strategies have shown the importance of particular MSLN epitopes for optimal therapeutic response, while other studies have found that certain MSLN-positive tumors can produce proteins that can bind to subsets of IgG1-type antibodies and suppress their immune effector activities. In an attempt to develop an improved anti-MSLN targeting agent, we engineered a humanized divalent anti-MSLN/anti-CD3ε bispecific antibody that avoids suppressive factors, can target a MSLN epitope proximal to the tumor cell surface, and is capable of effectively binding, activating, and redirecting T cells to the surface of MSLN-positive tumor cells. NAV-003 has shown significantly improved tumor cell killing against lines producing immunosuppressive proteins in vitro and in vivo. Moreover, NAV-003 demonstrated good tolerability in mice and efficacy against patient-derived mesothelioma xenografts co-engrafted with human peripheral blood mononuclear cells. Together these data support the potential for NAV-003 clinical development and human proof-of-concept studies in patients with MSLN-expressing cancers.


The effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin on the antioxidant system in mitochondrial and microsomal fractions of rat testis.
The ability of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) to induce oxidative stress in hepatic and some extrahepatic tissues of animals has been reported. The precise nature and mechanism of action of TCDD on the male reproductive system is not clear. In the present study, we have investigated the induction of oxidative stress in the testis of rat after exposure to low doses of TCDD. TCDD (1, 10, and 100 ng/kg body weight per day) was administered orally to the rat for 45 days. After 24 h of the last treatment the rats were killed using anesthetic ether. The weights of the testis, epididymis, seminal vesicles and ventral prostate decreased while the body weight remained unchanged in the rats administered with TCDD. Mitochondrial and microsomal fractions of the testis were obtained by the method of differential centrifugation. The activity of antioxidant enzymes such as superoxide dismutase, catalase, glutathione reductase, and glutathione peroxidase decreased significantly in the animals treated with TCDD in a dose-dependent manner in the mitochondrial and microsomal fractions of rat testis. The levels of hydrogen peroxide generation (H(2)O(2)) and lipid peroxidation increased in mitochondrial, and microsomal fractions of the testis. The results suggested that the low doses of TCDD elicit depletion of antioxidant enzymes and concomitant increase in the levels of H(2)O(2) and lipid peroxidation differentially in mitochondrial and microsomal fractions of rat testis. In conclusion the adverse effect of TCDD on male reproduction could be due to induction of oxidative stress.


Adrenal gland volume assessed by magnetic resonance imaging in women with polycystic ovary syndrome.
To determine adrenal gland volume (AGV) in women with polycystic ovary syndrome (PCOS) by comparison with healthy control subjects and to investigate the relationship between AGV and hormonal status. AGV was measured on transverse sections of T1-weighted MRI imaging data in 27 PCOS patients and 40 age-matched control subjects for this prospectively designed study. A comparative analysis of AGV in PCOS and controls was performed and possible correlations between AGV and hormonal parameters were evaluated. PCOS patients had significantly larger AGV compared to controls ((11.7±4.4 cm(3), 7.2±1.9 cm(3), respectively, P<0.001). A significant positive correlation was found between total AGV and dehydroepiandrosterone sulfate, 17-OH progesterone, and total and free testosterone levels in the PCOS group (r=+0.51, +0.48, +0.43, +0.62, respectively; P values<0.05). In addition, AGV was significantly negatively correlated with LH and LH/FSH ratio in the PCOS group (r= -0.55, P=0.02; r=-0.51, P=0.01, respectively). PCOS patients have significantly increased AGV as well as a positive correlation of AGV and androgens. We conclude that the assessment of AGV with MRI shows a significant correlation with the androgenic activity of the gland, and that hypertrophy of the adrenal gland may be involved in the pathogenesis of PCOS.


Improved enantiomeric separation of dihydrodiols of polycyclic aromatic hydrocarbons on chiral stationary phases by derivatization to O-methyl ethers.
K-region trans-dihydrodiol derivatives of phenanthrene, 1-methylphenanthrene, 4,5-methylenephenanthrene, pyrene, 1-bromopyrene, chrysene, benzo[c]phenanthrene, benz[a]anthracene, 1-, 4-, 6-, 7-, 11- and 12-methylbenz[a]anthracenes, 7,12-dimethylbenz[a]anthracene, 3-methylcholanthrene, and benzo[a]pyrene, and non-K-region trans-3,4-dihydrodiols of benz[a]anthracene, chrysene, and 7,12-dimethylbenz[a]anthracene are converted to O-methyl ethers. Enantiomers of these O-methyl ethers are generally more efficiently separated on Pirkle's chiral stationary phases than the enantiomers of underivatized dihydrodiols. O-Methyl ethers are substantially less polar than dihydrodiols, and O-methyl ethers are eluted with shorter retention times. Eluents of lower polarity can hence be used. This enhances chiral interactions between chiral stationary phase and solutes, allowing improved separation of enantiomers.


Progesterone transcriptionally regulates the beta 2-adrenergic receptor gene in pregnant rat myometrium.
Administration of 5 mg of progesterone to late pregnant rats induced an increase in myometrial beta-adrenergic receptors density detected by 125I-cyanopindolol binding. This increase was significant after 24 h (1.4-fold; p less than 0.05) and reached 1.6-fold (p less than 0.05) after 36 h. The antiprogestin RU 486 or cycloheximide completely suppressed the effect of progesterone injection. Quantification of the beta 1- and beta 2-receptor subtypes revealed that progesterone selectively up-regulated the beta 2-subtype. The increase in beta 2-adrenoreceptors was preceded by an elevation of their mRNA (2.3 kilobases) levels as determined by Northern blot hybridization with a rat heart beta 2-adrenoreceptor cDNA probe. This increase was significant after 18 h of exposure to progesterone (2.1-fold; p less than 0.05) and reached a maximum after 24 h (3.4-fold; p less than 0.01). The rate of beta 2-adrenergic gene transcription evaluated by nuclear run-on transcription assays, increased by 2.5-fold in myometria exposed for 4 h to progesterone. This study indicates that progesterone regulates myometrial beta 2-adrenergic receptor expression by controlling the rate of transcription of the gene.


miR-21-containing microvesicles from injured tubular epithelial cells promote tubular phenotype transition by targeting PTEN protein.
Renal fibrosis is inevitably progressive no matter what the initial insult is or whether the insult persists. In an experimental fibrosis model induced by unilateral ureteral obstruction, the accelerated pathological changes could hardly be explained by aggravated pressure caused by hydronephrosis after ligation. Moreover, at the initial stage, tubular phenotype transition and matrix deposition in obstructive kidneys are always local and scattered; however, these renal lesions expand and progress with time. In this study, cultured recipient tubular cells underwent phenotype transition after incubation with conditioned media derived from transforming growth factor-β1-treated donor tubular cells. Thus, it is reasonable to speculate that some secretable molecules from injured tubules contribute to the progression of renal fibrosis. Herein, we report that secreted miRNA-21 (miR-21) can serve as the molecule mediating intercellular communication. miR-21 was packaged into microvesicles, which enter and deliver miR-21 into recipient tubular cells, and exogenous miR-21 enhances Akt signaling by target depression of phosphatase and tensin homolog (PTEN) protein, and promotes tubular phenotype transition. These results demonstrate that tubular cells can secrete miR-21 and deliver it into recipient tubules by microvesicles, where the exogenous miR-21 can target PTEN protein and enhance Akt signaling in recipient cells. Microvesicle-mediated delivery of miR-21 among tubular epithelial cells might shed new light on the mechanism of progressive renal fibrosis.


