Trends in the incidence of female breast and cervical cancers in Miyagi Prefecture, Japan, 1959-1987.
Trends in the incidence of female breast and cervical cancers were examined, using the cancer registry data in Miyagi Prefecture, Japan, during 1959-1987. The age-standardized incidence rate of breast cancer has been increasing, while that of cervical cancer has been decreasing. Age-period-cohort models were applied to clarify the trends in incidence. For breast cancer incidence, the age-period model adequately represented the data, and demonstrated that the risk of developing breast cancer has been increasing in recent time periods. The effect of cohort on breast cancer incidence was insignificant and the full model containing age, period and cohort showed irregularities in the cohort effect. For cervical cancer incidence, the effect of period was significant, while the effect of cohort was marginal. The full model containing age, period and cohort showed that cervical cancer risk has been decreasing in recent time periods and younger birth cohorts. Using published reports, we investigated the trends in the prevalence of various risk factors and compared them with the trends in the incidence at both sites. It is suggested that the effects of period and cohort might be related to the changes in the prevalence of these risk factors as well as to improvements of the diagnostic procedures.


Major surgeries performed for gestational trophoblastic neoplasms in a teaching hospital in Tehran, Iran.
This study aim was to evaluate indications and outcomes of surgical interventions performed in patients with gestational trophoblastic neoplasm. During January 1995 to December 2005, 110 patients with a diagnosis of persistent gestational trophoblastic neoplasm were treated in our Gynecologic Oncologic Department. Risk score calculation was carried out based on the revised FIGO 2000 scoring system for gestational trophoblastic neoplasm. Data from the patients' records and pathologic reports were analyzed by the chi-square and Fisher's exact tests and logistic regression. The Kaplan-Meier method including the log rank test was used to compare survival and recurrence. Eight patients did not complete their treatment and were excluded from the study. We evaluated treatment responses and outcomes in 102 patients. Seventy-nine patients (77.5%) responded fully to chemotherapy while 23 patients (22.5%) required surgery. Among 23 patients who underwent surgery, 10 cases (43.5%) had bleeding, and 13 cases (56.5%) had drug resistance. Several factors were found to be significantly different between the groups who responded to chemotherapy and those who needed surgery, including age (p=0.001), antecedent non-molar pregnancy (0.028), tumor stage (p=0.009), and pre-treatment risk scores (p=0.008). But, the total courses of chemotherapy (p=0.521), need to salvage chemotherapy (p=0.074), survival rates (p=0.714), and disease free survival rates (p=0.206) were not significantly different. The data suggest that age, antecedent non-molar pregnancy, tumor stage and the prognostic score are clinical predictors of need for surgery. But, it dose not seem that surgery have any effect on the total course of chemotherapy, need for salvage chemotherapy, and patient prognosis.


Changes in thymopoiesis in myasthenia gravis.
This study was undertaken to investigate T-cell maturation in hyperplastic thymi of patients suffering from myasthenia gravis (MG). For this purpose, the expression of the major differentiational molecules (CD4, CD8, and CD3/TCRalphabeta) and that of the regulatory and activation molecules on thymocytes from MG patients and control subjects were estimated by flow cytometric analysis. In the MG patients the increase in relative proportion of immature (CD4-8- TCRalphabeta-) and the most mature (CD4+8- TCRalphabetahigh and CD4-8- TCRhigh encompassing immunoregulatory NKT) thymocytes followed by a decrease in that of CD4+8+CD3-/TCRalphabeta- cells was found. Furthermore, in these patients the relative proportion of CD4+HLA-DR+ and CD4+71+ cells was increased, whereas that of CD4+25+ cells was slightly, but significantly, decreased (reflecting, most likely, decreased contribution of T reg cells bearing this phenotype). Moreover, in MG thymi the percentage of CD45RA+ cells was reduced indicating changes in the selection processes. In keeping with this finding the reduced thymocyte apoptotic index and percentage of cells bearing apoptosing (CD4-8- TCRalphabetalow) phenotype were detected. In conclusion, the study demonstrates substantial changes in intrathymic differentiation of T cells in hyperplastic MG thymi and suggests alterations in selection events providing an increased escape of potentially autoreactive T-cell clones, on one side, and an altered maturation and/or selection of immunoregulatory cells (NKT and CD4+8-25+ T reg cells) keeping these cell clones under control, on the other side.


Epidemiology and challenges of dengue surveillance in the WHO South-East Asia Region.
Dengue poses a significant health and economic burden in the WHO South-East Asia Region. Approaches for control need to be aligned with current knowledge on the epidemiology of dengue in the region. Such knowledge will ensure improved targeting of interventions to reduce dengue incidence and its socioeconomic impact. This review was undertaken to describe the contemporary epidemiology of dengue and critically analyse the existing surveillance strategies in the region. Over recent decades, dengue incidence has continued to increase with geographical expansion. The region has now become hyper-endemic for multiple dengue virus serotypes/genotypes. Every epidemic cycle was associated with a change of predominant serotype/genotype and this was often associated with severe disease with intense transmission. Classical larval indices are widely used in vector surveillance and adult mosquito samplings are not implemented as a part of routine surveillance. Further, there is a lack of integration of entomological and disease surveillance systems, often leading to inaction or delays in dengue prevention and control. Disease surveillance does not capture all cases, resulting in under-reporting, and has thus failed to adequately represent the true burden of disease in the region. Possible solutions include incorporating adult mosquito sampling into routine vector surveillance, the establishment of laboratory-based sentinel surveillance, integrated vector and dengue disease surveillance and climate-based early warning systems using available technologies like mobile apps.


Modeling age and retest processes in longitudinal studies of cognitive abilities.
Mixed effects models were used to examine the separate effects associated with age and retest on changes in various cognitive abilities. Individuals (N > 800) ranging in age from 40 to 70 years at the 1st measurement occasion were assessed with measures of memory, spatial abilities, and speed on 4 occasions. All cognitive abilities showed decline associated with increased age and improvement across the 4 measurement occasions. The age-related effects were similar across variables, but the practice effects were largest for memory and smallest for speed. When retest effects were not included in the models, the age-related effects were underestimated, with the magnitude of bias depending on the size of the ignored retest effects. It is suggested that both age and retest should be modeled simultaneously when analyzing longitudinal data because part of the change across occasions may be attributable to practice or reactive effects.


Cloning and Molecular Characterization of Porcine β-casein Gene (CNS2).
The production of therapeutic proteins from transgenic animals is one of the most important successes of animal biotechnology. Milk is presently the most mature system for production of therapeutic proteins from a transgenic animal. Specifically, β-casein is a major component of cow, goat and sheep milk, and its promoter has been used to regulate the expression of transgenic genes in the mammary gland of transgenic animals. Here, we cloned the porcine β-casein gene and analyzed the transcriptional activity of the promoter and intron 1 region of the porcine β-casein gene. Sequence inspection of the 5'-flanking region revealed potential DNA elements including SRY, CdxA, AML-a, GATA-3, GATA-1 and C/EBP β. In addition, the first intron of the porcine β-casein gene contained the transcriptional enhancers Oct-1, SRY, YY1, C/EBP β, and AP-1, as well as the retroviral TATA box. We estimated the transcriptional activity for the 5'-proximal region with or without intron 1 of the porcine β-casein gene in HC11 cells stimulated with lactogenic hormones. High transcriptional activity was obtained for the 5'-proximal region with intron 1 of the porcine β-casein gene. The β-casein gene containing the mutant TATA box (CATAAAA) was also cloned from another individual pig. Promoter activity of the luciferase vector containing the mutant TATA box was weaker than the same vector containing the normal TATA box. Taken together, these findings suggest that the transcription of porcine β-casein gene is regulated by lactogenic hormone via intron 1 and promoter containing a mutant TATA box (CATAAAA) has poor porcine β-casein gene activity.


A novel mutation in GJA8 causing congenital cataract-microcornea syndrome in a Chinese pedigree.
To identify the underlying genetic defect in a four-generation family of Chinese origin with autosomal dominant congenital cataract-microcornea syndrome (CCMC). All individuals in the study underwent a full clinical examination and the details of history were collected . Genomic DNA extracted from peripheral blood was amplified by polymerase chain reaction (PCR) method and the exons of all candidate genes were sequenced. Direct sequencing of the encoding regions of the candidate genes revealed a heterozygous mutation c.592C-->T in exon 2 of the gap junction protein, alpha 8 (GJA8) gene. This mutation was responsible for the familial disorder through the substitution of a highly conserved arginine to tryptophan at codon 198 (p.R198W). This change co-segregated with all affected members of the family, but was not detected either in the non-carrier relatives or in the 100 normal controls. This report is the first to relate p.R198W mutation in GJA8 with CCMC. The result expands the mutation spectrum of GJA8 in associated with congenital cataract and microcornea, and implies that this gene has direct involvement with the development of the lens as well as the other anterior segment of the eye.


Advances and Perspectives in Applying Deep Learning for Drug Design and Discovery.
Discovering (or planning) a new drug candidate involves many parameters, which makes this process slow, costly, and leading to failures at the end in some cases. In the last decades, we have witnessed a revolution in the computational area (hardware, software, large-scale computing, etc.), as well as an explosion in data generation (big data), which raises the need for more sophisticated algorithms to analyze this myriad of data. In this scenario, we can highlight the potentialities of artificial intelligence (AI) or computational intelligence (CI) as a powerful tool to analyze medicinal chemistry data. According to IEEE, computational intelligence involves the theory, the design, the application, and the development of biologically and linguistically motivated computational paradigms. In addition, CI encompasses three main methodologies: neural networks (NN), fuzzy systems, and evolutionary computation. In particular, artificial neural networks have been successfully applied in medicinal chemistry studies. A branch of the NN area that has attracted a lot of attention refers to deep learning (DL) due to its generalization power and ability to extract features from data. Therefore, in this mini-review we will briefly outline the present scope, advances, and challenges related to the use of DL in drug design and discovery, describing successful studies involving quantitative structure-activity relationships (QSAR) and virtual screening (VS) of databases containing thousands of compounds.


