Pushing forward the limits of EVAR: new therapeutic solutions for extremely challenging AAAs using the Ovation® stent-graft.
Extreme complex aortic anatomies still represent the major limit of endovascular aneurysms repair (EVAR) for infrarenal abdominal aortic aneurysm (AAA). Aim of this study was to evaluate results of EVAR with Ovation® stent-graft in extremely complex aortic anatomies. A single center study was retrospectively conducted on a prospectively compiled computerized database between July 2012 and July 2014. Twenty-one elective patients with atherosclerotic AAA were included. All patients were judged unfit for or refused an open approach. In all of them, extremely complex anatomies features contraindicated EVAR by common endografts. Patients' outcomes were evaluated on the basis of anatomical features: challenging proximal aortic neck (non-cylindrical, short, severely angulated, enlarged, thrombosed) and challenging iliac artery accesses (angulated and narrowed). Technical and clinical successes were defined as the absence of intraoperative surgical conversion and aneurysm related mortality, respectively. Reintervention, morbidity and mortality rates during follow-up were also recorded. All patients were male; mean age was 75.6±7.2 years. In 14 patients (66.7%) neck length was <10 mm, a non-cylindrical neck was present in 15 patients (71.4%) and a severe neck thrombosis was registered in 13 patients (61.9%). Only 1 patient (4.8%) had no iliac tortuosity, 9 (42.8%) patients had severe tortuosity at least on one iliac access and 7 (33.3%) on both. Technical and clinical successes were achieved in all cases. Neither death nor reinterventions were observed in the present series. At a mean follow-up of 9±5 (3-27) months, only one patient presented an iliac leg occlusion. Our limited and preliminary experience seems to show that Ovation® stent-graft may widen the range of AAAs suitable for standard EVAR. Early results, even in patients with challenging anatomies, are encouraging but a longer follow-up is mandatory.


Ctf18 is required for homologous recombination-mediated double-strand break repair.
The efficient repair of double-strand breaks (DSBs) is crucial in maintaining genomic integrity. Sister chromatid cohesion is important for not only faithful chromosome segregation but also for proper DSB repair. During DSB repair, the Smc1-Smc3 cohesin complex is loaded onto chromatin around the DSB to support recombination-mediated DSB repair. In this study, we investigated whether Ctf18, a factor implicated in the establishment of sister chromatid cohesion, is involved in DSB repair in budding yeast. Ctf18 was recruited to HO-endonuclease induced DSB sites in an Mre11-dependent manner and to damaged chromatin in G2/M phase-arrested cells. The ctf18 mutant cells showed high sensitivity to DSB-inducible genotoxic agents and defects in DSB repair, as well as defects in damage-induced recombination between sister chromatids and between homologous chromosomes. These results suggest that Ctf18 is involved in damage-induced homologous recombination.


Betulinic acid protects the neuronal damage in new born rats from isoflurane-induced apoptosis in the developing brain by blocking FASL-FAS signaling pathway.
Betulinic acid (BA) is a naturally occurring pentacyclic lupane group triterpenoid, has reported to protect cerebral ischemia. Present study evaluates the protective effect of betulinic acid on the isoflurane-induced neuronal damage in neonatal mice. All the mice of 7days age were exposed to isoflurane (2%; 2h) for the duration of 3day. At the end of protocol cognitive function was evaluated by Morris water maze (MWM) test. However count of apoptotic cells were estimated by TUNEL staining. Concentration of oxidative stress parameters [superoxide dismutase (SOD); catalase (CAT) and reduced glutathione (GSH)], cytokines [tumor necrosis factor (TNF-α); interlukin-6 (IL-6) and IL-1β] and expressions of caspase 3, FAS and FASL were estimated in the neuronal cells. Result of the study suggested that treatment with betulinic acid significantly reduces the escape latency and enhances platform crossing time than negative control group. Count of apoptotic cells were also found to be reduced in BA treated group of mice than negative control group. Moreover treatment with BA significantly attenuates the concentration of inflammatory cytokines and oxidative stress in isoflurane induced neonatal mice. However expressions of caspase-3, FAS/FASL was found to be significantly reduced in BA treated group of mice than negative control group. Present study concludes the neuroprotective effect of betulinic acid in isoflurane-induced brain damage in developing brain by attenuating the apoptosis through Fas/FASL pathway inhibition.


Quality consciousness...auditing for HIPAA Privacy Compliance.
The Health Insurance Portability and Accountability Act (HIPAA) privacy deadline has passed. Now it is essential to comply with the regulations. The stakes are high; therefore, a HIPAA Privacy Compliance Program must be part of an organization's quality initiatives. This article provides guidelines for the challenges of continual program improvement, successful cultural change, and effective monitoring of the existing program. Healthcare organizations will attain compliance goals through internal audits on the processes, policies, and training efforts of their HIPAA program.


Standardising for reliability: the contribution of tools and checklists.
This article describes two initiatives from the National Patient Safety Agency, which were developed to address important areas of harm to patients. This harm stems from failing to recognise or respond appropriately to deteriorating patients and errors in pre-operative and peri-operative care of surgical patients. Both initiatives used principles of standardisation, reliability and human factors to develop tools and checklists to improve patient safety, with a common approach to supporting implementation. The article describes further advances and developments aimed at increasing and sustaining improvement, including the use of technology to reduce human error.


Diphtheroid endocarditis. Report of nine cases and review of the literature.
Diphtheroid endocarditis is a rare disease. A large proportion of the reported cases have occurred in the presence of prosthetic heart valves. Nine previously unreported cases of diphtheroid endocarditis are discussed along with 25 others taken from the literature. Eight out of the nine new cases occurred in patients with artificial heart valves. A high mortality was associated with infections occurring on prosthetic heart valves. Microbiological studies were frequently hampered by poor in vitro growth of the organisms. Resistance to penicillin and cephalothin was common. Erythromycin or penicillin in combination with streptomycin is suggested as a rational initial treatment for diphtheroid endocarditis involving prosthetic heart valves to be used until adequate in vitro antibiotic susceptibility testing is completed. Long-term suppressive therapy is suggested for those patients who are poor surgical candidates and for those patients who relapse after a reasonable course of antibiotic therapy.


Morphological abnormalities in vitamin B6 deficient tarsometatarsal chick cartilage.
The aim of this study was to test the hypothesis that deficiency of vitamin B6 would produce morphological characteristics of osteochondral lathyrism. To accomplish this goal, morphological characteristics of chick cartilage in which lathyrism was produced by two separate dietary regimens was compared to morphological changes encountered in vitamin B6 deficiency. Vitamin B6 deficiency should reduce activity of lysyloxidase needed for producing intermolecular cross-links. The question to be addressed was: would this latter deficiency impair collagen morphological features and secondarily other structures indirectly by reducing collagen molecular assembly? Failure of cross-linking of collagen in the positive controls was related to a lack of functional aldehyde cross-link intermediates which are blocked by homocysteine and aminoacetonitrile. Day-old-male Lohmann chicks were fed adequate (6 mg/kg) or vitamin B6-deficient diets. Cross-link defects were induced by homocysteine-rich diets (0.6% w/w) or a diet containing aminoacetonitrile (0.1% w/w). Animals were sacrificed at 6 weeks of age and Ossa tarsalia articular cartilage specimens, as well as the proximal end of tarsometatarsus were dissected from the tibial metatarsal joint, a major weight-bearing site. Light microscopic observations revealed reduction of subarticular trabecular bone formation, concurrent with overexpansion of the hypertrophic cell zone. Ultrastructural electron microscopy observation of articular fibro-cartilage indicated significant thickening of collagen fibers in vitamin B6 deficient birds, as well as the positive controls in comparison to that of cage-matched control birds. It was concluded that vitamin B6 deficient cross-linking may be responsible for the observed delay in bone development and aforementioned cartilage histological alterations.


A provisional complete genome-based genotyping system for rotavirus species C from terrestrial mammals.
Rotaviruses C (RVCs) have been detected in pigs, humans, cows, ferrets and dogs. Despite their zoonotic impact and pathogenicity, the genetic characterization of RVCs is incomplete, unlike rotaviruses A (RVAs), whose genetics are well studied. Several studies reported partial and complete genomic sequences for multiple porcine and canine RVCs. We aimed to establish a complete genome-based genotyping system for RVCs, by analysing complete genome data from 22 porcine RVCs identified in Japan from 2002 to 2010, along with those from multiple human, bovine, porcine, canine and ferret RVCs reported in several previous studies. Comparative sequence analyses among RVCs from various host species demonstrated that porcine RVCs had a high level of genetic diversity. In addition, phylogenetic analyses of all 11 RNA segments indicated that porcine RVCs could be classified into multiple genotypes. Notably, the VP4 dendrogram divided bovine RVCs into multiple genotypes. Consequently, the provisional genotype classification for RVCs from terrestrial mammals revealed the existence of genotypes 18G, 21P, 13I, 4R, 6C, 6M, 9A, 8N, 6T, 5E and 4H for the genes VP7, VP4, VP6, VP1, VP2, VP3, NSP1, NSP2, NSP3, NSP4 and NSP5, respectively, based on the cut-off values as defined by the Rotavirus Classification Working Group. The system established in this study deepens our understanding of RVC evolution and facilitates the discovery of genetic events (gene reassortment and interspecies transmission) among RVCs.


Nuclear factor-κB mediates the phenotype switching of airway smooth muscle cells in a murine asthma model.
Airway smooth muscle cells (ASMCs) phenotype modulation, characterized by reversible switching between contractile and proliferative phenotypes, is considered to contribute to airway proliferative diseases such as allergic asthma. Nuclear Factor-κB (NF-κB) has been reported as a key regulator for the occurrence and development of asthma. However, little is known regarding its role in ASM cell phenotypic modulation. To elucidate the role of NF-κB in regulating ASM cells phenotypic modulation, we investigated the effects of NF-κB on ASM cells contractile marker protein expression, and its impact on proliferation and apoptosis. We found that chronic asthma increased the activation of NF-κB in the primary murine ASM cells with a concomitant marked decrease in the expression of contractile phenotypic marker protein including smooth muscle alpha-actin (α-SMA). Additionally, we used the normal ASM cells under different processing to build the phenotype switching when we found the activation of NF-κB. Meanwhile, the expression of α-SMA in asthma was significantly increased by the NF-κB blocker. NF-κB blocker also suppressed asthma mouse ASM cell proliferation and promoted apoptosis. These findings highlight a novel role for the NF-κB in murine ASM cell phenotypic modulation and provide a potential target for therapeutic intervention for asthma.