Radiation therapy is associated with improved survival in the adjuvant and definitive treatment of intrahepatic cholangiocarcinoma.
Intrahepatic cholangiocarcinomas (IHC) are rare tumors for which large randomized studies regarding the use of radiation are not available. The purpose of this study was to examine the role of adjuvant and definitive radiation therapy in the treatment of IHC in a large group of patients. This is a retrospective analysis of 3,839 patients with IHC collected from the Surveillance, Epidemiology, and End Results (SEER) database. The primary endpoint was overall survival (OS). Patients received either surgery alone (25%), radiation therapy alone (10%), surgery and adjuvant radiation therapy (7%) or no treatment (58%). The median age of the patient population was 73 years (range, 22-102 years); 52% of patients were male and 81% were Caucasian. Median OS was 11 (95% confidence interval [CI], 9-13), 6 (95% CI, 5-6), 7 (95% CI, 6-8), and 3 months for surgery and adjuvant radiation therapy, surgery alone, radiation therapy alone, and no treatment, respectively. The OS was significantly different between surgery alone and surgery and adjuvant radiation therapy (p = 0.014) and radiation therapy alone and no treatment (p < 0.0001). Use of surgery and adjuvant radiation therapy conferred the greatest benefit on OS (HR = 0.40; 95% CI, 0.34-0.47), followed by surgery alone (hazard ratio [HR], 0.49; 95% CI, 0.44-0.54) and radiation therapy alone (HR, 0.68; 95% CI, 0.59-0.77) compared with no treatment, on multivariate analysis. Propensity score adjusted hazard ratios (controlling for age, race/ethnicity, stage, and year of diagnosis) were also significant (surgery and adjuvant radiation therapy vs. surgery alone (HR, 0.82; 95% CI, 0.70-0.96); radiation therapy alone vs. no treatment (HR, 0.67; 95% CI, 0.58-0.76)). The study results suggest that adjuvant and definitive radiation treatment prolong survival, although cure rates remain low. Future studies should evaluate the addition of chemotherapy and biologics to the treatment of IHC.


A severe persistent case of pemphigoid gestationis treated with intravenous immunoglobulins and cyclosporin.
Pemphigoid gestationis is an autoimmune bullous eruption specific to pregnancy. It usually presents in the second or third trimester and is characterized by postpartum exacerbations of the disease. Most cases resolve within a few months of delivery, but the disease may be more persistent, developing characteristics of bullous pemphigoid which can be difficult to treat. We now report a patient with severe pemphigoid gestationis, in whom the disease has persisted for 1.5 years postpartum and who developed features more typical of bullous pemphigoid. We discuss this phenomenon and the management of such cases.


Oral phytochemicals as photoprotectants in UVR exposed hairless mice: A study of hesperidin methyl chalcone, phloroglucinol, and syringic acid.
Ultraviolet radiation is the primary risk factor for keratinocyte carcinoma. Because of increasing incidence rates, new methods of photoprotection must be explored. Oral supplementation with photoprotective compounds presents a promising alternative. Phytochemical compounds like hesperidin methyl chalcone, phloroglucinol, and syringic acid are particularly of interest because of their antioxidant properties. Our primary outcome was to evaluate the effects of oral phytochemicals on photocarcinogenesis with time until tumour onset as the primary endpoint. A total of 125 hairless C3.Cg-Hrhr/TifBom Tac mice were randomised to receive tap water supplemented with either 100 mg/kg hesperidin methyl chalcone, phloroglucinol, or syringic acid, 600 mg/kg nicotinamide as a positive control, or no supplementation. The mice were irradiated with 3.5 standard erythema doses thrice weekly to induce photocarcinogenesis. Supplementation with the phytochemicals phloroglucinol and syringic acid and nicotinamide delayed tumour onset from a median of 140 days to 151 (p = 0.036), 157 days (p = 0.02), and 178 (p = 2.7·10-5), respectively. Phloroglucinol and nicotinamide supplementation reduced tumour number. Nicotinamide increased UV-induced pigmentation and reduced oedema formation, while phloroglucinol supplementation reduced epidermal thickness. These results indicate that oral supplementation with phloroglucinol and syringic acid protects against photocarcinogenesis in hairless mice, but not to the same extent as nicotinamide.


Laparoscopic repair of an extrahiatal hernia caused by congenital dysplasia: a case report.
A 40-year-old woman with complaints of relapse in the upper abdomen and dysphagia was referred for laparascopic hiatal hernia repair. Chest radiograph, barium-swallow, and upper endoscopy revealed a paraesophageal hernia. Esophageal manometry and 24-h-pH study showed no pathological findings. A laparoscopic gastropexy was planned. Intraoperatively, in contradiction to the preoperative findings, an extrahiatal hernia containing most of the stomach was found. After resection of the hernia sac, the beating heart without covering pericardium was seen. These findings were confirmed by an additional thoracoscopy at the end of the operation. The defect was closed by direct suturing. The postoperative course and 2-month follow-up were uneventful. The resected parts of the hernia sac showed an embryonic and dysgenetic etiology. This rare malformation has been reported in combination with complex syndromes, which appear with serious clinical and morphological signs in the neonatal period. In adults, the pericardial aplasia can be observed during diagnostic or surgical interventions. In these patients, complaints are usually not caused by the malformation but may be due to the occasional herniation of abdominal organs. We consider laparoscopic repair to be a gentle and safe procedure for the treatment of extrahiatal hernias.


Influence of infrastructure, ecology, and underpass-dimensions on multi-year use of Standard Gauge Railway underpasses by mammals in Tsavo, Kenya.
Rail and road infrastructure is essential for economic growth and development but can cause a gradual loss in biodiversity and degradation of ecosystem function and services. We assessed the influence of underpass dimensions, fencing, proximity to water and roads, Normalized Difference Vegetation Index (NDVI), presence of other species and livestock on underpass use by large and medium-sized mammals. Results revealed hyenas and leopards used the underpasses more than expected whereas giraffes and antelopes used the underpasses less than expected. Generalized linear mixed-effects models revealed that underpass height influenced use by wildlife, with several species preferring to use taller underpasses. Electric fencing increased underpass use by funneling species towards underpasses, except for elephants and black-backed jackal for which it reduced underpass passage. We also found that the use of underpasses by livestock reduced the probability of use by nearly 50% for wildlife species. Carnivore species were more likely to cross underpasses used by their prey. Buffalo, livestock, and hyenas used underpasses characterized by vegetation with higher NDVI and near water sources while baboons, dik-diks and antelope avoided underpasses with high NDVI. Our findings suggest a need for diverse and comprehensive approaches for mitigating the negative impacts of rail on African wildlife.