Understanding Social Network and Support for Older Immigrants in Ontario, Canada: Protocol for a Mixed-Methods Study.
Older adults are the fastest growing age group worldwide and in Canada. Immigrants represent a significant proportion of older Canadians. Social isolation is common among older adults and has many negative consequences, including limited community and civic participation, increased income insecurity, and increased risk of elder abuse. Additional factors such as the social, cultural, and economic changes that accompany migration, language differences, racism, and ageism heighten older immigrants' vulnerability to social isolation. This mixed-methods sequential (qualitative-quantitative) study seeks to clarify older immigrants' social needs, networks, and support and how these shape their capacity, resilience, and independence in aging well in Ontario. Theoretically, our research is informed by an intersectionality perspective and an ecological model, allowing us to critically examine the complexity surrounding multiple dimensions of social identity (eg, gender and immigration) and how these interrelate at the micro (individual and family), meso (community), and macro (societal) levels in diverse geographical settings. Methodologically, the project is guided by a collaborative, community-based, mixed-methods approach to engaging a range of stakeholders in Toronto, Ottawa, Waterloo, and London in generating knowledge. The 4 settings were strategically chosen for their diversity in the level of urbanization, size of community, and the number of immigrants and immigrant-serving organizations. Interviews will be conducted in Arabic, Mandarin, and Spanish with older women, older men, family members, community leaders, and service providers. The study protocol has received ethics approval from the 4 participating universities. Quantitative and qualitative data collection is ongoing. The project is funded by the Social Sciences and Humanities Council of Canada. Comparative analyses of qualitative and quantitative data within and across sites will provide insights about common and unique factors that contribute to the well-being of older immigrants in different regions of Ontario. Given the comprehensive approach to incorporating local knowledge and expert contributions from multilevel stakeholders, the empirical and theoretical findings will be highly relevant to our community partners, help facilitate practice change, and improve the well-being of older men and women in immigrant communities. DERR1-10.2196/12616.


General anesthesia for cesarean section in a pregnant woman with systemic vascular malformation: a case report.
Vascular malformations are composed of morphologically abnormal vascular tissue, and when located in the head and neck region, they can make it difficult to secure the airway during general anesthesia. A 28-year-old pregnant woman with vascular malformations in the pharynx was scheduled to undergo a cesarean section, for which spinal anesthesia was initially chosen. However, after magnetic resonance imaging results revealed the presence of multiple vascular malformations in the lumbar multifidus muscles, spinal anesthesia was considered to be of high risk. Thus, the patient was subjected to general anesthesia tracheal intubation under sedation, and the course of the surgery was without complications. Because the pathophysiology and clinical sequelae of vascular malformations may be involved in complications, thorough presurgical evaluation of the patient's physical condition and careful anesthesia planning should be done.


New developments in prevention and early intervention for alcohol abuse in youths.
This article summarizes a symposium held at the 2004 Annual Meeting of the Research Society on Alcoholism in Vancouver, British Columbia, Canada. It was prepared by the conference co-organizers/co-chairs with substantial input from each of the symposium participants. Increasingly, alcohol abuse interventions focus on preventing alcohol problems or intervening early before risky drinking behavior becomes ingrained. Universal prevention programs have produced no or only modest effects on the drinking behavior of youths. Although some existing targeted prevention programs have proved effective, they have not tapped the full range of potential intervention targets, such as the underlying motivations for alcohol misuse in youths who are at greatest risk. The set of papers presented in this symposium outline exciting new developments in the field of targeted prevention and early intervention programs for adolescent drinking problems, presented by an international panel of researchers. These developments include attention to making interventions relevant to adolescents' lives, focus on personality and motivational factors underlying alcohol misuse, and combining existing cognitive behavioral programs with expectancy challenge and motivational interviewing techniques.


Dementia Care Education Targeting Job Strain and Organizational Climate Among Dementia Care Specialists in Swedish Home Care Services.
An increasing number of older persons live at home with various limitations, such as dementia, requiring well-educated and trained home care staff to meet their complex care needs. Dementia care specialists working in home care service have reported high levels of job strain in comparison with home care staff in general. This pilot study aims to evaluate the effects of a dementia care education model targeting self-reported job strain and organizational climate, among dementia care specialists in home care service. A quasi-experimental, one-group pretest-posttest design was applied, with 12 months' follow-up. Participants were dementia care specialists who worked in home care service (n=34 baseline; n=30 follow-up). The data were collected using the Strain in Dementia Care Scale and Creative Climate Questionnaires, administered pre- and post-intervention. The intervention applied an educational model based on previous research in dementia care and a person-centered approach. The educational model was implemented in the context of home care services. Of 34 participants at baseline, only 21 responded to the questionnaires, due to a drop off of 13 participants and recruitment of 9 new participants (follow-up=30). A significantly reduced perceived job strain among the participants was detected, indicating perceiving less difficulty in "Balancing competing needs" when caring for the older persons. No significant difference was found in the self-reported creative organizational climate between the two occasions. The educational model could be integrated into dementia home care and it seemed to reduce job strain among dementia care specialists. Future studies are needed to evaluate the effects of the intervention using a stronger study design and a larger sample.


Patient satisfaction of primary care for musculoskeletal diseases: a comparison between Neural Therapy and conventional medicine.
The main objective of this study was to assess and compare patient satisfaction with Neural Therapy (NT) and conventional medicine (COM) in primary care for musculoskeletal diseases. A cross-sectional study in primary care for musculoskeletal disorders covering 77 conventional primary care providers and 18 physicians certified in NT with 241 and 164 patients respectively. Patients and physicians documented consultations and patients completed questionnaires at a one-month follow-up. Physicians documented duration and severity of symptoms, diagnosis, and procedures. The main outcomes in the evaluation of patients were: fulfillment of expectations, perceived treatment effects, and patient satisfaction. The most frequent diagnoses belonged to the group of dorsopathies (39% in COM, 46% in NT). We found significant differences between NT and COM with regard to patient evaluations. NT patients documented better fulfilment of treatment expectations and higher overall treatment satisfaction. More patients in NT reported positive side effects and less frequent negative effects than patients in COM. Also, significant differences between NT and COM patients were seen in the quality of the patient-physician interaction (relation and communication, medical care, information and support, continuity and cooperation, facilities availability, and accessibility), where NT patients showed higher satisfaction. Differences were also found with regard to the physicians' management of disease, with fewer work incapacity attestations issued and longer consultation times in NT. Our findings show a significantly higher treatment and care-related patient satisfaction with primary care for musculoskeletal diseases provided by physicians practising Neural Therapy.


Stochastic signaling in biochemical cascades and genetic systems in genetically engineered living cells.
Living cells, either prokaryote or eukaryote, can be integrated within whole-cell biochips (WCBCs) for various applications. We investigate WCBCs where information is extracted from the cells via a cascade of biochemical reactions that involve gene expression. The overall biological signal is weak due to small sample volume, low intrinsic cell response, and extrinsic signal loss mechanisms. The low signal-to-noise ratio problem is aggravated during initial detection stages and limits the minimum detectable signal or, alternatively, the minimum detection time. Taking into account the stochastic nature of biochemical process, we find that the signal is accompanied by relatively large noise disturbances. In this work, we use genetically engineered microbe sensors as a model to study the biochips output signal stochastic behavior. In our model, the microbes are designed to express detectable reporter proteins under external induction. We present analytical approximated expressions and numerical simulations evaluating the fluctuations of the synthesized reporter proteins population based on a set of equations modeling a cascade of biochemical and genetic reactions. We assume that the reporter proteins decay more slowly than messenger RNA molecules. We calculate the relation between the noise of the input signal (extrinsic noise) and biochemical reaction statistics (intrinsic noise). We discuss in further details two cases: (1) a cascade with large decay rates of all biochemical reactions compared to the protein decay rate. We show that in this case, the noise amplitude has a positive linear correlation with the number of stages in the cascade. (2) A cascade which includes a stable enzymatic-binding reaction with slow decay rate. We show that in this case, the noise strongly depends on the protein decay rate. Finally, a general observation is presented stating that the noise in whole-cell biochip sensors is determined mainly by the first reactions in the genetic system with weak dependence on the number of stages in the cascade.


Racial Disparities in Access and Use of Diabetes Technology Among Adult Patients With Type 1 Diabetes in a U.S. Academic Medical Center.
Recent studies highlight racial disparities in insulin pump (PUMP) and continuous glucose monitor (CGM) use in children and adolescents with type 1 diabetes (T1D). This study explored racial disparities in diabetes technology among adult patients with T1D. This was a retrospective clinic-based cohort study of adult patients with T1D seen consecutively from April 2013 to January 2020. Race was categorized into non-Black (reference group) and Black. The primary outcomes were baseline and prevalent technology use, rates of diabetes technology discussions (CGMdiscn, PUMPdiscn), and prescribing (CGMrx, PUMPrx). Multivariable logistic regression analysis evaluated the association of technology discussions and prescribing with race, adjusting for social determinants of health and diabetes outcomes. Among 1,258 adults with T1D, baseline technology use was significantly lower for Black compared with non-Black patients (7.9% vs. 30.3% for CGM; 18.7% vs. 49.6% for PUMP), as was prevalent use (43.6% vs. 72.1% for CGM; 30.7% vs. 64.2% for PUMP). Black patients had adjusted odds ratios (aORs) of 0.51 (95% CI 0.29, 0.90) for CGMdiscn and 0.61 (95% CI 0.41, 0.93) for CGMrx. Black patients had aORs of 0.74 (95% CI 0.44, 1.25) for PUMPdiscn and 0.40 (95% CI, 0.22, 0.70) for PUMPrx. Neighborhood context, insurance, marital and employment status, and number of clinic visits were also associated with the outcomes. Significant racial disparities were observed in discussions, prescribing, and use of diabetes technology. Further research is needed to identify the causes behind these disparities and develop and evaluate strategies to reduce them.


