The Long-Term Clinical and Endoscopic Outcomes of Cronkhite-Canada Syndrome.
The prognosis of Cronkhite-Canada syndrome (CCS) is considered poor. Despite the recent therapeutic improvements, the survival outcomes and prognostic factors have been less studied. This study aimed to investigate the long-term clinical and endoscopic outcomes of CCS. Thirty-one patients diagnosed since 1999 and followed up for over 6 months were included. Data regarding survival outcomes, clinical symptoms, endoscopic findings, and treatment were collected and analyzed. R (version 3.6.1) was used to perform the survival analyses. The median (interquartile range) follow-up time was 42.5 (19.5-85.8) months. The 5-year overall survival (OS) was 87.4%. The maximum gastric polyp size over 2 cm was associated with worse OS (Hazard ratio [HR]: 18, 95% confidence interval [CI]: 1.6-210, P = 0.021). The 3-year relapse-free survival (RFS) after corticosteroid treatment was 66.8%. Age older than 60 years (HR: 7.0, 95% CI: 1.5-33.0, P = 0.015) and maximum gastric polyp size over 2 cm (HR: 6.0, 95% CI: 1.6-23.0, P = 0.009) were associated with worse RFS. Twenty-three patients received follow-up endoscopic examinations, with a median (interquartile range) follow-up time of 29.0 (14.0-53.5) months. Eight (34.8%) and 12 (52.2%) patients achieved complete remission under gastroscopy and colonoscopy, respectively. Colonic lesions showed a tendency of earlier responses compared with gastric lesions (25.0 [11.3-39.8] months vs 31.0 [21.0-39.8] months). Patients with CCS usually responded well to glucocorticoids with a fairly good 5-year survival rate. Large gastric polyp was associated with worse OS and RFS, whereas age older than 60 years was another predictor for worse RFS. Diffuse gastrointestinal lesions partly or completely resolved after treatment, and colonic lesions showed a better response than gastric lesions.


Modifications in GPR21 and GPR82 genes expression as a consequence of metabolic syndrome etiology.
Metabolic syndrome (MS) has been related with alterations in expression levels of orphan G protein coupled receptors (GPCRs) such as GPR21 and GPR82, which could be involved in some of the elements that characterizes the metabolic syndrome. The aim of this work was to evaluate changes in GPR21 and GPR82 receptors expression in two models of metabolic syndrome: one genetic (Zucker rats), and the other based on a diet (70% fructose for 9 weeks). GPR21 and GPR82 gene expressions were evaluated in brain, heart, aorta, liver and kidney by RT-qPCR. Rats with a high fructose diet, as well as obese Zucker rats, showed initial stages of pancreatic damage and alterations in some biochemical parameters related to the model consistent with the classification of MS. GPR21 and GPR82 receptors expressed in all tissues. The expression of GPR21 decreased in heart, aorta and kidney, but in liver the expression was different: decreased in diet model and increased in genetic model. In contrast, GPR82 expression depended of tissue and metabolic syndrome model. The results highlight the possible role of GPR21 and GPR82 receptors in the development MS. We conclude that the expression of GPR21 and GPR82 in different tissues is related with MS and depend of the origin of the syndrome, so they could be a therapeutic target for that syndrome.


Survival and freedom from progression in autotransplant lymphoma patients is independent of stem cell source: further follow-up from the original randomised study to assess engraftment.
Peripheral blood progenitor cells (PBPCs) have become the stem cell source of choice in autologous transplantation. In a prospective randomised trial, we previously demonstrated that autologous transplantation using filgrastim-mobilised PBPCs resulted in faster haematopoietic recovery with shorter hospitalisation and reduced platelet transfusions compared to bone marrow transplant (BMT). This study is a follow-up analysis evaluating the long-term clinical outcome. Seventy-two patients with advanced Hodgkin's disease or high-grade lymphoma were randomised to receive either filgrastim-mobilised PBPCs (n = 37) or bone marrow (n = 35) after BEAM chemotherapy. Fourteen patients withdrew from the study before commencing high-dose chemotherapy. Fourteen of the 58 patients who received treatment with chemotherapy and transplant have died, 6 (19%) in the ABMT arm and 8 (30%) in the PBPC transplant (PBPCT) arm. Twenty-five patients (81%) in the ABMT arm and 17 (63%) in the PBPCT arm, who received treatment, were in complete remission at the date of last follow-up. Progression-free survival and overall survival (OS) were similar for both arms (OS 81% at 46 months for ABMT versus 63% for PBPC; p = 0.38). Further prospective studies with larger number of patients need to be done to assess which source of stem cells may translate into a long-term clinical benefit for the patient.


Maternal depression and loss of children under the one-child family planning policy in China: a cross-sectional study of 300 000 women.
This study aims to explore the association between maternal depression and the loss of the only child under the family-planning (FP) policy. Cross-sectional data from a Chinese population-based study were analysed. Population from 10 (5 rural and 5 urban) areas in China. Around 300 000 females were included in the study. The FP group was defined as women with one or two live births. Those with no surviving child were classified into the loss-of-only-child group. The non-FP group included women who had more than two live births. Logistic regression was used to assess the relationship between major depressive disorder (MDD) and family types, after stratification and adjustment. MDD was assessed using the Composite International Diagnostic Inventory. The odds of MDD are 1.42 times higher in the FP group in general (OR=1.42, 95% CI: 1.28 to 1.57), as opposed to the non-FP group. In particular, the odds of MDD are 1.36 times greater in the non-loss-of-only-child group (OR=1.36, 95% CI: 1.21 to 1.51) and 2.80 (OR=2.80, 95% CI: 0.88 to 8.94) times greater in the loss-of-only-child group, compared with the non-FP group. The associations between FP groups and MDD appeared to be stronger in the elderly population, in those who were married, less educated and those with a higher household income. The association was found progressively stronger in those who lost their only child. People in the FP group, especially those who lost their only child, are more susceptible to MDD than their counterparts in the non-FP group. Mental health programmes should give special care to those who lost their only child and take existing social policies and norms, such as FP policies, into consideration.


Trigger-Responsive Gene Transporters for Anticancer Therapy.
In the current era of gene delivery, trigger-responsive nanoparticles for the delivery of exogenous nucleic acids, such as plasmid DNA (pDNA), mRNA, siRNAs, and miRNAs, to cancer cells have attracted considerable interest. The cationic gene transporters commonly used are typically in the form of polyplexes, lipoplexes or mixtures of both, and their gene transfer efficiency in cancer cells depends on several factors, such as cell binding, intracellular trafficking, buffering capacity for endosomal escape, DNA unpacking, nuclear transportation, cell viability, and DNA protection against nucleases. Some of these factors influence other factors adversely, and therefore, it is of critical importance that these factors are balanced. Recently, with the advancements in contemporary tools and techniques, trigger-responsive nanoparticles with the potential to overcome their intrinsic drawbacks have been developed. This review summarizes the mechanisms and limitations of cationic gene transporters. In addition, it covers various triggers, such as light, enzymes, magnetic fields, and ultrasound (US), used to enhance the gene transfer efficiency of trigger-responsive gene transporters in cancer cells. Furthermore, the challenges associated with and future directions in developing trigger-responsive gene transporters for anticancer therapy are discussed briefly.


Sexual murderers' implicit theories.
Interviews with 28 sexual murderers were subjected to grounded theory analysis. Five implicit theories (ITs) were identified: dangerous world, male sex drive is uncontrollable, entitlement, women as sexual objects, and women as unknowable. These ITs were found to be identical to those identified in the literature as being present in rapists. The presence of dangerous world and male sex drive is uncontrollable were present, or absent, such that three groups could be identified: (a) dangerous world plus male sex drive is uncontrollable; (b) dangerous world, in the absence of male sex drive is uncontrollable; (c) male sex drive is uncontrollable in the absence of dangerous world. These three groups were found to differ in motivation: (a) were motivated by urges to rape and murder; (b) were motivated by grievance, resentment and/or anger toward women; (c) were motivated to sexually offend but were prepared to kill to avoid detection, or secure compliance.


Comparative study of two bowel preparation regimens for colonoscopy: senna tablets vs sodium phosphate solution.
To compare the efficacy and acceptance of senna tablet and sodium phosphate solution for bowel preparation before colonoscopy. One hundred and thirty four patients, who needed elective colonoscopy, were randomly allocated to take 180 mg senna tablet or 95 mL sodium phosphate solution on the day before colonoscopy. The efficacies of both laxatives were compared using the mean difference of colon-cleanliness score of the rectum, sigmoid segments, descending colon, transverse colon and cecum. The scores were rated by two observers who were blinded to the laxatives administered. The higher score means that the colon is cleaner. The efficacy of both laxatives were equivalent if the 95% confidence interval of the mean difference of the score of colon lie within -1 to +1. On intention-to-treat analysis, the mean cleanliness scores in the four segments of colon except the cecum were higher in the sodium phosphate group than those in senna group (7.9 +/- 1.7 vs 8.3 +/- 1.5, 8.0 +/- 1.8 vs 8.5 +/- 1.4, 7.9 +/- 2.0 vs 8.5 +/- 1.3, 7.9 +/- 2.0 vs 8.2 +/- 1.4 and 7.2 +/- 1.7 vs 6.9 +/- 1.4, respectively). The 95% confidence intervals (95% CI) of mean difference in each segment of colon were not found to lie within 1 point which indicated that their efficacies were not equivalent. The taste of senna was better than sodium phosphate solution. Also, senna had fewer side effects. The efficacy of senna is not equivalent to sodium phosphate solution in bowel preparation for colonoscopy, but senna may be considered an alternative laxative.


Theta rhythm of navigation: link between path integration and landmark navigation, episodic and semantic memory.
Five key topics have been reverberating in hippocampal-entorhinal cortex (EC) research over the past five decades: episodic and semantic memory, path integration ("dead reckoning") and landmark ("map") navigation, and theta oscillation. We suggest that the systematic relations between single cell discharge and the activity of neuronal ensembles reflected in local field theta oscillations provide a useful insight into the relationship among these terms. In rats trained to run in direction-guided (1-dimensional) tasks, hippocampal cell assemblies discharge sequentially, with different assemblies active on opposite runs, i.e., place cells are unidirectional. Such tasks do not require map representation and are formally identical with learning sequentially occurring items in an episode. Hebbian plasticity, acting within the temporal window of the theta cycle, converts the travel distances into synaptic strengths between the sequentially activated and unidirectionally connected assemblies. In contrast, place representations by hippocampal neurons in 2-dimensional environments are typically omnidirectional, characteristic of a map. Generation of a map requires exploration, essentially a dead reckoning behavior. We suggest that omnidirectional navigation through the same places (junctions) during exploration gives rise to omnidirectional place cells and, consequently, maps free of temporal context. Analogously, multiple crossings of common junction(s) of episodes convert the common junction(s) into context-free or semantic memory. Theta oscillation can hence be conceived as the navigation rhythm through both physical and mnemonic space, facilitating the formation of maps and episodic/semantic memories.