The Effect of Corticosteroids on Prostate Cancer Outcome Following Treatment with Enzalutamide: A Multivariate Analysis of the Phase III AFFIRM Trial.
The clinical impact of concurrent corticosteroid use (CCU) on enzalutamide-treated patients with metastatic castration-resistant prostate cancer (mCRPC) is unknown. We investigated the association of CCU with overall survival (OS), radiographic progression-free survival (rPFS), and time to prostate-specific antigen progression (TTPP) in post-chemotherapy, enzalutamide-treated patients with mCRPC. Post hoc analysis of AFFIRM (NCT00974311) with patients (n = 1,199) randomized 2:1 to enzalutamide 160 mg/day or placebo. Treatment group, CCU, and known prognostic factors were evaluated for impact on OS, rPFS, and TTPP using a multivariate Cox proportional hazards model. CCU was defined as "baseline" (use started at baseline) or "on-study" (baseline plus use that was started during the trial). Enzalutamide significantly improved OS, rPFS, and TTPP independent of baseline CCU but was associated with inferior clinical outcomes when compared with no baseline CCU, including a shorter OS [10.8 months vs. not reached (NR); HR for use vs. no use, 2.13; 95% confidence interval (CI), 1.79-2.54], rPFS (5.2 months vs. 8.0 months; HR, 1.49; 95% CI, 1.29-1.72], and TTPP (4.6 months vs. 5.7 months; HR, 1.50; 95% CI, 1.25-1.81). These findings held in a multivariate analysis adjusting for baseline prognostic factors wherein baseline CCU was independently associated with decreased OS (HR, 1.71; 95% CI, 1.43-2.04; P < 0.0001) and rPFS (HR, 1.28; 95% CI, 1.11-1.48; P = 0.0007). Patients with mCRPC benefited from enzalutamide treatment independent of CCU, but CCU was associated with worse baseline prognostic factors and outcomes.


New Concepts in Tuberculosis Host Defense.
Tuberculosis (TB) host defense depends on cellular immunity, including macrophages and adaptively acquired CD4+ and CD8+ T cells. More recently, roles for new immune components, including neutrophils, innate T cells, and B cells, have been defined, and the understanding of the function of macrophages and adaptively acquired T cells has been advanced. Moreover, the understanding of TB immunology elucidates TB infection and disease as a spectrum. Finally, determinates of TB host defense, such as age and comorbidities, affect clinical expression of TB disease. Herein, the authors comprehensively review TB immunology with an emphasis on new advances.


Applying computational geometry techniques for advanced feature analysis in atom probe data.
In this paper we present new methods for feature analysis in atom probe tomography data that have useful applications in materials characterisation. The analysis works on the principle of Voronoi subvolumes and piecewise linear approximations, and feature delineation based on the distance to the centre of mass of a subvolume (DCOM). Based on the coordinate systems defined by these approximations, two examples are shown of the new types of analyses that can be performed. The first is the analysis of line-like-objects (i.e. dislocations) using both proxigrams and line-excess plots. The second is interfacial excess mapping of an InGaAs quantum dot.


Interaction of Helicobacter pylori infection and low-dose aspirin in the upper gastrointestinal tract: implications for clinical practice.
Low-dose aspirin has been shown to increase the risk of upper gastrointestinal tract injury. Risk factors in upper gastrointestinal complications in low-dose aspirin users are less well defined than in other NSAID users, and there are enough intrinsic differences in the two agents to discuss them separately. In particularly, the role of Helicobacter pylori and the benefit of its eradication in decreasing the risk of upper gastrointestinal tract injury in low-dose ASA users remains controversial. Various consensus groups have recommended H. pylori testing and eradication in low-dose ASA users with a prior history of peptic ulcer or ulcer bleeding. The basis of this recommendation is derived from a limited, albeit expanding evidence on the role of H. pylori in upper gastrointestinal tract injury in low-dose ASA users and on the effectiveness of H. pylori eradication in reducing the risk of complications such as rebleeding in high-risk patients.


[Early operation in acute pancreatitis: operative procedures (author's transl)].
The failure of conservative treatment in severe acute hemorrhagic-necrotizing pancreatitis is one main reason for operative treatment of the diseases by removal of the necrotic masses. In cases of partial necrosis of the pancreas, mortality was significantly reduced by operative treatment; in subtotal and total necrosis only a few patients survived. Early diagnosis and early operation should be done before life-threatening complications occur.


Sexually transmitted diseases in 1161 HIV-positive patients: a 38-month prospective study in southern Spain.
HIV infection is primarily a sexually transmitted disease (STD), but intravenous drug use (IDU) is the main risk factor for HIV infection in certain areas, including southern Europe. A number of prospective studies of dermatological findings in HIV-1 infected patients have been published, almost all from countries where homosexuality is the main risk factor of HIV infection and without correlation with CD4 cell counts. No STD data is included in those studies. To determine the incidence of STDs in a cohort of 1161 HIV-1-positive patients from Spain, in the previous medical history and during the prospective study. We prospectively examined 1161 HIV-1-positive patients for 38 months, 986 men and 175 women. IDU was the risk factor in 74%, while homosexuality was a risk factor in only 9%. CDC stage II was predominant (51%), while stage IV was less frequent (39%). The mean CD4 cell count was 353/mm3. Patients' past and present medical history of STDs was obtained. CD4 cells/mm3 counts were measured at each visit. Six hundred and eighty-four patients had a past history of STD, whilst new infections were diagnosed in 258 individuals (22%) during the 38-month study. Pediculosis pubis (26%), gonorrhoea (22%), syphilis (13%), genital candida infection (11%) and condyloma acuminatum (10%) were the commonest previous STDs, followed by non-gonococcal urethritis (NGU) (5%), genital herpes (4%) and trichomoniasis (2%). During the 38-month study period and with strong recommendation of condom use for sexual intercourse, condyloma acuminatum (7%), scabies (6%), syphilis (4%) and genital herpes (3%) were commonly diagnosed, followed by gonorrhoea (1.8%), NGU (1.6%), genital candida infection (1.5%), pediculosis pubis (0.6%) and trichomoniasis (0.3%). Only genital herpes had a statistically significant association with advanced stage (P = 5.12 x 10(-6)) and low CD4 cell counts (180 +/- 166 cells/mm3). Despite the predominance of the IDU factor among our patients, the incidence of STDs in the past medical history was surprisingly high. The incidence of STD during the study was also high, despite the advice of using condoms after the diagnosis of HIV infection. STDs may accelerate the course of HIV infection and be a poor prognostic indicator in these patients. If an HIV-1-positive patient can acquire an STD, he/she can also transmit HIV infection. This indicates that new publicity campaigns are still needed to stop HIV and STDs infection among HIV-positive patients as well as in the general population.


Parasite dose determines the Th1/Th2 nature of the response to Leishmania major independently of infection route and strain of host or parasite.
Leishmania major causes cutaneous leishmaniasis in mice and man. Infection of mice with relatively low or high numbers of parasites leads respectively to parasite containment, associated with a Th1, cell-mediated response, or progressive disease, associated with a Th2, antibody response in all circumstances studied. These include different parasite strains, different routes of infection, and different hosts previously classified as susceptible, resistant or of intermediate susceptibility. This dose dependency appears to reflect a general rule. We argue that this rule may allow the design of a vaccination strategy that is effective among a genetically diverse population, and that it imposes severe constraints upon proposals for the nature of the "decision criterion" determining whether antigen induces a Th1 or Th2 response.


Perinatal DEHP exposure modulates pituitary estrogen receptor α and β expression altering lactotroph and somatotroph cell growth in prepuberal and adult male rats.
Phthalates are synthetic chemicals widely used to make polyvinylchloride (PVC) soft and flexible. Of these, Di-(2-ethylhexyl) phthalate (DEHP) is the most commonly used, with high human exposure occurring as early as the fetal developmental stage and affecting the endocrine system. We focused on the perinatal DEHP effects on pituitary estrogen receptor (ER) expression in male rats, explored their impact on lactotroph and somatotroph cell growth, and evaluated the direct effects of this phthalate on pituitary cell cultures. Our results showed that DEHP perinatal exposure was unable to modify the ERα+ pituitary cell number from prepuberal rats, but increased ERβ+ cells. In adulthood, the pituitary ERα+ cells underwent a slight decrease with ERβ showing the greatest changes, and with a significant increase observed in somatotroph cells. Also, in vitro, DEHP reduced the ERα+ cells, increased the percentage of ERβ+ pituitary cells and modified the Ki67 index, as well as decreasing the lactotrophs and increasing the somatotroph cells. In conclusion, the present study showed that DEHP induced ER expression changes in normal pituitary glands from male rats in in vivo and in vitro conditions, suggesting that DEHP could differentially modulate lactotroph and somatotroph cell growth, possibly as a consequence of ER imbalance.


