Gpr177 deficiency impairs mammary development and prohibits Wnt-induced tumorigenesis.
Aberrant regulation of the Wnt pathway, essential for various developmental processes, is tightly linked to human breast cancers. By hijacking this evolutionary conserved signaling pathway, cancer cells acquire sustaining proliferation ability, leading to modification of physiologic properties necessary for tumor initiation and progression. An enormous wealth of knowledge on the importance of Wnt signaling in breast development and cancer has been obtained, but the cell types responsible for production of this proliferative signal operating within normal and malignant tissues remains poorly understood. Here we report that Wnt production mediated by Gpr177 is essential for mammary morphogenesis. The loss of Gpr177 interferes with mammary stem cells, leading to deficiencies in cell proliferation and differentiation. Genetic analysis further demonstrates an indispensable role of Gpr177 in Wnt-induced tumorigenesis. The Gpr177-deficiency mice are resistant to malignant transformation. This study not only demonstrates the necessity of Wnt in mammary organogenesis but also provides a proof-of-principle for targeting of Gpr177 as a potential new treatment for human diseases with aberrant Wnt stimulation.


Carcinoembryonic antigen in sweat-gland carcinomas.
Using standard immunoperoxidase techniques, four cases of malignant sweat-gland carcinoma were examined for the presence of carcinoembryonic antigen (CEA). This substance was universally present in these lesions in spite of their wide spectrum of histologic features. CEA was mainly localized within the cytoplasm of tumor cells and in the lumina of neoplastic glands. The findings indicate that the presence of CEA in malignant skin adnexal tumors could help to identify and categorize these lesions as derived from eccrine or apocrine adnexal epithelium.


Capillary-Driven Ejection of a Droplet from a Micropore into a Channel: A Theoretical Model and a Computational Fluid Dynamics Verification.
In this work, the problem of re-ejection of a permeating droplet through a membrane pore back to the feed channel when the transmembrane pressure (TMP) becomes zero is investigated. This problem is important in the context of oily water filtration using membranes. In particular, in the novel periodic feed pressure technique (PFPT), which has been proposed to combat membrane fouling, the TMP alternates between the operating value and zero in a periodic manner. During the period in which TMP is high, filtration occurs, and when it is zero, cleaning commences. We are particularly interested in what happens to a droplet, initially undergoing permeation, when the TMP becomes zero. It is evident that when the TMP is zero the meniscus inside the pore reverses its motion toward the feed channel rather than toward the permeate side by the action of interfacial tension force. A theoretical model is built to determine the rate at which the meniscus inside the pore advances when the TMP is zero. The conservation of momentum equation is used to establish a one-dimensional model that updates the location of the meniscus with time. The derived model considers both quasi-static and dynamic scenarios. In addition, the model accounts for both the viscosity contrast between the two fluids, as well as the gravity. A computational fluid dynamics (CFD) simulation has been built to provide a framework for model verification and validation. The model, based on quasi-static conditions, provides an overall similar trend to that obtained via CFD analysis. Nevertheless, the quasi-static model predicts a more rapid meniscus advancement inside the pore than the CFD simulation. When the dynamic contact angle is incorporated, very good matching is observed.


Valuing dental practice.
Because new dentists are finding that initiating dental practices has become more problematic, the issues of practice purchase and valuation have become more salient. The purchase of a practice, although expensive, decreases the amount of time required before the dentist can experience a profit. This article discusses issues related to valuing, reviews some of the strategies related to the purchase of a practice, and recommends an objective approach to establishing fair market value.


Homologies and divergences in the transcription regulatory system of two related Bacillus subtilis phages.
Transcription regulation relies on the molecular interplay between the RNA polymerase and regulatory factors. Phages of the phi29-like genus encode two regulatory proteins, p4 and p6. In phi29, the switch from early to late transcription is based on the synergistic binding of proteins p4 and p6 to the promoter sequence, resulting in a nucleosome-like structure able to synergize or antagonize the binding of RNAP. We show that a nucleosome-like structure of p4 and p6 is also formed in the related phage Nf and that this structure is responsible for the coordinated control of the early and late promoters. However, in spite of their homologies, the transcriptional regulators are not interchangeable, and only when all of the components of the Nf regulatory system are present is fully active transcriptional regulation of the Nf promoters achieved.


A preliminary study of injectable collagen in human vocal fold augmentation.
Soluble bovine collagen was injected for vocal fold augmentation in 27 patients with glottic insufficiency. Preliminary observations show that glottic closure was enhanced in all patients with no serious complications. Subjective and objective measures of vocal efficiency indicated improvement with reduction in airflow, improved glottic closure, and increased vocal intensity. Recent studies that reveal distant migration of injected Teflon suggest the need for the development of a safe biologic material for soft tissue augmentation. Collagen appears to satisfy criteria as an ideal bioimplant, tends to soften scar tissue, and is structurally similar to natural collagen in the human vocal fold. Further longitudinal studies and the development of potentially more stable cross-linked collagen preparations seem indicated.


[Smartphone apps as a new psychiatric treatment].
The number of smartphone apps for people with mental health issues is undergoing a dramatical growth in these years. We review the available literature on the topic, discuss opportunities and theoretical considerations using smartphone apps in psychiatric treatment and provide an overview of approaches that are currently in progress in this field in Denmark. In a systematic literature search we found four small clinical trials with positive results. However, none of the studies were randomised controlled trials, and the results have to be interpreted with caution.


A Haspin promoter element induces tissue-specific methylation of a transcription region and the regulation of gene expression in mouse ova.
HASPIN is a nuclear serine-threonine kinase originally identified in the mouse testis. Its 193 bp DNA promoter element (hereafter, 193PE) regulates bidirectional, synchronous gene expression in the germ cells of male mice. Recent studies have shown that Haspin is also expressed in trace amounts in somatic cells; HASPIN also functions in oocytes. Haspin expression is regulated by the tissue-specific methylation of Haspin genomic DNA regions, including somatic cells. This study investigated relationship between 193PE and DNA methylation by examining methylation status of transgenic mice carrying 193PE and a reporter gene. In somatic (liver) cells carrying the reporter gene, 193PE induced methylation as well as trace expression of the reporter gene. In the testis, 193PE induced hypomethylation and intense reporter gene expression. Expression of HASPIN in an egg was assessed using human chorionic gonadotrophin to induce ovulation in female transgenic mice. The results showed that 193PE induced tissue-specific methylation, which resulted in reporter gene expression in a mouse egg.


Preliminary investigation on prevalence of osteoporosis and osteopenia: Should we tune our focus on healthy adults?
Osteoporosis and osteopenia are global health problems with increasing trend, particularly in developed regions. Apart from traditional well-recognized high-risk groups (i.e. postmenopausal women and elders), prevalence of such problems among adults should not be ignored because of the advantages of early detection and health promotion. Therefore, this preliminary study aims to investigate the prevalence of osteoporosis and osteopenia among adult office workers, which represented a relatively large proportion of the population in urbanized cities. An GE-Lunar Achilles ultrasonometer was used to screen the bone mineral density (BMD) of 80 participants. The BMD T-score ranged from -3 to 3.5. The majority of the participants had normal BMD result (T-score, ≥ -1), whereas 35% was classified as abnormal (T-score, < -1) including 31.3% osteopenia and 3.8% osteoporosis. High prevalence rate of abnormal BMD among healthy adults should be further studied in this population. The findings also suggest that the current ignorance in adulthood may increase the prevalence of osteoporotic fractures in the future.


The Period Prevalence of Mind and Body Practice Use by Adult Emergency Department Patients.
Mind and Body Practice (MBP) use (e.g., chiropractic, acupuncture, meditation) among Emergency Department (ED) patients is largely unknown. We aimed to determine the period prevalence, nature of MBP use, and perceptions of MBP among adult ED patients. We undertook a cross-sectional survey of a convenience sample of patients presenting to three EDs between February and June 2016. Patients were eligible for inclusion if they were aged 18 years or more and had presented for medical treatment. An anonymous, self-administered questionnaire, based upon a validated pediatric questionnaire, was completed by the patient, with assistance if required. The primary outcome was the nature and 12 month period prevalence of MBP use. Secondary outcomes were variables associated with use and patient perceptions of MBP. 674 patients were enrolled. In the previous 12 months, 500 (74.2%) patients had used at least one MBP. MBP users and nonusers did not differ in gender, ancestry, or chronic illness status (p > 0.05). However, users were significantly younger and more likely to have private health insurance (p < 0.001). A total of 2094 courses of 68 different MBP had been used including massage (75.0% of users), meditation (35.2%), chiropractic (32.6%), acupuncture (32.0%), and yoga (30.6%). Users were significantly more likely (p < 0.01) to believe that MBP prevented illness, treated illness, were more effective than prescription medicines, assisted prescription medications, and were safe and provided a more holistic approach. Forty-one (6.1%) patients used MBP for their ED presenting complaint. However, only 14 (34.1%) advised their ED physician of this. The period prevalence of MBP use among ED patients is high. Knowledge of the MBP used for a patient's presenting complaint may better inform the ED physician when making management decisions.


Hadamard-Transform Fluorescence Excitation-Emission-Matrix Spectroscopy.
We present a fluorescence excitation-emission-matrix spectrometer with superior data acquisition rates over previous instruments. Light from a white light emitting diode (LED) source is dispersed onto a digital micromirror array (DMA) and encoded using binary n-size Walsh functions ("barcodes"). The encoded excitation light is used to irradiate the liquid sample and its fluorescence is dispersed and detected using a conventional array spectrometer. After exposure to excitation light encoded in n different ways, the 2-dimensional excitation-emission-matrix (EEM) spectrum is obtained by inverse Hadamard transformation. Using this technique we examined the kinetics of the fluorescence of rhodamine B as a function of temperature and the acid-driven demetalation of chlorophyll-a into pheophytin-a. For these experiments, EEM spectra with 31 excitation channels and 2048 emission channels were recorded every 15 s. In total, data from over 3000 EEM spectra were included in this report. It is shown that the increase in data acquisition rate can be as high as [{n(n + 1)}/2]-fold over conventional EEM spectrometers. Spectral acquisition rates of more than two spectra per second were demonstrated.