Reducing Unplanned Extubations in the NICU Following Implementation of a Standardized Approach.
Unplanned extubations (UEs) have been associated with increased ventilator days, risk of infection, cardiopulmonary resuscitation, and resuscitation medication usage. The UE rate in our level 4 NICU is lower than the national average. Efforts to further reduce UE events at our institution led an interdisciplinary group to define steps to eliminate UEs. Steps included: (1) requiring at least 2 care providers at the bedside for movement of an intubated subject; (2) standardizing head and endotracheal tube (ETT) position; (3) defining a set methodology for ETT securing; (4) introducing a postoperative handoff to improve communication; and (5) implementing a post-UE assessment tool. A quality improvement initiative reviewed subjects and compared UE rates before (January 2013 to December 2013) and after (January 2014 to December 2014) implementation of UE prevention guidelines. A de-identified data set was used for analysis. 67 UE events were identified with 46 UE events at baseline in 2013 compared with 21 in 2014 post-implementation. This amounted to a 64% decrease in total UE events (from 46 to 21) (P < .001). Additionally, monthly UE rates decreased 50% (from 3.8 to 1.9), and UE events per 100 ventilator days decreased 53% (from 1.15 to 0.54). The development of standard guidelines to prevent UE and a quality review process to track UE provided important information for education and practice change. In our NICU, these changes have significantly improved the UE rate through improved teamwork, accountability, and communication.


Costs of treating primary open-angle glaucoma and ocular hypertension: a retrospective, observational two-year chart review of newly diagnosed patients in Sweden and the United States.
The objective of this study was to investigate what treatment strategies prevail in different countries for patients newly diagnosed with primary open-angle glaucoma (POAG) or ocular hypertension (OH) only and initiated on treatment with beta-blockers, and to estimate the total direct cost of treatment for two years. In addition, differences in costs between and within the countries and the determinants of variations in costs across patients were examined. The authors performed a retrospective medical record analysis in several academic and office-based study centers in Sweden and the United States. Standard costs for each resource item were determined and applied to all centers within the country. Differences in treatment costs within the countries are thus the effect of differences in treatment strategies, not of differences in prices. There was considerable variation between the centers of each country. Sweden had a higher number of surgical interventions, which may be explained by the fact that the Swedish cohort had a higher mean intraocular pressure (IOP) at baseline and a higher proportion of patients with definite POAG and exfoliation glaucoma. However, in both countries the mean IOP at study end was approximately 18 mm Hg. Total direct costs for two years were 15,119 SEK (US$2,160; $1US = 7 SEK) and $2,109, respectively. In a multiple regression analysis, the estimated effects of baseline IOP and of IOP change after treatment initiation on treatment costs were positively and negatively significant, respectively, in both countries. Despite differences in baseline diagnosis and in treatment strategies, mean IOP was decreased to 18 mm Hg in both countries. Baseline IOP was positively correlated with treatment costs, while the initial IOP-lowering effect of treatment was negatively correlated with two-year costs.


Pharmacological modulation of Kv3 voltage-gated potassium channels regulates fear discrimination and expression in a response-dependent manner.
Various psychiatric diseases are characterized by aberrant cognition and emotional regulation. This includes inappropriately attributing affective salience to innocuous cues, which can be investigated using translationally relevant preclinical models of fear discrimination. Activity in the underpinning corticolimbic circuitry is governed by parvalbumin-expressing GABAergic interneurons, which also regulate fear discrimination. Kv3 voltage-gated potassium channels are highly expressed in these neurons and are important for controlling their activity, suggesting that pharmacological Kv3 modulation may regulate fear discrimination. We determined the effect of the positive Kv3 modulator AUT00206 given systemically to female rats undergoing limited or extended auditory fear discrimination training, which we have previously shown results in more discrimination or generalization, respectively, based on freezing at retrieval. We also characterized darting and other active fear-related responses. We found that limited training resulted in more discrimination based on freezing, which was unaffected by AUT00206. In contrast, extended training resulted in more generalization based on freezing and the emergence of discrimination based on darting during training and, to a lesser extent, at retrieval. Importantly, AUT00206 given before extended training had dissociable effects on fear discrimination and expression at retrieval depending on the response examined. While AUT00206 mitigated generalization without affecting expression based on freezing, it reduced expression without affecting discrimination based on darting, although darting levels were low overall. These results indicate that pharmacological Kv3 modulation regulates fear discrimination and expression in a response-dependent manner. They also raise the possibility that targeting Kv3 channels may ameliorate perturbed cognition and emotional regulation in psychiatric disease.


Mechanisms of action of atypical antipsychotic drugs. Implications for novel therapeutic strategies for schizophrenia.
The mechanisms which contribute to the actions of atypical antipsychotic drugs, such as clozapine and the putative atypical agents remoxipride and raclopride, are reviewed. Examination of available preclinical and clinical data leads to two hypotheses concerning the mode of action of atypical antipsychotic drugs. The first hypothesis is that antagonism of the dopamine D2 receptor is both necessary and sufficient for the atypical profile, but that interaction with subtypes of the D2 receptor differentiates typical from atypical antipsychotic drugs. The second hypothesis has been previously advanced, and suggests that a relatively high ratio of serotonin 5-HT2:dopamine D2 receptor antagonism may subserve the atypical profile. It seems likely that the atypical antipsychotic drug profile may be achieved in more than one way.


Prevalence and risk factors of schistosomiasis and hookworm infection in seasonal transmission settings in northern Côte d'Ivoire: A cross-sectional study.
Schistosomiasis and hookworm infection remain public health problems in large parts of sub-Saharan Africa. The epidemiology of schistosomiasis and hookworm was studied in seasonal transmission settings in the northern part of Côte d'Ivoire. In August 2018, a cross-sectional study was conducted. Urine and stool samples were collected from 742 individuals aged 6-96 years in 16 localities from four departments in northern Côte d'Ivoire. Urine samples were examined by a filtration method for quantification of Schistosoma haematobium eggs. Stool samples were subjected to duplicate Kato-Katz thick smears and eggs of Schistosoma mansoni and soil-transmitted helminths (STHs) were counted. Additionally, a questionnaire was administered to determine demographic characteristics and to identify risk factors of schistosomiasis and STHs. Malacologic surveys were carried out at water points that are contacted by humans and animals. The prevalence of schistosomiasis was very low. Only two cases of S. mansoni were found (0.3%, 95% confidence interval [CI]: 0.1-1.0%). The distribution of S. haematobium was focal, with cases found only in two departments; Ferkessédougou (5.4%, 95% CI: 2.5-9.9%) and Ouangolodougou (2.7%, 95% CI: 0.9-6.3%). Hookworm was the only STH species observed with a prevalence of 1.5% (95% CI: 0.8-2.8%). A higher risk of S. haematobium infection was observed in males compared to females, but the difference was not statistically significant (2.3% versus 1.3%, odds ratio [OR]: 1.5, 95% CI: 0.8-2.7). Participants aged 16-20 years showed the highest prevalence of S. haematobium. A total of 111 human- and animal-water contact points were identified at 47 water sources. Three potential intermediate host snails of schistosomes were collected; namely, Bulinus forskalii (n = 761), Bulinus truncatus (n = 205), and Biomphalaria pfeifferi (n = 1). Yet, only one specimen of Bu. truncatus was found to be shedding schistosome cercariae. This study confirms very low transmission of schistosomiasis and hookworm in northern Côte d'Ivoire. The establishment and rigorous implementation of integrated surveillance-response systems could lead to the elimination of schistosomiasis and hookworm in this part of Côte d'Ivoire.


Fungal Spores Affect Peripheral Blood Counting in Sysmex-5000i Automated Hematology Counter and Relative Case Report.
Fungal spores can be observed on peripheral blood smears and may affect cell counting in an automated hematology counter. The purpose of this study was to evaluate the effects of fungal spores on cell counting in Sysmex-5000i automated hematology counter. The common clinical fungal spores we selected were C. albicans, C. krusei, C. tropicalis, and C. glabrata, using 0.9% normal saline to formulate a final concentration of 4 - 6 x 109/L fungal liquid, mixed with peripheral blood (containing high, medium and low concentrations of white blood cells and platelets), and formulated to different concentrations (4 - 6 x 108/L, 4 - 6 x 107/L, 4 - 6 x 106/L, 4 - 6 x 105/L). This study investigated the effects of different species and different concentrations of fungal spores on cell counting in a Sysmex-5000i automated hematology counter, the changes in the scatter plot, and taking a clinical case for example. C. tropicalis and C. krusei had an overt effect on the white blood cell count at concentrations of up to 4 - 6 x 107/L, and C. krusei had an overt effect on the platelet count. Fungal spores might have a greater impact on automated hematology analyzer cell counts. This effect is related to different species, different concentrations of fungal spores, and peripheral blood cells.


Spectrophotometric determination of pyridoxal and pyridoxal 5'-phosphate with 3-methyl-2-benzothiazolone hydrazone hydrochloride, and their selective assay.
A spectrophotometric method with 3-methyl-2-benzothiazolone hydrazone hydrochloride was developed for the determination of pyridoxal and pyridoxal 5'-phosphate, and for the selective determination of each in the presence of the other. Pyridoxal and pyridoxal 5'-phosphate react with the reagent to yield the azine derivatives, which give characteristic absorption spectra. The highest extinction values are obtained when pyridoxal and pyridoxal 5'-phosphate are incubated at pH values of about 3.4 and 8.0 respectively; their maxima are at 430nm. (in 2.74x10(4)) and 380nm. (in 2.24x10(4)) respectively. The azine of pyridoxal is only slightly soluble under the neutral and alkaline conditions, whereas that of pyridoxal 5'-phosphate is substantially insoluble in the acid pH range. This difference in solubility of the azines made possible the selective determination of pyridoxal and pyridoxal 5'-phosphate. alpha-Oxoglutarate and pyruvate are among the substances shown not to interfere with the assay of pyridoxal; their derivatives absorb appreciably only at wavelengths below 420nm. For the assay of pyridoxal 5'-phosphate in the presence of these compounds measurement at 390nm. is necessary.