Closed ruptures of the flexor digitorum tendons: MRI evaluation.
To assess the MRI findings in cases of closed rupture of the flexor digitorum tendons (FDT). Ten patients with a clinical suspicion of rupture of FDT underwent MRI before surgery. None of the patients presented a skin injury. Fingers were imaged using axial T1-weighted SE sequences, three-dimensional GE images, and curved reconstructions. Twelve FDT had surgical confirmation of rupture. Flexor digitorum profundus (FDP) and flexor pollicis longus (FPL) tendons were more frequently ruptured (n=8) than flexor digitorum superficialis (FDS) tendons (n=4). MR images accurately depicted the level of the rupture. The gap between the tendon ends (mean 45 mm, range 21-70 mm) was assessed best with curved reconstructions and was well correlated with the surgical findings. The proximal end mainly retracted into the palm or the carpal tunnel (n=8), and less frequently into the digital canal (n=4). In two cases, the proximal end curled up in the palm, clinically simulating a rupture of a lumbrical muscle in one case. MRI also showed the appearance of the adjacent tendons. MRI accurately depicted the level of rupture and the gap between the tendon ends, which assisted the surgical choice between suture, graft or tendon transfer.


Giant aneurysm of the circumflex artery.
In this paper, we describe a rare case of a giant aneurysm of the circumflex artery that we managed. A 59-year-old female patient presented in cardiogenic shock after partial aneurysm rupture. Giant aneurysms of the circumflex artery are extremely rare entities. The optimal surgical management dictates meticulous preoperative planning and the operation should be carried out on an elective basis.


Metabolic and antioxidant profiles of herbal infusions and decoctions.
This study implements NMR metabolomics and spectrophotometric studies (Folin-Ciocalteu, FRAP, ABTS) to infusions and decoctions of ten plant species in order to assess and compare the metabolic and antioxidant profiles for each botanical family. Multivariate and univariate data analyses highlighted the differences among the samples and pinpointed specific classes of compounds for each plant species as well as infusions and decoctions. The identified phenolic compounds by NMR, as well as the antioxidant profile, framed a trend of increased values in infusions compared to the decoctions. Moreover, the infusion procedure positively affected the extractability of the phenolic compounds compared to decoctions. The highest total phenolic content was found in Mentha spicata, while the lowest in Matricaria chamomilla preparations, irrespective of the preparation method. The preparation time for the decoctions was examined showing that the 15min preparations were generally found richer in phenolics and of higher antioxidant capacity.


Changes in refractive error for exotropes treated with overminus lenses.
The refractive changes of pediatric patients who were prescribed overminus lenses for exotropia were evaluated. Overminus lenses means additional minus power over the lenses required to correct the refractive error at distance. Forty exotropic patients, ages 1 to 15 years, were prescribed overminus lenses (-0.50 D to -3.75 D) for a period of 9 to 86 months. A small but significant correlation was found between the initial refractive error and the mean annual change toward myopia. Other factors such as age when treatment was given, duration of therapy, amount of overminus, and the amount of the exodeviation had little effect on the rate of myopic change. The mean annual changes in refractive error for hyperopes (-0.13 +/- 0.44 D, N = 15), emmetropes (-0.26 +/- 0.37 D, N = 17), and myopes (-0.75 +/- 0.77 D, N = 18) were similar to values reported in the literature for nonexotropic children.


Endoscopic evaluation of Crohn's disease activity: comparison of the CDEIS and the SES-CD.
Few data exist of prospective parallel scoring of the validated endoscopic scores in Crohn's disease (CD), Crohn's Disease Index of Severity (CDEIS), and Simple Endoscopic Score for Crohn's Disease (SES-CD). Both the CDEIS and the SES-D were scored immediately after each endoscopy of 86 CD patients referred for ileocolonoscopy in a cross-sectional study. Furthermore, after CD therapy, 32 CD patients underwent a follow-up endoscopy with scoring of the CDEIS and SES-CD. Endoscopic scorings were graded as inactive, mild, moderate, or severe. Clinical activity was assessed with the Crohn's Disease Activity Index (CDAI) and serum C-reactive protein (CRP) was measured. The SES-CD correlated with the CDEIS significantly (Spearman's r = 0.938, P < 0.0001). Weaker correlations were detected between the SES-CD and the CDAI (r = 0.473) or CRP (r = 0.525, both P < 0.0001). Grading of SES-CD from inactive to severe correlated significantly with grading of the CDEIS (r = 0.859, P < 0.0001). Changes between baseline and follow-up endoscopy scores correlated significantly (r = 0.828 between delta-CDEIS and delta-SES-CD, P < 0.001), but failed to correlate with delta-CDAI or delta-CRP (all P > 0.05). Both validated endoscopic scores, the CDEIS and SES-CD, and their changes during CD therapy demonstrated a close correlation. For scoring of endoscopic activity in clinical routine, the SES-CD could replace the CDEIS.


Impaired vascular reactivity in patients with chronic kidney disease.
Patients with chronic kidney disease (CKD) show increased cardiovascular morbidity. We hypothesized that vascular properties which can be routinely evaluated noninvasively are related to different stages of CKD and their clinical and biochemical characteristics. Arterial vascular properties were quantified by the reflective index using digital photoplethysmography in 260 patients with CKD. Patients were grouped according to estimated glomerular filtration rate (eGFR). Additional measurements were performed in 50 healthy control subjects. In patients with CKD stage 1 and 2 (n = 115; age 65 +/- 1 years) the reflective index was 30 +/- 1%, whereas in patients with CKD stage 3 and 4 (n = 60; age 72 +/- 1 years) the reflective index was 36 +/- 1%, and in patients with CKD stage 5 (n = 85; age 64 +/- 1 years) the reflective index was 36 +/- 1% (p < 0.01 by Kruskal-Wallis test) indicating increased arterial stiffness in advanced CKD. Arterial vascular reactivity was significantly impaired in patients with advanced stages of CKD (stage 1 and 2, 78 +/- 12%; stage 3 and 4, 32 +/- 12%; stage 5, 33 +/- 12%; p < 0.01). Univariate analysis showed a significant correlation of the reflective index and eGFR (Pearson r = -0.24; p < 0.0001). Multivariate regression analysis showed an independent association of the reflective index and eGFR (adjusted correlation coefficient, -0.24; p < 0.001). The advanced stages of CKD are associated with increased vascular stiffness and impaired vascular reactivity and these changes are already present in CKD stage 3 and 4.