"It's about having the choice": stakeholder perceptions of population-based genetic carrier screening for fragile X syndrome.
This project explored, the views of key stakeholders regarding population-based genetic carrier screening for fragile X syndrome (FXS). Interviews and focus groups were conducted with healthcare providers, relatives of individuals with FXS and members of the general population. Data were transcribed verbatim and coded into themes. 188 individuals took part in this study. Perceived benefits of carrier screening included: learning the risk of having a child with FXS; learning the risk of fragile X-associated primary ovarian insufficiency; and the opportunity for carriers to access reproductive options. Concerns included: the emotional impact of screening and receiving a carrier result; the predictive testing nature of the carrier test with respect to fragile X-associated tremor/ataxia syndrome; potential confusion created by receiving an intermediate result; and implications of genetic screening for society. Overall, population-based genetic carrier screening was perceived to be acceptable provided it is optional and offered at an appropriate stage of life. With the support of the participants to promote individual choice by offering a population-based carrier screening program for FXS, it is essential to carefully consider how screening might be offered in order to ensure broad accessibility and facilitation of decision-making.


N-myc proto-oncogene expression during organogenesis in the developing mouse as revealed by in situ hybridization.
The N-myc proto-oncogene is expressed during embryogenesis, suggesting that it plays a role in normal development. Since the myc-family oncogenes have been implicated in the control of cell growth, the embryonic expression may reflect rapid proliferation known to occur in development. Alternatively, N-myc expression may be involved in specific differentiation stages. In many embryonic tissues, early and late differentiation events occur in different locations. By in situ hybridization of tissue sections, we now demonstrate a restricted expression of N-myc mRNA to a few tissues and to areas where the first differentiation stages occur. N-myc expression was most strongly expressed in the developing kidney, hair follicles, and in various parts of the central nervous system. In these tissues, expression was restricted to a few cell lineages. In all lineages, expression was confined to early differentiation stages, and, at onset of overt differentiation, the level of expression decreased dramatically. Several rapidly proliferating tissues showed very little, if any, N-myc expression. In the brain, post-mitotic but not yet differentiated cells expressed high levels of N-myc mRNA. Therefore, N-myc expression is not a simple marker for proliferation in the embryo. Rather, N-myc expression seems to be a feature of early differentiation stages of some cell lineages in kidney, brain, and hair follicles, regardless of the proliferative status of the cell. The results raise the possibility that N-myc may participate in the control of these early differentiation events.


Tuning the self-organization of confined active particles by the steepness of the trap.
We consider the collective dynamics of self-propelling particles in two dimensions. They can align themselves according to the direction of propulsion of their neighbours, together with small rotational fluctuations. They also interact with each other via soft, isotropic, repulsive potentials. The particles are confined in a circular trap. The steepness of the trap is tuneable. The average packing fraction of the particles is low. When the trap is steep, particles flock along its boundary. They form a polar cluster that spreads over the boundary. The cluster is not spatially ordered. We show that when the steepness is decreased beyond a threshold value, the cluster becomes round and compact and eventually spatial order (hexagonal) emerges in addition to the pre-established polar order. We investigate the kinetics of such ordering. We find that while rotating around the centre of the trap along its circular boundary, the cluster needs to roll around its centre of mass to be spatially ordered. We have studied the stability of the order when the trap is suddenly switched off. We find that for the particles with velocity alignment interaction, the decay of the spatial order is much slower than the particles without the alignment interaction.


Preparation and pharmaceutical evaluation of glibenclamide slow release mucoadhesive buccal film.
Buccal mucoadhesive systems among novel drug delivery systems have attracted great attention in recent years due to their ability to adhere and remain on the oral mucosa and to release their drug content gradually. Buccal mucoadhesive films can improve the drug therapeutic effect by enhancement of drug absorption through oral mucosa increasing the drug bioavailability via reducing the hepatic first pass effect. The aim of the current study was to formulate the drug as buccal bioadhesive film, which releases the drug at sufficient concentration with a sustain manner reducing the frequency of the dosage form administration. One of the advantagees of this formulation is better patient compliances due to the ease of administration with no water to swallow the product. The mucoadhesive films of glibenclamide were prepared using hydroxypropyl methylcellulose (HPMC) K4M, K15M and Eudragit RL100 polymers and propylene glycol as plasticizer and co-solvent. Films were prepared using solvent casting method, and were evaluated with regard to drug content, thickness, weight variations, swelling index, tensile strength, ex vivo adhesion force and percentage of in vitro drug release. Films with high concentrations of HPMC K4M and K15M did not have favorable appearance and uniformity. The formulations prepared from Eudragit were transparent, uniform, flexible, and without bubble. The highest and the lowest percentages of swelling were observed for the films containing HPMC K15M and Eudragit RL100, respectively. Films made of HPMC K15M had adhesion force higher than those containing Eudragit RL100. Formulations with Eudragit RL100 showed the highest mean dissolution time (MDT). Drug release kinetics of all formulations followed Higuchi's model and the mechanism of diffusion was considered non-Fickian type. It was concluded that formulations containing Eudragit RL100 were more favorable than others with regard to uniformity, flexibility, rate and percentage of drug release.


Sutureless transconjunctival intrascleral intraocular lens fixation: the modified Yamane technique.
To evaluate the efficacy and safety of the modified Yamane technique with sutureless transconjunctival intrascleral intraocular lens fixation. Sutureless transconjunctival intrascleral haptic fixated intraocular lens implantation was performed in patients with aphakia and dislocated intraocular lenses. A clear corneal incision (2.8 mm) was made into the temporal quadrant and a three-piece intraocular lens was implanted into the anterior chamber. The haptics of the intraocular lens were externalized with a 27 G needle via transconjunctival scleral tunnels at the 6 and 12 o'clock positions. The transconjunctival scleral tunnels were prepared to conform to the haptic position and curvature. The site of the scleral tunnels was 2mm from the limbus with a length of 2 mm in the sclera and was aimed at the end of the posterior chamber. The tips of the haptics were cauterized to create a terminal knob. The haptics were pushed back and the knobs were implanted into the scleral tunnels. The study cohort included 21 patients with unilateral aphakia and dislocated intraocular lenses. All patients were examined postoperatively and at postoperative day 1, day 7, month 1, and month 3. All examinations revealed formation of the anterior chamber and well-centralized intraocular lenses. No haptic-related complications of exposure, foreign body sensation, or discomfort were observed. Sutureless transconjunctival intrascleral haptic fixated intraocular lensimplantation is an effective, safe, and practical surgical alternative. This technique was superior to the Yamane method with regard to comfort and surgical duration. Further studies with longer follow-up evaluations are warranted to verify long-term complications.


Long-term morphological, hormonal, and clinical follow-up in a single unit on 118 patients with adrenal incidentalomas.
To evaluate long-term morphological, functional, and clinical outcome in adrenal incidentalomas. A total of 118 patients (77 F and 47 M; age 62.3+/-1.0 years) with adrenal incidentalomas were evaluated at baseline and followed-up for median 3 years (range 1-10 years) by clinical, biochemical, hormonal, and morphological evaluation. Among them, six patients with diagnosis of subclinical Cushing's syndrome (SCS) underwent surgery. At entry, 86% (n=102) of tumors were nonfunctioning (NF) and 14% (n=16) showed SCS. Comparing NF with SCS patients, a significantly higher percentage of dyslipidemia was found in the group of SCS patients (50 vs 23%, P=0.033). During follow-up, adrenal function remained normal in all NF patients, none of them developed subclinical or overt endocrine disease. The cumulative risk of mass enlargement was globally low (25%), but progressive up to 8 years. SCS was confirmed in all patients, and none of them shifted to overt Cushing's syndrome. The cumulative risk of developing metabolic-cardiovascular abnormalities was globally low (22%), but progressive up to 8 years and new diseases were recorded in the group of NF patients only (three patients with dyslipidemia, four with impaired fasting glucose/impaired glucose tolerance, and three with diabetes mellitus). SCS patients who underwent surgery did not show any significant clinical improvement. The risk of mass enlargement, hormonal, and metabolic impairment over time is globally low. Conservative management seems to be appropriate, but further prospective studies are needed to establish the long-term outcome of such patients, especially for metabolic status, cardiovascular risk profile and their relationship with endocrine function.


Biosynthesis of silver nanoparticles using Acacia leucophloea extract and their antibacterial activity.
The immense potential of nanobiotechnology makes it an intensely researched field in modern medicine. Green nanomaterial synthesis techniques for medicinal applications are desired because of their biocompatibility and lack of toxic byproducts. We report the toxic byproducts free phytosynthesis of stable silver nanoparticles (AgNPs) using the bark extract of the traditional medicinal plant Acacia leucophloea (Fabaceae). Visual observation, ultraviolet-visible spectroscopy, and transmission electron microscopy (TEM) were used to characterize the synthesized AgNPs. The visible yellow-brown color formation and surface plasmon resonance at 440 nm indicates the biosynthesis of AgNP. The TEM images show polydisperse, mostly spherical AgNP particles of 17-29 nm. Fourier transform infrared spectroscopy revealed that primary amines, aldehyde/ketone, aromatic, azo, and nitro compounds of the A. leucophloea extract may participate in the bioreduction and capping of the formed AgNPs. X-ray diffraction confirmed the crystallinity of the AgNPs. The in vitro agar well diffusion method confirmed the potential antibacterial activity of the plant extract and synthesized AgNPs against the common bacterial pathogens Staphylococcus aureus (MTCC 737), Bacillus cereus (MTCC 1272), Listeria monocytogenes (MTCC 657), and Shigella flexneri (MTCC 1475). This research combines the inherent antimicrobial activity of silver metals with the A. leucophloea extract, yielding antibacterial activity-enhanced AgNPs. This new biomimetic approach using traditional medicinal plant (A. leucophloea) barks to synthesize biocompatible antibacterial AgNPs could easily be scaled up for additional biomedical applications. These polydisperse AgNPs green-synthesized via A. leucophloea bark extract can readily be used in many applications not requiring high uniformity in particle size or shape.