Modulation of membrane surface curvature by peptide-lipid interactions.
Recent reports on the interaction of cardiotoxin and melittin with phospholipid model membranes are reviewed and analyzed. These types of peptide toxins are able to modulate lipid surface curvature and polymorphism in a highly lipid-specific way. It is demonstrated that the remarkable variety of effects of melittin on the organization of different membrane phospholipids can be understood in a relatively simple model, based on the shape-structure concept of lipid polymorphism and taking into account the position of the peptide molecule with respect to the lipids. Based on the strong preference of the peptides for negatively charged lipids and the structural consequences thereof, and on preliminary studies of signal peptide-lipid interaction, a role of inverted or concave lipid structures in the process of protein translocation across membranes is suggested.


A protein phosphatase from human T cells augments tat transactivation of the human immunodeficiency virus type 1 long-terminal repeat.
HIV-1 Tat protein regulates viral gene expression by modulating the activity and association of cellular transcription factors with RNA polymerase II (RNAPII). Possible mechanisms include Tat-associated protein kinase(s) and phosphatase(s) that regulate phosphorylation of the C-terminal domain (CTD) of the large subunit of RNAPII. Hypophosphorylated RNAPII (RNAPIIa) is recruited to promoters during formation of a preinitiation complex, whereas hyperphosphorylated RNAPII (RNAPIIo) is associated with the elongation complex. The role of phosphatases in maintaining the equilibrium between the two phosphorylated states of RNAPII, which is required for sustained transcriptional activation from the HIV-1 LTR, is not clear. In this study, we discuss the properties of a Tat-associated CTD phosphatase fractionated from Jurkat T cells. The Tat-associated protein phosphatase (TAPP) is related to the serine/threonine, type 1, protein phosphatase (PP1) family. TAPP dephosphorylates the hyperphosphorylated form of recombinant CTD specifically on serine 2, and augments Tat-mediated transcriptional transactivation of HIV-1 LTR in an in vitro transcription reaction. TAPP is associated with the transcription complex during the early initiation steps, and its release from the HIV-1 promoter coincides with the Tat-specific activation of CDK9. The results suggest a unique role of the Tat-associated phosphatase which regulates viral transcription by target-specific dephosphorylation of RNAPII during the early stages of elongation.


Introduction to focus issue: design and control of self-organization in distributed active systems.
Spatiotemporal self-organization is found in a wide range of distributed dynamical systems. The coupling of the active elements in these systems may be local or global or within a network, and the interactions may be diffusive or nondiffusive in nature. The articles in this focus issue describe biological and chemical systems designed to exhibit spatiotemporal dynamics and the control of such dynamics through feedback methods.


The interaction between estradiol change and the serotonin transporter gene (5-HTTLPR) polymorphism is associated with postpartum depressive symptoms.
Although estrogenic fluctuation is considered a major risk factor for postpartum depression (PPD), the effects of the interactions between the genetic background and estradiol (E2) change on PPD are not well understood. Here, a cohort study with 437 postpartum women was carried out to evaluate the role of a serotonin transporter gene polymorphism (5-HTTLPR) and E2 change on the risk of PPD symptoms. The participants were assessed using the Edinburgh Postnatal Depression Scale and the Self-Rating Depression Scale at 1 and 6 weeks after delivery. The PCR-based restriction fragment length polymorphism method was utilized to examine the genotype distribution of the 5-HTTLPR polymorphism, and the serum levels of E2 were determined in individuals in the third trimester of pregnancy and at 1 week postpartum. A significant association was observed between E2 change and PPD susceptibility in the late postpartum period (6 weeks) [P = 0.002, odds ratio (OR) = 2.341, 95% confidence interval (CI) = 1.361-4.027], but it was not observed in the early postpartum period (1 week). There was no significant association between the 5-HTTLPR genotype and PPD risk at both the early and late postpartum periods (P > 0.05). However, the interaction between E2 change and the 5-HTTLPR polymorphism could reasonably influence PPD risk. The women who carried the SS genotype with large decreases in E2 showed a significantly higher risk for PPD at both the early (P = 0.002, OR = 2.525, 95% CI = 1.384-4.059) and late postpartum periods (P < 0.001, OR = 3.108, 95% CI = 1.562-4.436) compared with those who carried the SL/LL genotype. This study suggests that there is an association between E2 change in the perinatal period with the 5-HTTLPR genotype and the occurrence of PPD.


Crossover of feshbach resonances to shape-type resonances in electron-hydrogen atom excitation with a screened Coulomb interaction.
The effects of Coulomb interaction screening on electron-hydrogen atom excitation in the n=2 threshold region are investigated by using the R-matrix method with pseudostates. The interaction screening lifts the l degeneracy of n=2 Coulomb energy level, producing two distinct thresholds for 2s and 2p states. The phenomenon of transformation of ;{1,3}P and 1D Feshbach resonances into shape-type resonances is observed when they pass across the 2s and 2p threshold, respectively, as the interaction screening increases. It is shown that this resonance transformation leads to dramatic effects in the 1s-->2s and 1s-->2p excitation collision strengths in the n=2 threshold collision energy region.


A curated review of recent literature of biomarkers used for assessing air pollution exposures and effects in humans.
This is a cross-sectional review of biomarkers used in air pollution research from January 2009 through December 2012. After an initial keyword search in PubMed retrieving 426 articles, a comprehensive abstract review identified 54 articles of experimental design that used biomarkers of exposure or effect in human studies in the area of air pollution research during this specified time period. A thorough bibliographic search of the included articles retrieved an additional 65 articles meeting the inclusion criteria. This review presents these 119 studies and the 234 biomarkers employed in these air pollution research investigations. Data presented are 70 biomarkers of exposure with 54% relating to polycyclic aromatic hydrocarbons, 36% volatile organic carbons, and 10% classified as other. Of the 164 biomarkers of effect, 91 and 130 were used in investigating effects of short-term and chronic exposure, respectively. Results of biomarkers used in short-term exposure describe different lag times and pollutant components such as primary and secondary pollutants, and particle number associated with corresponding physiological mechanisms including airway inflammation, neuroinflammation, ocular, metabolic, early endothelial dysfunction, coagulation, atherosclerosis, autonomic nervous system, oxidative stress, and DNA damage. The review presents three different exposure scenarios of chronic, occupational, and extreme exposure scenarios (indoor cooking) with associated biomarker findings presented in three broad categories of (1) immune profile, (2) oxidative stress, and (3) DNA damage. This review offers a representation of the scope of data being explored by air pollution researchers through the use of biomarkers and has deliberately been restricted to this particular subject rather than an extensive or in-depth review. This article provides a contextualization of air pollution studies conducted with biomarkers in human subjects in given areas while also integrating this complex body of information to offer a useful review for investigators in this field of study.


Prevention of nausea and vomiting in caesarean section under spinal anaesthesia with midazolam or metoclopramide?
To evaluate the efficacy and safety of bolus dose of midazolam and metoclopramide in reducing emetic symptoms during caesarean delivery under spinal anaesthesia. In a double-blind study, 80 women undergoing elective caesarean section under spinal anaesthesia (using 0.5% bupivacaine 10 mg) were allocated randomly to receive midazolam 2 mg, or metoclopramide 10 mg at the beginning of surgery before skin incision. The frequency of nausea and vomiting, sedative score, respiratory depression, and side effects were recorded. The frequency of intraoperative nausea and vomiting was lower in the midazolam group compared with metoclopramide (15% versus 52.5%). Sedation scores within 3 hour postoperatively were significantly lower in the metoclopramide group. The frequency of respiratory depression was higher in midazolam group. There were some episodes of respiratory depression (respiratory rate of less than 10 bpm) in 17 patients in the midazolam group at the time of surgery treated by verbal stimulation, but no respiratory depression was seen in metoclopramide group. Neonatal outcome was similar in the two groups and all the neonates had Apgar scores > or = 8 at one and five minutes. A bolus dose of midazolam (2 mg) was more effective than metoclopramide (10 mg) for the prevention of nausea and vomiting in parturients patients undergoing caesarean section under spinal anaesthesia, however, further studies are needed to prove the safety of midazolam in parturient patients undergoing caesarean section.


Epidemiology and risk factors for notifiable Clostridium botulinum infections in Taiwan from 2003 to 2020.
Botulinum toxin is produced by Clostridium botulinum, a gram-positive anaerobic bacterium. This study aimed to examine the epidemiological characteristics, including sex, age, season in which infection occurred, place of residence, and epidemiological trends, of confirmed botulism cases in Taiwan from 2003 to 2020. This study examined the annual summary data on reported botulism in Taiwan' s Center for Disease Control from 2003 to 2020 available to the public on the internet. We found that there were 50 confirmed domestic cases of botulism. The incidence of botulism ranged from 0 to 0.48 per 1000,000 from 2003 to 2020 and peaked in 2008 and 2010. During the 18-year investigation period in which 6-year intervals were used, the study results showed a decreasing trend (2003-2008, 2009-14, and 2015-2020, had 22, 19, 9 cases each). In terms of patients' gender, age, and place of residence, most of the patients were females (56%), were aged ≥ 50 years (48%), and resided in Taipei and northern Taiwan (44%). The number of botulism cases in Taiwan from 2012 to 2020 compared with other years (from 2003 to 2011) found that there were significant differences among patients within an age group of <20 years (P = .003, odds ratio = 18.500, and 95% confidence interval = 3.287-104.111), and there were significant differences among patients whose place of residence was Taipei metropolitan area (P = .025, odds ratio = 5.667, and 95% confidence interval = 1.248-25.734). During 2003 to 2009, there was no case of botulism among those aged <20 years. Over the last 10 years, botulism in children showed an increasing trend. A total of 9 children were found to have botulism during 2010 to 2020; most of these children were male (66.7%) and were infected during spring and summer (66.7%). This study is the first to report the number of confirmed domestic cases with botulism from surveillance data from Taiwan's Center for Disease Control during 2003 to 2020. This study also found that the place of residence and age were associated with an increased risk of botulism in Taiwan. This information may be useful for policymakers and clinical experts to direct prevention- and control-based activities regarding botulism that result in the most severe illness and the greatest burden on Taiwanese.


Physical and Mental Functions of Cardiovascular Diseased Patients Decrease During the State of Emergency Initiated by the COVID-19 Pandemic in Japan.
We aimed to examine the differences in life-space mobility and quality of life (QoL) of patients with cardiovascular disease (CVD) between the pre- and postnationwide state of emergency initiated by the Coronavirus disease 2019 (COVID-19) pandemic in Japan and to show the factors associated with the decrease in life-space mobility and QoL in these patients. We undertook a longitudinal study of 20 out of 51 consecutive CVD patients with coronary artery disease (CAD) who met the study criteria. We used the Life-Space Assessment (LSA) tool to evaluate Life-space mobility and assessed QoL with the five-level EuroQoL five-dimensional questionnaire (EQ-5D-5L) in Japanese. The LSA scores and EQ-5D-5L QoL score decreased significantly from the pre- to postnationwide state of emergency in Japan (p < 0.01). ΔLSA was significantly positively associated with body mass index and significantly negatively associated with knee extensor muscle strength and pre-LSA score (p < 0.05). There were no significant relationships between ΔLSA and ΔEQ- 5D-5L QoL scores and between ΔEQ-5D-5L QoL scores and patient characteristics. The policies promoted to address the state of emergency in Japan might affect life-space mobility and QoL of CAD patients. Moreover, CAD patients in Japan who were not obese and maintained their physical function and activity tended to refrain from activity during the period between the pre- and post-nationwide state of emergency. Clarification of the effects of the COVID-19 pandemic on the relationship between living space motility and QoL in CAD patients will require further study.