Do emotional intelligence and previous caring experience influence student nurse performance? A comparative analysis.
Reports of poor nursing care have focused attention on values based selection of candidates onto nursing programmes. Values based selection lacks clarity and valid measures. Previous caring experience might lead to better care. Emotional intelligence (EI) might be associated with performance, is conceptualised and measurable. To examine the impact of 1) previous caring experience, 2) emotional intelligence 3) social connection scores on performance and retention in a cohort of first year nursing and midwifery students in Scotland. A longitudinal, quasi experimental design. Adult and mental health nursing, and midwifery programmes in a Scottish University. Adult, mental health and midwifery students (n=598) completed the Trait Emotional Intelligence Questionnaire-short form and Schutte's Emotional Intelligence Scale on entry to their programmes at a Scottish University, alongside demographic and previous caring experience data. Social connection was calculated from a subset of questions identified within the TEIQue-SF in a prior factor and Rasch analysis. Student performance was calculated as the mean mark across the year. Withdrawal data were gathered. 598 students completed baseline measures. 315 students declared previous caring experience, 277 not. An independent-samples t-test identified that those without previous caring experience scored higher on performance (57.33±11.38) than those with previous caring experience (54.87±11.19), a statistically significant difference of 2.47 (95% CI, 0.54 to 4.38), t(533)=2.52, p=.012. Emotional intelligence scores were not associated with performance. Social connection scores for those withdrawing (mean rank=249) and those remaining (mean rank=304.75) were statistically significantly different, U=15,300, z=-2.61, p$_amp_$lt;0.009. Previous caring experience led to worse performance in this cohort. Emotional intelligence was not a useful indicator of performance. Lower scores on the social connection factor were associated with withdrawal from the course.


Current treatment and future directions in heart failure.
Recent research in the pathophysiology of congestive heart failure has focused on the blockade of neurohormonal systems. Large clinical trials have clearly demonstrated morbidity and mortality benefits of angiotensin-converting-enzyme inhibitors and beta blockers. Indeed, all patients with heart failure should be treated with these agents unless there is a specific contraindication otherwise. Despite this treatment, however, mortality from heart failure remains high. Current investigation is now focused on other pathophysiological mechanisms and the interruption of these pathways.


Distribution of motoneurons involved in the prey-catching behavior in the Japanese toad, Bufo japonicus.
Coordinated activities of several muscles in the head region underlie the prey-catching behavior of anuran amphibians. As a step in elucidating the neural mechanisms generating these activity patterns in the Japanese toad, we labelled the motoneurons innervating 8 behaviorally relevant muscles using intramuscular (i.m.) injection technique of horseradish peroxidase (HRP), and examined their localization within the motor nuclei whose boundaries were determined by HRP application to the nerve trunk. All the motoneurons innervating the two jaw closer muscles (m. masseter major, m. temporalis) and m. submentalis were localized within the rostral subdivision of the trigeminal motor nucleus. The motoneurons innervating the only mouth opener muscle (m. depressor mandibulae) were scattered throughout the facial motor nucleus. The motoneurons innervating tongue (m. hypoglossus, m. genioglossus) and hyoid muscles (m. sternohyoideus, m. geniohyoideus) appeared within the hypoglossal nucleus with distribution patterns characteristic of the target muscles. Thus, we have revealed the neuroanatomical organization of the motoneurons relevant to the prey-catching behavior.


Implementing a Delirium Risk Stratification Tool and Rounds to Identify and Prevent Delirium in Hospitalized Older Adults.
Up to 40% of delirium cases are preventable, and early identification is key to improve patient outcomes. To implement and evaluate a multidisciplinary delirium intervention program. The delirium intervention program targeted patients at high risk for delirium and included patient and nurse education, risk stratification, multidisciplinary rounds, a nonpharmacological intervention bundle, and a treatment order set. After implementation, there was a reduction in length of stay of 6.3 days ( P = .01), a 24% decrease in disposition to a skilled nursing facility ( P = .05), and increased detection of delirium by nurses. Positive patient outcomes were achieved by employing a multifactorial approach for delirium identification, prevention, and management. The components of this quality improvement project provide guidance to hospitals seeking to develop a delirium intervention program.


"Writing About Medicine": an exercise in reflection at Mount Sinai (with five samples of student writing).
This paper describes the introduction of a new elective, "Writing About Medicine," into the Mount Sinai School of Medicine (MSSM) curriculum, part of a new trend of developing humanities programs at medical schools. This paper will first survey two exemplary programs at other schools, and discuss their impact on students. It will then detail the development of "Writing About Medicine," including its purpose and format. Finally, it will present focus group data evaluating the course and elaborate on its role in the MSSM educational process.


Western blotting analysis as a tool to study receptor tyrosine kinases.
Receptor tyrosine kinases (RTKs) are involved in critical aspects of cell physiology ranging from cell -survival, proliferation, growth, migration, and differentiation. A tight control of the extent and duration of signals elicited by activated RTKs is crucial for preventing over-stimulation, which can ultimately lead to unrestrained proliferative ability and neoplastic growth. Ligand-induced downregulation of RTKs has emerged as a key negative regulatory mechanism that can accomplish signaling attenuation, by removing activated receptors from the cell surface and committing them to degradation. The ability of RTKs to escape from ligand-induced downregulation has been reported as a recurrent mechanism of oncogenic deregulation in cancer.Western blotting procedures have been extensively proven as straightforward assays to evaluate -protein expression levels and have been widely applied to study RTKs downregulation.


Tooth whitening products and the risk of oral cancer.
Tooth whitening products (TWP) containing hydrogen peroxide (HPO) or carbamide peroxide (CPO) were evaluated in relation to potential oral cancer risk from their use. HPO is genotoxic in vitro, but such activity is not expressed in vivo. The genotoxic risk of HPO exposure of the oral mucosa encountered from TWP use is likely therefore to be vanishingly small. Available animal data on the carcinogenicity of HPO are of limited relevance to risk assessment of oral hazard of HPO exposure from TWP, and where relevant, do not indicate that there is an increased oral cancer risk for people using TWP. Clinical data on HPO-containing TWP only show evidence of mild, transient gingival irritation and tooth sensitivity, with no evidence for the development of preneoplastic or neoplastic oral lesions. Exposures to HPO received by the oral cavity, including areas commonly associated with oral cancer, are exceedingly low and do not plausibly pose a risk for the promotion of initiated cells or for induction of co-carcinogenic effects in conjunction with cigarette smoke or alcohol. The use of TWP was concluded not to pose an increased risk for oral cancer in alcohol abusers and/or heavy cigarette smokers. Furthermore, TWP were concluded to be safe for use by all members of the population, including potential accidental use by children.


Identification of a blood group A active hexaglycosylceramide with a type 1 carbohydrate chain in plasma of an A1 Le(a-b-) secretor.
A blood group A active hexaglycosylceramide with a type 1 carbohydrate chain was identified in the plasma of an A1 Le(a-b-) secretor. The analysis was done on the total non-acid glycosphingolipid fraction using mass spectrometry, NMR spectroscopy, and anti-A antibody immunostaining on thin-layer chromatograms.


Involvement of GABAB receptors in the regulation of the hypothalamo-pituitary-adrenocortical (HPA) axis in rats.
Previous experiments have shown that the GABAB receptor agonist L-baclofen given subcutaneously to male rats significantly enhanced plasma concentrations of adrenocorticotropic hormone (ACTH) and the adrenocortical hormones corticosterone and aldosterone. The goal of the present study was to investigate whether the stimulatory effects on adrenocortical steroids elicited by L-baclofen in vivo could be reversed by the selective GABAB antagonist CGP 35 348. One hour before subcutaneous administration of 3 mg/kg L-baclofen, a dose of 600 mg/kg CGP 35 348 or saline was administered intraperitoneally. The stimulatory effect of L-baclofen on ACTH, corticosterone and aldosterone was significantly reduced by 60% after pretreatment with CGP 35 348. The GABAB antagonist CGP 35 348 by itself had no effect on ACTH or the adrenocortical hormones. These results indicate that GABAB receptors are involved in the L-baclofen-induced activation of the HPA axis in rats. In vitro, however, neither L-baclofen nor CGP 35 348 had any effects on corticosterone and aldosterone release from perifused adrenal cells. These results suggest that the participation of GABAB receptors in the activation of the HPA axis induced by L-baclofen in vivo does not occur at the level of the adrenal gland, and therefore must occur at the level of the pituitary or the brain.