Workshop: mechanisms and cardiovascular damage in hypertension.
Angiotensin (Ang) II is considered a regulatory hormone stimulating vascular smooth muscle cell constriction, aldosterone release from the adrenal gland, and sodium reabsorption in the renal tubule. Furthermore, Ang II may be formed and act locally as a chemokine, inducing tyrosine phosphorylation, cell growth, hypertrophy, and differentiation. In addition, evidence has recently accrued showing that Ang II is important in stimulating the production of reactive oxygen species and the activation of ancient inflammatory mechanisms. The transcription factor nuclear factor kappa-B is pivotal to these processes. Nuclear factor kappa-B activation stimulates the expression of a gene menagerie important to chemoattraction, surface adhesion molecule expression, coagulation, and inflammation. Anti-inflammatory interventions may have therapeutic utility.


Ethnic differences in associations between fat deposition and incident diabetes and underlying mechanisms: the SABRE study.
To examine ethnic differences in ectopic fat and associations with incident diabetes. In a UK cohort study, 1338 Europeans, 838 South Asians, and 330 African Caribbeans living in London were aged 40-69 years at baseline. Baseline assessment included blood tests, anthropometry, and questionnaires. Anthropometry-based prediction equations estimated baseline visceral adipose tissue (VAT). Incident diabetes was ascertained from record review, self-report, or oral glucose tolerance testing. South Asians had more and African Caribbeans less estimated VAT than Europeans. Both ethnic minorities had larger truncal skinfolds than Europeans. In men, adjustment for risk factors (BMI, smoking, systolic blood pressure, and HDL-cholesterol) markedly attenuated the association between estimated VAT and diabetes in Europeans (standardized subhazard ratios [95% CI]: from 1.74 [1.49, 2.03] to 1.16 [0.77, 1.76]) and African Caribbeans (1.72 [1.26, 2.35] to 1.44 [0.69, 3.02]) but not South Asians (1.60 [1.38, 1.86] to 1.90 [1.37, 2.64]). In women, attenuation was observed only for South Asians (1.80 [1.01, 3.23] to 1.07 [0.49, 2.31]). Associations between truncal skinfolds and diabetes appeared less affected by multivariable adjustment in South Asians and African Caribbeans than Europeans (1.24 [0.97, 1.57] and 1.28 [0.89, 1.82] versus 1.02 [0.77, 1.36] in men; 1.91 [1.03, 3.56] and 1.42 [0.86, 2.34] versus 1.23 [0.74, 2.05] in women). Differences in overall truncal fat, as well as VAT, may contribute to the excess of diabetes in South Asian and African Caribbean groups, particularly for women.


Co-housing of Rift Valley Fever Virus Infected Lambs with Immunocompetent or Immunosuppressed Lambs Does Not Result in Virus Transmission.
Rift Valley fever virus (RVFV) is transmitted among susceptible animals by mosquito vectors. Although the virus can be isolated from nasal and oral swabs of infected animals and is known to be highly infectious when administered experimentally via oral or respiratory route, horizontal transmission of the virus is only sporadically reported in literature. We considered that immunosuppression resulting from stressful conditions in the field may increase the susceptibility to horizontally transmitted RVFV. Additionally, we reasoned that horizontal transmission may induce immune responses that could affect the susceptibility of contact-exposed animals to subsequent infection via mosquito vectors. To address these two hypotheses, viremic lambs were brought into contact with sentinel lambs. One group of sentinel lambs was treated with the immunosuppressive synthetic glucocorticosteroid dexamethasone and monitored for signs of disease and presence of virus in the blood and target organs. Another group of contact-exposed sentinel lambs remained untreated for three weeks and was subsequently challenged with RVFV. We found that none of the dexamethasone-treated contact-exposed lambs developed detectable viremia, antibody responses or significant increases in cytokine mRNA levels. Susceptibility of immunocompetent lambs to RVFV infection was not influenced by previous contact-exposure. Our results are discussed in light of previous findings.


GATA-2 restricts prolactin-like protein A expression to secondary trophoblast giant cells in the mouse.
An analysis of the pattern of expression of the mouse placental hormone prolactin-like protein A (PLP-A) has revealed that this hormone is expressed exclusively in secondary trophoblast giant cells but not in primary giant cells. Thus, PLP-A serves as a marker for a subset of giant cells. Recent results have indicated that PLP-A binds to and inhibits the activity of natural killer cells, and thus, the localized expression of PLP-A may be important for regulating the activity of this class of T lymphocytes in a restricted region of the implantation site. Previous studies indicated that the transcription factor GATA-2 is required for the trophoblast giant cell-specific expression of two other hormones in the prolactin family, placental lactogen I and proliferin. In the absence of GATA-2, PLP-A continues to be expressed, but in this mutant background, PLP-A mRNA is detected in both primary and secondary giant cells. Thus, GATA-2 contributes both to positive and negative regulation of trophoblast giant cell-specific gene expression, and this factor apparently plays an important role in generating or maintaining the distinct functions of secondary, compared with primary, trophoblast giant cells.


Moral Challenges in Transgender Care: A Thematic Analysis Based on a Focused Ethnography.
Treatment teams providing transgender-affirming medical care are inherently faced with various kinds of moral and ethical dilemmas and questions, which are becoming even more pressing due to increasing treatment numbers and public attention for transgender care. Little is known about what kinds of moral and ethical challenges manifest in clinical practice. The aim of the present research was to map the moral and ethical challenges of healthcare professionals working in a specialized multidisciplinary transgender care center. Over a period of 7 months, during a focused ethnographic study, data were collected through participant observation of multidisciplinary team meetings, observation of individual psychodiagnostic assessment sessions with clients, and analysis of transcripts and reports of a series of moral case deliberations. A thematic content analysis of the data identified various implicit and explicit moral and ethical challenges around the following six themes: (1) assessing eligibility; (2) content of treatment; (3) sequential order of the treatment steps; (4) role of the clinical guidelines; (5) differing notions regarding gender identity, and (6) decision-making process. Our research provides a detailed insight into the way healthcare professionals experience these moral and ethical challenges and how they are related to (local) guidelines, the multidisciplinary character of GD care, and its inherent implicit and explicit gender norms. Our findings suggest that good transgender care may profit from continuous multidisciplinary deliberation of and sensitivity toward the normative dimension of transgender care. The paper ends with recommendations for ethics support mechanisms in transgender care.


[Pre- and postseptal orbital rhinosinusogenic complications].
The authors present examination and surgical data on 78 patients with different forms of orbital rhinosinusogenic complication. One of the major factors for the course and therapeutic policy in such complications is pre- or postseptal location of the process in the orbit. Such local signs as exophthalmos, chemosis, dislocation, reduced motility of the eye ball and, later on, sight disorders indicate the lesion focus location behind the orbital septum. Clinical comparisons of the pre- and postseptal orbital complications evidence for more severe and prognostically unfavorable course of the inflammation in the posterior part of the orbit. This urges early active combined therapy and cleansing of the affected paranasal sinuses in such patients.


Category-Based Deep CCA for Fine-Grained Venue Discovery From Multimodal Data.
In this work, travel destinations and business locations are taken as venues. Discovering a venue by a photograph is very important for visual context-aware applications. Unfortunately, few efforts paid attention to complicated real images such as venue photographs generated by users. Our goal is fine-grained venue discovery from heterogeneous social multimodal data. To this end, we propose a novel deep learning model, category-based deep canonical correlation analysis. Given a photograph as input, this model performs: 1) exact venue search (find the venue where the photograph was taken) and 2) group venue search (find relevant venues that have the same category as the photograph), by the cross-modal correlation between the input photograph and textual description of venues. In this model, data in different modalities are projected to a same space via deep networks. Pairwise correlation (between different modality data from the same venue) for exact venue search and category-based correlation (between different modality data from different venues with the same category) for group venue search are jointly optimized. Because a photograph cannot fully reflect rich text description of a venue, the number of photographs per venue in the training phase is increased to capture more aspects of a venue. We build a new venue-aware multimodal data set by integrating Wikipedia featured articles and Foursquare venue photographs. Experimental results on this data set confirm the feasibility of the proposed method. Moreover, the evaluation over another publicly available data set confirms that the proposed method outperforms state of the arts for cross-modal retrieval between image and text.


Metformin as targeted treatment in fragile X syndrome.
Individuals with fragile X syndrome (FXS) have both behavioral and medical comorbidities and the latter include obesity in approximately 30% and the Prader-Willi Phenotype (PWP) characterized by severe hyperphagia and morbid obesity in less than 10%. Metformin is a drug used in individuals with type 2 diabetes, obesity or impaired glucose tolerance and it has a strong safety profile in children and adults. Recently published studies in the Drosophila model and the knock out mouse model of FXS treated with metformin demonstrate the rescue of multiple phenotypes of FXS. We present 7 cases of individuals with FXS who have been treated with metformin clinically. One case with type 2 diabetes, 3 cases with the PWP, 2 adults with obesity and/or behavioral problems and, a young child with FXS. These individuals were clinically treated with metformin and monitored for behavioral changes with the Aberrant Behavior Checklist and metabolic changes with a fasting glucose and HgbA1c. We found consistent improvements in irritability, social responsiveness, hyperactivity, and social avoidance, in addition to comments from the family regarding improvements in language and conversational skills. No significant side-effects were noted and most patients with obesity lost weight. We recommend a controlled trial of metformin in those with FXS. Metformin appears to be an effective treatment of obesity including those with the PWP in FXS. Our study suggests that metformin may also be a targeted treatment for improving behavior and language in children and adults with FXS.