Lipid Bilayer Disruption by Amphiphilic Janus Nanoparticles: The Role of Janus Balance.
Amphiphilic nanoparticles are known to cause defects in lipid bilayers. However, we have shown recently that their disruptive effects are significantly enhanced when surface charges and hydrophobic groups are spatially segregated on opposite hemispheres of a single particle. Using the same amphiphilic cationic/hydrophobic Janus particle system, here we investigate the role of the hydrophilic-lipophilic balance of the particles (namely the Janus balance) in their interaction with zwitterionic lipid bilayers. We show that Janus nanoparticles induce holes in lipid bilayers only when the hydrophobic side of particles occupies 20% or more of their surfaces. Beyond this threshold, the larger the hydrophobic surface area, the more attractive the particles are to lipid bilayers, and a lower particle concentration is needed for causing defects in the bilayers. The results establish a quantitative relationship between the surface coverage of hydrophobicity on the Janus particles and the particle-induced disruption to the lipid membranes.


Histology-based screen for zebrafish mutants with abnormal cell differentiation.
The power of histology to define states of cell differentiation was used as the basis of a mutagenesis screen in zebrafish. In this screen, 7-day-old parthenogenetic half-tetrad larvae from potential carrier females were screened for mutations affecting cell differentiation in hematoxylin and eosin-stained tissue sections. Seven, noncomplementing, recessive mutations were found. Two mutations affect only the retina: segmented photoreceptors (spr) show a discontinuous photoreceptor cell layer; vestigial outer segments (vos) has fewer photoreceptor cells and degenerated outer segments within this cell layer. Three mutants have gut-specific defects: the epithelial cells of kirby (kby) are replaced by ballooned cells; the intestines of stuffy (sfy) and stuffed (sfd) contain increased luminal mucus. Two mutations affect multiple organs: disordered neural retina (dnr) has disrupted retinal layering and mild nuclear abnormalities in the gut and liver; and in huli hutu (hht), the retinal cell layers are disorganized and multiple organs have mild to severe nuclear abnormalities that are reminiscent of the atypia of human neoplasia. Each mutation appears to be homozygous lethal. This screen is proof of principle for the feasibility of histologic screens to yield novel mutations, including potential models of human disease. The throughput for this type of screen may be enhanced by automation.


Non-compliance with medical recommendations results in delayed hospitalization and poorer prognosis in patients with cerebral ischemic stroke in Poland: Non-compliance effects on post-ischemic stroke prognosis.
This study aimed to reveal and analyze the causes of delays in reaching the hospital of patients with cerebral ischemic stroke and to assess their clinical picture. The study group included 161 patients with stroke, who reported to the hospital beyond the thrombolytic treatment therapeutic window. The control group consisted of 85 patients recruited consecutively with stroke who received thrombolytic treatment per eligibility criteria. Laboratory and medical imaging tests essential for neurological condition assessment were conducted in the study group. Control group research was based on retrospective analysis of medical records. The rate of deaths during hospitalization was lower in the control group (4.7%) compared to the study group (14.9%). In the study group, more patients (16.8%) admitted to non-compliance with medical recommendations than in the control group (5.9%). There were no statistically significant differences in nicotinism and alcohol dependence syndrome frequency between both groups. Based on each group inclusion criteria, a lower mortality rate in the control group indicates a crucial role of the therapeutic window in cerebral stroke treatment. Analysis of reasons for delay points out that efficient prophylaxis is the education of patients with stroke risk factors and their families.


Search for faster methods of fitting the regressive models to quantitative traits.
The regressive models describe familial patterns of dependence of quantitative measures by specifying regression relationships among a person's phenotype and genotype and the phenotypes and genotypes of antecedents. When the number of sibs in the pattern of dependence increases, as in the class D regressive model, computation of the likelihood becomes time consuming, since the Elston-Stewart algorithm cannot be used generally. On the other hand, the simpler class A regressive model, which imposes a restriction on the sib-sib correlation, may lead to inference of a spurious major gene, as already observed in some instances. A simulation study is performed to explore the robustness of class A model with respect to false inference of a major gene and to search for faster methods of computing the likelihood under class D model. The class A model is not robust against the presence of a sib-sib correlation exceeding that specified by the model, unless tests on transmission probabilities are performed carefully: false detection of a major gene is reduced from a number of 26-30 to between 0 and 4 data sets out of 30 replicates after testing both the Mendelian transmission and the absence of transmission of a major effect against the general transmission model. Among various approximations of the likelihood formulation of the class D model, approximations 6 and 8 are found to work appropriately in terms of both the estimation of all parameters and hypothesis testing, for each generating model. These approximations lessen the computer time by allowing use of the Elston-Stewart algorithm.


HPV vaccine acceptance among Latina mothers by HPV status.
We investigated whether Latina mothers who were and were not human papillomavirus (HPV) positive differed in their knowledge and acceptance of the HPV vaccine for their children. We conducted a cross-sectional survey among women aged 18-64 years between April 2007 and April 2008. Data collectors conducted in-person interviews in community clinics with 215 HPV-negative women and 190 HPV-positive women (with respective response rates of 64% and 84%). Most (83%) HPV-positive women were recruited at dysplasia clinics. Although no HPV-negative women were recruited at dysplasia clinics, they were recruited at other low-income public and private clinics. After adjustment for age, marital status, and health insurance, women who were HPV positive were more likely than HPV-negative women to have heard about the HPV vaccine, to indicate they would have their daughters and sons vaccinated against cervical cancer even if they had to pay themselves, and to be in favor of the proposed Texas law requiring girls to receive the HPV vaccine before entry into sixth grade but less likely to be in favor of girls receiving the vaccine at age > or =13. Our findings indicate that >90% of Latinas living on the Texas-Mexico border find the HPV vaccine acceptable for their own daughters and sons.


Thrombotic microangiopathy from Australian brown snake (Pseudonaja) envenoming.
Australian brown snake (genus Pseudonaja) envenoming causes a venom-induced consumptive coagulopathy (VICC). A proportion of cases go on to develop thrombotic microangiopathy characterized by thrombocytopenia, microangiopathic haemolytic anaemia (MAHA) and acute renal failure (ARF). The aim of the study was to define better the natural history and empirical treatments for thrombotic microangiopathy in brown snake envenoming. A review of brown snake bites recruited to the Australian Snakebite Project (ASP), a national multicentre study of snake envenoming was undertaken. Serial data are recorded on clinical effects and laboratory results, including measurement of venom concentrations. We describe cases of thrombotic microangiopathy and compare these to cases without thrombotic microangiopathy. From 32 cases of brown snake envenoming with severe VICC, four (13%) developed thrombotic microangiopathy, we also included two cases of thrombotic microangiopathy from prior to ASP. All six developed severe thrombocytopenia (<20 x 10(-9)/L), worst 3 days after the bite and resolving over a week, MAHA with fragmented red blood cells on the blood film and five developed anuric ARF requiring dialysis and lasting 2-8 weeks. All six received antivenom, which was delayed compared with other brown snake-envenoming cases. Four were treated with plasmapheresis. The severity and recovery of the thrombocytopenia, anaemia and renal function were similar with and without plasmapheresis. The median length of stay for MAHA cases was 14 days (interquartile range (IQR) 12-14) compared to 1.8 days (IQR 1.3-2) for all other cases. Thrombotic microangiopathy resulting from brown snake bite appears to have a good prognosis and management should focus on early antivenom therapy and supportive care including dialysis. The role of plasmapheresis is yet to be defined.


Neoechinulin a imparts resistance to acute nitrosative stress in PC12 cells: a potential link of an elevated cellular reserve capacity for pyridine nucleotide redox turnover with cytoprotection.
Treatment of PC12 cells with fungus-derived alkaloid neoechinulin A for more than 12 h renders the cells resistant to subsequent superoxide (O₂⁻)/nitric oxide (NO) insults derived from 3-morpholinosydnonimine (SIN-1). However, the underlying mechanism(s) remains largely unclear. To elucidate the mechanism(s), we assessed the specificity of the cytoprotection afforded by neoechinulin A treatment using other cytocidal stressors and also clarified the resulting cellular alterations, focusing on the antioxidant and metabolic enzymes systems. Neoechinulin A treatment for more than 12 h endowed PC12 cells with significant resistance to transient NO toxicity, but not persistent NO toxicity, bolus H₂O₂ toxicity, or oxidative insult from the redox cycling quinone menadione. Cellular antioxidant system profiling revealed no substantial potentiation of the activity of any antioxidant enzyme in lysate from the neoechinulin A-treated cells excluding glutathione (GSH) content, which was significantly decreased (>50%), resulting in a proportional compromise in the thiol-reducing activity of the intact cells. In addition, no differences were observed in the activity for any nicotinamide adenine dinucleotide (phosphate) reduced form (NAD(P)H)-generating enzyme, steady-state NAD(P)H/nicotinamide adenine dinucleotide (phosphate) oxidized form (NAD(P)⁺) ratios, or the levels of total NAD(P)H. Nevertheless, the neoechinulin A-treated intact cells exhibited increased NAD(P)H redox turnover when driven by extracellular tetrazolium. The structurally inactive analog preechinulin failed to protect cells against NO toxicity or induce these alterations, suggesting their link with the cytoprotective mechanism. These results suggest that neoechinulin A, despite disabling the GSH defense system, confers cytoprotection against nitrosative stresses by elevating the cellular reserve capacity for NAD(P)H generation, which could offset crippling of energy-supplying systems due to nitrosative stress.