A Phase II Study on the Effect of Taurisolo® Administered via AEROsol in Hospitalized Patients with Mild to Moderate COVID-19 Pneumonia: The TAEROVID-19 Study.
Polyphenols are the largest class of bioactive compounds in plants, which are synthesized as secondary metabolites. In the last few years, interesting studies have demonstrated the efficacy of polyphenols against coronavirus infections. we conducted a phase II multicentric clinical trial (TAEROVID-19) during the first wave of the COVID-19 pandemic in order to assess the safety and feasibility of Taurisolo® aerosol formulation in hospitalized patients suffering from SARS-CoV-2 pneumonia. we observed a rapid decline of symptoms and a low rate of intensive care in patients treated with Taurisolo®, with a faster decline of symptoms. This is the first trial assessing the safety and feasibility of Taurisolo® aerosol formulation. We could argue that this treatment could act as an add-on therapy in the treatment of COVID-19 patients, owing to both its anti-inflammatory and antioxidant effects. Further controlled trials are needed, which may be of interest to evaluate the compound's efficacy.


Monitoring improvements in the nutritional quality of new packaged foods launched between 2016 and 2020.
Food and beverage companies reformulate packaged foods and to better align their products with public health policies and evolving consumer needs. The nutritional quality of packaged foodscan be tracked using nutrient profiling methods. The present study compared the nutritional quality of packaged foods launched globally between 2016 and 2018 and those launched in 2018-2020, as reported in the Mintel Global New Products Database. Nutrient profiling analyses showed that the nutrient composition of product categories shifted for almost 40% of newly launched products between 2016-2018 and 2018-2020. For example, pizzas that had been assigned to one nutritionally homogenous category in 2016-2018 separated in two nutritionally distinct subgroups in 2018-2020. The new products that were reduced in protein, saturated fat, and sodium were now nutritionally distinct from the traditional pizza offer. By 2018-2020 "best of category" products were significantly lower in sugar and sodium than before; however, no clear trend was observed for saturated fats, proteins, or fibers. The relative speed of product reformulation was category specific. This analysis of the Mintel Global New Products Database suggests that the WHO nutritional recommendations focusing on sugar and sodium reduction did have a positive impact on the composition of new packaged foods, whether through reformulation of existing products, launches of line extensions or new product development.


Oligomycin and antimycin A prevent nitric oxide-induced apoptosis by blocking cytochrome C leakage.
Nitric oxide (NO) is a potent inducer of apoptosis, and its cytotoxicity is closely related to mitochondrial dysfunction. In this study we investigated the effects of a F0F1-ATPase inhibitor, oligomycin, and a mitochondrial respiratory chain complex III inhibitor, antimycin A, on NO-induced apoptosis. We used a normal rat gastric-epithelium cell line, RGM-1, treated with a pure NO donor, NOC-1 -1-hydroxy-2-oxo-3,3-bis(2-aminoethyl)-1-triazene - in the presence or absence of oligomycin or antimycin A. Changes in the expressions of Bax or Bcl-2 proteins, release of cytochrome C from mitochondria into the cytosol, activation of caspase-3, and changes in the mitochondrial membrane potential (DeltaPsi) were measured with the use of Western blotting, c43 lorimetric assays, and a mitochondrial potential sensor, JC-1 dye. Treatment with NOC-18 induced dose-dependent apoptotic cell death in RGM-1 cells. Cell death was accompanied by mitochondrial depolarization, increases in Bax protein expression and cytochrome C leakage, and, subsequently, caspase-3 activation. Oligomycin and antimycin A prevented NO-induced apoptosis in a dose-dependent fashion by preventing cytochrome C release independent of Bcl-2 expression. However, neither compound affected the up-regulation of Bax protein. On the one hand, oligomycin treatment was not accompanied by a decline in DeltaPsi. On the other hand, antimycin A treatment decreased DeltaPsi regardless of NOC-18 treatment. The findings of this study suggest that various functional molecules that constitute the mitochondrial respiratory chain may contribute to cytochrome C release that occurs during NO-induced apoptosis.


Biliary tract large cell neuroendocrine carcinoma: current evidence.
Primary neuroendocrine carcinomas of the gallbladder and biliary tract are rare, with pure large cell neuroendocrine carcinomas (LCNEC) being exceedingly rare and with a particularly poor prognosis. We performed a review of published data on biliary tract large cell neuroendocrine carcinomas in PubMed. Preliminary search revealed over 2000 results but we found only 12 cases of pure large cell neuroendocrine carcinomas of biliary tract noted in literature to date. Because it commonly presents with non-specific symptoms of abdominal pain and jaundice, diagnosis is made after resection with histo-pathological and immunohistochemical analysis. These cancers are particularly aggressive with high recurrence rates, most often presenting with metastasis to regional lymph nodes and/or the liver resulting in a poor prognosis. Overall, complete surgical excision with systemic chemotherapy is the treatment mainstay. If the cancer is unresectable due to multiple metastases, medical management with systemic chemotherapy is the primary treatment modality. The prognosis of hepatobiliary LCNEC remains poor with median survival of only 11 months from initial diagnosis. Studies focusing on high grade neuroendocrine carcinoma are needed to enhance our understanding of biology and therapeutics in this rare but aggressive cancer.


NSILA-carrier protein abolishes the action of nonsuppressible insulin-like activity (NSILA-S) on perfused rat heart.
Human serum in a concentration of 10% in the perfusion medium failed to increase glucose uptake by the isolated perfused rat heart, indicating that nonsuppressible insulin-like activity (NSILA) in whole serum was inactive in this system. When NSILA-carrier protein was added to partially purified NSILA-S, its biological activity on the rat heart disappeared. In contrast, the action of insulin was not affected by the presence of NSILA-carrier protein. Binding of 125I-labelled NSILA-S to rat heart was inhibited by NSILA-carrier protein. 125I-labelled insulin binding was not inhibited. These results support the hypothesis that NSILA-S bound to serum carrier protein is a large molecular compound which does not readily diffuse out of the capillary bed and therefore does not exert insulin-like effects in vivo.