Schizophrenia: glutathione deficit in cerebrospinal fluid and prefrontal cortex in vivo.
Schizophrenia is a major psychiatric disease, which affects the centre of the personality, with severe problems of perception, cognition as well as affective and social behaviour. In cerebrospinal fluid of drug-free schizophrenic patients, a significant decrease in the level of total glutathione (GSH) by 27% (P<0.05) was observed as compared to controls, in keeping with the reported reduced level of its metabolite gamma-glutamylglutamine. With a new non-invasive proton magnetic resonance spectroscopy methodology, GSH level in medial prefrontal cortex of schizophrenic patients was found to be 52% (P = 0.0012) lower than in controls. GSH plays a fundamental role in protecting cells from damage by reactive oxygen species generated among others by the metabolism of dopamine. A deficit in GSH would lead to degenerative processes in the surrounding of dopaminergic terminals resulting in loss of connectivity. GSH also potentiates the N-methyl-D-aspartate (NMDA) receptor response to glutamate, an effect presumably reduced by a GSH deficit, leading to a situation similar to the application of phencyclidine (PCP). Thus, a GSH hypothesis might integrate many established biological aspects of schizophrenia.


Invasive group A streptococcal infections in children.
Invasive group A streptococcal infections and STSS have increased as causes of morbidity and mortality among children and adults. In children, respiratory foci appear to be the most common, but skin and soft tissue infection, particularly associated with varicella, also are common. Early diagnosis requires awareness of the presenting features and a high index of suspicion. Antimicrobial therapy that includes clindamycin, therapy with IVIG for those with STSS, and surgical intervention for patients with necrotizing fasciitis may improve outcome. Chemoprophylaxis should be considered among household contacts of patients with severe group A streptococcal disease in high-risk settings. Further studies are ongoing to evaluate the hypothesized link of invasive group A streptococcal infection in children with varicella and NSAID use, to better clarify the pathogenesis of STSS and necrotizing fasciitis, and to better document the risk of secondary spread among close contacts of case patients.


A highly potent agonist to protease-activated receptor-2 reveals apical activation of the airway epithelium resulting in Ca2+-regulated ion conductance.
The airway epithelium provides a barrier that separates inhaled air and its various particulates from the underlying tissues. It provides key physiological functions in both sensing the environment and initiating appropriate innate immune defenses to protect the lung. Protease-activated receptor-2 (PAR2) is expressed both apically and basolaterally throughout the airway epithelium. One consequence of basolateral PAR2 activation is the rapid, Ca(2+)-dependent ion flux that favors secretion in the normally absorptive airway epithelium. However, roles for apically expressed PAR2 activation have not been demonstrated, in part due to the lack of specific, high-potency PAR2 ligands. In the present study, we used the newly developed PAR2 ligand 2at-LIGRLO(PEG3-Pam)-NH2 in combination with well-differentiated, primary cultured airway epithelial cells from wild-type and PAR2 (-/-) mice to examine the physiological role of PAR2 in the conducting airway after apical activation. Using digital imaging microscopy of intracellular Ca(2+) concentration changes, we verified ligand potency on PAR2 in primary cultured airway cells. Examination of airway epithelial tissue in an Ussing chamber showed that apical activation of PAR2 by 2at-LIGRLO(PEG3-Pam)-NH2 resulted in a transient decrease in transepithelial resistance that was due to increased apical ion efflux. We determined pharmacologically that this increase in ion conductance was through Ca(2+)-activated Cl(-) and large-conductance K(+) channels that were blocked with a Ca(2+)-activated Cl(-) channel inhibitor and clotrimazole, respectively. Stimulation of Cl(-) efflux via PAR2 activation at the airway epithelial surface can increase airway surface liquid that would aid in clearing the airway of noxious inhaled agents.


Phylogeny of dengue viruses circulating in Jeddah, Saudi Arabia: 1994 to 2006.
The nucleotide sequence of the 240 bp E/NS1 junction of 81 dengue viruses isolated from cases in Jeddah, Saudi Arabia was determined and used to serotype the viruses. The nucleotide sequences of the complete Envelope (E) genes of 19 isolates were used for a phylogenetic analysis of the dengue viruses circulating in Saudi Arabia from 1994 to 2006. Three of the four dengue serotypes (DENV-1, DENV-2 and DENV-3) were found to circulate, often with more than one serotype in each outbreak. There was a major outbreak caused by DENV-1 and DENV-2 in 1994 while DENV-3 emerged in 1997. In the summer of 2004, all three serotypes were isolated and this gave way to an extended outbreak of DENV-1 that stretched from the summer of 2005 through early 2006. In the 1994 outbreak, the DENV-1 circulating was from the America-Africa genotype (lineage India-2) while the most recent outbreak in 2005 and 2006 was caused by a different DENV-1 strain from genotype Asia (lineage Asia-2), suggesting a re-introduction of DENV-1 a decade after the first introduction in 1994. There has been no change in the genotypes of DENV-2 (cosmopolitan genotype) and DENV-3 (genotype III) circulating since introduction in 1994 and 1997, respectively.


Few-Shot Calibration of Set Predictors via Meta-Learned Cross-Validation-Based Conformal Prediction.
Conventional frequentist learning is known to yield poorly calibrated models that fail to reliably quantify the uncertainty of their decisions. Bayesian learning can improve calibration, but formal guarantees apply only under restrictive assumptions about correct model specification. Conformal prediction (CP) offers a general framework for the design of set predictors with calibration guarantees that hold regardless of the underlying data generation mechanism. However, when training data are limited, CP tends to produce large, and hence uninformative, predicted sets. This paper introduces a novel meta-learning solution that aims at reducing the set prediction size. Unlike prior work, the proposed meta-learning scheme, referred to as meta-XB, i) builds on cross-validation-based CP, rather than the less efficient validation-based CP; and ii) preserves formal per-task calibration guarantees, rather than less stringent task-marginal guarantees. Finally, meta-XB is extended to adaptive non-conformal scores, which are shown empirically to further enhance marginal per-input calibration.


Generic nitric oxide (NO) generating surface by immobilizing organoselenium species via layer-by-layer assembly.
A universal nitric oxide (NO) generating surface is assembled via Layer-by-Layer (LbL) deposition of sodium alginate (Alg) and organoselenium modified polyethyleneimine (SePEI) on quartz and polymeric substrates. The immobilized SePEI species is capable of catalytically decomposing S-nitrosothiol species (RSNO) to NO in the presence of thiol reducing agents (e.g., glutathione, cysteine, etc.). The stepwise buildup of the multilayer films is monitored by UV-vis spectroscopy, SEM and surface contact angle measurements. X-ray photoelectron spectroscopy is used to study the stoichiometry between the polyanion and polycation, and also the presence of Se in the catalytic LbL film. A reductive annealing process is necessary to improve the stability of freshly coated multilayer films via chain rearrangement. Chemiluminescence measurements illustrate the ability of the LbL films to generate NO from S-nitrosoglutathione (GSNO) in the presence of glutathione (GSH). Enhanced NO fluxes can be achieved by increasing the number of catalytic (SePEI/Alg) bilayers coated on the substrates. Nitric oxide generation is observed even after prolonged contact with sheep whole blood. Preliminary applications of this LbL on silicone rubber tubings and polyurethane catheters reveal similar NO generation behavior from these biomedical grade polymeric substrates.


The prevalence of exercise-induced bronchospasm in soccer player children, ages 7 to 16 years.
This study represents an attempt to determine the prevalence of exercise-induced bronchospasm among soccer player children. A total of 234 soccer player boys of all soccer schools from Shahr-Rey enrolled in this study. They did not have any history of a recent or chronic respiratory tract disease, a history of allergic diseases, and history of bronchodilator drugs consumption during the 24 hours prior to the study. Pulmonary function test (PFT) was performed for each participant before exercise and 6 and 15 minutes after playing soccer. The diagnosis of EIB was by a decrease in forced expiratory volume in 1 second (FEV1) by at least 10% and in peak expiratory flow rate (PEFR) by at least 15% with exercise challenge. If there was reduction in one parameter alone, the participants were considered as prone to EIB. Considering both FEV1 and PEFR the prevalence of EIB was 2.1% and 18.4% were prone to EIB. If FEV1 or PEFR tests were used as criteria for diagnosis of airway obstruction, the prevalence of EIB would be 6% and 15.8%, respectively. There was no significant difference between the post of players, family history of allergic disease and EIB in soccer players. This study suggests that at least 2.1% of soccer players will develop bronchospasm even if they do not have any history of asthma and allergy.


The design of adaptive systems: optimal parameters for variation and selection in learning and development.
Some aspects of learning and development are based on evolutionary change within the organism. In trial and error learning, variant ideas or behaviors are generated and selective filters (learning rules) choose among the population of variants. Development may, in some cases, proceed by selection within a population of variant cellular lineages. This paper analyses abstract properties of selective systems to understand the evolutionary dynamics that occur within organisms. The Price Equation and Fisher's fundamental theorem of natural selection, two of the most powerful concepts in evolutionary genetics, are applied in a general way to internal selective systems in learning and development. This analysis emphasizes generative mechanisms and selective filters as genetically controlled phenotypes of individual organisms. Generative mechanisms create the variation on which selection acts. Selective filters determine the extent to which selection within the organism optimizes organismal performance. The methods of Price and Fisher provide a general way in which to partition evolutionary change into improvements caused by selection and the tendency of high performance variants to deteriorate because of competition or environmental change. This balance between selective improvement, at a rate equal to the variance in fitness, and a matching deterioration in performance, provides general insight into the common properties of adaptive systems in genetics, learning and development. These ideas are applied to a model of honey bee foraging. This example clarifies the relation between genes and phenotypes controlled by internal selective systems.