An epidemiological study of plasma renin activity in schoolchildren in Japan: distribution and its relation with family history of hypertension.
Plasma renin activity (PRA) was determined in a group of 610 Japanese schoolchildren aged 10-14 years in order to investigate the relationship between PRA distribution and a family history of hypertension. Plasma renin activity was higher in the subjects with a family history of hypertension (FH+) than in those without a family history of hypertension (FH-). Systolic blood pressure (SBP) was also higher in the FH+ group than in the FH- group. The FH- group showed a significant negative correlation between PRA and SBP (boys, r = -0.254, P less than 0.01; girls, r = -0.225, P less than 0.01), whereas the FH+ group showed no correlation between PRA and blood pressure. These results suggested that schoolchildren with a family history of hypertension might have an enhanced renin-aldosterone (R-A) system, resulting in elevation of blood pressure.


Inferior Outcomes of EU Versus US Patients Treated With CD19 CAR-T for Relapsed/Refractory Large B-cell Lymphoma: Association With Differences in Tumor Burden, Systemic Inflammation, Bridging Therapy Utilization, and CAR-T Product Use.
Real-world evidence suggests a trend toward inferior survival of patients receiving CD19 chimeric antigen receptor (CAR) T-cell therapy in Europe (EU) and with tisagenlecleucel. The underlying logistic, patient- and disease-related reasons for these discrepancies remain poorly understood. In this multicenter retrospective observational study, we studied the patient-individual journey from CAR-T indication to infusion, baseline features, and survival outcomes in 374 patients treated with tisagenlecleucel (tisa-cel) or axicabtagene-ciloleucel (axi-cel) in EU and the United States (US). Compared with US patients, EU patients had prolonged indication-to-infusion intervals (66 versus 50 d; P < 0.001) and more commonly received intermediary therapies (holding and/or bridging therapy, 94% in EU versus 74% in US; P < 0.001). Baseline lactate dehydrogenase (LDH) (median 321 versus 271 U/L; P = 0.02) and ferritin levels (675 versus 425 ng/mL; P = 0.004) were significantly elevated in the EU cohort. Overall, we observed inferior survival in EU patients (median progression-free survival [PFS] 3.1 versus 9.2 months in US; P < 0.001) and with tisa-cel (3.2 versus 9.2 months with axi-cel; P < 0.001). On multivariate Lasso modeling, nonresponse to bridging, elevated ferritin, and increased C-reactive protein represented independent risks for treatment failure. Weighing these variables into a patient-individual risk balancer (high risk [HR] balancer), we found higher levels in EU versus US and tisa-cel versus axi-cel cohorts. Notably, superior PFS with axi-cel was exclusively evident in patients at low risk for progression (according to the HR balancer), but not in high-risk patients. These data demonstrate that inferior survival outcomes in EU patients are associated with longer time-to-infusion intervals, higher tumor burden/LDH levels, increased systemic inflammatory markers, and CAR-T product use.


[Bilio-pancreatic diversion with duodenal switch (DS) in morbid obesity--surgical technique].
Obesity is one of the biggest health problems nowadays with growing prevalence. Co morbidities and decreasing life-expectancy have imposed various treatments, of which surgery has the best efficiency. Bilio-pancreatic diversion modified with duodenal switch represents the procedure with both malabsorbtive and restrictive effects. This procedure has the best results in reducing excessive body mass and in maintaining this loss. Complexity of this procedure, early and late complications suggests that the main operative indication is for morbid obesity patients (body mass index BMI > 50 kg/mp). The procedure that we have done was a success in efficiency and in quality of life, but for conclusions is necessary more experience.


Covalent functionalization of reduced graphene oxide aerogels with polyaniline for high performance supercapacitors.
Covalent functionalization of reduced graphene oxide aerogel (RGOA), which has undergone diazotization and amidation, was achieved by grafting polyaniline (PANI) onto the surface of RGOA. Diazotization and amidation could introduce amino groups, which were directly responsible for the chemical oxidative polymerization of aniline on the surface of RGOA. The resultant PANI-grafted RGOA (RGOA-PANI) could be used for high performance supercapacitors.


The relationship between suicidal attempts and menstrual cycle in women.
The purpose of the study was to explore relationship between the menstrual cycle and suicidal attempts. A study was performed on 151 fertile females who were admitted to the Clinic of Internal Diseases and Acute Poisonings Medical University of Gdańsk during the years 2002-2003 because of suicidal attempts. The inclusion criteria were as follows: fertility, regular menstrual cycle, lack of oral contraceptives, willingness to attend the follow up and willingness to see a psychiatrist. Using the anamnesis the patients were also grouped according to the menstrual cycle into menstrual, follicular, midcycle and luteal phase. According to psychiatric investigations every female was classified to the respective category: situational reaction, depression, schizophrenia, alcohol addiction and sociopathy. Severity of intoxication was classified according to Poisoning Severity Score (PSS). Statistical analysis was done with the use of chi-square test with Pearson correction. Suicidal attempts were the most frequent among females during menstrual phase. The most common diagnosis in females who have attempted suicide were situational reactions which dominated in patients aged 14-21 years. Among attempters with the psychiatric diagnosis of depression, schizophrenia and alcohol addiction the degree of poisoning was significantly more severe than in the patients with situational reaction.


Superior memorizers employ different neural networks for encoding and recall.
Superior memorizers often employ the method of loci (MoL) to memorize large amounts of information. The MoL, known since ancient times, relies on a complex process where information to be memorized is bound to landmarks along mental routes in a previously memorized environment. However, functional magnetic resonance imaging data on groups of trained superior memorizer are rare. Based on the memorizing strategy reported by superior memorizers, we developed a scheme of the processes successively employed during memorizing and recalling digits and relate these to brain activation that is specific for the encoding and recall period. In the examined superior memorizers several regions, suggested to be involved in mental navigation and digit-to-word processing, were specifically activated during encoding: bilateral early visual cortex, retrosplenial cortex, left parahippocampus, left visual cortex, and left superior parietal cortex. Although the scheme suggests that some steps during encoding and recall seem to be analog, none of the encoding areas were specifically activated during the recall. Instead, we found strong activation in left anterior superior temporal gyrus, which we relate to recalling the sequential order of the digits, and right motor cortex that may be related to reciting the digits.


Concurrent cisplatin-based radiotherapy and chemotherapy for locally advanced cervical cancer.
On behalf of the Gynecologic Oncology Group, we performed a randomized trial of radiotherapy in combination with three concurrent chemotherapy regimens -- cisplatin alone; cisplatin, fluorouracil, and hydroxyurea; and hydroxyurea alone -- in patients with locally advanced cervical cancer. Women with primary untreated invasive squamous-cell carcinoma, adenosquamous carcinoma, or adenocarcinoma of the cervix of stage IIB, III, or IVA, without involvement of the para-aortic lymph nodes, were enrolled. The patients had to have a leukocyte count of at least 3000 per cubic millimeter, a platelet count of at least 100,000 per cubic millimeter, a serum creatinine level no higher than 2 mg per deciliter (177 micromol per liter), and adequate hepatic function. All patients received external-beam radiotherapy according to a strict protocol. Patients were randomly assigned to receive one of three chemotherapy regimens: 40 mg of cisplatin per square meter of body-surface area per week for six weeks (group 1); 50 mg of cisplatin per square meter on days 1 and 29, followed by 4 g of fluorouracil per square meter given as a 96-hour infusion on days 1 and 29, and 2 g of oral hydroxyurea per square meter twice weekly for six weeks (group 2); or 3 g of oral hydroxyurea per square meter twice weekly for six weeks (group 3). The analysis included 526 women. The median duration of follow-up was 35 months. Both groups that received cisplatin had a higher rate of progression-free survival than the group that received hydroxyurea alone (P<0.001 for both comparisons). The relative risks of progression of disease or death were 0.57 (95 percent confidence interval, 0.42 to 0.78) in group 1 and 0.55 (95 percent confidence interval, 0.40 to 0.75) in group 2, as compared with group 3. The overall survival rate was significantly higher in groups 1 and 2 than in group 3, with relative risks of death of 0.61 (95 percent confidence interval, 0.44 to 0.85) and 0.58 (95 percent confidence interval, 0.41 to 0.81), respectively. Regimens of radiotherapy and chemotherapy that contain cisplatin improve the rates of survival and progression-free survival among women with locally advanced cervical cancer.


Effect of variation in endogenous levels of ascorbic acid on the in vitro immunological release of histamine and slow reacting substance of anaphylaxis from actively sensitized guinea-pig lung fragments.
1. The in vitro immunological release of histamine and slow reacting substance of anaphylaxis (SRS-A) from actively sensitized guinea-pig lung fragments was greatly reduced when the animals were maintained on an ascorbic acid-deficient diet. Excessive dietary levels of ascorbic acid did not increase mediator release above normal levels. 2. Restoration of ascorbic acid in the diet of scorbutic guinea-pigs restored in vitro immunological histamine to normal levels. 3. Variation in dietary levels of ascorbic acid had no effect on lung histamine content. 4. The lung ascorbic acid content was proportional to the dietary intake. Approximately 60% of the total lung ascorbic acid was removed by the process of chopping and washing of the tissue. This relationship was independent of dietary intake. 5. The results indicate that the immunological release of mediators of inflammation from guinea-pig lung is dependent on adequate endogenous levels of ascorbic acid.


Intrinsic coherence resonance in an electrochemical cell.
We study the interaction of intrinsic electrochemical noise with autonomous nonlinear dynamics of a three-electrode electrochemical cell. The amplitude of this intrinsic (internal) noise, regulated by the concentration of chloride ions, is monotonically increased and the provoked dynamics is analyzed. The experimentally constructed coherence factor beta versus the concentration of the chloride ions' curve has a unimodal shape indicating the emergence of intrinsic coherence resonance. The abscissa for the maxima of this unimodal curve corresponds to the optimum value of intrinsic noise where maximum regularity of the invoked dynamics is observed.


Two purine biosynthetic enzymes that are required for cadmium tolerance in Schizosaccharomyces pombe utilize cysteine sulfinate in vitro.
In plants and in certain fungi, exposure to heavy metals induces the synthesis of metal-binding peptides commonly known as phytochelatins. With cadmium, phytochelatins can sequester the metal into a sulfide-containing complex. From genetic analysis of fission yeast mutants, we previously reported that two genes in purine biosynthesis, encoding adenylosuccinate synthetase and succinoaminoimidazole carboxamide ribonucleotide (SAICAR) synthetase, are required for the biogenesis of the phytochelatin-cadmium-sulfide complex in vivo. We suggested that a sulfur analog of aspartate, cysteine sulfinate, might be utilized by these enzymes and that the cysteine sulfinate-derived products would then become intermediates or carriers in a sulfur transfer pathway leading to the sulfide found within the metal chelate. In this paper, we report that partially purified adenylosuccinate synthetase and SAICAR synthetase are capable of utilizing cysteine sulfinate in vitro to form sulfur analog products. Adenylosuccinate lyase, however, fails to catalyze further conversion of these sulfur derivatives. These observations support the genetic data implicating a link among purine biosynthetic enzymes, sulfur metabolism, and cadmium tolerance.