Atrial pacing and administration of nifekalant hydrochloride for unstable atrial fibrillation: a case report.
Atrial fibrillation (AF) is a common arrhythmia in patients with hypertrophic cardiomyopathy (HCM) and can deteriorate haemodynamic status. We report a case of a 77-year-old woman with cardiogenic shock due to paroxysmal AF, complicated with HCM and aortic stenosis. Atrial fibrillation was successfully managed with temporary atrial pacing and administration of nifekalant hydrochloride without invasive mechanical circulatory support until surgery. Septal myectomy, aortic valve replacement, and pulmonary vein isolation were performed. This case suggests that atrial pacing and nifekalant may be safe and effective for rhythm control.


Joint associations of asthma and sleep duration with cardiovascular disease and all-cause mortality: a prospective cohort study.
This study aimed to investigate the joint association of asthma and sleep duration with cardiovascular disease (CVD) and mortality risk. This prospective cohort study included 366,387 participants from the UK Biobank. The participants were divided into three groups based on their sleep duration (short: <7 h/d; referent: 65+ years: 7-8 h/d; ages 39-64 years: 7-9 h/d; and long: 65+ years: >8 h/d; ages 39-64 years: >9 h/d). Cox proportional hazards models were used to examine the association between asthma and sleep duration on CVD and all-cause mortality. Participants with asthma and short sleep duration showed increased risk of CVD (hazard ratio [HR] 1.42; 95% confidence interval [CI] 1.34-1.51) and all-cause mortality (HR, 1.26; 95% CI, 1.17-1.36), compared with participants with no asthma in the referent sleep duration group. We documented significant additive interactions between asthma and short sleep duration in relation to CVD (relative excess risk due to interaction [RERI], 0.13; 95% CI, 0.04-0.23) and all-cause mortality (RERI, 0.12; 95% CI, 0.01-0.23). Asthma and short sleep duration may have additive interactions on CVD and all-cause mortality risk, highlighting the importance of controlling asthma in combination with improving sleep duration.


Association of Single-Nucleotide Polymorphisms of C-Reactive Protein Gene with Susceptibility to Infantile Sepsis in Southern China.
BACKGROUND C-reactive protein (CRP) is an important biomarker of sepsis. Several single-nucleotide polymorphisms (SNPs) in the CRP gene can determine plasma CRP levels and are risk factors in many diseases, such as cancer, arteritis, and diabetes. However, it is unknown whether polymorphisms in CRP are associated with susceptibility to and outcome of infantile sepsis. We explored the effect of these SNPs on CRP response in infantile sepsis, and compared genetic data on patients with sepsis. MATERIAL AND METHODS A total of 49 infants with sepsis and 20 healthy infants were enrolled during hospitalization, and 3 SNPs in the CRP gene region (rs1205, rs2808530, and rs3091244) were genotyped and then analyzed for associations with CRP levels and sepsis. RESULTS The CRP means concentration results showed that mean CRP concentration was different in the 4 groups (healthy, sepsis, severe sepsis, and septic shock) and was positively correlated with the severity of infantile sepsis. There was also a difference in CRP SNP rs1205 between infants with septic shock and healthy infants, and between infants with septic shock and infants with sepsis. No differences were observed in SNP rs2808630 and SNP rs3091244. CONCLUSIONS Our study suggests that rs1205 genetic variability in the CRP gene determines the CRP levels in sepsis of different severities, while SNP rs3091244 and SNP rs2808630 are not associated with sepsis. However, the results of the present study on SNP rs1205, rs3091244, and rs2808630 in the CRP gene should be interpreted with caution due to limited sample size and sample heterogeneity. Large-scale, well-designed studies are needed to validate our findings.


The clubfoot painted by Jusepe de Ribera: a controversial diagnosis.
The Clubfoot painted by José de Ribera depicts a young beggar affected by a typical equinus clubfoot. He shows a contorted right hand and wrist. His left hand holds a begging note, suggesting some difficulty to speak. This condition may be caused by a cerebral palsy, consisting of a brain injury in the left hemisphere responsible for right hemiplegia and speech disturbance. Recently, it was suggested that the boy's condition is a consequence of arthrogryposis, perhaps amyoplasia or distal arthrogryposis type A1. Some clinical features may suggest the diagnosis of Sheldon-Hall syndrome. Considering all the signs represented on the painting, the diagnosis of hemiplegia due to cerebral palsy cannot be discarded. The present article is a novel analysis of the painting based on previously proposed diagnoses of the boy's condition, namely, hemiplegia and arthrogryposis.


The cytologic diagnosis of clear cell adenocarcinoma of the cervix uteri.
Four cases are presented of clear cell adenocarcinoma of the cervix uteri. Two are early cases of limited histologic extent and two are more advanced examples. The cytologic features are presented with particular reference to differences between the earlier and the more advanced cases. When the early cases are separated in this manner, a source of diagnostic difficulty, which does not arise in the advanced lesions, is identified and discussed.


Does School-Based Health Promotion Affect Physical Activity on Weekends? And, Does It Reach Those Students Most in Need of Health Promotion?
To determine whether a school-based health promotion program affects children's weekend physical activity and whether this effect varies according to socioeconomic-status. This was a quasi-experimental trial of school-based programs on physical activity levels implemented in disadvantaged neighborhoods in Alberta, Canada. In 2009 and 2011, 7 full days of pedometer data were collected from cross-sectional samples of grade 5 students (age 10-11 years) from 10 intervention schools in low-socioeconomic neighbourhoods and 20 comparison schools in middle-socioeconomic neighbourhoods. Multilevel models assessed differences in step-counts between intervention and comparison groups over-time by weight (objectively measured) and socioeconomic status subgroups. In 2009, children from intervention schools were less active on weekends relative to comparison schools (9212 vs. 11186 steps/day p<0.01). Two years later, daily step-counts on weekend days among children in low socioeconomic intervention schools increased such that they approximated those of children from middle socioeconomic comparison schools (12148 vs. 12121 steps/day p = 0.96). The relative difference in steps between intervention and comparison schools on weekends reduced from -21.4% to 0.2% following the intervention. The normalization of weekend step counts was similar for normal weight (-21.4% to +2.0%) and overweight (-19.1 to +3.9%) children, and was balanced across socioeconomic subgroups. These data suggest that school-based health promotion is effective for reducing inequities in physical activity levels outside school hours. Investments in school-based health promotion lead to behavior modification beyond the school environment. ClinicalTrials.gov NCT01914185.


[A lymphogranulomatosis simulating an ovarian tumour (author's transl)].
A case of lymphogranulomatosis involving the left broad ligament in a 68-year-old patient is reported. The lymphogranuloma with the extent of two fists presented like an immobile ovarian tumour on palpation. An abdominal hysterectomy with bilateral salpingo-oophorectomy and lymphnode resection was performed. No complications occurred during the postoperative course. Haematologic treatment was subsequently initiated.


The therapeutic alliance in managed care mental health practice.
The author uses Lazare et al.'s "negotiated approach to patienthood" model to address ethical and clinical problems of establishing a therapeutic alliance in the managed care setting. Lazare et al. identified five potential conflicts between therapist and patient that can threaten the therapeutic alliance: conflict over 1) defining the patient's problem; 2) goals of treatment; 3) methods of treatment; 4) conditions of treatment; and 5) the relationship. Case examples illustrate clinically and ethically acceptable ways to work with these conflicts within an expeditious, resource-limited practice style. At times, however, the ethical clinician must act as an advocate for the patient and for change of the system itself.


The critical power function is dependent on the duration of the predictive exercise tests chosen.
The linear relationship between work accomplished (W(lim)) and time to exhaustion (t(lim)) can be described by the equation: W(lim) = a + CP x t(lim). Critical power (CP) is the slope of this line and is thought to represent a maximum rate of ATP synthesis without exhaustion, presumably an inherent characteristic of the aerobic energy system. The present investigation determined whether the choice of predictive tests would elicit significant differences in the estimated CP. Ten female physical education students completed, in random order and on consecutive days, five all-out predictive tests at preselected constant-power outputs. Predictive tests were performed on an electrically-braked cycle ergometer and power loadings were individually chosen so as to induce fatigue within approximately 1-10 mins. CP was derived by fitting the linear W(lim)-t(lim) regression and calculated three ways: 1) using the first, third and fifth W(lim)-t(lim) coordinates (I135), 2) using coordinates from the three highest power outputs (I123; mean t(lim) = 68-193 s) and 3) using coordinates from the lowest power outputs (I345; mean t(lim) = 193-485 s). Repeated measures ANOVA revealed that CPI123 (201.0+/-37.9W) > CPI135 (176.1+/-27.6W) > CPI345 (164.0+/-22.8W) (P<0.05). When the three sets of data were used to fit the hyperbolic Power-t(lim) regression, statistically significant differences between each CP were also found (P<0.05). The shorter the predictive trials, the greater the slope of the W(lim)-t(lim) regression; possibly because of the greater influence of 'aerobic inertia' on these trials. This may explain why CP has failed to represent a maximal, sustainable work rate. The present findings suggest that if CP is to represent the highest power output that an individual can maintain "for a very long time without fatigue" then CP should be calculated over a range of predictive tests in which the influence of aerobic inertia is minimised.


Hysteroscopic sterilization.
Hysteroscopic methods of tubal occlusion have not satisfied the criteria of an ideal contraceptive, although this technology still appears to be evolving. The aforementioned studies report the success and complication rates of very experienced hysteroscopists. A good potential exists for these techniques, but their widespread use will not come before greater experience and familiarity with the basics of hysteroscopy.


Direct measurement of sediment sound speed in Shallow Water '06.
Knowledge of sediment sound speed is crucial for predicting sound propagation. During the Shallow Water '06 experiment, in situ sediment sound speed was measured using the Sediment Acoustic-speed Measurement System (SAMS). SAMS consists of ten fixed sources and one receiver that can reach a maximal sediment depth of 3 m. Measurements were made in the frequency range 2-35 kHz. Signal arrival times and propagation distances were recorded, from which sediment sound speed was determined. Preliminary results from three deployments show that SAMS was capable of determining sediment sound speed with uncertainties less than 1.6%. Little dispersion in sediment sound speed was observed.