PI3Kδ inhibition prevents IL33, ILC2s and inflammatory eosinophils in persistent airway inflammation.
Phosphoinositide-3-kinase-delta (PI3Kδ) inhibition is a promising therapeutic approach for inflammatory conditions due to its role in leucocyte proliferation, migration and activation. However, the effect of PI3Kδ inhibition on group 2 innate lymphoid cells (ILC2s) and inflammatory eosinophils remains unknown. Using a murine model exhibiting persistent airway inflammation we sought to understand the effect of PI3Kδ inhibition, montelukast and anti-IL5 antibody treatment on IL33 expression, group-2-innate lymphoid cells, inflammatory eosinophils, and goblet cell metaplasia. Mice were sensitised to house dust mite and after allowing inflammation to resolve, were re-challenged with house dust mite to re-initiate airway inflammation. ILC2s were found to persist in the airways following house dust mite sensitisation and after re-challenge their numbers increased further along with accumulation of inflammatory eosinophils. In contrast to montelukast or anti-IL5 antibody treatment, PI3Kδ inhibition ablated IL33 expression and prevented group-2-innate lymphoid cell accumulation. Only PI3Kδ inhibition and IL5 neutralization reduced the infiltration of inflammatory eosinophils. Moreover, PI3Kδ inhibition reduced goblet cell metaplasia. Hence, we show that PI3Kδ inhibition dampens allergic inflammatory responses by ablating key cell types and cytokines involved in T-helper-2-driven inflammatory responses.


Facilitative Effect of a Generalist Herbivore on the Recovery of a Perennial Alga: Consequences for Persistence at the Edge of Their Geographic Range.
Understanding the impacts of consumers on the abundance, growth rate, recovery and persistence of their resources across their distributional range can shed light on the role of trophic interactions in determining species range shifts. Here, we examined if consumptive effects of the intertidal grazer Scurria viridula positively influences the abundance and recovery from disturbances of the alga Mazzaella laminarioides at the edge of its geographic distributions in northern-central Chilean rocky shores. Through field experiments conducted at a site in the region where M. laminarioides overlaps with the polar range edge of S. viridula, we estimated the effects of grazing on different life stages of M. laminarioides. We also used long-term abundance surveys conducted across ~700 km of the shore to evaluate co-occurrence patterns of the study species across their range overlap. We found that S. viridula had positive net effects on M. laminarioides by increasing its cover and re-growth from perennial basal crusts. Probability of occurrence of M. laminarioides increased significantly with increasing density of S. viridula across the range overlap. The negative effect of S. viridula on the percentage cover of opportunistic green algae-shown to compete for space with corticated algae-suggests that competitive release may be part of the mechanism driving the positive effect of the limpet on the abundance and recovery from disturbance of M. laminarioides. We suggest that grazer populations contribute to enhance the abundance of M. laminarioides, facilitating its recolonization and persistence at its distributional range edge. Our study highlights that indirect facilitation can determine the recovery and persistence of a resource at the limit of its distribution, and may well contribute to the ecological mechanisms governing species distributions and range shifts.


Epidemiology and Clinical Characteristics of COVID-19.
Since December 2019, there has been an outbreak of a novel coronavirus (COVID-19) infection in Wuhan, China. Meanwhile, the outbreak also drew attention and concern from the World Health Organization (WHO). COVID-19 is another human infectious disease caused by coronavirus. The transmission of COVID-19 is potent and the infection rate is fast. Since there is no specific drug for COVID-19, the treatment is mainly symptomatic supportive therapy. In addition, it should be pointed out that patients with severe illness need more aggressive treatment and meticulous care. Recently, accurate RNA detection has been decisive for the diagnosis of COVID-19. The development of highly sensitive RT-PCR has facilitated epidemiological studies that provide insight into the prevalence, seasonality, clinical manifestations and course of COVID-19 infection. In this review, we summarize the epidemiology and characteristics of COVID-19.


IκB kinase complex (IKK) triggers detachment-induced autophagy in mammary epithelial cells independently of the PI3K-AKT-MTORC1 pathway.
Adherent cells require proper integrin-mediated extracellular matrix (ECM) engagement for growth and survival; normal cells deprived of proper ECM contact undergo anoikis. At the same time, autophagy is induced as a survival pathway in both fibroblasts and epithelial cells upon ECM detachment. Here, we further define the intracellular signals that mediate detachment-induced autophagy and uncover an important role for the IκB kinase (IKK) complex in the induction of autophagy in mammary epithelial cells (MECs) deprived of ECM contact. Whereas the PI3K-AKT-MTORC1 pathway activation potently inhibits autophagy in ECM-detached fibroblasts, enforced activation of this pathway is not sufficient to suppress detachment-induced autophagy in MECs. Instead, inhibition of IKK, as well as its upstream regulator, MAP3K7/TAK1, significantly attenuates detachment-induced autophagy in MECs. Furthermore, function-blocking experiments corroborate that both IKK activation and autophagy induction result from decreased ITGA3-ITGB1 (α3β1 integrin) function. Finally, we demonstrate that pharmacological IKK inhibition enhances anoikis and accelerates luminal apoptosis during acinar morphogenesis in three-dimensional culture. Based on these results, we propose that the IKK complex functions as a key mediator of detachment-induced autophagy and anoikis resistance in epithelial cells.


Cyclic AMP levels, adenylyl cyclase activity, and their stimulation by serotonin quantified in intact neurons.
In molluscan central neurons that express cAMP-gated Na+ current (INa,cAMP), estimates of the cAMP binding affinity of the channels have suggested that effective native intracellular cAMP concentrations should be much higher than characteristic of most cells. Using neurons of the marine opisthobranch snail Pleurobranchaea californica, we applied theory and conventional voltage clamp techniques to use INa,cAMP to report basal levels of endogenous cAMP and adenylyl cyclase, and their stimulation by serotonin. Measurements were calibrated to iontophoretic cAMP injection currents to enable expression of the data in molar terms. In 30 neurons, serotonin stimulated on average a 23-fold increase in submembrane [cAMP], effected largely by an 18-fold increase in adenylyl cyclase activity. Serotonin stimulation of adenylyl cyclase and [cAMP] was inversely proportional to cells' resting adenylyl cyclase activity. Average cAMP concentration at the membrane rose from 3.6 to 27.6 microM, levels consistent with the expected cAMP dissociation constants of the INa,cAMP channels. These measures confirm the functional character of INa,cAMP in the context of high levels of native cAMP. Methods similar to those employed here might be used to establish critical characters of cyclic nucleotide metabolism in the many cells of invertebrates and vertebrates that are being found to express ion currents gated by direct binding of cyclic nucleotides.


[Ultrastructure of villous adenomas of the large intestine].
7 villous adenomas of the colon from patients of 44 to 63 years are studied electron-microscopically. Their cells are shown to preserve the capacity for specific differentiation. 4 types of differentiated cells are distinguished and changes connected with the processes of structural-functional restructuration are described. The existence of two ultrastructural variants of villous adenomas depending upon the proportion of differentiated and nondifferentiated cells is noted. Prognostic value of these findings is discussed.


Cellular changes involved in conversion of normal to malignant breast: importance of the stromal reaction.
Reciprocal interactions between epithelium and mesenchyme mediate crucial aspects of embryonic development and direct the coordinated organogenesis, correct spatial orientation, and the timely expression of functional activity consistent with physiological demands. The mesenchymal equivalent in the adult organism is the stroma, i.e., the loose connective tissue that is separated from the epithelial compartment by an intact basement membrane. In carcinomas, the cellular organization is dramatically changed, and the stroma is extensively modified. The basement membrane is penetrated in a process of degradation and/or decreased synthesis, and direct contact between tumor cells and the surrounding stroma coincides with neovascularization, inflammatory cell influx, and extensive remodeling of extracellular matrix. In this review, we highlight our current knowledge of tumor cell stromal interactions in the mammary gland with particular emphasis on cellular origins and functional phenotypes. We focus both on normal mammary gland and breast tumors and on culture systems developed to dissect individual aspects of cell-cell and cell-extracellular matrix interactions.


Soluble aluminum silicates: stoichiometry, stability, and implications for environmental geochemistry.
Soluble aluminum silicate (Al-Si) complexes are critical species for the development and application of geochemical models. A fluorescence probe technique was used to show that Al-Si complexes account for up to 95% of the total inorganic mononuclear Al in natural waters. The presence of these soluble Al-Si species affects the solubility of Al-Si minerals. Soluble Al-Si species may be important intermediates in the weathering reactions of primary Al-Si minerals and should be considered in dissolution models. Soluble Al-Si species may be key components controlling the formation of metastable and new stable minerals during interactions between water and rocks or soils.


Immersive virtual environment technology: a promising tool for future social and behavioral genomics research and practice.
Social and behavioral research needs to get started now if scientists are to direct genomic discoveries to address pressing public health problems. Advancing social and behavioral science will require innovative and rigorous communication methodologies that move researchers beyond reliance on traditional tools and their inherent limitations. One such emerging research tool is immersive virtual environment technology (virtual reality), a methodology that gives researchers the ability to maintain high experimental control and mundane realism of scenarios; portray and manipulate complex, abstract objects and concepts; and implement innovative implicit behavioral measurement. This report suggests the role that immersive virtual environment technology can play in furthering future research in genomics-related education, decision making, test intentions, behavior change, and health-care provider behaviors. Practical implementation and challenges are also discussed.


An Introduction to Software Tools, Data, and Services for Geospatial Analysis of Stroke Services.
Background: There is interest in the use geospatial data for development of acute stroke services given the importance of timely access to acute reperfusion therapy. This paper aims to introduce clinicians and citizen scientists to the possibilities offered by open source softwares (R and Python) for analyzing geospatial data. It is hoped that this introduction will stimulate interest in the field as well as generate ideas for improving stroke services. Method: Instructions on installation of libraries for R and Python, source codes and links to census data are provided in a notebook format to enhance experience with running the software. The code illustrates different aspects of using geospatial analysis: (1) creation of choropleth (thematic) map which depicts estimate of stroke cases per post codes; (2) use of map to help define service regions for rehabilitation after stroke. Results: Choropleth map showing estimate of stroke per post codes and service boundary map for rehabilitation after stroke. Conclusions The examples in this article illustrate the use of a range of components that underpin geospatial analysis. By providing an accessible introduction to these areas, clinicians and researchers can create code to answer clinically relevant questions on topics such as service delivery and service demand.