Pubertal development in Rett syndrome deviates from typical females.
Rett syndrome is a unique neurodevelopmental disorder, affecting approximately one in 10,000 live female births, most experiencing reduced growth. We characterized pubertal trajectories in females with Rett syndrome. We hypothesized that pubertal trajectory deviates from the general female population with early pubertal onset and delayed menarche. Participants were individuals enrolled in the Rett Syndrome Natural History Study with clinical diagnosis of Rett syndrome or mutations in MECP2. Intervals to thelarche, adrenarche, and menarche were assessed by survival analysis; body mass index, mutation type, clinical severity, and pubertal milestone relationships were assessed by log-likelihood test; pathway synchrony (relationship between thelarche, adrenarche, and menarche) was assessed by chi-squared analysis. Compared with the general female population, more than 25% initiated puberty early, yet entered menarche later (median age 13.0 years). A total of 19% experienced delayed menarche. Median length of puberty, from thelarche to menarche, was 3.9 years. Higher body mass index correlated with earlier thelarche and adrenarche but not menarche; milder mutations correlated with earlier menarche; and milder clinical presentation correlated with earlier thelarche and menarche. Fifty-two percent entered puberty in synchrony, but different from the general population, 15% led with thelarche and 32% with adrenarche. Pubertal trajectories in Rett syndrome differ from general population, entering puberty early and reaching menarche later. Body mass index affects pubertal timing, but the relationship between specific mutations, clinical presentation, and underlying neuroendocrine pathology is less clear.


Neural correlates of emotional inhibitory control in autism spectrum disorders.
Atypical inhibitory function is often present in individuals with autism spectrum disorder (ASD), who may have difficulty suppressing context-inappropriate behaviors. We investigated the neural correlates of inhibition in ASD in response to both emotional and non-emotional stimuli using an fMRI Go/NoGo inhibition task with human faces and letters. We also related neural activation to behavioral dysfunction in ASD. Our sample consisted of 19 individuals with ASD (mean age=25.84) and 22 typically developing (TD) control participants (mean age=29.03). As expected, no group differences in task performance (inhibition accuracy and response time) were found. However, adults with ASD exhibited greater angular gyrus activation in face response inhibition blocks, as well as greater fusiform gyrus activation than controls, in a condition comparing face inhibition to letter inhibition. In contrast, control participants yielded significantly greater anterior cingulate cortex (ACC) activation in letter inhibition blocks. A positive relationship between communication and language impairment and angular gyrus activation during face inhibition was also found. Group activation differences during inhibition tasks in the context of comparable task performance and the relationship between activation and dysfunction highlight brain regions that may be related to ASD-specific dysfunction.


Intravenous ketorolac versus metoclopramide in adult patients with migraine headaches: An updated systematic review and meta-analysis.
Intravenous ketorolac and metoclopramide are common emergency treatments for adult patients with migraine headaches. The comparison between ketorolac and metoclopramide for migraine treatment is an intriguing issue for research and clinical practice. To provide an updated systematic review and meta-analysis of randomized clinical trials (RCTs) to help determine which treatment has better effects for migraine patients. Intravenous ketorolac and metoclopramide were compared to evaluate whether intravenous ketorolac is associated with significant benefits for pain intensity, short-term headache relief and sustained headache relief among adult patients with migraines. Adverse effects were also analyzed. Five studies with a total of 674 adult patients were included in the analysis, which focused on the outcomes of pain intensity, short-term headache relief, sustained headache relief, and adverse effects. The meta-analysis showed that the only modest but statistically significant difference was present in short-term headache relief when comparing intravenous ketorolac with intravenous metoclopramide. There were no significant differences between intravenous ketorolac and metoclopramide in terms of pain intensity, sustained headache relief or adverse effects. The results suggest that there are no significant differences in most treatment effects (aside from short-term headache relief) and adverse effects when comparing intravenous ketorolac with intravenous metoclopramide. However, the paucity of literature on this topic might have limited the interpretation of the current results. Thus, more relevant studies are warranted.


Substance Use in Healthcare Professionals During the COVID-19 Pandemic in Latin America: A Systematic Review and a Call for Reports.
The COVID-19 pandemic has generated a remarkable change in the behaviour of Healthcare workers (HCWs) around the world. However, there is a lack of evidence on substance use among HCWs in Latin America. Therefore, this study aimed to determine the current frequency of substance use among Latin American among HCWs. We searched 8 databases (PubMed, Scopus, ScientDirect, Web of Science, Cochrane, Scielo, LILACS and Latindex), 4 public prepublication servers (SocArXiv, medRxiv, bioRxiv and Preprints) and Google scholar from 1/9/2019 to 11/1/2021. We determined the frequency of each study based on original studies, scientific letters, and clinical trials in English, Spanish and Portuguese. A total of 17 175 study articles were identified from electronic databases and preprints, and 2 cross-sectional studies conducted in 2020 were included in the qualitative analysis. Both studies included HCWs but did not perform a differential analysis. The first was developed by the Pan-American Health Organization and included interviewees from 35 countries, while the second was conducted with 1145 Brazilian participants. Both studies showed increases in substance use during the pandemic, with alcohol being the most commonly used substance (30%), but PAHO's study reported a 13.8% increase in self-reported heavy-episodic drinking, with differences among genders (males, 15.4%), age groups (highest increase in the 40-49 age group, 16.5%) and area of residence (urban with 14%). The second study showed that 21 32% of participants reported initiating psychoactive substance use, 29.3% added some substance to their initial use and 4% of them had to replace the substance, mainly due to difficulty of access. Other substances of abuse that showed significant increases were tobacco (0.5%) and marijuana (0.3%). Overall, despite the analysis of the 2 studies, the results provided are not a conclusive description of the frequency of substance use by HCWs in Latin America during the COVID-19 pandemic. Further research is required to understand the impact of the pandemic on drug abuse in the region. The protocol has been registered on 30 November 2021 on the International Prospective Register of Systematic Reviews (PROSPERO) with ID: CRD420212919700.


[Experience with methylprednisolone-acetate therapy of juvenile bone cysts].
Authors injected until 1989 in 92 patients with juvenile bone cyst Methylprednisolone-acetate locally after punction of the cyst. They report on the results and give a short literary review.


Identification of hearing loss in the neonatal intensive care unit population.
A protocol was designed to evaluate babies in neonatal intensive care units by means of the auditory brain stem response (ABR) audiometric technique during their hospitalization. This article presents the results obtained from 200 babies. Twenty-three infants failed the ABR test. Fifteen babies were followed. Ten of these infants had significant sensorineural hearing loss. Three had unilateral involvement and seven had bilateral impairment. The seven bilaterally affected infants were fitted with appropriate hearing aid amplification and enrolled in audiologic habilitation programs. Continued follow-up of these babies has confirmed the hearing loss diagnosis. These data estimate that 5 percent of babies in neonatal intensive care units have some degree of hearing loss. The findings encourage the use of the ABR technique as a means of identifying hearing loss in the neonatal intensive care unit population.


Trends in the epidemiology of opportunistic fungal infections: predisposing factors and the impact of antimicrobial use practices.
In the past decade, the frequency of opportunistic fungal infections has increased, and the spectrum of fungal pathogens has changed. The increasing number of susceptible hosts, the introduction of newer modalities for hematopoietic stem cell transplantation, the evolution of organ transplantation practices, the use of novel immunosuppressive agents, and current antimicrobial prophylactic strategies have likely contributed to the changing epidemiology of invasive mycoses. The introduction of azoles more than a decade ago has had a profound impact on curtailing candidal infections. However, a dramatic increase in azole-resistant Candida species and mold infections has been documented. The trends in time of onset, spectrum, and frequency of infections due to invasive molds and opportunistic yeasts are unique for different fungi and vary between subsets of immunocompromised hosts. This review discusses the implications of these trends for guiding judicious use of antimicrobial prophylactics and for unraveling the pathophysiological basis of fungal infections.


Polymer micelle formulation for the proteasome inhibitor drug carfilzomib: Anticancer efficacy and pharmacokinetic studies in mice.
Carfilzomib (CFZ) is a peptide epoxyketone proteasome inhibitor approved for the treatment of multiple myeloma (MM). Despite the remarkable efficacy of CFZ against MM, the clinical trials in patients with solid cancers yielded rather disappointing results with minimal clinical benefits. Rapid degradation of CFZ in vivo and its poor penetration to tumor sites are considered to be major factors limiting its efficacy against solid cancers. We previously reported that polymer micelles (PMs) composed of biodegradable block copolymers poly(ethylene glycol) (PEG) and poly(caprolactone) (PCL) can improve the metabolic stability of CFZ in vitro. Here, we prepared the CFZ-loaded PM, PEG-PCL-deoxycholic acid (CFZ-PM) and assessed its in vivo anticancer efficacy and pharmacokinetic profiles. Despite in vitro metabolic protection of CFZ, CFZ-PM did not display in vivo anticancer efficacy in mice bearing human lung cancer xenograft (H460) superior to that of the clinically used cyclodextrin-based CFZ (CFZ-CD) formulation. The plasma pharmacokinetic profiles of CFZ-PM were also comparable to those of CFZ-CD and the residual tumors that persisted in xenograft mice receiving CFZ-PM displayed an incomplete proteasome inhibition. In summary, our results showed that despite its favorable in vitro performances, the current CFZ-PM formulation did not improve in vivo anticancer efficacy and accessibility of active CFZ to solid cancer tissues over CFZ-CD. Careful consideration of the current results and potential confounding factors may provide valuable insights into the future efforts to validate the potential of CFZ-based therapy for solid cancer and to develop effective CFZ delivery strategies that can be used to treat solid cancers.