Adjunctive memantine for schizophrenia: a meta-analysis of randomized, double-blind, placebo-controlled trials.
Dysfunction of N-methyl-D-aspartate receptor (NMDAR) is involved in the pathophysiology of schizophrenia. A meta-analysis of randomized controlled trials (RCTs) was conducted to examine the efficacy and safety of memantine, a non-competitive NMDAR antagonist, in the treatment of schizophrenia. Standardized/weighted mean differences (SMDs/WMDs), risk ratio (RR), and their 95% confidence intervals (CIs) were calculated and analyzed. Included in the meta-analysis were eight RCTs (n = 452) of 11.5 ± 2.6 weeks duration, with 229 patients on memantine (20 mg/day) and 223 patients on placebo. Adjunctive memantine outperformed placebo in the measures of Positive and Negative Syndrome Scale and Brief Psychiatric Rating Scale negative symptoms [SMD: -0.63 (95% CI -1.10 to -0.16), p = 0.009, I 2 = 77%], but not in the total, positive and general symptoms [SMD: -0.46 to -0.08 (95% CI -0.93 to 0.22), p = 0.06-0.60, I 2 = 0-74%] or the Clinical Global Impression Severity Scale [WMD: 0.04 (95% CI -0.24 to 0.32), p = 0.78]. The negative symptoms remained significant after excluding one outlying RCT [SMD: -0.41 (95% CI -0.72 to -0.11), p = 0.008, I 2 = 47%]. Compared with the placebo group, adjunctive memantine was associated with significant improvement in neurocognitive function using the Mini-Mental State Examination (MMSE) [WMD: 3.09, (95% CI 1.77-4.42), p < 0.00001, I 2 = 22%]. There was no significant difference in the discontinuation rate [RR: 1.34 (95% CI 0.76-2.37), p = 0.31, I 2 = 0%] and adverse drug reactions between the two groups. This meta-analysis showed that adjunctive memantine appears to be an efficacious and safe treatment for improving negative symptoms and neurocognitive performance in schizophrenia. Higher quality RCTs with larger samples are warranted to confirm these findings.


Circles on pommel horse with a suspended aid: mass-centre rotation and hip joint moment.
This is the second study of the series, and its aim was to investigate the influence of using the suspended aid on circle kinetics. In addition to the kinematic data recorded for part one (Fujihara & Gervais, 2012), the pommel reaction forces and the force applied from the suspended aid (aid reaction force) were analysed in relation to the motion of a whole-body mass centre. The hip joint moment was also computed by combining all segments in the lower extremities into a single rigid segment. Generally, the use of the aid changed the magnitude of the mass-centre trajectory or horizontal pommel reaction forces but not their patterns. The results also showed that the net hip joint moment was altered during circles with the aid. In summary, a suspended aid can be used as a progression for a variety of goals because it allows gymnasts to practise circles which would not be possible without the aid. When a suspended aid is used, however, practitioners should be aware of the possible kinetic alteration caused by the external force from the aid.


A tentative explanation of the stimulatory effect of methylxanthines (pentoxifylline and isobutylmethylxanthine) on the secretory process in rat extraorbital lacrimal gland.
In the present paper we report the effect of two methylxanthines (pentoxifylline and isobutylmethylxanthine) on the protein secretion in a model of exocrine gland (rat lacrimal gland). Both compounds are able to increase the protein release. This effect is dependent on the calcium concentration gradient between the extra- and intracellular media. The larger the difference, the greater the pentoxifylline or isobutylmethylxanthine effect. Moreover, pentoxifylline and isobutylmethylxanthine can potentiate the norepinephrine or isoproterenol effect by inhibiting phosphodiesterases (even in the absence of calcium). All these data suggest pentoxifylline and isobutylmethylxanthine can act on the cell functions in two ways: (a) by a calcium-dependent mechanism, either by increasing the influx of calcium into the cell or by mobilizing the pool of intracellular calcium; (b) by a mechanism independent of calcium and dependent on a system involving cyclic nucleotides. The first possibility seems to be very attractive for further investigations of the mechanism of action of pentoxifylline and especially when this drug is used to affect the cell motility or deformability controlled by calcium.


Breast tomosynthesis. 3-D mammography reaches the U.S. market.
After many years of anticipation, FDA has approved a device for breast tomosynthesis applications: The Hologic Selenia Dimensions 3-D. But despite the advantages of the technology, certain issues--such as increased radiation dose, higher costs, and lack of insurance reimbursement--may impede widespread clinical adoption. We take a look at breast tomosynthesis and give our view on its clinical outlook.


Direct glyphosate soil monitoring at the triazine-based covalent organic framework with the theoretical study of sensing principle.
Covalent organic frameworks (COFs) are emerging as promising sensing materials due to their controllable structure and function properties, as well as excellent physicochemical characteristics. Here, specific interactions between a triazine-based COF and a mass-used herbicide - glyphosate (GLY) have been utilized to design a disposable sensing platform for GLY detection. This herbicide has been extensively used for decades, however, its harmful environmental impact and toxicity to humans have been recently proven, conditioning the necessity for the strict control and monitoring of its use and its presence in soil, water, and food. Glyphosate is an organophosphorus compound, and its detection in complex matrices usually requires laborious pretreatment. Here, we developed a direct, miniaturized, robust, and green approach for disposable electrochemical sensing of glyphosate, utilizing COF's ability to selectively capture and concentrate negatively charged glyphosate molecules inside its nanopores. This process generates the concentration gradient of GLY, accelerating its diffusion towards the electrode surface. Simultaneously, specific COF-glyphosate binding catalyses the oxidative cleavage of the C-P bond and, together with pore nanoconfinement, enables sensitive glyphosate detection. Detailed sensing principles and selectiveness were scrutinized using DFT-based modelling. The proposed electrochemical method has a linear working range from 0.1 μM to 10 μM, a low limit of detection of 96 nM, and a limit of quantification of 320 nM. The elaborated sensing approach is viable for use in real sample matrices and tested for GLY determination in soil and water samples, without pretreatment, preparation, or purification. The results showed the practical usefulness of the sensor in the real sample analysis and suggested its suitability for possible out-of-laboratory sensing.


Female sterilisation: a five-year follow-up in Auckland.
During the year 1972/73 sterilisation by tubal occlusion was performed at National Women's Hospital on 831 women with a mean age of 32.5 years and a mean parity of 4.6. Two were unknowingly pregnant at the time of operation and eight became pregnant within five years mainly because or recanalization of the tube. Eighty-one percent had no regrets about being sterilised but eleven women experienced a major degree of regret. Eight patients had sought reversal of their sterilisation. Following the operation libido was decreased in 10% of Europeans and 45% of Maoris. Menorrhagia was a common complaint after sterilisation and 7.5% had a hysterectomy within five years.


IA-2 autoantibodies restricted to the IgG4 subclass are associated with protection from type 1 diabetes.
The tyrosine phosphatase-like protein IA-2 is a major target antigen for autoantibodies in the preclinical period of type 1 diabetes. In this study, we examined whether immunoglobulin isotypes and IgG subclass specific autoantibodies directed at IA-2 discriminate between children at risk of type 1 diabetes who progressed to diabetes vs. those who remained diabetes-free. IgG1-4, IgA and the IgE-specific IA-2 antibody (IA-2A) were measured by radioligand assays in 50 patients with type 1 diabetes and 41 ICA-positive siblings of patients with type 1 diabetes who were followed for diabetes development. Of 41 siblings, 32 were positive for IA-2A; of these, 59 % had IA-2 IgG1, 59 % IgG4, 16 % IgG3, 9 % IgG2, 16 % IgA and 13 % IgE antibodies. IA-2 IgG1 was the dominant isotype in prediabetic children (n = 14, 86 % positive) and patients with type 1 diabetes (98 % positive) whereas only 7 of 18 (39 %) non-progressors had antibodies of this isotype. In subjects that remained diabetes-free, a significantly higher frequency of IA-2 IgG4 in the absence of IgG1 was observed (50 %) compared to progressors (7 %) and patients with type 1 diabetes (0 %). Life-table analysis revealed that IA-2A restricted to IgG4 correlated with protection from type 1 diabetes (p < 0.003). In contrast, IA-2 IgG2, IgG3, IgE and IgA did not differ significantly between study groups. Our findings suggest that the measurement of IA-2 IgG1 and IgG4 subclass antibodies can serve as surrogate marker to discriminate between antibody positive subjects at high or low risk for rapid development of diabetes.


Phase-sensitive stimulated Raman adiabatic passage in dipolar extended lambda systems.
The authors investigate the possible phase-sensitive behavior of (multiphoton) stimulated Raman adiabatic passage population transfer in extended lambda systems, if more than one state of an anharmonic progression of target levels is accessible in transitions of different photonicities. They use a minimal model four-level system (4LS) with one initial state separated from two target states by an apex state. The parameters of the 4LS are adapted from the bend states of the HCN-HNC system. Using a dressed-state analysis within the rotating wave approximation (RWA), the authors identify phase-dependent diabatic transitions between the two dressed states contributing to the state vector as the mechanism leading to phase-sensitive target populations. The essential features giving rise to the phase dependence are found to be different (non-zero-) diagonal elements of the dipole matrix, i.e., permanent dipole moments, and the presence of a direct two-photon overtone coupling between the apex state and the lower target state which formally enters the RWA Hamiltonian upon inclusion of permanent dipole moments. Among the parameters controlling the extent of the effect are the anharmonic properties of the target progression and the absolute values of the field frequencies, so that in view of the requirement to tune the driving fields into the vicinity of resonance, details of the level structure are of importance. A comparative numerical study executed without invoking RWA shows that qualitatively there are similar trends in the appearance of phase sensitivity, although the effects are considerably more pronounced in the full treatment. In the full treatment the authors also explore off-resonance conditions and discuss the signatures of phase sensitivity in the target populations.