Current issues in prevention of mother-to-child transmission of HIV-1.
To review new evidence in prevention of mother-to-child-transmission of HIV-1, which establishes, in principle, the feasibility of greatly improved effectiveness in developing countries. This review presents evidence that demonstrates that a large gap in prevention of mother-to-child-transmission [MTCT] is being increasingly bridged. Recent studies have addressed issues on postnatal transmission of HIV-1 through breastfeeding. Breastfeeding transmission affects the majority of HIV-infected pregnant women and children in the world and who live in Africa and are often poor. Prevention of unwanted pregnancies in all women living in high HIV prevalence regions will probably reduce the risk of HIV-positive pregnancies. These studies demonstrate the success of the following three types of interventions:primary prevention of HIV-1 in women;prophylaxis with antiretroviral drugs in breastfeeding infants;prophylaxis with antiretroviral drugs for lactating mothers.It is also clear that key barriers to implementing these findings in developing countries are weak and ineffectual health systems. Therefore, identifying needs for improving health service delivery are critical; an example of the synergy between prevention and treatment through integrated services is given. Recent data on primary prevention of HIV-1 in women of child-bearing age, and use of antiretrovirals in breastfeeding infants and lactating mothers, report successful interventions for the prevention of breastfeeding transmission of HIV-1. Health infrastructure improvement in developing countries is central to the application of research findings to implementation of MTCT programmes.


Cutaneous melanoma attributable to sunbed use: systematic review and meta-analysis.
To estimate the burden of melanoma resulting from sunbed use in western Europe. Systematic review and meta-analysis. PubMed, ISI Web of Science (Science Citation Index Expanded), Embase, Pascal, Cochrane Library, LILACS, and MedCarib, along with published surveys reporting prevalence of sunbed use at national level in Europe. Observational studies reporting a measure of risk for skin cancer (cutaneous melanoma, squamous cell carcinoma, basal cell carcinoma) associated with ever use of sunbeds. Based on 27 studies ever use of sunbeds was associated with a summary relative risk of 1.20 (95% confidence interval 1.08 to 1.34). Publication bias was not evident. Restricting the analysis to cohorts and population based studies, the summary relative risk was 1.25 (1.09 to 1.43). Calculations for dose-response showed a 1.8% (95% confidence interval 0% to 3.8%) increase in risk of melanoma for each additional session of sunbed use per year. Based on 13 informative studies, first use of sunbeds before age 35 years was associated with a summary relative risk of 1.87 (1.41 to 2.48), with no indication of heterogeneity between studies. By using prevalence data from surveys and data from GLOBOCAN 2008, in 2008 in the 15 original member countries of the European Community plus three countries that were members of the European Free Trade Association, an estimated 3438 cases of melanoma could be attributable to sunbed use, most (n=2341) occurring among women. Sunbed use is associated with a significant increase in risk of melanoma. This risk increases with number of sunbed sessions and with initial usage at a young age (<35 years). The cancerous damage associated with sunbed use is substantial and could be avoided by strict regulations.


Respiratory diseases caused by coal mine dust.
To provide an update on respiratory diseases caused by coal mine dust. This article presents the results of a literature review initially performed for an International Conference on Occupational and Environmental Lung Disease held in summer 2013. Coal mine dust causes a spectrum of lung diseases collectively termed coal mine dust lung disease (CMDLD). These include Coal Workers' Pneumoconiosis, silicosis, mixed dust pneumoconiosis, dust-related diffuse fibrosis (which can be mistaken for idiopathic pulmonary fibrosis), and chronic obstructive pulmonary disease. CMDLD continues to be a problem in the United States, particularly in the central Appalachian region. Treatment of CMDLD is symptomatic. Those with end-stage disease are candidates for lung transplantation. Because CMDLD cannot be cured, prevention is critical. Coal mine dust remains a relevant occupational hazard and miners remain at risk for CMDLD.


Modelling climate change impacts on and adaptation strategies for agriculture in Sardinia and Tunisia using AquaCrop and value-at-risk.
In Europe, there is concern that climate change will cause significant impacts around the Mediterranean. The goals of this study are to quantify the economic risk to crop production, to demonstrate the variability of yield by soil texture and climate model and to investigate possible adaptation strategies. In the Rio Mannu di San Sperate watershed, located in Sardinia (Italy) we investigate production of wheat, a rainfed crop. In the Chiba watershed located in Cap Bon (Tunisia), we analyze irrigated tomato production. We find, using the FAO model AquaCrop that crop production will decrease significantly in a future climate (2040-2070) as compared to the present without adaptation measures. Using "value-at-risk", we show that production should be viewed in a statistical manner. Wheat yields in Sardinia are modelled to decrease by 64% on clay loams, and to increase by 8% and 26% respectively on sandy loams and sandy clay loams. Assuming constant irrigation, tomatoes sown in August in Cap Bon are modelled to have a 45% chance of crop failure on loamy sands; a 39% decrease in yields on sandy clay loams; and a 12% increase in yields on sandy loams. For tomatoes sown in March; sandy clay loams will fail 81% of the time; on loamy sands the crop yields will be 63% less while on sandy loams, the yield will increase by 12%. However, if one assume 10% less water available for irrigation then tomatoes sown in March are not viable. Some adaptation strategies will be able to counteract the modelled crop losses. Increasing the amount of irrigation one strategy however this may not be sustainable. Changes in agricultural management such as changing the planting date of wheat to coincide with changing rainfall patterns in Sardinia or mulching of tomatoes in Tunisia can be effective at reducing crop losses.


[Spectrum of von Willebrand-Jürgens syndrome. A study on 53 patients].
Von Willebrand-Jürgens syndrome was diagnosed in 53 patients on the basis of bleeding symptoms and blood clotting analytical findings. It was possible to classify the patients into four types using the recommendations of the European Thrombosis Research Organization. Type I, 56%, was most common, 15% belonged to type II, 13% to type III and 16% to type IV. Whereas type I corresponds to the so-called classical von Willebrand-Jürgens syndrome, types II-IV demonstrate the heterogeneity of the disease.


Fabrication and characterization of gratings based on thermal shrinkable reactive cholesteric mesogens.
Gratings were successfully fabricated by photolithography by using a particular reactive cholesteric liquid crystal at two different temperatures. The reflection band of the grating was found to be wider than that of a film having a single helical order, because the grating exhibited a binary helical order. Moreover, the surface topography of the grating was regulated by using photomasks with different pitches. The optical reflection spectrum of this grating structure spans two reflection spectra of cholesteric liquid crystal films that were prepared by UV curing at two heating temperatures. Experimental results reveal that the method proposed in this study can be used to produce broadband circular polarizing films.


HIV Testing Strategies, Types of Tests, and Uptake by Men Who have Sex with Men and Transgender Women: A Systematic Review and Meta-analysis.
This systematic review and meta-analysis investigated the effectiveness of strategies and types of tests on HIV testing uptake by men who have sex with men (MSM) and transgender women (TGW), and in reaching PLWH. Articles published up to July 2020 were identified from major electronic databases and grey literature. Data were extracted and assessed for risk of bias. Estimates were pooled using random-effect meta-analysis while heterogeneity was evaluated by Cochran's Q test and I2. This study is registered with PROSPERO (CRD42020192740). Of 6820 titles, 263 studies (n = 67,288 participants) were included. The testing strategies reported in most studies were community- (71.2%) and facility-based (28.8%). Highest uptake, with facility-based testing, occurred and reached more PLWH while with standard laboratory tests, it occurred with the highest HIV prevalence among MSM. However, urine test showed a highest rate of new HIV infection. Multiple test combinations had the highest uptake and reached more PLWH among TGW. Various testing strategies, considering barriers and regional differences, and different test types, need be considered, to increase uptake among MSM and TGW.


Drug-Drug Interaction between Metformin and Sorafenib Alters Antitumor Effect in Hepatocellular Carcinoma Cells.
Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and is one of the leading causes of cancer-related deaths worldwide. The multitarget inhibitor sorafenib is a first-line treatment of patients with advanced unresectable HCC. Recent clinical studies have evidenced that patients treated with sorafenib together with the antidiabetic drug metformin have a survival disadvantage compared with patients receiving sorafenib only. Here, we examined whether a clinically relevant dose of metformin (50 mg/kg per day) could influence the antitumoral effects of sorafenib (15 mg/kg per day) in a subcutaneous xenograft model of human HCC growth using two different sequences of administration, i.e., concomitant versus sequential dosing regimens. We observed that the administration of metformin 6 hours prior to sorafenib was significantly less effective in inhibiting tumor growth (15.4% tumor growth inhibition) than concomitant administration of the two drugs (59.5% tumor growth inhibition). In vitro experiments confirmed that pretreatment of different human HCC cell lines with metformin reduced the effects of sorafenib on cell viability, proliferation, and signaling. Transcriptomic analysis confirmed significant differences between xenografted tumors obtained under the concomitant and the sequential dosing regimens. Taken together, these observations call into question the benefit of parallel use of metformin and sorafenib in patients with advanced HCC and diabetes, as the interaction between the two drugs could ultimately compromise patient survival. SIGNIFICANCE STATEMENT: When drugs are administered sequentially, metformin alters the antitumor effect of sorafenib, the reference treatment for advanced hepatocellular carcinoma, in a preclinical murine xenograft model of liver cancer progression as well as in hepatic cancer cell lines. Defective activation of the AMP-activated protein kinase pathway as well as major transcriptomic changes are associated with the loss of the antitumor effect. These results echo recent clinical work reporting a poorer prognosis for patients with liver cancer who were cotreated with metformin and sorafenib.