Possible involvement of integrin-mediated signalling in oocyte activation: evidence that a cyclic RGD-containing peptide can stimulate protein kinase C and cortical granule exocytosis in mouse oocytes.
Mammalian sperm-oocyte interaction at fertilization involves several combined interactions between integrins on the oocyte and integrin ligands (disintegrins) on the sperm. Recent research has indicated the ability of peptides containing the RGD sequence that characterized several sperm disintegrins, to induce intracellular Ca2+ transients and to initiate parthenogenetic development in amphibian and bovine oocytes. In the present study, we investigate the hypothesis that an integrin-associated signalling may participate in oocyte activation signalling by determining the ability of a cyclic RGD-containing peptide to stimulate the activation of protein kinase C (PKC) and the exocytosis of cortical granules in mouse oocytes. An In-Vitro-Fertilization assay (IVF) was carried in order to test the condition under which a peptide containing the RGD sequence, cyclo(Arg-Gly-Asp-D-Phe-Val), was able to inhibit sperm fusion with zona-free mouse oocytes at metaphase II stage. PKC activity was determined by means of an assay based on the ability of cell lysates to phosphorylate MARKS peptide, a specific PKC substrate. Loss of cortical granules was evaluated by measuring density in the oocyte cortex of cortical granules stained with LCA-biotin/Texas red-streptavidin. In all the experiments, effects of a control peptide containing a non RGD sequence, cyclo(Arg-Ala-Asp-D-Phe-Val), were evaluated. The IVF assay revealed that the fusion rate declined significantly when insemination was carried out in the presence of cyclic RGD peptide at concentrations > or = 250 microM (P < 0.05, Student-Newman-Keuls Method). When the peptide was applied to the oocytes at these concentrations, a dose-dependent increase of PKC activity was observed, in association with a loss of cortical granules ranging from 38+/-2.5 % to 52+/-5.4 %. Evaluation of meiotic status revealed that cyclic RGD peptide was ineffective in inducing meiosis resumption under conditions used in the present study. The presents results provide evidence that a cyclic RGD peptide highly effective in inhibiting sperm-oocyte interaction stimulates in mouse oocytes the activation of PKC and the exocytosis of cortical granules. These data support the view that RGD-binding receptors may function as signalling receptors giving rise integrated signalling not sufficient for a full oocyte activation response. This study may contribute to the understanding of possible negative effects of skipping gamete interaction in IVF techniques.


'Fundamental causes' of inequalities in mortality: an empirical test of the theory in 20 European populations.
The 'fundamental causes' theory stipulates that when new opportunities for lowering mortality arise, higher socioeconomic groups will benefit more because of their greater material and non-material resources. We tested this theory using harmonised mortality data by educational level for 22 causes of death and 20 European populations from the period 1980-2010. Across all causes and populations, mortality on average declined by 2.49 per cent (95%CI: 2.04-2.92), 1.83% (1.37-2.30) and 1.34% (0.89-1.78) per annum among the high, mid and low educated, respectively. In 69 per cent of cases of declining mortality, mortality declined faster among the high than among the low educated. However, when mortality increased, less increase among the high educated was found in only 46 per cent of cases. Faster mortality decline among the high educated was more manifest for causes of death amenable to intervention than for non-amenable causes. The difference in mortality decline between education groups was not larger when income inequalities were greater. While our results provide support for the fundamental causes theory, our results suggest that other mechanisms than the theory implies also play a role.


Blood microRNA-15a Correlates with IL-6, IGF-1 and Acute Cerebral Ischemia.
This study aims to explore the function of blood microRNA-15a (miR-15a) in the pathogenesis of acute cerebral ischemia (AIS). Blood samples were collected from healthy control and AIS patients within 72 h after onset. A model of ischemia in human umbilical vein endothelial cells (HUVECs) was established through oxygen and glucose deprivation (OGD). MiR-15a in patients and in cells was measured using real-time quantitative polymerase chain reaction (qPCR). The predicted target of miR-15a such as interleukin-6 (IL-6) and insulin-like growth factors-1 (IGF-1) in plasma was detected by enzyme-linked immunosorbent assay (ELISA). The relations between blood miR-15a and stroke severity, stroke etiology, infarct location, stroke prognosis, predicted targets were analyzed by Statistical Product and Service Solutions (SPSS) software respectively. Higher miR-15a levels were found in AIS patients and ischemic cells within 72 h, compared to control (p < 0.05). Receiver Operating Characteristic (ROC) analysis showed that blood miR-15a predicted stroke onset with 98.67% specificity. Blood miR-15a had a negative correlation with National Institutes of Health Stroke Scale (NIHSS) scores (r = -0.3695, p < 0.01). The AIS patients with increased miR-15a levels had a better prognosis. MiR-15a was up-regulated in anterior circulation infarction and small-artery atherosclerosis stroke. Plasma levels of IL-6 and IGF-1 were associated with blood miR-15a (r = -0.6051, 0.3231, p < 0.05, respectively). Blood miR-15a associates with IL-6, IGF-1 and acute cerebral ischemia. It could serve as a potential diagnostic biomarker and therapeutic target for stroke.


Influence of prolonged dalteparin treatment on coagulation, fibrinolysis and inflammation in unstable coronary artery disease.
Unstable coronary artery disease (CAD) is a multi-factorial disease involving thrombotic and inflammatory processes. Short-term low molecular weight (LMW) heparin treatment reduces coagulation activity and clinical events. We investigated the influence of prolonged treatment on coagulation, fibrinolysis and inflammation. Serial blood samples were obtained from 555 of 2,267 unstable CAD patients in the FRISC II study. Patients were treated with the LMW heparin dalteparin 120 IU kg(-1) s.c. twice daily for 5-7 days and randomized to placebo (n=285) or gender and weight-adjusted doses of dalteparin (5,000 or 7,500 IU) twice daily (n=270) for 3 months. Dalteparin persistently depressed coagulation activity with, when compared with placebo, lower median levels of factor VIIa (63 IU mL(-1) vs. 84 IU mL(-1)), prothrombin fragment 1 + 2 (0.86 nmol L(-1) vs. 1.09 nmol L(-1)) and D-dimer (21 microg L(-1) vs. 43 microug L(-1)) after 3 months, all P<0.01. Reactivation of coagulation activity was observed after cessation of both short-term and prolonged dalteparin treatment. Higher levels of tPA/PAI-1 complex (11.7 microg L(-1) vs. 6.5 microg L(-1), P<0.001) and von Willebrand factor (162% vs. 136%, P<0.001) were found during prolonged dalteparin treatment. Interleukin-6, C-reactive protein and fibrinogen levels were unaffected by dalteparin treatment. Three months dalteparin treatment resulted in a sustained and pronounced reduction of coagulation activity, which corresponds to the observed reduction in death and myocardial infarction during the initial 6 weeks in the FRISC II study. The persistently elevated levels of tPA/PAI-1 complex and von Willebrand factor might reflect effects on platelets and endothelial cells and thus contribute to the gradually decreased efficacy by prolonged dalteparin treatment in unstable CAD.


Elucidation of a specific binding site for angiotensin II(3-8), angiotensin IV, in mammalian heart membranes.
Data are presented describing a new angiotensin binding site in rabbit and guinea pig heart, distinct from AT1 and AT2, that demonstrates high specificity and affinity for the hexapeptide fragment angiotensin II(3-8), which will be referred to here as angiotensin IV (AIV). Equilibrium binding in rabbit heart membranes was achieved in 2 hr at 37 degrees C and produced a calculated kinetic KD of .174 +/- .018 nM. Saturation equilibrium binding data for rabbit and guinea pig heart were best fit to a one-site model with Hill coefficients near unity. Guinea pig membranes exhibited a KD = 1.33 +/- .02 nM and a Bmax = 144 +/- 19 fmol/mg protein, and rabbit heart membranes had a KD = 1.70 +/- .50 nM and a Bmax = 731 +/- 163 fmol/mg protein. The binding site showed a high specificity for AIV, although it exhibited low affinity for angiotensin II, angiotensin III, Sar1,Ile8-angiotensin II, DuP 753, CGP42112A and PD123177. A large number of nonangiotensin-related peptides were unable to compete effectively for 125I-AIV binding. Deletions made from the C-terminal end of AIV caused a decrease in affinity: AIV > AII(3-7) >> AII(3-6) >> AII(3-5). Extension of the C-terminal end of AIV corresponding to the amino acids of human angiotensinogen caused little change in affinity. GTP gamma S had no effect on binding, suggesting non-G protein linkage. Binding was widely distributed throughout the heart; it was observed on cardiocytes and blood vessels as well as in the epicardium and the endocardium.


Core Needle Biopsy Guidance Based on Tissue Morphology Assessment with AI-OCT Imaging.
This paper presents a combined optical imaging/artificial intelligence (OI/AI) technique for the real-time analysis of tissue morphology at the tip of the biopsy needle, prior to collecting a biopsy specimen. This is an important clinical problem as up to 40% of collected biopsy cores provide low diagnostic value due to high adipose or necrotic content. Micron-scale-resolution optical coherence tomography (OCT) images can be collected with a minimally invasive needle probe and automatically analyzed using a computer neural network (CNN)-based AI software. The results can be conveyed to the clinician in real time and used to select the biopsy location more adequately. This technology was evaluated on a rabbit model of cancer. OCT images were collected with a hand-held custom-made OCT probe. Annotated OCT images were used as ground truth for AI algorithm training. The overall performance of the AI model was very close to that of the humans performing the same classification tasks. Specifically, tissue segmentation was excellent (~99% accuracy) and provided segmentation that closely mimicked the ground truth provided by the human annotations, while over 84% correlation accuracy was obtained for tumor and non-tumor classification.


Are population cycles recovering?
The dynamics of populations of small mammals of Central Siberia was analyzed. The studies were carried out at the Yenisei ecological station "Mirnoye" of the A.N. Severtsov Institute of Ecology and Evolution, Russian Academy of Sciences. The time series analysis was performed by the wavelet transform using the statistical data processing language R. In the 20th century, the dynamics of the population of the community and some of its constituent species (Sorex araneus; S. caecutiens; S. isodon; S. tundrensis; S. minutus; Craseomys rufocanus; Clethrionomys rutilus; Microtus oeconomus; M. agrestis) were characterized by a 4-year periodicity. The type of dynamics changed to noncyclic by the nineties, but by 2022, four species (S. araneus, S. isodon, C. rutilus, and M. oeconomus) and the community as a whole showed a tendency toward recovery of population cycles. The remaining species were characterized by consistently low numbers with irregular low amplitude fluctuations.