Pronounced population genetic differentiation in the rock bream Oplegnathus fasciatus inferred from mitochondrial DNA sequences.
The population genetic structure of the rock bream (Oplegnathus fasciatus) along the coastal waters of China was estimated based on three mtDNA fragments (D-loop, COI, and Cytb). A total of 112 polymorphic sites were checked, which defined 63 haplotypes. A pattern with high levels of haplotype diversity (hCOI = 0.886 ± 0.034, hCytb = 0.874 ± 0.023) and low levels of nucleotide diversity (лCOI = 0.009 ± 0.005, лCytb = 0.006 ± 0.003) was detected based on the COI and Cytb fragments, and high levels of genetic diversity (hD-loop = 0.995 ± 0.007, лD-loop = 0.021 ± 0.011) were detected from the mtDNA D-loop. The population genetic diversity of O. fasciatus in south China was significantly higher than those of north China. Three genealogical clades were checked in the O. fasciatus populations based on the NJ and MST analyses of mtDNA COI gene sequence, and the genetic distances among the clades ranged from 0.018 to 0.025. Significant population genetic differentiation was also checked based on the Fst (0.331, p = 0.000) and exact p (0.000) test analyses. No significant population differentiations were checked based on mtDNA D-loop and Cytb fragments. Using a variety of phylogenetic methods, coalescent reasoning, and molecular dating interpreted in conjunction with paleoclimatic and physiographic evidences, we inferred that the genetic make-up of extant populations of O. fasciatus was shaped by Pleistocene environmental impacts on the historical demography of this species. Coalescent analyses (neutrality tests, mismatch distribution analysis, and Bayesian skyline analyses) showed that the species along coastline of China has experienced population expansions originated in its most recent history at about 169-175 kya before present.


Cantú Syndrome Associated with Ovarian Agenesis.
Cantú syndrome is a very rare autosomal dominant disorder characterized by generalized congenital hypertrichosis, neonatal macrosomia, coarse face, cardiomegaly, and occasionally, skeletal abnormalities. The syndrome has been attributed to mutated ABCC9 or KCNJ8 genes. We present a 4-year-old girl with developmental delay, distinctive coarse facial features, and generalized hypertrichosis apparent since birth. The investigation revealed absent ovaries and a hypoplastic uterus which have not been previously described. Conventional karyotyping was normal. DNA sequencing analysis of the ABCC9 gene was performed, and a heterozygous point mutation c.3460C>T (p.Arg1154Trp) was revealed. This missense gain-of-function mutation was located in exon 27 of the ABCC9 gene and has been reported in patients with the full phenotype of Cantú syndrome. However, the absence of the ovaries could be an expansion of the phenotype and not attributed to mutations in other genes important for ovarian development. Unfortunately, it has not been proven so far if the ABCC9 gene is expressed in the ovarian tissue.


Pulmonary embolism and mortality in patients with fractured hips--a prospective consecutive series.
To find out the causes of death with particular reference to venous thromboembolism all patients being operated on for hip fractures who were taking part in a trial of two methods of prophylaxis against thromboembolism were consecutively and prospectively registered. A total of 806 patients were included, 66 of whom died within three months (8%). The necropsy rate was 64%. The patients who died were significantly older than those who did not. Pulmonary emboli were diagnosed in 17 of the 42 necropsies: 3 fatal, 5 contributory, and 9 incidental. The patients with fatal and contributory emboli died a median of 31 days postoperatively. In the 24 patients who did not have necropsies the clinical cause of deaths were cardiac insufficiency (n = 11), pneumonia (n = 8), pulmonary embolism (n = 2), and myocardial infarction, cerebral infarction, and pancreatic cancer (n = 1 each). The incidence of fatal pulmonary embolism therefore varies between a minimum of 0.37% and a theoretical maximum of 3.3%. In conclusion, fatal pulmonary embolism after operations for fractured hips is low where routine thromboprophylaxis is used. Most patients who develop large pulmonary emboli are old but live independently. To study causes of death a high necropsy rate is essential.


Lactate promotes glioma migration by TGF-beta2-dependent regulation of matrix metalloproteinase-2.
Lactate dehydrogenase type A (LDH-A) is a key metabolic enzyme catalyzing pyruvate into lactate and is excessively expressed by tumor cells. Transforming growth factor-beta2 (TGF-beta2) is a key regulator of invasion in high-grade gliomas, partially by inducing a mesenchymal phenotype and by remodeling the extracellular matrix. In this study, we tested the hypothesis that lactate metabolism regulates TGF-beta2-mediated migration of glioma cells. Small interfering RNA directed against LDH-A (siLDH-A) suppresses, and lactate induces, TGF-beta2 expression, suggesting that lactate metabolism is strongly associated with TGF-beta2 in glioma cells. Here we demonstrate that TGF-beta2 enhances expression, secretion, and activation of matrix metalloproteinase-2 (MMP-2) and induces the cell surface expression of integrin alpha(v)beta(3) receptors. In spheroid and Boyden chamber migration assays, inhibition of MMP-2 activity using a specific MMP-2 inhibitor and blocking of integrin alpha(v)beta(3) abrogated glioma cell migration stimulated by TGF-beta2. Furthermore, siLDH-A inhibited MMP2 activity, leading to inhibition of glioma migration. Taken together, we define an LDH-A-induced and TGF-beta2-coordinated regulatory cascade of transcriptional regulation of MMP-2 and integrin alpha(v)beta(3). This novel interaction between lactate metabolism and TGF-beta2 might constitute a crucial mechanism for glioma migration.


Heterogeneous Nanostructure Based on 1T-Phase MoS2 for Enhanced Electrocatalytic Hydrogen Evolution.
As an electrocatalyst, conventional 2H-phase MoS2 suffers from limited active sites and inherently low electroconductivity. Phase transitions from 2H to 1T have been proposed as an effective strategy for optimization of the catalytic activity. However, complicated chemical exfoliation is generally involved. Here, MoS2 heterogeneous-phase nanosheets with a 1T phase (1T/2H-MoS2) generated in situ were prepared through a facile hydrothermal method. The locally introduced 1T-phase MoS2 can not only contribute more active sites but also markedly promote the electronic conductivity. Because of this unique structure, the as-synthesized 1T/2H-MoS2 nanosheets exhibit remarkable performance for the hydrogen evolution reaction with a small overpotential of 220 mV at 10 mA/cm2, a small Tafel slope of 61 mV/decade, and robust stability. This work facilitates the development of a two-dimensional heterogeneous nanostructure with enhanced applications.


ADC Shows Effectiveness in SCLC.
Results from a phase I trial presented during the 2015 European Cancer Congress suggest that an experimental antibody-drug conjugate, rovalpituzumab tesirine, may be effective against recurrent small cell lung cancer, for which there are few treatment options.


Undercut reproducibility of functional impression materials (tissue conditioners).
Impressions of a laboratory model of an edentulous ridge were made with three commercial tissue conditioners (FITT, Hydro-Cast and Coe-Comfort). Combinations of undercut dimensions and tray relief were tested by using three different sized trays with each tissue conditioner. Greater tray relief increased the accuracy of all materials tested; increasing ageing time from 7 to 24 h resulted in little change of accuracy of the stone models poured from the impressions taken.


Defining the detection mechanisms for symmetric and rectified flicker stimuli.
Symmetric flicker modulates about a background light level and effects no change in the time-average luminance. Rectified flicker is achieved by modulating a luminance-increment and results in both a flickering component and an increase in the time-averaged luminance (luminance-pedestal) above the adapting background light level. We studied the effect that changes in adapting light level and local luminance (within the area of the flickering target) have on thresholds. We measured thresholds for single and multiple cycles of flicker over a range of adapting light levels (Threshold versus Intensity paradigm) and defined their gain as a function of luminance-pedestal amplitude (Threshold versus Amplitude paradigm). The dynamics of symmetric and rectified flicker responses were determined using a Stimulus Onset Asynchrony paradigm. The data show rectified flicker thresholds differ from symmetric flicker thresholds due to two factors that can be contrast-dependent or contrast-independent: (1) local adaptation, which varies with stimulus duration and (2) surround interactions that depend on adapting light level. The dynamics of the thresholds for symmetric and rectified flicker stimuli suggest the detection mechanisms occur early in the visual pathways, involving the magnocellular pathway.


Apoptosis in schistosomes: toward novel targets for the treatment of schistosomiasis.
Schistosomiasis is one of the world's major neglected tropical diseases. Recent advances in schistosome genomics and transcriptomics have identified components of an intrinsic, B cell lymphoma-2 (Bcl-2)-regulated apoptotic cell death pathway. Molecular characterization of this pathway demonstrates its similarity to that in mammals. Gene expression and functional data indicate that apoptosis is active throughout the lifecycle. Moreover, drugs that activate apoptosis in human cells kill schistosome cells, raising the prospect of developing new treatments against schistosomiasis of humans. The development of new drugs is increasingly important in the face of the potential for resistance to currently available treatments, and the lack of an effective vaccine.


26,27-cyclosterols and other polyoxygenated sterols from a marine sponge Topsentia sp.
Thirty sterols (1-30) were isolated from bioactive fractions of a marine sponge Topsentia sp., of which 16 were new (1, 2, 8, 10-14, 16, 17, 19, 21, 24, 25, 27, and 30). They were characterized as sterols with 10 different side chains and as having various functionalities including 5alpha,8alpha-epidioxy (1-9), 5alpha,6alpha-epoxy-7-ol (10-15), 5,8-dien-7-one (24-28), 5-en-3beta-ol (29), and 1(10-->6)abeo-5,7,9-triene-3alpha,11alpha-diol (30) units and included polyoxygenated sterols (16-23). One of the key features of these new sterols is the presence of the (24R,25R,27R)-26,27-cyclo-24,27-dimethylcholestane side chain, whose absolute stereochemistry was defined by an acid-catalyzed ring-opening method and by comparison with the four synthetic isomers of known absolute stereochemistry. The occurrence of several known fungal sterols and relevant new sterols in this sponge suggested their possible origin from symbiotic fungi. Selected compounds were tested against a panel of five human solid tumor cell lines and displayed moderate to marginal cytotoxicity.


Impact of Coronavirus Disease 2019 Pandemic on Crowding: A Call to Action for Effective Solutions to "Access Block".
Healthcare patterns change during disease outbreaks and pandemics. Identification of modified patterns is important for future preparedness and response. Emergency department (ED) crowding can occur because of the volume of patients waiting to be seen, which results in delays in patient assessment or treatment and impediments to leaving the ED once treatment is complete. Therefore, ED crowding has become a growing problem worldwide and represents a serious barrier to healthcare operations. This observational study was based on a retrospective review of the epidemiologic and clinical records of patients who presented to the Foundation IRCCS Policlinic San Matteo in Pavia, Italy, during the coronavirus disease 2019 (COVID-19) outbreak (February 21-May 1, 2020, pandemic group). The methods involved an estimation of the changes in epidemiologic and clinical data from the annual baseline data after the start of the COVID-19 pandemic. We identified reduced ED visits (180 per day in the control period vs 96 per day in the pandemic period; P < 0.001) during the COVID-19 pandemic, irrespective of age and gender, especially for low-acuity conditions. However, patients who did present to the ED were more likely to be hemodynamically unstable, exhibit abnormal vital signs, and more frequently required high-intensity care and hospitalization. During the pandemic, ED crowding dramatically increased primarily because of an increased number of visits by patients with high-acuity conditions, changes in patient management that prolonged length of stay, and increased rates of boarding, which led to the inability of patients to gain access to appropriate hospital beds within a reasonable amount of time. During the pandemic, all crowding output indices increased, especially the rates of boarding (36% vs 57%; P < 0.001), "access block" (24% vs 47%; P < 0.001), mean boarding time (640 vs 1,150 minutes [min]; P 0.001), mean "access block" time (718 vs 1,223 min; P < 0.001), and "access block" total time (650,379 vs 1,359,172 min; P < 0.001). Crowding in the ED during the COVID-19 pandemic was due to the inability to access hospital beds. Therefore, solutions to this lack of access are required to prevent a recurrence of crowding due to a new viral wave or epidemic.