Transfer factors for natural radioactivity into olive mill pomace.
The transfer factor (TF) of naturally occurring radioactivity between soil and olive mill pomace (OMP) was calculated in this study. Nine samples were collected from three locations in north Jordan. The study focused on calculating the 226Ra, 232Th, 40K, and 137Cs activity concentrations in both soil and OMP samples using high-purity germanium (HPGe) gamma-ray spectrometry. The average activity levels in the soil samples were determined to be 24.0±10.1, 31.3±9.1, 323.7±68.4, and 1.0±0.4 (Bqkg-1), respectively. In the OMP samples, the average activity levels of 226Ra, 232Th, and 40K were 6.7±1.8, 3.2±1.2, and 185.5±56.6 (Bqkg-1), respectively, while no trace of 137Cs was detected. The activity concentrations of 226Ra, 232Th, and 40K in the soils and OMP samples are within the average worldwide ranges. The calculated values of the TF geometric mean (geometric standard deviation) for 226Ra, 232Th, and 40K were determined to be 0.35 (0.2), 0.11 (0.05), and 0.59 (0.19), respectively. This research offers valuable information about the behavior and movement of radionuclides in the environment.


Trends in survival after surgery for breast cancer metastatic to the brain and spinal column in medicare patients: a population-based analysis.
Central nervous system (CNS) metastases are a common occurrence in patients with breast cancer and are identified in up to 30% of patients at autopsy. To determine population-based estimates of survival times after surgical intervention for Medicare patients with metastatic breast cancer to the brain and spinal column. Female breast cancer patients with metastases to the brain and spinal column and undergoing neurosurgical treatment were identified through the Surveillance, Epidemiology, and End Results-Medicare database. Estimates of survival were calculated with Kaplan-Meier estimation and a Cox proportional hazards model. There were 643 patients who underwent neurosurgical treatment of metastatic disease from 1986 to 2005. Of these patients, 264 underwent cranial surgery and 379 underwent spinal surgery. There were 40 deaths during the postoperative hospital admission for an inpatient postoperative death rate of 6.2%. Inpatient death has declined by approximately 50% for surgeries performed in the most recent decade; however, the 30-day mortality rate of 9.0% has remained constant. The median postoperative survival after cranial surgery was 7.8 months (95% confidence interval, 6.2-9.2), after laminectomy was 9.4 months (95% confidence interval, 6.3-15.7), and after spinal fusion was 15.7 months (95% confidence interval, 11.9-18.5). Survival after spinal fusion has increased by approximately 50% in the recent decade. Patients with increased survival after cranial surgery were younger, had fewer comorbidities, and had longer periods from breast cancer diagnosis to surgery. Patients with increased survival after spinal neurosurgery had lower-grade lesions and longer time periods from breast cancer diagnosis to surgical treatment. After surgically treated metastases, one-third of cranial patients and one-half of spinal patients are alive at 1 year. The overall postoperative survival has increased over time only for spinal fusion procedures.


Improved detection of cortical MS lesions with phase-sensitive inversion recovery MRI.
Cortical grey matter lesions are common in multiple sclerosis (MS), but usually not seen on MRI. The authors compared the performance of double inversion recovery (DIR, currently considered the best available imaging sequence for detecting cortical lesions) with phase-sensitive inversion recovery (PSIR, a sequence allowing much higher resolution scans to be obtained in a clinically feasible time). Sixty MS patients and 30 healthy controls underwent MRI scanning on a 3 Tesla scanner. The authors compared intracortical (IC) and leucocortical (LC) lesion counts obtained with a standard DIR sequence (1×1×3 mm resolution, obtained in 4 min) and a PSIR sequence (0.5×0.5×2 mm, 11 min). Lesions were marked separately on DIR and PSIR scans. In the whole MS cohort, more cortical lesions were seen on the higher-resolution PSIR than the DIR scans (IC mean±SD: 18.1±9.8 vs 5.9±4.5, p<0.001; LC mean±SD: 13.4±12.9 vs 7.3±8.0, p<0.001). On PSIR, ≥1 IC lesion was seen in 60/60 MS patients and 1/30 controls, and ≥1 LC lesion in 60/60 patients and 6/30 controls. On DIR, ≥1 IC lesion was seen in 50/60 patients and 0/30 controls, and ≥1 LC lesion(s) in 60/60 patients and 5/30 controls. Compared with DIR, using PSIR the authors are able to detect a significantly greater number of cortical grey matter lesions. The presence of at least one IC lesion in every MS patient, but very few healthy controls, suggests that it may be a useful adjunct to conventional MRI when a diagnosis of MS is suspected but not confirmed.


Overexpression of VLA-4 in glial-restricted precursors enhances their endothelial docking and induces diapedesis in a mouse stroke model.
The loss of oligodendrocytes after stroke is one of the major causes of secondary injury. Glial-restricted progenitors (GRPs) have remylenating potential after intraparenchymal cerebral transplantation. The intraarterial (IA) injection route is an attractive gateway for global brain delivery, but, after IA infusion, naive GRPs fail to bind to the cerebral vasculature. The aim of this study was to test whether overexpression of Very Late Antigen-4 (VLA-4) increases endothelial docking and cerebral homing of GRPs in a stroke model. Mouse GRPs were co-transfected with DNA plasmids encoding VLA-4 subunits (α4, β1). The adhesion capacity and migration were assessed using a microfluidic assay. In vivo imaging of the docking and homing of IA-infused cells was performed using two-photon microscopy in a mouse middle cerebral artery occlusion (MCAO) model. Compared to naïve GRPs, transfection of GRPs with VLA-4 resulted in >60% higher adhesion (p < 0.05) to both purified Vascular Cell Adhesion Molecule-11 (VCAM-11) and TNFα-induced endothelial VCAM-1. VLA-4+GRPs displayed a higher migration in response to a chemoattractant gradient. Following IA infusion, VLA-4+GRPs adhered to the vasculature at three-fold greater numbers than naïve GRPs. Multi-photon imaging confirmed that VLA-4 overexpression increases the efficiency of GRP docking and leads to diapedesis after IA transplantation. This strategy may be further exploited to increase the efficacy of cellular therapeutics.


Belonolaimus longicaudatus: An Emerging Pathogen of Peanut in Florida.
Sting nematode (Belonolaimus longicaudatus) is an economically important ectoparasitic nematode that is highly pathogenic on a wide range of agricultural crops in sandy soils of the southeastern United States. Although this species is commonly found in Florida in hardwood forests and as a soilborne pathogen on turfgrasses and numerous agronomic and horticultural crops, it has not been reported infecting peanut. In the summers of 2012 and 2013, sting nematode was found infecting three different peanut cultivars being grown on two separate peanut farms in Levy County, FL. The damage consisted of large irregular patches of stunted, chlorotic plants at both farms. The root systems were severely abbreviated and there were numerous punctate-like isolated lesions observed on pegs and pods of infected plants. Sting nematodes were extracted from soil collected around the roots of diseased peanut over the course of the peanut season at both farm sites. Peanut yield from one of these nematode-infested sites was 64% less than that observed in areas free from sting nematodes. The morphological characters of the nematode populations in these fields were congruous with those of the original and other published descriptions of B. longicaudatus. Moreover, the molecular analyses based on the sequences of D2/D3 expansion fragments of 28S rRNA and internal transcribed spacer (ITS) rRNA genes from the nematodes further collaborates the identification of the sting nematode isolates as B. longicaudatus. The sequences were deposited in GenBank (accession no. KF963097, KF963098 for ITS, and KF96399, KF963100 for D2-D3). The results of the phylogenetic analysis using the sequences of these isolates from peanut compared with those of other isolates from Florida suggests that the sting nematode from both peanut farms are genetically close to B. longicaudatus populations occurring in the state. Peanut plants inoculated with both nematode isolates showed punctate-like isolated lesions on pods and pegs, and an abbreviation of their root systems, whereas those symptoms were not observed on noninoculated peanut plants. To our knowledge, this is the first report of large-scale field damage caused by sting nematode infecting peanut grown under field conditions in Florida.


[Effect of electrostimulation of the dorsolateral funiculus of the spinal cord on changes in the cardiac rhythm in acute myocardial ischemia].
The experiments were carried out on inbred white male rats. Cardiac rhythm changes revealed in acute myocardial ischemia under conditions of electrostimulation (ES) of descending sympathicoinhibitory pathways, constituting part of spinal dorsolateral funiculi (DLF) were studied. 10-min stimulation of DLF, started immediately after ligation of the left coronary artery, checked the development of severe cardiac arrhythmia, or considerably weakened the already existing one. The data obtained substantiate the assumption that the onset of cardiac arrhythmia in acute ischemia is associated with the involvement of sympathic preganglionic neurons into the pathologic system, which may be suppressed by the activation of the functionally opposite systems.


Pentoxifylline in diabetic kidney disease (VA PTXRx): protocol for a pragmatic randomised controlled trial.
Diabetic kidney disease (DKD) is the most frequent cause of end-stage renal disease (ESRD) in the USA and worldwide. Recent experimental and clinical data suggest that the non-specific phosphodiesterase inhibitor pentoxifylline (PTX) may decrease progression of chronic kidney disease. However, a large-scale randomised clinical trial is needed to determine whether PTX can reduce ESRD and death in DKD. Veterans Affairs (VA) PTXRx is a pragmatic, randomised, placebo-controlled multicentre VA Cooperative Study to test the hypothesis that PTX, when added to usual care, leads to a reduction in the time to ESRD or death in patients with type 2 diabetes with DKD when compared with usual care plus placebo. The study aims to enrol 2510 patients over a 4-year period with an additional up to 5-year follow-up to generate a total of 646 primary events. The primary objective of this study is to compare the time until ESRD or death (all-cause mortality) between participants randomised to PTX or placebo. Secondary endpoints will be: (1) health-related quality of life, (2) time to doubling of serum creatinine, (3) incidence of hospitalisations for congestive heart failure, (4) incidence of a three-point major adverse cardiovascular events composite (cardiovascular death, non-fatal myocardial infarction, non-fatal stroke), (5) incidence of peripheral vascular disease, (6) change in urinary albumin-to-creatinine ratio from baseline to 6 months and (7) rate of annual change in estimated glomerular filtration rate (eGFR) during the study period. This study was approved by the VA Central Institutional Review Board (cIRB/18-36) and will be conducted in compliance with the Declaration of Helsinki and the Guidelines for Good Clinical Practice. The Hines Cooperative Studies Programme will finalise the study results, which will be published in accordance with the Consolidated Standards of Reporting Trials statement in a peer-reviewed scientific journal. NCT03625648.