Long-term Effectiveness and Safety of Upadacitinib for Atopic Dermatitis in a Real-world Setting: An Interim Analysis Through 48 Weeks of Observation.
Janus kinase (JAK) inhibitors, including upadacitinib, have been recently approved for the treatment of moderate-severe atopic dermatitis (AD) and real-world data on upadacitinib effectiveness and safety are limited. This interim analysis aimed to assess effectiveness and safety of upadacitinib throughout 48 weeks of observation in a real-world adult AD population. This prospective study collected data on adult patients affected by moderate-to-severe AD and treated with upadacitinib at the dosage of either 15 mg or 30 mg daily based on the physician decision. Upadacitinib was prescribed in the context of a national compassionate use programme. In this interim analysis, within patient comparisons of continuous scores of different scales (namely Eczema Area and Severity Index [EASI], body surface area [BSA], Dermatology Life Quality Index [DLQI], Patient Oriented Eczema Measure [POEM], Numeric Rating Scale [NRS] subtests) were performed. The percentage of patients achieving EASI 75, EASI 90 and EASI 100 at Week 16, 32 and 48 was also evaluated. One hundred and forty-six patients were included in the analysis. Upadacitinib 15 mg or 30 mg daily was prescribed as monotherapy in most cases (127/146, 87.0%). Upadacitinib was initially prescribed at the dosage of 30 mg daily in 118 of 146 (80.8%) patients and 15 mg daily in 28/146 (19.2%) patients. A significant improvement in the clinical signs and symptoms of AD was detected by Week 16 and throughout the study period. EASI 75, EASI 90 and EASI 100 responses were achieved by 87.6%, 69.1% and 44.3% at Week 48, associated with a sustained reduction in the mean values of all physician-reported (EASI and BSA) and patient-reported (Itch- Sleep- and Pain-NRS, DLQI, and POEM) disease severity outcomes, up to 48 weeks of treatment. Treatment response observed in 15 mg upadacitinib-treated patients was comparable with that detected in 30 mg upadacitinib-treated patients, revealing no statistical difference between the two patient sub-cohorts. Through the observation period, dose reduction or escalation was observed in 38/146 (26%) of treated cases. Overall, 26 of 146 (17.8%) patients experienced at least one adverse event (AE) during the treatment period. In total, 29 AEs were recorded and most of them were evaluated as mild to moderate, while in 4 cases the occurrence of AE led to drug discontinuation, for a total of 7/146 (4.8%) dropouts. This study provides strong evidence of a sustained response obtained by upadacitinib in AD patients, who had failed to respond to conventional or biological systemic agents, through 48 weeks of observation. Upadacitinib was also demonstrated to be advantageous in terms of flexibility in dose reduction or escalation as upadacitinib dose was shaped on clinical needs that, in a real-world setting, might frequently change.


Endothelium-dependent relaxant effect of neurokinins on rabbit aorta is mediated by the NK1 receptor.
Several neurokinins, namely substance P, neurokinin A, neurokinin B, [beta-Ala8]neurokinin A-(4-10) and senktide, were tested on noradrenaline-precontracted rabbit aortic rings to characterize the receptor mediating their endothelium-dependent relaxant effect in this preparation. CP-96,345, the new nonpeptide antagonist selective for the NK1 receptor, was also studied. Substance P, neurokinin A and neurokinin B, in that order of potency, were effective in relaxing precontracted rings, indicating the involvement of the NK1 receptor; [beta-Ala8]neurokinin A-(4-10) and senktide, which are selective agonists for NK2 and NK3 receptors, respectively, had no significant relaxant effect. The relaxant effects of substance P, neurokinin A and neurokinin B were competitively antagonized by nanomolar concentrations of CP-96,345. These findings support the view that the NK1 receptor mediates the endothelium-dependent relaxant effect of the neurokinins in rabbit aorta.


Quercetin and interferon-beta modulate immune response(s) in peripheral blood mononuclear cells isolated from multiple sclerosis patients.
The study is aimed to determine the role of quercetin (3,3'4',5,7-pentahydroxy flavone), alone and in combination with human interferon-beta (IFN-beta), in modulating the immune response(s) of peripheral blood mononuclear cells (PBMC) isolated from multiple sclerosis (MS) patients and from normal healthy subjects. PBMC proliferation in the presence or absence of these drugs was determined and the production of proinflammatory cytokines (IL-1beta, TNF-alpha), and the ratio of cell migration mediator MMP-9, and its inhibitor, TIMP-1 were assessed in the culture supernatants. Quercetin reduced, in a dose-dependent manner, the proliferation of PBMC and modulated the level of IL-1beta and TNF-alpha released by PBMC in the culture supernatants. Quercetin reduced the MMP-9/TIMP-1 ratio via lowering MMP-9 production. Quercetin, when combined with IFN-beta, had additive effects in modulating TNF-alpha and MMP-9. These immunomodulatory responses to quercetin were similar between MS patients and healthy control (HC) subjects.


Radial strain gradient across the normal myocardial wall in open-chest pigs measured with doppler strain rate imaging.
One of the reasons for the large variation in radial strain measured with Doppler strain rate imaging in normal myocardium might be the different strain length (SL) used during analyses. The aim of this study was to evaluate the effect of different SL settings on strain recordings and the method's ability to detect transmural radial strain gradients. In 8 anesthetized pigs (mean weight 54 kg) epicardial echocardiography was performed. Strain analysis was carried out by defining the wall as a 1-, 2-, 3-, and 4-layer structure with suitable regions of interest. Peak ejection strain was measured with SL settings of 2 to 14 mm. The systolic (ejection) strain showed large variation with SL. Sampling in one layer gave no significant reduction in strain for increasing SL. The strain in the subepicardial layer was low and decreased when the wall was divided into several layers (15.9 +/- 4.8% [2 layers]-2.1 +/- 2.4% [4 layers]; both measurements with SL = 4 mm). The method could separate 4 layers with SL of 4 mm or less, 3 layers with SL of 6 mm or less, and 2 layers with SL of 8 mm or less. When measuring radial strain in the myocardial wall the SL must be low to evaluate transmural strain gradients. With correct settings of SL and region of interest, strain in 4 layers can be distinguished. As a rule of thumb the SL should be set to approximately half the systolic thickness of the wall or half the wall layer.


Household food insecurity, income loss, and symptoms of psychological distress among adults following the Cyclone Amphan in coastal Bangladesh.
Cyclone Amphan swept into Bangladesh's southwestern coast at the end of May 2020, wreaking havoc on food security and economic stability, as well as possibly worsening mental health. We studied the prevalence of post-cyclone stressors in adults following the cyclone and its association with symptoms of psychological distress. We conducted a cross-sectional study in a coastal district of Bangladesh. A five-item brief symptom rating scale was used to measure the symptoms of psychological distress. Household food insecurity was measured using the USAID Household Food Insecurity Access Scale questionnaire. We estimated adjusted prevalence ratios (aPRs) using robust log-linear models adjusted for potential confounders. A total of 478 adults (mean [SD] age, 37.0[12.6] years; 169[35.4%] women) participated in the study. The prevalence of moderate-to-severe psychological symptoms and suicidal ideation was 55.7% and 10.9%, respectively. Following the cyclone, 40.8% of the adults reported severe food insecurity, and 66% of them reported moderate-to-severe mental health symptoms. Also, 54.4% of women and 33.7% of men reported severe food insecurity in the households. Moreover, 25.5% of respondents reported no income or a significant income loss after the cyclone, and 65.5% of them had moderate-to-severe psychological symptoms. Also, 13.8% of respondents reported housing displacement because of severely damaged houses, and 68.2% of them reported moderate-to-severe psychological symptoms. The high prevalence of mental health symptoms was found in women (aPR = 1.41, 95% CI = 1.06-1.82), people with severe food insecurity (aPR = 1.63, 95% CI = 1.01-2.64), and people who lost jobs or lost a major income source (aPR = 1.25, 95% CI = 1.02-1.54). Following cyclone Amphan, many low-income individuals saw their income drop drastically while others were unemployed and living with severe food insecurity. The result suggests gender inequalities in food-security after the cyclone. Immediate action is needed to ensure household food-security for reducing the burden of mental illness. Rising opportunities of paid-jobs and decreasing income-loss, especially for the poor people, can have a protective impact on psychological distress. However, due to the high prevalence of severe psychological symptoms, long-term mental health services are required among the population of coastal Bangladesh.