Development, optimization and validation of gas chromatographic fingerprinting of Brazilian commercial diesel fuel for quality control.
A three-step development, optimization and validation strategy is described for gas chromatography (GC) fingerprints of Brazilian commercial diesel fuel. A suitable GC-flame ionization detection (FID) system was selected to assay a complex matrix such as diesel. The next step was to improve acceptable chromatographic resolution with reduced analysis time, which is recommended for routine applications. Full three-level factorial designs were performed to improve flow rate, oven ramps, injection volume and split ratio in the GC system. Finally, several validation parameters were performed. The GC fingerprinting can be coupled with pattern recognition and multivariate regressions analyses to determine fuel quality and fuel physicochemical parameters. This strategy can also be applied to develop fingerprints for quality control of other fuel types.


Brain functional specialization and cooperation in Parkinson's disease.
Cerebral specialization and inter-hemispheric cooperation are two of the most prominent functional architectures of the human brain. Their dysfunctions may be related to pathophysiological changes in patients with Parkinson's disease (PD), who are characterized by unbalanced onset and progression of motor symptoms. This study aimed to characterize the two intrinsic architectures of hemispheric functions in PD using resting-state functional magnetic resonance imaging. Seventy idiopathic PD patients and 70 age-, sex-, and education-matched healthy subjects were recruited. All participants underwent magnetic resonance image scanning and clinical evaluations. The cerebral specialization (Autonomy index, AI) and inter-hemispheric cooperation (Connectivity between Functionally Homotopic voxels, CFH) were calculated and compared between groups. Compared with healthy controls, PD patients showed stronger AI in the left angular gyrus. Specifically, this difference in specialization resulted from increased functional connectivity (FC) of the ipsilateral areas (e.g., the left prefrontal area), and decreased FC in the contralateral area (e.g., the right supramarginal gyrus). Imaging-cognitive correlation analysis indicated that these connectivity were positively related to the score of Montreal Cognitive Assessment in PD patients. CFH between the bilateral sensorimotor regions was significantly decreased in PD patients compared with controls. No significant correlation between CFH and cognitive scores was found in PD patients. This study illustrated a strong leftward specialization but weak inter-hemispheric coordination in PD patients. It provided new insights to further clarify the pathological mechanism of PD.


Nonclinical Exon Skipping Studies with 2'-O-Methyl Phosphorothioate Antisense Oligonucleotides in mdx and mdx-utrn-/- Mice Inspired by Clinical Trial Results.
Duchenne muscular dystrophy is a severe, progressive muscle-wasting disease that is caused by mutations that abolish the production of functional dystrophin protein. The exon skipping approach aims to restore the disrupted dystrophin reading frame, to allow the production of partially functional dystrophins, such as found in the less severe Becker muscular dystrophy. Exon skipping is achieved by antisense oligonucleotides (AONs). Several chemical modifications have been tested in nonclinical and clinical trials. The morpholino phosphorodiamidate oligomer eteplirsen has been approved by the Food and Drug Administration, whereas clinical development with the 2'-O-methyl phosphorothioate (2OMePS) AON drisapersen was recently stopped. In this study, we aimed to study various aspects of 2OMePS AONs in nonclinical animal studies. We show that while efficiency of exon skipping restoration is comparable in young and older C57BL/10ScSn-Dmdmdx/J (mdx/BL10) mice, functional improvement was only observed for younger treated mice. Muscle quality did not affect exon skipping efficiency as exon skip and dystrophin levels were similar between mdx/BL10 and more severely affected, age-matched D2-mdx mice. We further report that treadmill running increases AON uptake and dystrophin levels in mdx/BL10 mice. Finally, we show that even low levels of exon skipping and dystrophin restoration are sufficient to significantly increase the survival of mdx-utrn-/- mice from 70 to 97 days.


Infants born to mothers under phenobarbital treatment: correlation between serum levels and clinical features of neonates.
Phenobarbital crosses the placenta quickly, and the balance between maternal and fetal blood is achieved in a few minutes. Data on the clinical outcomes of infants born to mothers under phenobarbital treatment during pregnancy show that they are at risk of adverse events, such as sedation and abstinence syndrome. The aim of this study was to analyse the correlation between serum levels of phenobarbital and clinical features of neonates. Twenty-three infants born between 2001 and 2008 were studied. Maternal, neonatal and pharmacological variables were considered. Eleven infants displayed symptoms related to phenobarbital. Withdrawal syndrome was seen in seven infants and sedation syndrome was seen in four infants. One infant had severe cardiorespiratory depression at birth. None of the infants had severe neonatal abstinence syndrome. No statistically significant differences were found between symptomatic and asymptomatic infants. At birth, the mean serum level of phenobarbital of the 23 infants was 15.4 [standard deviation (SD) 6.2] μg/ml. A peak (16.1 μg/ml, SD 5.5) was seen on Day 3, followed by a gradual decrease to non-therapeutic levels (<10 μg/ml) by Day 8 (9.3 μg/ml, SD 1.0). Phenobarbital levels were higher in symptomatic infants than asymptomatic infants, although the difference was not statistically significant. Serum levels of phenobarbital remained in the therapeutic range for both mothers and infants, and reduced gradually in infants. However, some infants displayed symptoms related to phenobarbital. As such, a clinical pharmacological surveillance protocol is necessary.


The growth discordant twin.
The study of growth discordancy in twin gestation has gathered great momentum in recent years. Divergent intertwin growth is believed to be a direct result of the process of twinning and of the inability of the uterine environment to provide for the increased demand of multiple fetuses. The smaller twin faces increased risk of perinatal mortality and morbidity as well as reduced physical and mental development in later life. The advent of ultrasonography enabled a fairly accurate prediction of growth disparity. Although extensive investigative efforts have clarified many questions regarding divergent twin growth, the question how to manage such pregnancies remains to be answered. The present article is a review of the literature concerning the clinical aspects of growth discordant twins.


[Correlation of estrogen receptors and histologic and cytologic grading of breast cancer].
Correlations between estrogen receptors and other prognostic criteria have been examined. These criteria are clinical extent, status of lymph nodes, histologic differentiation, histologic and cytologic grading. Cancers with a good prognosis are much more receptor positive than those with a bad prognosis. The quantity of receptors does not allow any prognostic statement. Possible reasons for it are discussed.


[Endoscopic treatment of bladder diverticula].
Since February 1993 six patients with bladder diverticula have undergone resection of the diverticular neck and fulguration of the diverticular mucosa at the time of transurethral resection of the prostate in 5 cases and urethral dilation in one case. The mean dimension of the diverticular was 5.2 cm. After a mean follow-up of 20 months the diverticulum has largely shrunk in one case and has completely disappeared in 5 cases. Our paper demonstrates the effectiveness of this technique in the treatment of bladder diverticular. In our opinion endoscopic fulguration represents a valid alternative to open surgery for the treatment of small bladder diverticular.


[Management of intractable epistaxis and bleeding points localization].
To investigate the common nasal bleeding points and the management of intractable epistaxis. The bleeding points and its correlation with age distribution, surgical techniques as well as its effects were studied retrospectively in 92 patients, in whom the bleeding points were not found by routine nasal endoscopy and the hemorrhage was not controlled with standard nasal packing. The bleeding points were found in the following different sites: superior wall of inferior nasal meatus (56.5%, 52/92), olfactory cleft of nasal septum (27.2%, 25/92), posterosuperior wall of middle nasal meatus (8.7%, 8/92) and uncertain (7.6%, 7/92). The results showed that the bleeding points had correlation with age. Epistaxis was well controlled by electrocoagulation in 83 cases, gelfoam packing in 8 cases, and transcatheter maxillary artery embolization in 1 case. There were no complications during a followed-up for 1 - 3 months after management. Among the 92 cases, the numbers of treatment needed to stop bleeding were 82 cases (89.1%) after 1 time of treatment, 9 cases (9.8%) after 2 times and in one case (1.1%) after 4 times. Endoscopy combined with displacement of the middle and inferior turbinate gives good visualization and direct management of the deeply-sited bleeding points, which were difficult in localization. The combined method provides an effective and safe way to control intractable epistaxis.


MIS-C: A COVID-19-as sociated condition between hypoimmunity and hyperimmunity.
Multisystem inflammatory syndrome in children (MIS-C) is a rare, severe complication of COVID-19. A better knowledge of immunological, cellular, and genetic characteristics of MIS-C could help better understand the pathogenesis of the disease and contribute to identifying specific diagnostic biomarkers and develop targeted therapies. We studied 37 MIS-C children at hospital admission and 24 healthy controls analyzing serum cytokines (IFN-α, IFN-β, IFN-γ, IL-6, IL-10, IL-17A, IL-12p70 and TNF), lymphocyte populations by flow cytometry and 386 genes related to autoimmune diseases, autoinflammation and primary immunodeficiencies by NGS. MIS-C patients showed a significant increase of serum IFNγ (despite a significant reduction of activated Th1) and ILs, even if with a great heterogeneity among patients, revealing different pathways involved in MIS-C pathogenesis and suggesting that serum cytokines at admission may help to select the inflammatory pathways to target in each patient. Flow cytometry demonstrated a relevant reduction of T populations while the percentage of B cell was increased in agreement with an autoimmune pathogenesis of MIS-C. Genetic analysis identified variants in 34 genes and 83.3% of patients had at least one gene variant. Among these, 9 were mutated in more patients. Most genes are related to autoimmune diseases like ATM, NCF1, MCM4, FCN3, and DOCK8 or to autoinflammatory diseases associated to the release of IFNγ like PRF1, NOD2, and MEF. Thus, an incomplete clearance of the Sars-CoV2 during the acute phase may induce tissue damage and self-antigen exposure and genetic variants can predispose to hyper-reactive immune dysregulation events of MIS-C-syndrome. Type II IFN activation and cytokine responses (mainly IL-6 and IL-10) may cause a cytokine storm in some patients with a more severe acute phase of the disease, lymphopenia and multisystemic organ involvement. The timely identification of such patients with an immunocytometric panel might be critical for targeted therapeutic management.