Structure and catalytic mechanism of a cyclic dipeptide prenyltransferase with broad substrate promiscuity.
Fungal indole prenyltransferases (PTs) typically act on specific substrates, and they are able to prenylate their target compounds with remarkably high regio- and stereoselectivity. Similar to several indole PTs characterized to date, the cyclic dipeptide N-prenyltransferase (CdpNPT) is able to prenylate a range of diverse substrates, thus exhibiting an unusually broad substrate promiscuity. To define the structural basis for this promiscuity, we have determined crystal structures of unliganded CdpNPT and of a ternary complex of CdpNPT bound to (S)-benzodiazepinedione and thiolodiphosphate. Analysis of the structures reveals a limited number of specific interactions with (S)-benzodiazepinedione, which projects into a largely hydrophobic surface. This surface can also accommodate other substrates, explaining the ability of the enzyme to prenylate a range of compounds. The location of the bound substrates suggests a likely reaction mechanism for the conversion of (S)-benzodiazepinedione. Structure-guided mutagenesis experiments confirm that, in addition to (S)-benzodiazepinedione, CdpNPT can also act on (R)-benzodiazepinedione and several cyclic dipeptides, albeit with relaxed specificity. Finally, nuclear magnetic resonance spectroscopy demonstrates that CdpNPT is a C-3 reverse PT that catalyzes the formation of C-3β prenylated indolines from diketopiperazines of tryptophan-containing cyclic dipeptides.


Inhibition of NF-kappaB-mediated transcription and induction of apoptosis in human breast cancer cells by epoxypseudoisoeugenol-2-methyl butyrate.
Breast cancer is one of the most prevalent woman cancers. Genomic instability, accumulative mutations, and subsequent changes in intracellular signaling cascades play key roles in the development of human breast cancers. Activation of nuclear factor-kappaB (NF-kappaB) has been implicated in oncogenesis of breast cancers and is known to be associated with resistance to anticancer agents and apoptosis. Blocking NF-kappaB signaling may represent a therapeutic strategy in breast cancer therapy. The objective of this study is to investigate the in vitro effects of epoxypseudoisoeugenol-2-methyl butyrate (EPB), a phenylpropranoid isolated from Pimpinella corymbosa, on the activation of NF-kappaB, cell growth, cell cycle progression and apoptosis in MCF-7 (estrogen-dependent) and BT-549 (estrogen-independent) breast cancer cells. Transcriptional activity of NF-kappaB was measured by cell based reporter gene assay. Cell proliferation was determined by MTT assay. Cell cycle analysis was carried out by flow cytometry and apoptosis was observed by DAPI staining assy. EPB inhibited the NF-kappaB-mediated transcription activity induced by tumor necrosis factor-alpha (TNF-alpha) and phorbol myristate acetate (PMA) in MCF-7 cells. EPB also inhibited constitutive NF-kappaB transcriptional activity in BT-549 cells. EPB inhibited the proliferation of both MCF-7 and BT-549 cells in a concentration- and time-dependent manner. EPB induced cell cycle arrest in G(1)/G(0) phase and apoptosis in both MCF-7 and BT 549 cells. These in vitro results indicated that EPB has a potential for use against both hormone-dependent and hormone-independent breast cancers and its effects seem to be mediated by inhibiting the NF-kappaB activity.


[Anesthetic Management of Three Patients with Chronic Inflammatory Demyelinating Polyradiculoneuropathy].
Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a chronically progressing or relapsing disease caused by immune-mediated peripheral neuropathy. We report the anesthetic management of three CIDP patients who underwent elective orthopedic surgeries. Owing to the risk of neuraxial anesthetics triggering demyelination, general anesthesia was selected to avoid epidural or spinal anesthesia or other neuraxial blockade. It was also judged prudent to avoid prolonged perioperative immobilization, which might compress vulnerable peripheral nerves. For Patient 1, general anesthesia was induced with propofol, remifentanil, and sevoflurane, and was maintained with sevoflurane and remifentanil. For Patients 2 and 3, general anesthesia was induced and maintained with propofol and remifentanil. For tracheal intubation, under careful monitoring with peripheral nerve stimulators, minimal doses of rocuronium (0.6-0.7 mg x kg(-1)) were administered. When sugammadex was administered to reverse the effect of rocuronium, all patients rapidly regained muscular strength. Postoperative courses were satisfactory without sequelae.


Multiple dens evaginatus: diagnosis, management, and complications: case report.
Dens evaginatus is a disturbance in tooth formation that appears clinically as an accessory occlusal tuberculated cusp composed of enamel and dentin, usually enclosing pulp tissue. The tubercle often fractures or is worn away, with subsequent pulp exposure leading to pulpal inflammation, necrosis, and periapical inflammation. When this happens to an immature tooth, diagnosis may be complicated by the similarity in radiographic appearance of the periapical lesion and the dental follicle. The management of such teeth may be complicated because of their immaturity. A case report of multiple abraded dens evaginatus with pulp necrosis is presented that illustrates 1) the difficulty of diagnosing otherwise apparently healthy teeth associated with periapical lesions and sinus tracts, and 2) their management and treatment complications including recurrent infections and root fractures.


[Diet, physical activity and other cardiometabolic risk factors in the immigrant population in Spain: a review].
The "epidemiological transition" of the immigrant population in the world, and particularly in Spain, is insufficiently understood, due to the multi-causality of the morbi-mortality and the limitations of the information about the lifestyles of immigrants. Thus, the objective of this work was to know behavioural and biological risk factors of cardiometabolic disease in the immigrant population in Spain. Scoping review of the literature published in the period 1998-2012. We selected articles in Spanish or English, with study participants from Latin-America, Africa, Asia and Eastern Europe or who comply with the immigrant definition from the International Organization for Migration. Bibliographic search was performed in Medline and MEDES. We identified 117 articles, and 16 were included in this review. Thirteen studies were published since 2009. In total, 15 articles corresponded to cross-sectional studies and one to a non-randomized trial; five were population-based, seven were conducted within a clinical setting, and four in mixed settings (population and clinic). In nine studies the sample was less than 500 participants, and 15 studies were conducted at the local or regional level. Thirteen articles focused on food habits and nutritional status, but showed substantial heterogeneity in objectives and results. Some studies found that the frequency of obesity was higher in the immigrant than in the Spanish native population, that the length of residence in Spain was not associated with obesity, and that the immigrants consumed less tobacco and alcohol but did less physical activity than the people born in Spain. The scientific production on the lifestyle and cardiometabolic risk factors among the immigrants in Spain is quite recent and scarce. Thus, it does not allow for characterizing the risk profile of this population.


Advances in CT and MR Technology.
This article will review recent advances in computed tomography (CT) and magnetic resonance (MR) hardware and software techniques that have dramatically changed the use of CT and MR angiography. For CT angiography, technology has increased the speed of acquisition, reduced the radiation dose necessary to diagnose disease, and simplified the ability to characterize disease. Similarly, advances in MR angiography have focused on safer techniques that do not require the use of intravenous contrast agents, increased the speed of acquisition, and improved spatial resolution. In addition, new MR angiography methods have expanded the use of MR angiography beyond purely anatomical information toward quantitative hemodynamic analyses.


Ternary MgTiX-alloys: a promising route towards low-temperature, high-capacity, hydrogen-storage materials.
In the search for hydrogen-storage materials with a high gravimetric capacity, Mg(y)Ti((1-y)) alloys, which exhibit excellent kinetic properties, form the basis for more advanced compounds. The plateau pressure of the Mg--Ti--H system is very low (approximately 10(-6) bar at room temperature). A way to increase this pressure is by destabilizing the metal hydride. The foremost effect of incorporating an additional element in the binary Mg--Ti system is, therefore, to decrease the stability of the metal hydride. A model to calculate the effect on the thermodynamic stability of alloying metals was developed by Miedema and co-workers. Adopting this model offers the possibility to select promising elements beforehand. Thin films consisting of Mg and Ti with Al or Si were prepared by means of e-beam deposition. The electrochemical galvanostatic intermittent titration technique was used to obtain pressure-composition isotherms for these ternary materials and these isotherms reveal a reversible hydrogen-storage capacity of more than 6 wt. %. In line with the calculations, substitution of Mg and Ti by Al or Si indeed shifts the plateau pressure of a significant part of the isotherms to higher pressures, while remaining at room temperature. It has been proven that, by controlling the chemistry of the metal alloy, the thermodynamic properties of Mg-based hydrides can be regulated over a wide range. Hence, the possibility to increase the partial hydrogen pressure, while maintaining a high gravimetric capacity creates promising opportunities in the field of hydrogen-storage materials, which are essential for the future of the hydrogen economy.


Effect of embryonic treatment with oestradiol benzoate on reproductive morphology, ovulation and oviposition and plasma LH concentrations in female quail (Coturnix coturnix japonica).
Quail eggs were injected on Day 10 of incubation with 0, 5, 10, 20 or 40 micrograms oestradiol benzoate. Females hatching from these eggs were reared on a 16L: 8D photoperiod and egg laying was recorded. Blood samples were taken at 37, 40, 43, 46, 49, 52, 55, 58 or 61 days of age and LH concentrations were measured by a double-antibody radioimmunoassay. Birds were killed at 61 days of age; ovaries and oviducts were weighed and examined. Egg laying was greatly reduced by oestradiol benzoate treatment, but for birds that did lay, age at first oviposition was normal. LH levels were not affected by oestradiol benzoate treatment, and were highest at 40 and 49 days of age. Oestradiol benzoate had no effect on ovarian weight, number of follicles with diameter greater than 1 cm, or number of post-ovulatory follicles. Oestradiol benzoate had a dose-related effect on the likelihood that females would have two oviducts, and for those females that had retained the right oviduct, the left oviduct was smaller than normal. Oestradiol benzoate-treated females were more likely to have ovulated yolks in the body cavity. Embryonic treatment with oestradiol benzoate therefore appears to inhibit egg laying by causing oviduct abnormalities, rather than by (as happens in mammals) inhibiting ovulation.


A study on professional stress, depression and alcohol use among Indian IT professionals.
Stress has touched almost all professions posing threat to mental and physical health. India being the Information Technology (IT) hub with lakhs involved as IT Professionals, there is a need to assess prevalence of professional stress, depression and problem alcohol use and understand their association. (1) To screen for the prevalence of professional stress, risk for depression and harmful alcohol use among software engineers. (2) To study the association between professional stress, risk for depression and harmful alcohol use. This is a cross-sectional online study conducted using screeing questionnaires like professional life stress scale, centre for epidemiological studies depression scale and alcohol use disorders identification test. This study was conducted specifically on professionals working in an IT firm with the designation of a software engineer. A total of 129 subjects participated in the study. 51.2% of the study sample was found to be professionally stressed at the time of the interview. 43.4% of the study population were found to be at risk for developing depression. 68.2% of those who were professionally stressed were at risk for developing depression compared with only 17.5% of those who were not professionally stressed. Odds ratio revealed that subjects who were professionally stressed had 10 times higher risk for developing depression compared to those who were not professionally stressed. Subjects who were professionally stressed had 5.9 times higher prevalence of harmful alcohol use compared to those who were not professionally stressed. Subjects who were at risk for developing depression had 4.1 times higher prevalence of harmful alcohol use compared with those who were not at risk for developing depression. Such higher rates of professional stress, risk for developing depression and harmful alcohol use among software engineers could hinder the progress of IT development and also significantly increase the incidence of psychiatric disorders.