Proton beam stereotactic radiosurgery for pediatric cerebral arteriovenous malformations.
For cerebral arteriovenous malformations (AVMs) determined to be high risk for surgery or endovascular embolization, stereotactic radiosurgery (SRS) is considered the mainstay of treatment. To determine the outcomes of pediatric patients with AVMs treated with proton SRS. We reviewed the records of 44 consecutively treated pediatric patients (younger than 18 years of age) who underwent proton SRS at our institution from 1998 to 2010. The median target volume was 4.5 ± 5.9 mL (range, 0.3-29.0 mL) and the median maximal diameter was 3.6 ± 1.5 cm (range, 1-6 cm). Radiation was administered with a median prescription dose of 15.50 ± 1.87 CGE to the 90% isodose. At a median follow-up of 52 ± 25 months, 2 patients (4.5%) had no response, 24 patients (59.1%) had a partial response, and 18 patients (40.9%) experienced obliteration of their AVM. The median time to obliteration was 49 ± 26 months, including 17 patients who underwent repeat proton radiosurgery. Four patients (9%) experienced hemorrhage after treatment at a median time of 45 ± 15 months. Univariate analysis identified modified AVM scale score (P = .045), single fraction treatment (0.04), larger prescription dose (0.01), larger maximum dose (<0.001), and larger minimum dose (0.01) to be associated with AVM obliteration. High-risk AVMs can be safely treated with proton radiosurgery in the pediatric population. Because protons deposit energy more selectively than photons, there is the potential benefit of protons to lower the probability of damage to healthy tissue in the developing brain.


The differential susceptibility of specific neuronal populations: insights from Huntington's disease.
Recent successes in identifying the genes and associated proteins underlying several familial neurodegenerative conditions have not always resulted in accounts as to why the associated patterns of neuronal damage are so specific and limited. Here, with reference to Huntington's disease, we present a general scheme to show how the mutant protein could interact with associated proteins to form an aggregation product. This could lead to neuronal death by direct actions on caspases, or by raising the levels of intracellular calcium ions and reactive oxygen species above a threshold that cannot be resisted by the protection normally conferred by endogenous factors such as calcium binding proteins, free radical scavengers and trophic factors. The local distributions of vulnerability and protective factors could ultimately dictate the pattern of damage induced by the mutant gene.


Virus particles and glycoprotein excreted from cultured cells infected with varicella-zoster virus (VZV).
Virus particles and virus proteins excreted from cultured human embryonic lung (HEL) cells infected with varicella-zoster virus (VZV) were examined by electron microscopy and affinity column chromatography using an antibody to VZV followed by SDS-polyacrylamide gel electrophoresis (SDS-PAGE). Approximately 1 X 10(9) to 2 X 10(9) virus particles/ml with no detectable infectivity, of which 30 to 80% were enveloped, were observed in the culture fluid 48 to 72 h after infection, when cytopathic effect (c.p.e.) appeared. In the sonicated infected cell suspension, 1 X 10(9) to 2 X 10(9) virus particles/ml, of which 30 to 50% were enveloped, were observed and the virus particle/infectivity ratio was approx. 10(6):1. The culture fluid of infected HEL cells labelled with [35S]methionine or [3H]glucosamine was centrifuged at 1000000 g for 2 h to remove virus particles and the supernatant was examined for excreted virus proteins. Affinity column chromatography of the supernatant using immobilized human zoster convalescent serum, led to the isolation of virus antigens which were analyzed by SDS-PAGE. Polypeptides with mol. wt. of approx. 115K and 45K, both of which were glycosylated, were detected, suggesting that these VZV glycoproteins were excreted from the infected cells.


Insulin resistance and HIV infection: a review.
Highly active antiretroviral therapy (HAART) has markedly improved the prognosis of people with HIV infection. However, there are long-term side effects associated with HAART. Alterations in metabolic parameters are common and include hyperlipidaemia and insulin resistance (IR), either in isolation or as part of the lipodystrophy and metabolic syndromes. Insulin resistance is common in HIV-infected people, particularly among those being treated with protease inhibitor therapy. The prevalence of hyperglycaemia and diabetes mellitus is significantly higher in people with HIV infection being treated with antiretrovirals (ARVs), as compared with the general population. Hyperglycaemia is an important risk factor for the development of secondary pathology, including cardiovascular disease. It is therefore important to consider the effects of IR in HIV-infected individuals, and take measures to prevent or manage it appropriately. There is limited evidence for the benefit of pharmacological interventions for IR alone although the metabolic changes and body shape changes of lipodystrophy might benefit from the combined use of metformin with exercise. At present, therefore, it is best to concentrate on preventative measures, including lifestyle modification, the careful selection of ARV drugs, and changing drug combinations where appropriate.


A geographical analysis of ethnic distribution of jaw ameloblastoma in Nigerians.
Ameloblastoma is the most common odontogenic tumour in Nigeria. A definite geographic variation has been observed in the frequency of odontogenic tumors from different parts of the world. However, there is no study on the regional variations in Nigeria. Hence, this study was designed to document the ethnic and geographical distribution of jaw ameloblastoma in Nigeria. Archival data on ameloblastoma from 10 health facilities were obtained. Global Moran's I detected geographic clustering in its distribution while Local Getis Ord indicated the location of ameloblastoma clusters. Chi-square tested associations between variables at 0.05 level of significance. A total of 1,246 ameloblastoma cases were recorded in Nigeria. Besides substantial state variations, a South-North gradient was noticed in its distribution. Significant positive spatial autocorrelation was observed in the three major groups while ameloblastoma hotspots were found in the SouthWestern and Northwestern Nigeria. The Igbos had a higher prevalence of ameloblastoma outside their home region than within. The study hypothesized that the geographical distribution of ameloblastoma in Nigeria is the result of all or one of the following: the country's tropical climate, migration patterns and health seeking behavior. Hopefully, these claims should lead to further enquiry on the underlying causes.


The relationship to age and cerebral vascular accidents of fibrin and fibrinolytic activity.
Three ;normal' groups of people-young, middle-aged, and old-have been investigated with regard to the fibrin content and fibrinolytic activity of the blood. The fourth group consisted of middle-aged people who had previously sustained a cerebral vascular accident matched statistically for age with the middle-aged normals. It was concluded that fibrin increases with age but there is an interaction between age and sex, the female having a higher level in the young group and the male a higher level in the middle-aged group. There was no sex difference in the levels of fibrin in the old age group. Fibrinolytic activity increases with age and there is a positive correlation between fibrin and fibrinolytic activity but no age-sex interaction. Those with cerebral vascular accidents tended to have higher fibrin levels and lower fibrinolytic activity but the differences were not statistically significant. There did, however, appear to be an increase in antifibrinolytic activity in the cerebral vascular group.


Profiling the specificity of neutralizing antibodies in a large panel of plasmas from patients chronically infected with human immunodeficiency virus type 1 subtypes B and C.
Identifying the viral epitopes targeted by broad neutralizing antibodies (NAbs) that sometimes develop in human immunodeficiency virus type 1 (HIV-1)-infected subjects should assist in the design of vaccines to elicit similar responses. Here, we investigated the activities of a panel of 24 broadly neutralizing plasmas from subtype B- and C-infected donors using a series of complementary mapping methods, focusing mostly on JR-FL as a prototype subtype B primary isolate. Adsorption with gp120 immobilized on beads revealed that an often large but variable fraction of plasma neutralization was directed to gp120 and that in some cases, neutralization was largely mediated by CD4 binding site (CD4bs) Abs. The results of a native polyacrylamide gel electrophoresis assay using JR-FL trimers further suggested that half of the subtype B and a smaller fraction of subtype C plasmas contained a significant proportion of NAbs directed to the CD4bs. Anti-gp41 neutralizing activity was detected in several plasmas of both subtypes, but in all but one case, constituted only a minor fraction of the overall neutralization activity. Assessment of the activities of the subtype B plasmas against chimeric HIV-2 viruses bearing various fragments of the membrane proximal external region (MPER) of HIV-1 gp41 revealed mixed patterns, implying that MPER neutralization was not dominated by any single specificity akin to known MPER-specific monoclonal Abs. V3 and 2G12-like NAbs appeared to make little or no contribution to JR-FL neutralization titers. Overall, we observed significant titers of anti-CD4bs NAbs in several plasmas, but approximately two-thirds of the neutralizing activity remained undefined, suggesting the existence of NAbs with specificities unlike any characterized to date.


Matrilin-3 as a putative effector of C-type natriuretic peptide signaling during TGF-β induced chondrogenic differentiation of mesenchymal stem cells.
C-type natriuretic peptide (CNP) signaling has been implicated as an important regulator of chondrogenic differentiation during endochondral bone development. This preliminary study further investigated the putative effectors and/or targets of CNP signaling in transforming growth factor (TGF)-β induced in vitro chondrogenic differentiation of mesenchymal stem cells (MSCs). Previously characterized human trabecular bone derived MSCs were induced either with only TGF-β1 or with a combination of TGF-β1 and CNP in micromass culture for 10 or 20 days. Genome wide gene expression profile changes in between these two groups were analyzed on day-10 or day-20 of culture. Results revealed that there were only 7 genes, whose expression change was fourfolds or higher in TGF-β1 and CNP fed group in comparison to only TGF-β1 fed group. The up-regulated genes included matrilin-3 (MATN3), engulfment and cell motility 1 (ELMO1), CD24, and DCN1, defective in cullin neddylation 1, domain containing 1 (DCUN1D1). The down-regulated genes, on the other hand, included LIM domain kinase 2 (LIMK2), Ewing sarcoma breakpoint region 1, and guanine nucleotide binding protein (G protein), gamma 12 (GNG12). The up-regulation of MATN3 was confirmed on the basis of RT-PCR. The known literature on both CNP signaling and MATN3 function in chondrogenesis match with each other and suggest MATN3 as a putative effector and/or target of CNP signaling during this process.