Resistance of breast cancer cells to paclitaxel is associated with low expressions of miRNA-186 and miRNA-7.
Aim: Neo-adjuvant chemotherapy is a common approach for the complex treatment of breast cancer (BC) and paclitaxel (PTX) is frequently included in the therapeutic regimen. However, the effect of PTX-based treatment is hard to predict precisely based on routinely used markers. As microRNAs are considered a new promising class of biomarkers, the link between miRNA expression and PTX resistance of BC cells needs to be well investigated. This study aimed at the identification of miRNAs associated with responses of BC cells to PTX. Methods: Intrinsic PTX sensitivity and miRNA profiling were assayed in five BC cell lines to identify candidate miRNAs. Selected miRNA (n. 15) expressions were analyzed by real-time-quantitative polymerase chain reaction (RT-qPCR) in BC tissue samples (n. 31) obtained from a diagnostic biopsy. Results were analyzed in the context of the effect of two cycles of PTX and the effect of the completed scheme of neoadjuvant therapy. The study's design facilitated the evaluation of the effect of PTX on cells and the identification of features of the microRNA expression profiles associated exclusively with sensitivity to this drug. Results: miR-186 and miR-7 expression in BC tissues was higher in patients with better outcomes of PTX-based neoadjuvant therapy. Conclusion: High expressions of miR-186 and miR-7 are associated with good response to PTX, whereas their low expressions may be associated with resistance to PTX in BC, indicating the possibility of developing innovative test systems for the prediction of the PTX response, which can be used before the start of neo-adjuvant chemotherapy for BC.


MUC3 and MCA serum levels and steroid receptor content in breast cancer.
Mucins are an important class of complex glycoproteins expressed by many epithelial cells and their malignant counterparts. The aim of this study was to determine the serum levels of MUC3 and mucin-like carcinoma-associated antigen (MCA) in patients with primary breast cancer and to analyze the possible relationships between these two mucins and the steroid receptor status. The preoperative basal serum levels of MUC3 (ELISA assay with monoclonal antibody 1143/B7) and MCA (EIA assay with anti-MCA mouse monoclonal antibody b-12) were determined in 44 patients with breast cancer while estrogen receptor (ER) and progesterone receptor (PgR) levels were measured by the dextran-coated charcoal method in the cytosol of neoplastic tissue. MUC3 was expressed in 43/44 serum samples while high MCA serum levels were found in 16/44 only; the mean values of both markers did not correlate with menopausal status, tumor size, nodal involvement or ER. The only significant difference observed was a lower median value of MCA in patients with small tumors (T1-T2). No statistically significant correlation between MUC3 and MCA, MUC3 and ER or MCA and ER was observed; a statistically significant direct correlation between MUC3 and PgR+ status and a statistically significant inverse correlation between MCA and PgR+ were observed. Our results suggest that further investigations are necessary to establish whether progesterone can modulate MUC3 and MCA expression in breast cancer.


The Role of Macrophage Lipophagy in Reverse Cholesterol Transport.
Macrophage cholesterol efflux is a central step in reverse cholesterol transport, which helps to maintain cholesterol homeostasis and to reduce atherosclerosis. Lipophagy has recently been identified as a new step in cholesterol ester hydrolysis that regulates cholesterol efflux, since it mobilizes cholesterol from lipid droplets of macrophages via autophagy and lysosomes. In this review, we briefly discuss recent advances regarding the mechanisms of the cholesterol efflux pathway in macrophage foam cells, and present lipophagy as a therapeutic target in the treatment of atherosclerosis.


TNF-α -308 A allele is associated with an increased risk of distant metastasis in rectal cancer patients from Southwestern China.
Tumor necrosis factor-α (TNF-α), an important factor in systematic inflammation, is reportedly involved in several cancer types. The TNF-α -308 G>A (rs1800629) polymorphism in the promoter region influences TNF-α production. The association between TNF-α -308 G>A polymorphism and colorectal cancer (CRC) is not fully understood, especially the connections between TNF-α -308 G>A polymorphism and clinical features of CRC. In this study, TNF-α -308 G>A polymorphism was genotyped in 1140 individuals with or without CRC from Southwestern China. In case-control studies, we found no association between TNF-α -308 G>A polymorphism and CRC risk. Analysis of the correlations between TNF-α -308 G>A polymorphism and clinical features of CRC revealed that TNF-α -308 A allele was associated with higher body mass index (BMI) larger tumor size, and distant tumor metastasis in all CRC patients. Notably, rectal cancer (a subtype of CRC) patients with TNF-α -308 A allele had a very high risk of distant tumor metastasis [odds ratio (OR) = 4.481; 95% confidence interval (CI): 2.072-9.693; P = 0.00025]. The association between TNF-α -308 A allele and distant tumor metastasis remained even significant after adjusting all clinical characteristics (OR = 7.099; 95% CI: 2.482-20.301; P = 0.000256) in rectal cancer patients. Our results suggested that TNF-α -308 A allele was significantly associated with distant tumor metastasis in rectal cancer patients.


[Experimental renal transplantation of cirrhotic donors. I. Morphologic, immunofluorescence, and ultrastructural study].
The cirrhotic kidney can be successfully transplanted into healthy recipients. The histological lesions have not been well defined or correlated with the functional changes observed in cirrhosis. Methods to induce experimental cirrhosis in the rat that reliably reproduce this disease have been developed. The development of microsurgical techniques have made it possible to perform transplantation in the rat. We analyzed the renal lesions of cirrhotic rats and the evolution of the graft after transplantation into a healthy rat.


Tramadol dependence: a case series from India.
Tramadol is an atypical, centrally acting, synthetic analgesic, acting through opioid and non-opioid systems. We present a series of seven cases, all men, who sought treatment at our centre for tramadol-dependence. The majority were using other opioids at some point in their lives. Their tramadol use had begun with a prescription of tramadol for opioid detoxification, for headache and body pains, and as an alternative to injectable opioids. The doses of tramadol used varied from 50 to 1500 mg per day. All subjects reported an experience of euphoria with tramadol use. Four patients were put on naltrexone, but had poor compliance. This case series underscores the need for caution, while using tramadol in substance-dependent patients.


Expression of somatostatin receptor types 1-5 in 81 cases of gastrointestinal and pancreatic endocrine tumors. A correlative immunohistochemical and reverse-transcriptase polymerase chain reaction analysis.
Somatostatin receptors (SSTRs) have been extensively mapped in human tumors by means of autoradiography, reverse-transcriptase polymerase chain reaction (RT-PCR), in situ hybridization (ISH) and immunohistochemistry (IHC). We analyzed the SSTR type 1-5 expression by means of RT-PCR and/or IHC in a series of 81 functioning and non-functioning gastroenteropancreatic (GEP) endocrine tumors and related normal tissues. Moreover, we compared the results with clinical, pathological and hormonal features. Forty-six cases (13 intestinal and 33 pancreatic) were studied for SSTR 1-5 expression using RT-PCR, IHC with antibodies to SSTR types 2, 3, 5 and ISH for SSTR2 mRNA. The vast majority of tumors expressed SSTR types 1, 2, 3 and 5, while SSTR4 was detected in a small minority. Due to the good correlation between RT-PCR and IHC data on SSTR types 2, 3, and 5, thirty-five additional GEP endocrine tumors were studied with IHC alone. Pancreatic insulinomas had an heterogeneous SSTR expression, while 100% of somatostatinomas expressed SSTR5 and 100% gastrinomas and glucagonomas expressed SSTR2. Pre-operative biopsy material showed an overlapping immunoreactivity with that of surgical specimens, suggesting that the SSTR status can be detected in the diagnostic work-up. It is concluded that SSTRs 1-5 are heterogeneously expressed in GEP endocrine tumors and that IHC is a reliable tool to detect SSTR types 2, 3 and 5 in surgical and biopsy specimens.


A method to optimize PEG-coating of red blood cells.
Alloimmunization to donor blood group antigens remains a significant problem in transfusion medicine. A proposed method to overcome donor-recipient blood group incompatibility is to mask the blood group antigens by the covalent attachment of poly(ethylene glycol) (PEG) to the red blood cell (RBC) membrane. Despite much work in the development of PEG-coating of RBCs, there is a paucity of data on the optimization of the PEG-coating technique; it is the aim of this study to determine the optimum conditions for PEG coating using a cyanuric chloride reactive derivative of methoxy-PEG as a model polymer. Activated PEG of molecular mass 5 kDa was covalently attached to human RBCs under various reaction conditions. Inhibition of binding of a blood-type specific antiserum (anti-D) was employed to evaluate the effect of the PEG-coating, quantified by hemocytometry and flow-cytometry. RBC morphology was examined by light and scanning electron microscopy. Statistical analysis of experimental design together with microscopy results showed that the optimum PEGylation conditions are pH = 8.7, temperature = 14 degrees C, and reaction time = 30 min. An optimum concentration of reactive PEG could not be determined. At high polymer concentrations (>25 mg/mL) a predominance of type III echinocytes was observed, and as a result, a concentration of 15 mg/mL is the highest recommended concentration for a linear PEG of molecular mass 5 kDa.


[Hepatitis E--epidemiology and clinical aspects].
Hepatitis E virus (HEV) is a newly identified and molecularly characterized RNA virus. HEV has a worldwide distribution. Large epidemics were observed on the Indian subcontinent, in Central and in Southeast Asia. The enterically transmitted HEV infection also occurs in sporadic form. Only few cases of HEV infection with clinically apparent hepatitis were diagnosed in Western Europe and in the USA. HEV infection causes symptoms of a self-limiting, acute, icteric disease similar to those of hepatitis A. Severe and fulminant courses occur more often than with HAV infection. Chronic liver disease or persistent viremia have not been observed. Diagnosis of HEV infection is based on the detection of anti-HEV-antibodies.


Management of Mechanical Ventilation in Decompensated Heart Failure.
Mechanical ventilation (MV) is a life-saving intervention for respiratory failure, including decompensated congestive heart failure. MV can reduce ventricular preload and afterload, decrease extra-vascular lung water, and decrease the work of breathing in heart failure. The advantages of positive pressure ventilation must be balanced with potential harm from MV: volutrauma, hyperoxia-induced injury, and difficulty assessing readiness for liberation. In this review, we will focus on cardiac, pulmonary, and broader effects of MV on patients with decompensated HF, focusing on practical considerations for management and supporting evidence.