Discovery of τ Neutrino Appearance in the CNGS Neutrino Beam with the OPERA Experiment.
The OPERA experiment was designed to search for ν_{μ}→ν_{τ} oscillations in appearance mode, i.e., by detecting the τ leptons produced in charged current ν_{τ} interactions. The experiment took data from 2008 to 2012 in the CERN Neutrinos to Gran Sasso beam. The observation of the ν_{μ}→ν_{τ} appearance, achieved with four candidate events in a subsample of the data, was previously reported. In this Letter, a fifth ν_{τ} candidate event, found in an enlarged data sample, is described. Together with a further reduction of the expected background, the candidate events detected so far allow us to assess the discovery of ν_{μ}→ν_{τ} oscillations in appearance mode with a significance larger than 5σ.


Barakat syndrome.
Barakat syndrome, also known as HDR syndrome, is a clinically heterogenous, autosomal dominant rare genetic disease, which frequency is unknown. It is primarily caused by deletion of chromosome 10p14 or mutation of GATA3 gene, located on chromosome 10. Although this syndrome is phenotypically defined by its triad of HDR: hypoparathyroidism (H), deafness (D), renal disease (R), the literature identifies cases with different components, consisting of HD, DR, HR (1). The syndrome was first described by Amin J. Barakat et al. in 1977 in siblings with hypocalcemia and proteinuria (2). So far, about 180 cases have been reported in the worldwide medical literature (3). In this report we present our own case report of patient with Barakat syndrome with hypoparathyrodism, unilateral deafness and renal impairment.


Linoleate and fatty acid compositions in the serum lipids of Japanese patients with multiple sclerosis.
Serum fatty acid compositions were determined in 21 Japanese patients with multiple sclerosis and 14 neurological controls. No statistical difference was found either for linoleic acid or for arachidonic acid between the 2 groups. It may be that neither serum linoleic acid nor arachidonic acid is inevitably associated with the pathogenesis of multiple sclerosis.


Bacterial strain for bast fiber crops degumming and its bio-degumming technique.
The research and development of bio-degumming technology is under a slow progress due to the shortage of proper efficient bacterial strains and processes. A degumming bacterial strain-Pectobacterium wasabiae (PW)-with broad-spectrum degumming abilities was screened out in this study. After the fermentation for 12 h, the residual gum contents of kenaf bast, ramie bast, hemp bast, flax bast, and Apocynum venetum bast were all lower than 15%. This bacterial strain could realize the simultaneous extracellular secretion of pectinase, mannase, and xylanase with the maximum enzyme activity levels of 130.25, 157.58, and 115.24 U/mL, respectively. The optimal degumming conditions of this bacterial strain were as follows: degumming time of 12 h, bath ratio of 1:10, temperature of 33 °C, and inoculum size of 2%. After the bio-degumming through this bacterial strain, the COD in wastewater was below 4000 mg/L, which was over 60% lower than that in boiling-off wastewater generated by chemical degumming. This technology achieves higher efficiency, higher quality, and lower pollution.


Platelet activation: a promoter for psoriasis and its comorbidity, cardiovascular disease.
Psoriasis is a chronic inflammatory skin disease with a prevalence of 0.14% to 1.99%. The underlying pathology is mainly driven by the abnormal immune responses including activation of Th1, Th17, Th22 cells and secretion of cytokines. Patients with psoriasis are more likely to develop cardiovascular disease (CVD) which has been well recognized as a comorbidity of psoriasis. As mediators of hemostasis and thromboinflammation, platelets play an important part in CVD. However, less is known about their pathophysiological contribution to psoriasis and psoriasis-associated CVD. A comprehensive understanding of the role of platelet activation in psoriasis might pave the path for more accurate prediction of cardiovascular (CV) risk and provide new strategies for psoriasis management, which alleviates the increased CV burden associated with psoriasis. Here we review the available evidence about the biomarkers and mechanisms of platelet activation in psoriasis and the role of platelet activation in intriguing the common comorbidity, CVD. We further discussed the implications and efficacy of antiplatelet therapies in the treatment of psoriasis and prevention of psoriasis-associated CVD.


[Stage T1 tumor of the bladder. From research to prognosis].
The reserved prognosis of stage T1 (A) bladder tumours is emphasised in relation to a series of 41 cases: 95% of tumours recurred, one third of these recurrent tumours posed a therapeutic problem because of their diffuse nature (15%) or tumour progression (24%). The risk of allowing a limited tumour to progress towards and extensively infiltrating carcinoma justifies the search for a prognostic factor allowing the early recognition of the more aggressive lesions. At the present time, no one prognostic element can indicate with certainty the course of the T1 tumour. All of the data obtained from detailed histological examination of the tumour and the adjacent urothelium and from the early course of the tumour allow a better evaluation of the prognosis. The search for surface antigens (ABO) and, more recently, chromosome analysis and study of the DNA content of the tumour by flow cytometry, may complete this prognostic evaluation.


HIV neuropathogenesis: a tight rope walk of innate immunity.
During the course of HIV-1 disease, virus neuroinvasion occurs as an early event, within weeks following infection. Intriguingly, subsequent central nervous system (CNS) complications manifest only decades after the initial virus exposure. Although CNS is commonly regarded as an immune-privileged site, emerging evidence indicates that innate immunity elicited by the CNS glial cells is a critical determinant for the establishment of protective immunity. Sustained expression of these protective immune responses, however, can be a double-edged sword. As protective immune mediators, cytokines have the ability to function in networks and co-operate with other host/viral mediators to tip the balance from a protective to toxic state in the CNS. Herein, we present an overview of some of the essential elements of the cerebral innate immunity in HIV neuropathogenesis including the key immune cell types of the CNS with their respective soluble immune mediators: (1) cooperative interaction of IFN-γ with the host/virus factor (platelet-derived host factor (PDGF)/viral Tat) in the induction of neurotoxic chemokine CXCL10 by macrophages, (2) response of astrocytes to viral infection, and (3) protective role of PDGF and MCP-1 in neuronal survival against HIV Tat toxicity. These components of the cerebral innate immunity do not act separately from each other but form a functional immunity network. The ultimate outcome of HIV infection in the CNS will thus be dependent on the regulation of the net balance of cell-specific protective versus detrimental responses.


Effects of low levels of herbicides on prairie species of the Willamette Valley, Oregon.
The relative sensitivity of 17 noncrop plant species from Oregon's Willamette Valley was determined in response to glyphosate, tribenuron methyl (tribenuron), and fluazifop-p-butyl (fluazifop) herbicides. For glyphosate, Elymus trachycaulus, Festuca arundinacea, Madia elegans, Potentilla gracilis, and Ranunculus occidentalis were the most sensitive species, based on a concentration calculated to reduce shoot dry weight by 25% (IC25 values) of 0.02 to 0.04 × a field application rate of 1112 g active ingredient (a.i.) per hectare. Clarkia amoena and Lupinus albicaulis were the most tolerant to glyphosate, with IC25 values near the field application rate. Clarkia amoena, Prunella vulgaris, and R. occidentalis were the most sensitive to tribenuron, with IC25 values of 0.001 to 0.004 × a field application rate of 8.7 g a.i. ha(-1) for shoot dry weight. Five grass species were tolerant to tribenuron with no significant IC25 values. For fluazifop, 2 native grasses, E. trachycaulus and Danthonia californica, were the most sensitive species, with IC25 values of 0.007 and 0.010 × a field application rate of 210 g a.i. ha(-1) , respectively, for shoot dry weight, while a native grass, Festuca roemeri, and nearly all forbs showed little or no response. These results also indicated that the 3 introduced species used in the present study may be controlled with 1 of the tested herbicides: glyphosate (F. arundinacea), tribenuron (Leucanthemum vulgare), and fluazifop (Cynosurus echinatus).


Immune reconstitution inflammatory syndrome in acquired immunodeficiency syndrome.
A 33-year-old male presented with a history of fever and cough and was diagnosed to have pulmonary tuberculosis and acquired immunodeficiency syndrome (AIDS). He was started on antituberculosis therapy (ATT) followed by highly active anti-retroviral treatment (HAART) after one week. He developed an immune reconstitution inflammatory syndrome (IRIS) leading to an exacerbation of the tuberculosis disease. After HAART was stopped his condition improved dramatically.


The amyloid precursor protein copper binding domain histidine residues 149 and 151 mediate APP stability and metabolism.
One of the key pathological hallmarks of Alzheimer disease (AD) is the accumulation of the APP-derived amyloid β peptide (Aβ) in the brain. Altered copper homeostasis has also been reported in AD patients and is thought to increase oxidative stress and to contribute to toxic Aβ accumulation and regulate APP metabolism. The potential involvement of the N-terminal APP copper binding domain (CuBD) in these events has not been investigated. Based on the tertiary structure of the APP CuBD, we examined the histidine residues of the copper binding site (His(147), His(149), and His(151)). We report that histidines 149 and 151 are crucial for CuBD stability and APP metabolism. Co-mutation of the APP CuBD His(149) and His(151) to asparagine decreased APP proteolytic processing, impaired APP endoplasmic reticulum-to-Golgi trafficking, and promoted aberrant APP oligomerization in HEK293 cells. Expression of the triple H147N/H149N/H151N-APP mutant led to up-regulation of the unfolded protein response. Using recombinant protein encompassing the APP CuBD, we found that insertion of asparagines at positions 149 and 151 altered the secondary structure of the domain. This study identifies two APP CuBD residues that are crucial for APP metabolism and suggests an additional role of this domain in APP folding and stability besides its previously identified copper binding activity. These findings are of major significance for the design of novel AD therapeutic drugs targeting this APP domain.