A materials approach to site-isolation of Grubbs catalysts from incompatible solvents and m-chloroperoxybenzoic acid.
The development of a method for site-isolation of Grubbs second-generation catalyst from MCPBA is described. In these reactions, Grubbs catalyst was dissolved in a solvent consisting of a mixture (1:1 v/v) of 1-butyl-3-methylimidazolium hexafluorophosphate and methylene chloride and completely encapsulated within a thimble fabricated from polydimethylsiloxane (PDMS). A series of molecules that react by cross metathesis or ring-closing metathesis were added to the interior of the thimble and allowed to react. In the last step, m-chloroperoxybenzoic acid (MCPBA) dissolved in MeOH/H(2)O (1:1 v/v) was added to the exterior of the PDMS thimble. Small organic molecules diffused through the PDMS to react with MCPBA to form epoxides, but the Grubbs catalyst remained encapsulated. This result is important because Grubbs catalyst catalytically decomposes MCPBA at ratios of MCPBA to Grubbs of 3000 to 1. The yields for this two-step cascade sequence ranged from 67 to 83 %. The concept behind this sequence is that small organic molecules have high flux through PDMS but large molecules--such as Grubbs catalyst--and ionic reagents--such as MCPBA--have much lower flux through PDMS. Small molecules can thus react both outside and inside PDMS thimbles, whereas incompatible catalysts and reagents remain site-isolated from each other. This method does not require alteration of structures of the catalysts or reagents, so it may be applied to a wide range of homogeneous catalysts and reagents. To demonstrate further that the catalyst was encapsulated, the Grubbs catalyst was successfully recycled within the cascade sequence.


Evolution of REP diversity: a comparative study.
Repetitive extragenic palindromic elements (REPs) constitute a group of bacterial genomic repeats known for their high abundance and several roles in host cells´ physiology. We analyzed the phylogenetic distribution of particular REP classes in genomic sequences of sixty-three bacterial strains belonging to the Pseudomonas fluorescens species complex and ten strains of Stenotrophomonas sp., in order to assess intraspecific REP diversity and to gain insight into long-term REP evolution. Based on proximity to RAYT (REP-associated tyrosine transposase) genes, twenty-two and thirteen unique REP classes were determined in fluorescent pseudomonads and stenotrophomonads, respectively. In stenotrophomonads, REP elements were typically found in tens or a few hundred copies per genome. REPs of fluorescent pseudomonads were generally more numerous, occurring in hundreds or even over a thousand perfect copies of particular REP class per genome. REP sequences showed highly heterogeneous distribution. The abundances of REP classes roughly followed host strains´ phylogeny, differing markedly among individual clades. High abundances of particular REP classes appeared to depend on the presence of the cognate RAYT gene, and deviations from this state could be attributed to recent or ancient mutations of rayt-flanking REPs, or RAYT loss. RAYTs of both studied bacterial groups are monophyletic, and their cognate REPs show species-specific characteristics, suggesting shared evolutionary history of REPs, RAYTs and their hosts. The results of our large-scale analysis show that REP elements constitute intriguingly dynamic components of genomes of fluorescent pseudomonads and stenotrophomonads, and indicate that REP diversification and proliferation are ongoing processes. High numbers of REPs have apparently been retained during the entire evolutionary time since the establishment of these two bacterial lineages, probably because of their beneficial effect on host long-term fitness. REP elements in these bacteria represent a suitable platform to study the interplay between repeated elements, their mobilizers and host bacterial cells.


What drives social in-group biases in face recognition memory? ERP evidence from the own-gender bias.
It is well established that memory is more accurate for own-relative to other-race faces (own-race bias), which has been suggested to result from larger perceptual expertise for own-race faces. Previous studies also demonstrated better memory for own-relative to other-gender faces, which is less likely to result from differences in perceptual expertise, and rather may be related to social in-group vs out-group categorization. We examined neural correlates of the own-gender bias using event-related potentials (ERP). In a recognition memory experiment, both female and male participants remembered faces of their respective own gender more accurately compared with other-gender faces. ERPs during learning yielded significant differences between the subsequent memory effects (subsequently remembered - subsequently forgotten) for own-gender compared with other-gender faces in the occipito-temporal P2 and the central N200, whereas neither later subsequent memory effects nor ERP old/new effects at test reflected a neural correlate of the own-gender bias. We conclude that the own-gender bias is mainly related to study phase processes, which is in line with sociocognitive accounts.


Unusual incidence of chronic pneumonia associated with cholesterol deposits in stranded and bycaught franciscanas Pontoporia blainvillei.
Franciscanas Pontoporia blainvillei are small dolphins endemic to Brazil, Uruguay and Argentina. During routine pathologic examinations, chronic pneumonia associated with cholesterol deposits was found in 16.7% of stranded and incidentally bycaught franciscanas (n = 60), and was more frequent in dolphins from the Brazilian state of São Paulo (Franciscana Management Area II) and frequently accompanied by splenic lymphoid hyperplasia. It is unclear why these otherwise uncommon lesions were relatively frequent in the studied dolphins, and further research is advised.


Aversive learning and generalization predict subclinical levels of anxiety: a six-month longitudinal study.
The identification of premorbid markers of risk for psychopathology is one of the most important challenges for present-day psychiatric research. This study focuses on behavioral vulnerability factors that contribute to the development of anxiety. Little is known about the role of aversive learning and generalization in the development of pathological anxiety. In this study, a large student sample (N=375) completed a differential aversive learning task followed by a test of generalization. Anxiety was assessed at that moment and after a six-month follow-up. Results showed that both predictors (discrimination learning and generalization) added significantly to the explained variance in anxiety symptomatology at follow-up. These results highlight the importance of longitudinal designs and indicate that screening for individual differences in aversive learning and generalization may foster prediction of anxiety disorders, paving the way for targeted prevention.


COVID-19: Considerations for Medical Education during a Pandemic.
This article was migrated. The article was marked as recommended. Clinical placement has been the cornerstone of medical training since the early foundations of the medical profession. The COVID-19 pandemic generates unprecedented challenges for the delivery of medical education, particularly in the setting of 'flatten the curve' public health initiatives to curtail transmission. As the number of cases of COVID-19 increase, hospitals are limiting medical students' attendance at ward rounds, clinics and theatre, representing a fundamental shift in clinical education from the bedside to online formats. We discuss the considerations behind these changes, review the strategies implemented during previous global infectious disease epidemics, and suggest strategies for maximising clinical education going forward.


The impact of psychoeducational interventions on the outcomes of caregivers of patients with heart failure: A systematic review and meta-analysis.
Heart failure is a global health care problem that causes a significant economic burden. Despite medical advancements, it's prognosis remains poor as many patients with heart failure experience symptoms that negatively impact Quality of Life. Caregivers are often responsible for helping and supporting family members manage their heart failure symptoms at home. In addition to managing their own medical problems and maintaining social and personal lives, significant burden and stress can occur. At present, caregivers receive little guidance or information to support them in their caregiving role. This review aims to determine the impact of psychoeducational interventions on the outcomes of caregivers of patients with heart failure. Systematic review and meta-analysis. Five electronic databases: PsycINFO, Medline, CINAHL Plus, EMBASE and SCOPUS were searched from June 2007 to August 2019. The conduct and reporting of this review was based on the Cochrane Handbook for Systematic Reviews of Interventions and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. The Cochrane Risk of Bias Tool was used to assess the risk of bias amongst randomised controlled trials, and the Newcastle Ottawa Scale was used to assess risk of bias in one quasi-experimental study. Ten articles met the inclusion criteria, consisting of seven studies, with a total sample size of 953 participants. The pooled result from two studies, conducted in America and China, reported that psychoeducational interventions significantly reduced depression at six months' follow-up (SMD -0.82; 95% CI -1.17 to -0.47; p = 0.73, I2 =0%). The pooled result from two studies conducted in Sweden and Taiwan showed a significant improvement in heart failure knowledge at six months' follow-up (SMD 0.97; 95% CI 0.70 to 1,25; p < 0.00001, I2 =0%). Finally, pooled results from three studies conducted in Sweden, China and Taiwan found a significant improvement in Quality of Life at 3 months' follow- up (SMD 0.25; 95% CI 0.25 to 0.48; p = 0.03). The three most common intervention components included: group based educational sessions, telemonitoring and telephone support, and written resources. There was no specific type of psychoeducational intervention found to have a significant impact on caregiver outcomes, as interventions were heterogeneous consisting of multiple components. Further research is needed to determine the effectiveness of individual and combined components to identify the ideal intervention format and design for caregivers of patients with heart failure.


Physical activity of children and adolescents who use a wheelchair: a systematic review.
Physical activity has numerous health benefits for people with physical disabilities. Nevertheless, activity levels are often below recommended levels. To promote physical activity among children and adolescents who use a wheelchair as their primary source of mobility, this systematic review explores the physical activity patterns of this group. A systematic search of PubMed, Sports Medicine & Education Index, Web of Science, and SPORTDiscus was performed, included articles were synthesized in terms of duration, intensity, and settings in which physical activity occurred, as well as the physical activity measurement methods. Nine articles were included. The mean overall physical activity level across the included studies was 98 minutes per day (range: 78-115 minutes per day). Two articles analysed the duration of physical activity at different intensities (very light physical activity, light physical activity (LPA), moderate to vigorous physical activity (MVPA) and intensities near to maximum). Within the included articles, both subjective and objective measurement methods were used. Due to the small number of articles, combined with small sample sizes, there is not enough evidence to answer the research questions sufficiently. Nevertheless, the review provides an overview of actual research and clearly shows that the physical activity values are insufficiently researched. There is a need for further research on the scope, types and settings of physical activity in the target group.