Cr2S3-Cr2O3/Poly-2-aminobenzene-1-thiol as a Highly Photocatalytic Material for Green Hydrogen Generation from Sewage Water.
This study highlights the utilization of the Cr2S3-Cr2O3/P2ABT nanocomposite photoelectrode for efficient and highly sensitive photon absorption, enabling the generation of green hydrogen through the production of hot electrons upon illumination. The nanocomposite is synthesized via a one-pot reaction using K2Cr2O7 and 2-aminobenzene-1-thiol monomer, and the presence of Cr2S3-Cr2O3 is confirmed by XRD and XPS analysis within the composite. The optical properties of the Cr2S3-Cr2O3/poly-2-aminobenzene-1-thiol composite exhibit wide spectral coverage from UV to IR, with a bandgap of 1.6 eV. The diverse morphological behavior observed in the composite correlates with its optical properties, with the cleft spherical particles of the pure polymer transforming into rod-like structures embedded within the polymer matrix. The generated hydrogen gas demonstrates an impressive efficiency of 40.5 mole/10.cm2.h through electrochemical testing. The current density (Jph) values are evaluated under different light frequencies using optical filters ranging from 730 to 340 nm, resulting in Jph values of 0.012 and 0.014 mA.cm-2, respectively. These findings present a promising avenue as green hydrogen for industrial applications, leveraging the potential of the Cr2S3-Cr2O3/P2ABT nanocomposite photoelectrode.


Usage and comparison of artificial intelligence algorithms for determination of growth and development by cervical vertebrae stages in orthodontics.
Growth and development can be determined by cervical vertebrae stages that were defined on the cephalometric radiograph. Artificial intelligence has the ability to perform a variety of activities, such as prediction-classification in many areas of life, by using different algorithms, In this study, we aimed to determine cervical vertebrae stages (CVS) for growth and development periods by the frequently used seven artificial intelligence classifiers, and to compare the performance of these algorithms with each other. Cephalometric radiographs, that were obtained from 300 individuals aged between 8 and 17 years were included in our study. Nineteen reference points were defined on second, third, and 4th cervical vertebrae, and 20 different linear measurements were taken. Seven algorithms of artificial intelligence that are frequently used in the field of classification were selected and compared. These algorithms are k-nearest neighbors (k-NN), Naive Bayes (NB), decision tree (Tree), artificial neural networks (ANN), support vector machine (SVM), random forest (RF), and logistic regression (Log.Regr.) algorithms. According to confusion matrices decision tree, CSV1 (97.1%)-CSV2 (90.5%), SVM: CVS3 (73.2%)-CVS4 (58.5%), and kNN: CVS 5 (60.9%)-CVS 6 (78.7%) were the algorithms with the highest accuracy in determining cervical vertebrae stages. The ANN algorithm was observed to have the second-highest accuracy values (93%, 89.7%, 68.8%, 55.6%, and 78%, respectively) in determining all stages except CVS5 (47.4% third highest accuracy value). According to the average rank of the algorithms in predicting the CSV classes, ANN was the most stable algorithm with its 2.17 average rank. In our experimental study, kNN and Log.Regr. algorithms had the lowest accuracy values. SVM-RF-Tree and NB algorithms had varying accuracy values. ANN could be the preferred method for determining CVS.


Pan-cancer methylation analysis reveals an inverse correlation of tumor immunogenicity with methylation aberrancy.
Tumor immunogenicity is driven by various genomic and transcriptomic factors but the association with the overall status of methylation aberrancy is not well established. We analyzed The Cancer Genome Atlas pan-cancer database to investigate whether the overall methylation aberrancy links to the immune evasion of tumor. We created the definitions of hypermethylation burden, hypomethylation burden and methylation burden to establish the values that represent the degree of methylation aberrancy from human methylation 450 K array data. Both hypermethylation burden and hypomethylation burden significantly correlated with global methylation level as well as methylation subtypes defined in previous literatures. Then we evaluated whether methylation burden correlates with tumor immunogenicity and found that methylation burden showed a significant negative correlation with cytolytic activity score, which represent cytotoxic T cell activity, in pan-cancer (Spearman rho = - 0.37, p < 0.001) and 30 of 33 individual cancer types. Furthermore, this correlation was independent of mutation burden and chromosomal instability in multivariate regression analysis. We validated the findings in the external cohorts and outcomes of patients who were treated with immune checkpoint inhibitors, which showed that high methylation burden group had significantly poor progression-free survival (Hazard ratio 1.74, p = 0.038). Overall, the degree of methylation aberrancy negatively correlated with tumor immunogenicity. These findings emphasize the importance of methylation aberrancy for tumors to evade immune surveillance and warrant further development of methylation biomarker.


The midbrain of sauropsides shares a common subdivision pattern defined by embryonic radial glia.
In a previous study of the embryonic midbrain radial glia in a lizard, we observed that these cells define boundaries and regional subdivisions in a pattern that largely supports the adult model [C. Diaz, C. Yanes, C.M feminine. Trujillo, L. Puelles, Cytoarchitectonic subdivisions in the subtectal midbrain of the lizard Gallotia galloti, J. Neurocytol. 29 (2000) 569-593]. With the goal to check whether the midbrain of chick embryos has a similar pattern, we examined the radial glia distribution in this model using a lipophilic dye (DiI) injected intraventriculary. As in the lizard, chick radial glia distribution and fasciculation defines at least six regional subdivisions in the midbrain, five of which are alar and one basal. Each territory corresponds to a particular cytoarchitectonic area, recognized previously. The rostral mesencephalic limit (m/d) is underlined in the alar zone by a thick band of fasciculated radial glia intercalated between the griseum tectale and the posterior commissure. A fasciculated radial glia band also defines the caudal mesencephalic limit (m/r) across the alar and basal zones. These glial specializations, not described previously in the chick, give physical entity to the limits deduced from gene expression studies and suggested by descriptive cytoarchitectonic analysis. We conclude that the midbrain of sauropsides shares a common subdivision pattern co-defined by radial glia arrangements.


Archaeal and bacterial community dynamics and bioprocess performance of a bench-scale two-stage anaerobic digester.
Two-stage technologies have been developed for anaerobic digestion of waste-activated sludge. In this study, the archaeal and bacterial community structure dynamics and bioprocess performance of a bench-scale two-stage anaerobic digester treating urban sewage sludge have been studied by the means of high-throughput sequencing techniques and physicochemical parameters such as pH, dried sludge, volatile dried sludge, acid concentration, alkalinity, and biogas generation. The coupled analyses of archaeal and bacterial communities and physicochemical parameters showed a direct relationship between archaeal and bacterial populations and bioprocess performance during start-up and working operation of a two-stage anaerobic digester. Moreover, results demonstrated that archaeal and bacterial community structure was affected by changes in the acid/alkalinity ratio in the bioprocess. Thus, a predominance of the acetoclastic methanogen Methanosaeta was observed in the methanogenic bioreactor at high-value acid/alkaline ratio, while a predominance of Methanomassilicoccaeceae archaea and Methanoculleus genus was observed in the methanogenic bioreactor at low-value acid/alkaline ratio. Biodiversity tag-iTag sequencing studies showed that methanogenic archaea can be also detected in the acidogenic bioreactor, although its biological activity was decreased after 4 months of operation as supported by physicochemical analyses. Also, studies of the VFA producers and VFA consumers microbial populations showed as these microbiota were directly affected by the physicochemical parameters generated in the bioreactors. We suggest that the results obtained in our study could be useful for future implementations of two-stage anaerobic digestion processes at both bench- and full-scale.


Invasion costs, impacts, and human agency: response to Sagoff 2020.
Article impact statement: In an era of profound biodiversity crisis, invasion costs, invader impacts, and human agency should not be dismissed.