The epidemiology of hospitalized influenza in children, a two year population-based study in the People's Republic of China.
The epidemiology and disease burden of annual influenza in children in mainland People's Republic of China have not been reported in detail. To understand the incidence and epidemiology of laboratory-proven influenza hospitalization in children in China, a review of available laboratory and hospital admission data was undertaken. We conducted a retrospective population-based study in Suzhou and the surrounding area of Jiangsu province, China for hospitalized cases of respiratory illness at Suzhou Children's Hospital. Cases of pneumonia or respiratory illness were identified from hospital computer data bases. Routine virological testing by fluorescent monoclonal antibody assay of all hospitalized children identified influenza and other viruses. We calculated incidence rates using census population denominators. Of 7,789 specimens obtained during 2007 and 2008, 85 were positive for influenza A and 25 for influenza B. There were 282 specimens with parainfluenza virus and 1392 with RSV. Influenza occurred throughout the year, with peaks in the winter, and in August/September. Overall estimated annual incidence of laboratory-proven influenza hospitalization was 23-27/100,000 children 0-4 years old, and 60/100,000 in infants 0-6 months, with an average hospitalization of 9 days. Influenza disease in young children in this part of China is a relatively common cause of hospitalization, and occurs throughout the year. The use of influenza vaccine in Chinese children has the potential to reduce the effect of influenza in the children, as well as in their communities. Studies are needed to further assess the burden of influenza, and to develop and refine effective strategies of immunization of young children in China.


Two-Dimensional Materials for Halide Perovskite-Based Optoelectronic Devices.
Halide perovskites have high light absorption coefficients, long charge carrier diffusion lengths, intense photoluminescence, and slow rates of non-radiative charge recombination. Thus, they are attractive photoactive materials for developing high-performance optoelectronic devices. These devices are also cheap and easy to be fabricated. To realize the optimal performances of halide perovskite-based optoelectronic devices (HPODs), perovskite photoactive layers should work effectively with other functional materials such as electrodes, interfacial layers and encapsulating films. Conventional two-dimensional (2D) materials are promising candidates for this purpose because of their unique structures and/or interesting optoelectronic properties. Here, we comprehensively summarize the recent advancements in the applications of conventional 2D materials for halide perovskite-based photodetectors, solar cells and light-emitting diodes. The examples of these 2D materials are graphene and its derivatives, mono- and few-layer transition metal dichalcogenides (TMDs), graphdiyne and metal nanosheets, etc. The research related to 2D nanostructured perovskites and 2D Ruddlesden-Popper perovskites as efficient and stable photoactive layers is also outlined. The syntheses, functions and working mechanisms of relevant 2D materials are introduced, and the challenges to achieving practical applications of HPODs using 2D materials are also discussed.


Treatment of chronic bacterial prostatitis.
The pathogenesis, clinical signs and symptoms, diagnosis and treatment of chronic bacterial prostatitis (CBP) are reviewed. The most common organism associated with CBP is Escherichia coli, although infections with Klebsiella, Enterobacter, Proteus, Pseudomonas, and enterococci have also been documented. The only symptoms of CBP may be those of an acute urinary-tract infection. The use of simultaneous quantitative urine cultures represents the most accurate method for diagnosing CBP. The use of trimethoprim-sulfamethoxazole, the current drug of choice for CBP, is based on results in animals showing good penetration of trimethoprim into acidic prostatic fluid and the knowledge that normal human prostatic fluid is acidic. Studies in patients with CBP, who have alkaline prostatic fluid, have demonstrated poor penetration of trimethoprim into prostatic fluid, which may explain the cure rate of about 40% seen with trimethoprim-sulfamethoxazole. A few patients have been treated successfully with kanamycin and streptomycin, but these drugs must be given by injection. Carbenicillin indanyl sodium has been associated with cure rates of almost 70% in a small number of studies. Both doxycycline and minocycline have been used to treat CBP, but inadequate urine-culture data make these studies difficult to evaluate. Erythromycin produced a cure rate of 88% in one study in patients who received 500 mg (as the stearate salt) four times daily for 14 days. Local injection of antibiotics into the prostate has been reported to be effective in a few cases. Although controlled comparative trials with trimethoprim-sulfamethoxazole are needed, carbenicillin indanyl sodium and erythromycin appear to be the drugs of choice for treating CBP; trimethoprim-sulfamethoxazole should be reserved for patients with CBP unable to tolerate or unresponsive to therapy with these agents.


Characteristic reaction of the mouse adrenal cortical cell to osmium impregnation.
The fine structural localization of osmium impregnation in the mouse adrenal cortical cell was studied using the electron microscope. After osmication for 40--48 hrs all kinds of adrenal cortical cells of the mouse exhibited a selective localization of osmium impregnation in almost all the cisternae of the smooth endoplasmic reticulum in addition to 1--2 or 3 stacks and vesicles of cis-side of the Golgi apparatus. This fact might be implicated with the steroid hormones which may be localized in the cisternae of smooth endoplasmic reticulum. Moreover, the cisternae of the nuclear envelope, and of the characteristic lamellar body closely related to the smooth endoplasmic reticulum, were also stained with OsO4.


The sleep, subjective fatigue, and sustained attention of commercial airline pilots during an international pattern.
International commercial airline pilots may experience heightened fatigue due to irregular sleep schedules, long duty days, night flying, and multiple time zone changes. Importantly, current commercial airline flight and duty time regulations are based on work/rest factors and not sleep/wake factors. Consequently, the primary aim of the current study was to investigate pilots' amount of sleep, subjective fatigue, and sustained attention before and after international flights. A secondary aim was to determine whether prior sleep and/or duty history predicted pilots' subjective fatigue and sustained attention during the international flights. Nineteen pilots (ten captains, nine first officers; mean age: 47.42+/-7.52 years) participated. Pilots wore wrist activity monitors and completed sleep and duty diaries during a return pattern from Australia to Europe via Asia. The pattern included four flights: Australia-Asia, Asia-Europe, Europe-Asia, and Asia-Australia. Before and after each flight, pilots completed a 5 min PalmPilot-based psychomotor vigilance task (PVT) and self-rated their level of fatigue using the Samn-Perelli Fatigue Checklist. Separate repeated-measures ANOVAs were used to determine the impact of stage of flight and flight sector on the pilots' sleep in the prior 24 h, self-rated fatigue, and PVT mean response speed. Linear mixed model regression analyses were conducted to examine the impact of sleep in the prior 24 h, prior wake, duty length, and flight sector on pilots' self-rated fatigue and sustained attention before and after the international flights. A significant main effect of stage of flight was found for sleep in the prior 24 h, self-rated fatigue, and mean response speed (all p < 0.05). In addition, a significant main effect of flight sector on self-rated fatigue was found (p < .01). The interaction between flight sector and stage of flight was significant for sleep in the prior 24 h and self-rated fatigue (both p < .05). Linear mixed model analyses indicated that sleep in the prior 24 h was a significant predictor of self-rated fatigue and mean response speed after the international flight sectors. Flight sector was also a significant predictor of self-rated fatigue. These findings highlight the importance of sleep and fatigue countermeasures during international patterns. Furthermore, in order to minimize the risk of fatigue, the sleep obtained by pilots should be taken into account in the development of flight and duty time regulations.


HMGA2 rearrangement in a case of vulvar aggressive angiomyxoma.
The histogenesis of aggressive angiomyxoma, an uncommon mesenchymal neoplasm of the vulvar, pelvic, and perineal soft tissues, is poorly understood, although the neoplastic cells exhibit a myofibroblastic phenotype. Cytogenetic studies of aggressive angiomyxoma are scarce; however, a nonrandom involvement of the 12q15 region where the high mobility group (HMG) protein HMGA2, an architectural transcription factor expressed primarily during embryogenesis, is located has been suggested. HMGA2 involvement has also been described in a variety of benign gynecologic mesenchymal neoplasms. We report an additional case of HMGA2 rearrangement in vulvar aggressive angiomyxoma, using fluorescence in situ hybridization.


Genetic parameters for performance and carcass traits in a paternal 1 lineage of broiler.
The objective of this study was to estimate variance components for performance and carcass traits in a paternal broiler line. The (co)variance components were estimated by the restricted maximum likelihood method applied to the animal model, including the fixed effect of group (sex and hatch) and additive genetic and residual as random effects. Estimated heritability for performance traits ranged from 0.09 to 0.42. The genetic correlations between traits ranged from -0.50 to 0.97. The heritability estimates of feed intake, weight gain, and feed conversion from 35 to 41 days of age were of low magnitude. The genetic correlations among them were favorable to genetic selection. These results suggest that moderate genetic gain can be obtained to the feed intake and weight gain when the selection criterion is the body weight and prime cuts traits. The feed conversion that had low heritability estimation and low genetic correlation with the body weight and prime cut traits needs to pay greater attention due to the economic importance in the high-meat production lineage breeding programs.


The membrane of the mammalian spermatozoa: much more than an inert envelope.
Sperm plasma membrane is a very important structure that functions to protect sperm against extracellular injuries and to respond to physiological challenges. It plays a crucial role during sperm capacitation, in sperm-egg interaction and, finally, in fertilization. Concerning sperm technology, possibly the most important factors causing damage in mammalian spermatozoa membranes are initiated by the osmotic stress generated by dehydration of the cells during freezing and thawing. These changes are rapidly derived to the plasma and organelle membranes that gradually experiment loss of membrane architecture, causing unbalanced production of reactive oxygen species and increased lipid peroxidation. Other procedures such as sperm sorting or liquid storage of sperm also induce harmful changes in the integrity of the membrane. The specific composition of lipids of the sperm membranes may provide clues for understanding the mechanisms behind the differences found in the response to stress in different species. In the present review, we deal with the composition, architecture and organization of the sperm plasma membrane, emphasizing the factors that can affect membrane integrity. The intracellular signalling pathways related with membrane reorganization during capacitation and acrosome reaction are also reviewed.


School composition, school culture and socioeconomic inequalities in young people's health: Multi-level analysis of the Health Behaviour in School-aged Children (HBSC) survey in Wales.
Health inequalities emerge during childhood and youth, before widening in adulthood. Theorising, testing and interrupting the mechanisms through which inequalities are perpetuated and sustained is vital. Schools are viewed as settings through which inequality in young people's health may be addressed, but few studies examine the social processes via which institutional structures reproduce or mitigate health inequalities. Informed by Markham and Aveyard's theory of human functioning and school organisation, including their concept of institutional boundaries, critical theories of marketisation and the concept of micro-political practices within schools, this paper presents analysis of student survey data (N = 9055) from 82 secondary schools in Wales. It examines the role of socioeconomic composition, social relationships at school and institutional priorities in mitigating or perpetuating health inequality. It finds that affluent schools were most unequal in terms of student health behaviours and subjective wellbeing. In relation to health behaviours, students from affluent families accrue a disproportionate benefit. For wellbeing, students from poorer families reported lower subjective wellbeing where attending more affluent schools. Student-staff relationships appear to be a key mechanism underpinning these effects: poor relationships with staff were predicted by a pupil's position within schools' socioeconomic hierarchy and associated with worse health outcomes. That is, students from the poorest families reported better relationships with teachers where attending less affluent schools. Universal approaches engaging with these social processes are needed to reduce health inequalities.