Jordanian professional nurses' attitudes and experiences of having family members present during cardiopulmonary resuscitation of adult patients.
The presence of family members during cardiopulmonary resuscitation (CPR) of an adult patient remains a contentious area of practice that has attracted wide international debate. However, the attitude and experience of Jordanian nurses concerning this area of practice are not known yet. This descriptive quantitative study was aimed at identifying the attitudes and experiences of Jordanian nurses toward the presence of family members during CPR of adult patients. A questionnaire that was developed by Fulbrook et al was completed by 136 nurses. There were 91.9% (n = 125) nurses who did not have any experience or a protocol or policy document on family presence during CPR and 97.7% (n = 133) nurses stated that they did not have any experience of inviting a family member to be present during CPR. Also, the result of this study revealed that Jordanian nurses had negative attitudes toward the presence of family members during CPR of an adult patient. Before initiating hospital policy regarding the option of family presence during resuscitation, attitudes and experiences of patients and relatives on witnessed resuscitation should be explored. Also, educating nurses about the importance of practicing to have the presence of family members during CPR of adult patients should be considered.


Fellowship training in academic general internal medicine: a curriculum survey.
To determine whether current fellowships in general internal medicine (FGIM) meet the perceived needs and objectives of physicians entering careers in academic internal medicine. A modified Delphi method yielded the 18 curricular elements included in the mailed survey. Participants outlined both actual and ideal fellowship experiences by rating the degree of emphasis of each curricular element on a Likert scale. Respondents then prioritized elements by rank-ordering them on perceived importance. Current job descriptions and opinions on related issues in FGIM were collected. Potential fellows, current fellows, and recent graduates were surveyed. Individuals were identified through the Society of General Internal Medicine associates' mailing list and solicitation of program directors. Nonfellow associates served as the proxy group for potential fellows. 579 surveys were mailed; 348 (60%) responses were received, of which 288 (50%) were suitable for analysis. Of all respondents, 38% were current fellows and 40% were recent graduates. When asked to prioritize educational needs during fellowship training, respondents ranked research methodology, ambulatory medicine, critical review of the literature, epidemiology, biostatistics, teaching skills, medical consultation, grant writing, preventive medicine, and design of educational curriculum as the top ten. Only minor deviations in rank order were found between graduates and nongraduates. Mean Likert scale scores for degree of emphasis of each curricular element in graduates' actual fellowships were compared with mean scores for graduates' ideal fellowship descriptions. High-priority elements that were perceived as adequately emphasized included research methodology, critical analysis of the literature, epidemiology, and biostatistics. High-priority elements that were perceived as inadequately emphasized included ambulatory medicine, teaching skills, medical consultation, grant writing, preventive medicine, and design of educational curricula. FGIM largely meet the expectations of their fellows for preparation for research responsibilities. However, several curricular elements concerned with preparation for future clinical and teaching responsibilities are perceived by graduates as underemphasized. These areas deserve increased emphasis during fellowship training to better prepare fellows for their future roles in academic general internal medicine.


Anemia, differentiating between thalassemia minor and iron deficiency.
Many of the conditions noted in examination of the blood of patients with thalassemia minor are much like those observed in patients with iron deficiency anemia. A study was made of similarities and contrasts between blood and bone marrow features in both conditions for purposes of differential diagnosis. A salient distinction is that bone marrow hemosiderin is present in normal amount in patients with thalassemia minor, but not in those with iron deficiency anemia. If therapy with iron does not restore hemoglobin values to normal, thalassemia minor is strongly suspect. Even in the latter disease, however, there may be small fluctuations in hemoglobin values, particularly in pregnancy. One must be alert to this possibility lest a slight, fleeting increase in hemoglobin be mistakenly ascribed to iron therapy.


Personalized treatment of hepatitis C genotype 1a in Norway and Sweden 2014-2016: a study of treatment outcome in patients with or without resistance-based DAA-therapy.
Resistance-associated substitutions (RASs) may impair treatment response to direct-acting antivirals (DAA) in hepatitis C virus (HCV) treatment. We investigated the effects of baseline NS3-RASs (Q80K and R155K) and clinically relevant NS5A-RASs in patients with HCV genotype (GT) 1a infection on treatment outcome, with or without resistance-based DAA-treatment. This multi-center study was carried out between 2014 and 2016. Treatment in the intervention group (n = 92) was tailored to baseline resistance. Detection of NS3-RAS led to an NS5A-inhibitor-based regimen and detection of NS5A-RAS to a protease-inhibitor regimen. Patients without baseline RAS in the intervention group and all patients in the control group (n = 101) received recommended standard DAA-treatment. The sustained virologic response rates (SVR) in the intervention and control groups were 97.8% (90/92) and 93.1% (94/101), respectively (p = .174). A trend toward higher SVR-rate in cirrhotic patients (p = .058) was noticed in the intervention group compared to the control group with SVR-rates 97.5% (39/40) and 83.3% (35/42), respectively. All patients with baseline NS3 (Q80K/R155K) or NS5A-RASs in the intervention group achieved SVR with personalized resistance-based treatment. In the control group, five patients with Q80K or R155K at baseline were treated with simeprevir + sofosbuvir and treatment failed in two of them. Furthermore, one of three patients who failed ledipasvir + sofosbuvir treatment had NS5A-RASs at baseline. In line with the findings of the OPTIMIST-2 trial for Q80K and the EASL-guidelines 2016 for NS5A-RASs, baseline RASs appeared to have an impact on treatment outcome albeit a statistical significance was not observed in this low-prevalence population.


Computational protein design with electrostatic focusing: experimental characterization of a conditionally folded helical domain with a reduced amino acid alphabet.
Automated methodologies to design synthetic proteins from first principles use energy computations to estimate the ability of the sequences to adopt a targeted structure. This approach is still far from systematically producing native-like sequences, due, most likely, to inaccuracies when modeling the interactions between the protein and its aqueous environment. This is particularly challenging when engineering small protein domains (with less polar pair interactions than with the solvent). We have re-designed a three-helix bundle, domain B, using a fixed backbone and a four amino acid alphabet. We have enlarged the rotamer library with conformers that increase the weight of electrostatic interactions within the design process without altering the energy function used to compute the folding free energy. Our synthetic sequences show less than 15% similarity to any Swissprot sequence. We have characterized our sequences in different solvents using circular dichroism and nuclear magnetic resonance. The targeted structure achieved is dependent on the solvent used. This method can be readily extended to larger domains. Our method will be useful for the engineering of proteins that become active only in a given solvent and for designing proteins in the context of hydrophobic solvents, an important fraction of the situations in the cell.


Development and clinimetric properties of the Dutch Breast Edema Questionnaire (BrEQ-Dutch version) to diagnose the presence of breast edema in breast cancer patients.
To develop a diagnostic tool, the Breast Edema Questionnaire (BrEQ) and to determine its clinimetric properties. The BrEQ was developed based on information from literature, experts and breast edema patients. Content validity, construct validity, test-retest reliability, internal consistency and cut-off point were investigated in a group of breast cancer patients. Construct validity made up two parts; convergent and known-groups validity. Convergent validity was tested by correlating the BrEQ with skin thickness measured with ultrasound (US). In part 1 of the BrEQ, symptoms of breast edema were scored from 0 to 10: pain, heaviness, swelling, tensed skin, redness, pitting sign, enlarged skin pores and hardness. Taking into account the International Classification of Functioning, Disability and Health, several activity limitations and participation restrictions were scored from 0 to 10 in part 2. Clinimetric properties of part 1 were examined in 55 patients. US showed that 35 women had breast edema. Content validity was good. Regarding convergent validity, all breast symptoms correlated moderately with skin thickness. The total symptom score had a strong correlation with skin thickness. Concerning known-groups validity, patients with breast edema had a higher total symptom score. Test-retest reliability ranged between moderate and strong. The internal consistency was good for all items and the total symptom score. We identified that a score cut-off point of ≥ 8.5 discriminates between patients with breast edema and those without. Part 1 of the BrEQ-Dutch version is a valid and reliable tool for assessing clinical indicators of breast edema.


Australian nurses in general practice based heart failure management: implications for innovative collaborative practice.
The growing global burden of heart failure (HF) necessitates the investigation of alternative methods of providing co-ordinated, integrated and client-focused primary care. Currently, the models of nurse-coordinated care demonstrated to be effective in randomized controlled trials are only available to a relative minority of clients and their families with HF. This current gap in service provision could prove fertile ground for the expansion of practice nursing [The Nurse in Family Practice: Practice Nurses and Nurse Practitioners in primary health care. 1988, Scutari Press, London: Impact of rural living on the experience of chronic illness. Australian Journal of Rural Health, 2001. 9: 235-240]. This paper aims to review the published literature describing the current and potential role of the practice nurse in HF management in Australia. Searches of electronic databases, the reference lists of published materials and the internet were conducted using key words including 'Australia', 'practice nurse', 'office nurse', 'nurs*', 'heart failure', 'cardiac' and 'chronic illness'. Inclusion criteria for this review were English language literature; nursing interventions for heart failure (HF) and the role of practice nurses in primary care. There is currently a paucity of data evaluating the potential role for practice nurses in a reconfigured, collaborative health care system. Those studies that were identified were, largely, of a descriptive nature. In addition to identifying the practice nurse as a largely unexplored resource, key themes that emerged from the review include: (1) current general practice services face significant barriers to the implementation of evidence-based HF practice; (2) there is considerable variation in the practice nurse role between general practices; (3) there are significant barriers to the expansion of the practice nurse role; (4) multidisciplinary interventions can effectively deliver secondary prevention strategies; (5) practice nurses can potentially facilitate these multidisciplinary interventions; and (6) practice nurses are favorably perceived by consumers although there is some confusion about the nature of their role. On the basis of this literature review, practice nurses represent a potentially useful adjunct to current models of service provision in HF management. Further research needs to comprehensively investigate the role of the practice nurse in the Australian context with a view to developing effective and sustainable frameworks for clinical practice. In particular, high-level evidence is required to evaluate the efficacy of the practice nurse role compared to current disease management strategies.


[Catamnestic study of ecological brief therapy].
Ecological brief psychotherapy has been practised at the Psychiatric Outpatient Clinic at the University Hospital Zurich since 1990. The aim is to use the development-oriented challenges posed by important others in the therapeutic process. The effectiveness of this form of therapy is investigated by reviewing the outcome of 28 completed treatment cases. While results at completion of therapy come up to the expectations, the long-term results were surprisingly positive. 96.4% of those surveyed reported they felt considerably better at final assessment 1 to 6 years after the therapy than they did at the beginning. Positive changes continued after the completion of therapy. We presume that our coevolutive focus brought resolution of blocked developmental steps in relationships that further stimulated changes that continued after the conclusion of therapy, even without further therapeutic support. Furthermore, the treatment effects provided by ecological brief psychotherapy apply to personality disorders as well.


Xenobiotics, drug metabolism, and liver injury.
The covalent binding hypothesis has been and remains a dominant organizing principle in biochemical pathology. Cellular injury mediated by the interaction of chemically reactive metabolites with macromolecules has been invoked to account for the liver cell death produced by a wide variety of xenobiotic chemicals and drugs. The evidence to support such a role for covalent binding is largely circumstantial and is based on the persistent correlation between the extent of binding and the severity of the accompanying liver necrosis. The more recent studies of the toxicity of haloalkanes (e.g., carbon tetrachloride), aryl halides (e.g., bromobenzene), and compounds capable of redox cycling with dioxygen (e.g., acetaminophen) have suggested alternative mechanisms for coupling mixed function oxidation to lethal cell injury. In this review, I have sketched the outlines of an emerging scheme that places emphasis on variations in the normal mixed function oxidation cycle that derive from the chemical properties of the hepatotoxin in question. I discussed three different causes--biochemical lesions, if you will--of variations with three classic hepatotoxins, carbon tetrachloride, acetaminophen, and bromobenzene. The nature of the variation and how it presumably leads to liver cell injury was reviewed.


Mcm10 associates with the loaded DNA helicase at replication origins and defines a novel step in its activation.
Mcm10 is essential for chromosome replication in eukaryotic cells and was previously thought to link the Mcm2-7 DNA helicase at replication forks to DNA polymerase alpha. Here, we show that yeast Mcm10 interacts preferentially with the fraction of the Mcm2-7 helicase that is loaded in an inactive form at origins of DNA replication, suggesting a role for Mcm10 during the initiation of chromosome replication, but Mcm10 is not a stable component of the replisome subsequently. Studies with budding yeast and human cells indicated that Mcm10 chaperones the catalytic subunit of polymerase alpha and preserves its stability. We used a novel degron allele to inactivate Mcm10 efficiently and this blocked the initiation of chromosome replication without causing degradation of DNA polymerase alpha. Strikingly, the other essential helicase subunits Cdc45 and GINS were still recruited to Mcm2-7 when cells entered S-phase without Mcm10, but origin unwinding was blocked. These findings indicate that Mcm10 is required for a novel step during activation of the Cdc45-MCM-GINS helicase at DNA replication origins.


Impacts of the COVID-19 pandemic on unmet social needs, self-care, and outcomes among people with diabetes and poor glycemic control.
The purpose of this study was to examine whether pandemic exposure impacted unmet social and diabetes needs, self-care behaviors, and diabetes outcomes in a sample with diabetes and poor glycemic control. This was a cross-sectional analysis of participants with diabetes and poor glycemic control in an ongoing trial (n = 353). We compared the prevalence of unmet needs, self-care behaviors, and diabetes outcomes in successive cohorts of enrollees surveyed pre-pandemic (prior to March 11, 2020, n = 182), in the early stages of the pandemic (May-September, 2020, n = 75), and later (September 2020-January 2021, n = 96) stratified by income and gender. Adjusted multivariable regression models were used to examine trends. More participants with low income reported food insecurity (70% vs. 83%, p < 0.05) and needs related to access to blood glucose supplies (19% vs. 67%, p < 0.05) during the pandemic compared to pre-pandemic levels. In adjusted models among people with low incomes, the odds of housing insecurity increased among participants during the early pandemic months compared with participants pre-pandemic (OR 20.2 [95% CI 2.8-145.2], p < 0.01). A1c levels were better among participants later in the pandemic than those pre-pandemic (β = -1.1 [95% CI -1.8 to -0.4], p < 0.01), but systolic blood pressure control was substantially worse (β = 11.5 [95% CI 4.2-18.8, p < 0.001). Adults with low-incomes and diabetes were most impacted by the pandemic. A1c may not fully capture challenges that people with diabetes are facing to manage their condition; systolic blood pressures may have worsened and problems with self-care may forebode longer-term challenges in diabetes control.


Exact solutions for internuclear vectors and backbone dihedral angles from NH residual dipolar couplings in two media, and their application in a systematic search algorithm for determining protein backbone structure.
We have derived a quartic equation for computing the direction of an internuclear vector from residual dipolar couplings (RDCs) measured in two aligning media, and two simple trigonometric equations for computing the backbone (phi,psi) angles from two backbone vectors in consecutive peptide planes. These equations make it possible to compute, exactly and in constant time, the backbone (phi,psi) angles for a residue from RDCs in two media on any single backbone vector type. Building upon these exact solutions we have designed a novel algorithm for determining a protein backbone substructure consisting of alpha-helices and beta-sheets. Our algorithm employs a systematic search technique to refine the conformation of both alpha-helices and beta-sheets and to determine their orientations using exclusively the angular restraints from RDCs. The algorithm computes the backbone substructure employing very sparse distance restraints between pairs of alpha-helices and beta-sheets refined by the systematic search. The algorithm has been demonstrated on the protein human ubiquitin using only backbone NH RDCs, plus twelve hydrogen bonds and four NOE distance restraints. Further, our results show that both the global orientations and the conformations of alpha-helices and beta-strands can be determined with high accuracy using only two RDCs per residue. The algorithm requires, as its input, backbone resonance assignments, the identification of alpha-helices and beta-sheets as well as sparse NOE distance and hydrogen bond restraints.


Optimal physical preprocessing for example-based super-resolution.
Fourier ptychographic microscopy is a technique that achieves a high space-bandwidth product, i.e. high resolution and high field-of-view. In Fourier ptychographic microscopy, variable illumination patterns are used to collect multiple low-resolution images. These low-resolution images are then computationally combined to create an image with resolution exceeding that of any single image from the microscope. Due to the necessity of acquiring multiple low-resolution images, Fourier ptychographic microscopy has poor temporal resolution. Our aim is to improve temporal resolution in Fourier ptychographic microscopy, achieving single-shot imaging without sacrificing space-bandwidth product. We use example-based super-resolution to achieve this goal by trading off generality of the imaging approach. In example-based super-resolution, the function relating low-resolution images to their high-resolution counterparts is learned from a given dataset. We take the additional step of modifying the imaging hardware in order to collect more informative low-resolution images to enable better high-resolution image reconstruction. We show that this "physical preprocessing" allows for improved image reconstruction with deep learning in Fourier ptychographic microscopy. In this work, we use deep learning to jointly optimize a single illumination pattern and the parameters of a post-processing reconstruction algorithm for a given sample type. We show that our joint optimization yields improved image reconstruction as compared with sole optimization of the post-processing reconstruction algorithm, establishing the importance of physical preprocessing in example-based super-resolution.


Access to psycho-social resources and health: exploratory findings from a survey of the French population.
We study the psycho-social determinants of self-assessed health in order to explain social inequalities in health in France. We use a unique general population survey to assess the respective impact on self-assessed health status of subjective perceptions of social capital, social support, and sense of control, controlling for standard socio-demographic factors (SES, income, education, age, and gender). The survey is unique in that it provides a variety of measures of self-perceived psycho-social resources (trust and civic engagement, social support, sense of control, and self-esteem). We find empirical support for the link between the subjective perception of psycho-social resources and health. Sense of control at work is the most important correlate of health status after income. Other important ones are civic engagement and social support. To a lesser extent, sense of being lower in the social hierarchy is associated with poorer health status. On the contrary, relative deprivation does not affect health in our survey. Since access to psycho-social resources is not equally distributed in the population, these findings suggest that psycho-social factors can partially explain of social inequalities in health in France.


Mechanisms of inhibition by ascorbate of microbial mutagenesis induced by N-nitroso compounds.
Mutagenesis induced by N-methyl-N-nitrosoguanidine (MNNG) and dimethylnitrosamine (DMN) in Salmonella TA 1530 was inhibited by ascorbate. Inhibition of MNNG-induced mutagenesis resulted from a reaction between ascorbate and MNNG that led to consumption of MNNG. The rate of this reaction was considerably enhanced by catalytic amounts of Cu(II) and Fe(III). No direct reaction between DMN and ascorbate was detectable, but relatively high concentrations of Cu(II) enchanced inhibition of DMN-induced mutagenesis by ascorbate. Added protein reduced the effectiveness of Cu(II) as a catalyst of the reaction between ascorbate and MNNG, which suggested that the microsomal protein necessary to activate DMN, may reduce the concentration of free Cu(II) and thereby lower its catalytic efficiency. Mutagenesis by N-methyl-N-nitrosourea was not inhibited by ascorbate.