Comparison of central SBP in children estimated from a brachial cuff alone, brachial cuff-calibrated applanation radial tonometry and brachial cuff-calibrated carotid wall-tracking.
We compared the agreement between different techniques to estimate central SBP (cSBP) in children and the relative impact of different methods of measuring peripheral blood pressure (BP). A total of 135 children, aged 12.9 ± 3.0 years including 67 boys, 85 with chronic kidney disease were studied. We measured cSBP using radiofrequency ultrasound carotid wall-tracking (Esaote ART.LAB system, a previously validated reference method), transformation of the radial artery pressure waveform obtained by tonometry (SphygmoCor) and a cuff-based system (cBP301; Centron Diagnostics) during a single visit. Carotid and radial tonometric-derived values were calibrated from mean and diastolic values of brachial BP obtained by aneroid sphygmomanometer. Brachial cuff only values were calibrated from the same aneroid sphygmomanometer values and from oscillometric values obtained from the brachial cuff. cSBP values estimated from radial tonometry were closely correlated with those obtained from the carotid (r = 0.959, mean difference -0.61 ± 3.5 mmHg). cSBP values estimated by the brachial cuff only method agreed reasonably well with those obtained from the carotid (r = 0.847, mean difference 5 ± 7.4 mmHg) when calibrated by the same method but when calibrated by oscillometric values from the brachial cuff, agreement was less good (r = 0.659, mean difference 8.7 ± 11.4 mmHg). Radial tonometry with a radial-to-central transfer function can be used to estimate cSBP in children with acceptable accuracy when compared with the invasively validated carotid reference method. All methods are subject to errors introduced by calibration from peripheral BP.


Pediatric Caries Risk Assessment as a Predictor of Caries Outcomes.
To determine cumulative dental treatment experience in a retrospective clinical cohort, according to baseline caries risk assessment (CRA) information. Evaluated were electronic records from a university pediatric dental clinic (2009 to 2014) of new, six- to 72- month-old patients who were not treated under sedation or general anesthesia (<small>N</small> equals 750). The mean number of teeth restored or extracted (two-year total and omitting the first 190 days post-baseline to discount initial treatment needs) was compared by baseline CRA category and CRA items (caries risk indicators, protective items, and clinical disease indicators). The CRA category was associated with mean treated teeth over two years (low equals 0.53, moderate equals 1.02, high/extreme equals 4.47) and post 190 days (low equals 0.51, moderate equals 0.89, high/extreme equals 2.11). Any treatment probability was greatest for high/extreme-risk children but not statistically significantly different between low- and moderate-risk. Age-standardized means were greater for all individual baseline clinical indicators and most risk indicators, but lower for most protective items (not statistically significantly for all items). Clinical indicators were the strongest outcome correlates. In this population, baseline risk information was associated with clinical outcomes. CRA can help identify patients needing more intensive caries prevention.


Wolf-hound vs. sled-dog: neurolinguistic evidence for semantic decomposition in the recognition of German noun-noun compounds.
Animacy is an intrinsic semantic property of words referring to living things. A long line of evidence shows that words with animate referents require lower processing costs during word recognition than words with inanimate referents, leading among others to a decreased N400 amplitude in reaction to animate relative to inanimate objects. In the current study, we use this animacy effect to provide evidence for access to the semantic properties of constituents in German noun-noun compounds. While morphological decomposition of noun-noun compounds is well-researched and illustrated by the robust influence of lexical constituent properties like constituent length and frequency, findings for semantic decomposition are less clear in the current literature. By manipulating the animacy of compound modifiers and heads, we are able to manipulate the relative ease of lexical access strictly due to intrinsic semantic properties of the constituents. Our results show additive effects of constituent animacy, with a higher number of animate constituents leading to gradually attenuated N400 amplitudes. We discuss the implications of our findings for current models of complex word recognition, as well as stimulus construction practices in psycho-and neurolinguistic research.


Fibrin gel as a scaffold for photoreceptor cells differentiation from conjunctiva mesenchymal stem cells in retina tissue engineering.
Stem cell-based therapies are attraction approaches for regenerative medicine for treating retinal diseases. One of the limitations in cell therapy is cell death following post-injection whit preventing functional integration with retinal tissue. Fibrin gel, a bio-polymeric material with excellent biocompatibility, provides numerous advantages as a tissue engineering scaffold and a stem cell carrier. Therefore, current research is focusing on developing fibrin hydrogel scaffolds to protect stem cells during delivery and to stimulate endogenous regeneration through interactions of transplanted stem cells and retinal tissue. In this study fibrin gel was used as hydrogel scaffold for immobilization of cells. The structural characteristics of fibrin gel scaffold were examined with SEM. Rheological properties of fibrin gel were measured by rheometer and biodegradation rate of fibrin were assayed for 2 weeks. After isolation of stem cells CJMSCs, the cells were differentiated into photoreceptor-like cells by exposing with taurin for 14 days in tissue culture plate (TCP group) and fibrin hydrogel (3 D group). The attachment of cells was analyzed with SEM and MTT. The expression of rhodopsin, PKC, CRX, recoverin, peripherin, nestin and RPE65 as photoreceptor-like cell markers was evaluated by immunocytochemistry and quantitative real-time PCR (RT-PCR) in TCP and 3 D groups. The results of SEM analysis showed CJMSCs were well attached in fibrin gels and there were good integrity between cells and scaffold. The elastic modulus and constant degradation of the gel contributes to the growth and proliferation of cells. There was no toxicity effect of fibrin hydrogel on cells and the viability of cultured cells was higher in 3 D fibrin gels in comparison with TCP groups. After 2 weeks, the expression of rhodopsin, PKC, CRX, peripherin, recoverin, nestin and RPE65 as special markers of photoreceptor cells were detected by Real time PCR and immunofluorescence that these expressions in 3 D groups were higher than TCP groups. In conclusion, our findings showed that application of readily available sources of adult stem cells like human conjunctiva stem cells encapsulated in fibrin gel could be interesting strategy to enhance photoreceptor progenitor cell numbers for repair and regeneration of retina disease such as photoreceptor injury.


Tuning Sugar-Based Chiral and Flower-Like Microparticles.
Unique supermolecular structures as chiral and flower-like microparticles and the precise tuning of the morphologies hold immense promise for a variety of applications. Examples of such structures deriving from monosaccharides are still rare, and a general understanding is also lacking. Herein, it is shown that chiral, flower-like, or solid microparticles can be tuned by only using monosaccharide esters without external stimuli. Chiral "left-handed" (counterclockwise) and "right-handed" (clockwise) morphologies can be induced by d- and l-glucose stearoyl esters. In comparison, other monosaccharides, i.e., galactose, mannose, and xylose, cannot formed chiral particles and generated diverse other morphologies of the supermolecular microparticles based on their distinct molecular configurations. Due to the numbers of side chains and the bond orientations, microparticles with solid and porous flower-like morphologies can be obtained. While glucose and xylose esters only lead to solid microparticles, mannose and galactose generate porous flower-like particles. These findings suggest a general method to design and control the superstructures by using monosaccharide backbones with diverse molecular configurations.


Inflammatory breast cancer: advances in therapy.
Inflammatory breast cancer is the most aggressive breast neoplasm and one of the most ominous solid tumors. Because of distinct clinical characteristics, diagnosis can usually be made on clinical grounds. Biopsy including the overlying skin may demonstrate dermal lymphatic invasion, although the absence of dermal lymphatic invasions should not deter aggressive therapy. Surgery or irradiation alone has little effect on the natural history of this disease since lymphatic invasion and distant metastases are often present at presentation. Inflammatory breast cancer should be considered a systemic disease. Accordingly, aggressive combined modality therapy including multi-drug chemotherapy, surgery, and irradiation have prolonged disease-free survival and overall survival.


Relationship between angiogenesis and inflammation in experimental arthritis.
Background. Angiogenesis is involved in rheumatoid arthritis (RA) leading to leucocyte recruitment and inflammation in the synovium. Furthermore, synovial inflammation itself further potentiates endothelial proliferation and angiogenesis. In this study, we aimed at evaluating the reciprocical relationship between synovial inflammation and angiogenesis in a RA model, namely collagen-induced arthritis (CIA). Methods. CIA was induced by immunization of DBA/1 mice with collagen type II in adjuvant. Endothelial cells were detected using a GSL-1 lectin-specific immunohistochemical staining on knee joint sections. Angiogenesis, clinical scores and histological signs of arthritis were evaluated from the induction of CIA until the end of the experiment. Angiogenesis was quantified by counting both the isolated endothelial cells and vessels stained on each section. To evaluate the effect of increased angiogenesis on CIA, VEGF gene transfer was performed using an adeno-associated virus encoding VEGF (AAV-VEGF), by intra-muscular or intra-articular injection in mice with CIA. Results. We showed an increase in synovial angiogenesis from day 6 to day 55 after CIA induction, and, moreover, joint vascularization and clinical scores of arthritis were correlated (p < 0.0001, r = 0.61). Vascularization and histological scores were also correlated (p = 0.0006, r = 0.51). Systemic VEGF overexpression in mice with CIA was followed by an aggravation of arthritis as compared to AAV-lacZ control group (p < 0.0001). In contrast, there was no difference in clinical scores between control mice and mice injected within the knee with AAV-VEGF, even if joint vascularization was higher in this group than in all other groups (p = 0,05 versus non-injected group). Intra-articular AAV-VEGF injections induced more severe signs of histological inflammation and bone destruction than AAV-Lac Z or no injection. Conclusion. Angiogenesis and joint inflammation evolve in parallel during collagen-induced arthritis. Furthermore, this work shows that exogenous VEGF can aggravate CIA. It is direct evidence that the increase in joint vascularization leads to an exacerbation of arthritis. Taken together, these results emphasize the role of angiogenesis in inflammatory arthritis. It also suggests an early involvement of angiogenesis in joint inflammation.