The analysis of epidemiological characteristics of road traffic crashes in a mountain city in western China.
To study the epidemiological characteristics and preventive methods of road traffic crashes in a mountain city in western China through sampling investigation of traffic crashes in different regions of Chongqing city in recent years. Two police teams of traffic management in downtown, two teams in suburb, one team in county and one freeway team were randomly selected, and road traffic crashes between 1988 and 1997 were investigated and analyzed. A total of 13121 road traffic crashes with 6201 crashes with casualties were analyzed. The incidence of crashes was higher in May, June and July, and on Friday and Wednesday and at 8:00-12:00 and 14:00-18:00 within a day. Casualties were 44.0% in pedestrians and 42.5% in passengers of total casualties. The deaths and severe injuries in pedestrians were 59.1% of total deaths and 56.4% of total severe injuries. The age of drivers and passengers were mainly at 18-30 years, followed by 31-40 years. People over 60 years old accounted for 24.1% of total pedestrian casualty. Head injury was the most common reason for deaths. The main reasons for these crashes were improper driving and violating traffic laws. Violating traffic laws by pedestrian was one of the main reasons for pedestrian casualty. The crashes are related to the characteristics of geography, climate, society activity of people, and the sense of traffic safety, the basic traffic construction and management in Chongqing. The traffic casualty of pedestrian is a big problem in Chongqing. To prevent and decrease road traffic injuries effective methods should be worked out and propaganda on traffic safety and traffic management should be strengthened according to different characteristics of different regions. To strengthen the first aid and treatment of cranium-brain injury and chest-back injury is also helpful in decreasing traffic deaths.


[Study of the intracardiac flow by real-time bidimensional color-coded Doppler echocardiography. Preliminary experience].
The new technique of real-time two-dimensional color Doppler echocardiography has been recently developed to allow visualization of the blood flow inside the cardiac chambers. The blood flow informations are color coded and displayed in real-time into the two-dimensional echocardiographic images of the cardiac structures. The flow informations which are given are velocity, direction and variance, calculated from the Doppler signals obtained from all the sample points. Flow directed toward the transducer is coded in red; flow away from the transducer is coded in blue, while the echoes from the cardiac structures are imaged in gray scale. The magnitude of the velocity of flow is represented by the brightness of the color, with an 8-steps scale of brightness, beginning from the lowest grade, which is not colored on the screen. To represent the velocity spectrum variance, green is added to each color in proportion to the extent of turbulence. We report our preliminary experience with this technique in 91 subjects by using an Aloka SSD 880 commercial equipment (age range 18 days-82 years): 5 were normal, 15 had cardiomyopathy, 21 had congenital, 40 valvular, 6 ischemic and 4 other forms of heart disease. Color display of intracavitary flow allowed to identify normal and abnormal patterns. Valvular regurgitation and abnormal intracavitary shunts were easy to identify, suggesting the possibility of a semiquantitative assessment of the lesions. The possibility of a quantitative approach should be further investigated in the future.(ABSTRACT TRUNCATED AT 250 WORDS)


Interventions to improve social circumstances of people with mental health conditions: a rapid evidence synthesis.
Poor social circumstances can induce, exacerbate and prolong symptoms of mental health conditions, while having a mental health condition can also lead to worse social outcomes. Many people with mental health conditions prioritise improvement in social and functional outcomes over reduction in clinical symptoms. Interventions that improve social circumstances in this population should thus be considered a priority for research and policy. This rapid evidence synthesis reports on randomised controlled trials of interventions to improve social circumstances across eight social domains (Housing and homelessness; money and basic needs; work and education; social isolation and connectedness; family, intimate and caring relationships; victimisation and exploitation; offending; and rights, inclusion and citizenship) in people with mental health conditions. Economic evaluations were also identified. A comprehensive, stepped search approach of the Cochrane library, MEDLINE, Embase, PsycINFO, Web of Science and Scopus was conducted. One systematic review and 102 randomised controlled trials were included. We did not find RCT evidence for interventions to improve family, intimate and caring relationships and only one or two trials for each of improving money and basic needs, victimisation and exploitation, and rights, inclusion and citizenship. Evidence from successful interventions in improving homelessness (Housing First) and employment (Individual Placement and Support) suggests that high-intensity interventions which focus on the desired social outcome and provide comprehensive multidisciplinary support could influence positive change in social circumstances of people with mental health conditions. Objective social isolation could be improved using a range of approaches such as supported socialisation and social skills training but interventions to reduce offending showed few benefits. Studies with cost and cost-effectiveness components were generally supportive of interventions to improve housing and vocational outcomes. More research is needed to ensure that social circumstances accompanied by high risks of further exacerbation of mental health conditions are adequately addressed. Although there is a large body of literature examining how to support some aspects of life for people with mental health conditions, more high-quality evidence is required in other social domains. Integration into mental health services of interventions targeting social circumstances could significantly improve a number of social outcomes.


Effects of feed crops and boiling on chicken egg yolk and white determined by a metabolome analysis.
Compositional analyses of eggs have primarily focused on nutritional components, including large molecules, such as proteins. However, few reports have investigated the effects of heating and hen feed crops on taste components, such as free amino acids and sugars. Herein, water-soluble metabolites in raw and boiled eggs produced from chickens raised with corn- or rice-fed were analyzed. Each egg was separated into yolk and white, and freeze-dried samples were analyzed by CE-MS and LC-MS. Abundant metabolites included amino acids in yolks and sugars in whites. Compared to corn-fed, rice-fed resulted in three times higher betaine and uridine monophosphate concentrations in yolks and whites, respectively. Boiled whites contained more than four times higher concentrations of amino acids and fructose than raw whites. Metabolites in yolks exhibited minimal changes after boiling. Our findings support the use of water-soluble metabolomics to evaluate the effects of heating and feed crops on taste components.


Farm Vehicle Following Distance Estimation Using Deep Learning and Monocular Camera Images.
This paper presents a comprehensive solution for distance estimation of the following vehicle solely based on visual data from a low-resolution monocular camera. To this end, a pair of vehicles were instrumented with real-time kinematic (RTK) GPS, and the lead vehicle was equipped with custom devices that recorded video of the following vehicle. Forty trials were recorded with a sedan as the following vehicle, and then the procedure was repeated with a pickup truck in the following position. Vehicle detection was then conducted by employing a deep-learning-based framework on the video footage. Finally, the outputs of the detection were used for following distance estimation. In this study, three main methods for distance estimation were considered and compared: linear regression model, pinhole model, and artificial neural network (ANN). RTK GPS was used as the ground truth for distance estimation. The output of this study can contribute to the methodological base for further understanding of driver following behavior with a long-term goal of reducing rear-end collisions.


Ilaprazole for the treatment of duodenal ulcer: a randomized, double-blind and controlled phase III trial.
The new proton pump inhibitor (PPI), ilaprazole performed better at the dose of 10 mg/d relative to 5 or 20 mg/d in a previous phase II trial. A larger phase III trial was carried out to confirm the efficacy and safety of ilaprazole (10 mg/d) compared with omeprazole (20 mg/d) and provide some characteristics of the relationship between ilaprazole metabolism and CYP2C19 for later studies. Patients with at least one endoscopically diagnosed active duodenal ulcer (DU) were enrolled in a multicenter, randomized, double-blind, positive controlled trial and then assigned randomly to the ilaprazole group (10 mg/d) or the omeprazole group (20 mg/d) with a sample allocation ratio 2:1. The course of treatment was 4 weeks. ClinicalTrials.gov registration number: NCT00952978. The primary endpoint was endoscopically diagnosed ulcer healing rate at week 4. Symptom relief was evaluated as a secondary endpoint by graded scores. Safety and tolerability were evaluated on basis of clinical assessments. In addition, blood samples were collected at baseline for CYP2C19 genotypes identification. Efficacy analyses were based on 494 patients. At week 4, the ulcer healing rates were 93.0% in ilaprazole group and 90.8% in omeprazole group (rate difference: 2.2%; 95% confidence interval: -2.8% to 7.2%). No obvious variation of healing rate on different CYP2C19 genotypes was found in ilaprazole group. The majority of patients (>80%) became asymptomatic after treatment. Incidences of adverse drug reactions were similar between ilaprazole group and omeprazole group (8.5% vs. 11.5%). Ilaprazole (10 mg/d) is as effective as omeprazole (20 mg/d) in the treatment of DU with similar side effects. The efficacy of ilaprazole is not affected by CYP2C19 polymorphisms.


Distribution of Calcium and Chitin in the Tardigrade Feeding Apparatus in Relation to its Function and Morphology.
The cuticular portion of the tardigrade feeding apparatus is a complex structure that can be schematically divided into four parts: a buccal ring, a buccal tube, a stylet system (formed by two piercing stylets, each within a stylet coat, and two stylet supports), and the lining of a myoepithelial sucking pharynx. To better understand the function and evolution of the feeding apparatus, the morpho-functional traits and chemical composition of the structures forming the feeding apparatuses of eight different species of tardigrades were analyzed. These eight species are representative of almost all main phylogenetic lineages of the phylum. The calcium and chitin in the feeding apparatus were examined by light microscopy, scanning electron microscopy, confocal laser scanning microscopy, energy dispersive X-ray spectroscopy, and Raman microspectroscopy (Raman). In all species, the feeding apparatus had been subjected to biomineralization due to CaCO3 encrustations organized in the crystalline form of aragonite. Aragonite and chitin are present in different concentrations in the feeding apparatus according to the structures and species considered. Generally, where the structures are rigid there is more aragonite than chitin, and vice versa. The buccal tube and piercing stylets are rich in calcium, with the piercing stylets apparently composed exclusively of aragonite. In eutardigrades, chitin is in higher concentration in the structures subject to higher mechanical stresses, such as the crests of the buccal crown and the condyles of the stylet furca.


The natural selection of fidelity in social learning.
Social learning mechanisms are usually assumed to explain both the spread and the persistence of cultural behavior. In a recent article, we showed that the fidelity of social learning commonly found in transmission chain experiments is not high enough to explain cultural stability. Here we want to both enrich and qualify this conclusion by looking at the case of song transmission in song birds, which can be faithful to the point of being true replication. We argue that this high fidelity results from natural selection pressure on cognitive mechanisms. This observation strengthens our main argument. Social learning mechanisms are unlikely to be faithful enough to explain cultural stability because they are generally selected not for high fidelity but for generalization and adjustment to the individual's needs, capacities and situation.