Somatic SNPs of the BRCA2 gene at the fragments encoding RAD51 binding sites of canine mammary tumors.
Mammary tumors are the most common tumor type both in women and in female dogs. In women, heritable breast cancers have been linked mutations in the breast cancer susceptibility gene BRCA2 and it contains eight BRC repeats in exon 11 that bind to RAD51. In this study, we investigated the sequence variations of BRC1-BRC8 and C-terminus of canine BRCA2 gene. From a total of 64 canine patients with mammary tumors, 31 mammary tumors with benign and malign carcinomas and the 3 normal mammary glands were used for the study. In this study, 19 SNPs of exon 11 of BRCA2 in canine mammary tumors were detected for the first time. The c.2383A>C (T1425P) SNP was found to be the most probable disease-associated nsSNP. Our findings suggest that T1425P variation in BRC3 to be the most probable disease-associated nsSNP and may affect RAD51 binding strength.


Increased brown adipose tissue oxidative capacity in cold-acclimated humans.
Recent studies examining brown adipose tissue (BAT) metabolism in adult humans have provided convincing evidence of its thermogenic potential and role in clearing circulating glucose and fatty acids under acute mild cold exposure. In contrast, early indications suggest that BAT metabolism is defective in obesity and type 2 diabetes, which may have important pathological and therapeutic implications. Although many mammalian models have demonstrated the phenotypic flexibility of this tissue through chronic cold exposure, little is known about the metabolic plasticity of BAT in humans. Our objective was to determine whether 4 weeks of daily cold exposure could increase both the volume of metabolically active BAT and its oxidative capacity. Six nonacclimated men were exposed to 10°C for 2 hours daily for 4 weeks (5 d/wk), using a liquid-conditioned suit. Using electromyography combined with positron emission tomography with [(11)C]acetate and [(18)F]fluorodeoxyglucose, shivering intensity and BAT oxidative metabolism, glucose uptake, and volume before and after 4 weeks of cold acclimation were examined under controlled acute cold-exposure conditions. The 4-week acclimation protocol elicited a 45% increase in BAT volume of activity (from 66 ± 30 to 95 ± 28 mL, P < .05) and a 2.2-fold increase in cold-induced total BAT oxidative metabolism (from 0.725 ± 0.300 to 1.591 ± 0.326 mL·s(-1), P < .05). Shivering intensity was not significantly different before compared with after acclimation (2.1% ± 0.7% vs 2.0% ± 0.5% maximal voluntary contraction, respectively). Fractional glucose uptake in BAT increased after acclimation (from 0.035 ± 0.014 to 0.048 ± 0.012 min(-1)), and net glucose uptake also trended toward an increase (from 163 ± 60 to 209 ± 50 nmol·g(-1)·min(-1)). These findings demonstrate that daily cold exposure not only increases the volume of metabolically active BAT but also increases its oxidative capacity and thus its contribution to cold-induced thermogenesis.


Monolithic cells for solar fuels.
Hybrid energy generation models based on a variety of alternative energy supply technologies are considered the best way to cope with the depletion of fossil energy resources and to limit global warming. One of the currently missing technologies is the mimic of natural photosynthesis to convert carbon dioxide and water into chemical fuel using sunlight. This idea has been around for decades, but artificial photosynthesis of organic molecules is still far away from providing real-world solutions. The scientific challenge is to perform in an efficient way the multi-electron transfer reactions of water oxidation and carbon dioxide reduction using holes and single electrons generated in an illuminated semiconductor. In this tutorial review the design of photoelectrochemical (PEC) cells that combine solar water oxidation and CO2 reduction is discussed. In such PEC cells simultaneous transport and efficient use of light, electrons, protons and molecules has to be managed. It is explained how efficiency can be gained by compartmentalisation of the water oxidation and CO2 reduction processes by proton exchange membranes, and monolithic concepts of artificial leaves and solar membranes are presented. Besides transferring protons from the anode to the cathode compartment the membrane serves as a molecular barrier material to prevent cross-over of oxygen and fuel molecules. Innovative nano-organized multimaterials will be needed to realise practical artificial photosynthesis devices. This review provides an overview of synthesis techniques which could be used to realise monolithic multifunctional membrane-electrode assemblies, such as Layer-by-Layer (LbL) deposition, Atomic Layer Deposition (ALD), and porous silicon (porSi) engineering. Advances in modelling approaches, electrochemical techniques and in situ spectroscopies to characterise overall PEC cell performance are discussed.


Regulation of serotonin2 (5-HT2) receptors labeled with [3H]spiroperidol by chronic treatment with the antidepressant amitriptyline.
Recently, we reported that chronic administration of several antidepressants of different classes produced larger reductions in numbers of serotonin2 (5-HT2) receptors in rat brain labeled by [3H[spiroperidol than in beta adrenergic receptors. In the present study, we examine detailed properties of 5-HT2 receptor regulation by chronic treatment with amitriptyline. Chronic but not acute treatment with the tricyclic antidepressant amitriptyline reduces binding to 5-HT2 receptors by [3H]spiroperidol and beta adrenergic receptor binding of [3H]dihydroalprenolol in brain membranes. The decrease is time-dependent, gradually reversible and represents a change in the number of binding sites with no alteration in drug affinities for 5-HT2 receptors. The effect can be observed at daily doses of 2.5 mg/kg, similar to clinically effective doses in humans. At all doses and time intervals, the decrease in 5-HT2 receptors is more marked than the concurrent change in total beta adrenergic receptor binding. The properties of 5-HT2 receptor reduction after chronic antidepressant treatment indicate that this alteration could be associated with therapeutic response.


Molecular evolution of Wnt2b orthologs.
WNT family proteins transduce signals through Frizzled (FZD) receptors with extracellular WNT-binding domain and cytoplasmic Dishevelled-binding domain. WNT2B-ST7L and WNT2-ST7 loci are paralogous regions within the human genome. WNT2B isoform 2 and WNT2 are canonical WNTs to activate the beta-catenin - TCF pathway in human cancer, especially in gastric cancer. Here, the rat Wnt2b gene was identified and characterized by using bioinformatics. The rat Wnt2b gene, consisting of five exons, was located within AC106372.5 genome sequence. Wnt2b core promoter region (nucleotide position 234449-233652 of AC106372.5 rat genome sequence) was identified as an evolutionarily conserved region. GC content of rat Wnt2b promoter was 71.8%. Nucleotide identity between human and rat Wnt2b promoters was 71.2%. E box, CP2-binding site, CCAAT box and ZNFN1A1 (IKAROS)-binding site were located within the conserved region of rat Wnt2b, mouse Wnt2b, and human WNT2B promoters. Rat Wnt2b (391 aa), human WNT2B isoform 2 and other vertebrate Wnt2b orthologs were type II transmembrane proteins with cleavable extracellular WNT domain, while vertebrate Wnt2 orthologs were secreted proteins. Twenty-four Cys residues were conserved among vertebrate Wnt2b and Wnt2 orthologs. Glycosylation sites at Asn 283 of rat Wnt2b and RGD motif were identified within mammalian Wnt2b orthologs, but not within vertebrate Wnt2 orthologs and zebrafish wnt2b. Zebrafish wnt2b acquired N-terminal cytoplasmic region to evolve into type II transmembrane protein, and then mammalian Wnt2b orthologs acquired integrin-targeting RGD motif within the extracellular WNT domain. This is the first report on the rat Wnt2b gene as well as on molecular evolution of the Wnt2b orthologs.


Comparative evaluation of genome-wide gene expression profiles in ruptured and unruptured human intracranial aneurysms.
Few studies have evaluated the over or the underexpression of genes directly in samples of aneurysmal wall and extracranial pericranial vascular tissue to investigate the genetic influence in formation and rupture of intracranial aneurysms. We present the results obtained using the DNA microarray technique analysis on sample tissues collected during surgery. We collected and analyzed 12 aneurismal and 9 peripheral arteries (superficial temporal (STA) and middle meningeal artery (MMA) specimens from ruptured aneurysm group patients (13 cases), 10 aneurismal and 12 STA and MMA samples from unruptured aneurysm group patients (14 cases) and 5 STA and MMA artery specimens from control group patients (4 cases). Total RNA was isolated from samples and subjected to cDNA microarray analysis with the use of the human genome U133A GeneChip oligonucleotide microarray (Affymetrix, Santa Clara, CA), which allows to analyze a total number of 14,500 genes in the same time. For genes of interest, real-time RT-PCR was performed to confirm their expression level. Total RNA was isolated from samples and subjected to DNA microarray analysis with the use of the human genome U133A GeneChip oligonucleotide microarray, which allows to analyze a total number of 14,500 genes at the same time. For genes of interest, real-time RT-PCR was performed to confirm their expression level. Regarding ruptured aneurysms, genes were identified showing differential expressions (overexpressed or downregulated) pertaining to specific pathways, particularly those for the structural proteins of the extracellular matrix, members of matrix metalloproteinase (MMP) family (which resulted as being overexpressed) and genes involved in apoptotic phenomena. Particularly, real-time RT-PCR analysis confirmed the upregulation of MMP-2, MMP-9 and pro-apoptotic genes, such as Fas, Bax and Bid, and the downregulation of anti-apoptotic genes, such as Bcl-X(L) and Bcl-2. In a compared analyses of ruptured vs unruptured aneurysms, a different expression was also detected regarding gene coding the tissue inhibitor of matrix metalloproteinases 3 (TIMP-3), which appeared markedly downregulated in unruptured aneurysms, where its expression in unruptured aneurysms was similar to that observed in controls. Another gene differently expressed is nitric oxide synthase (iNOS), which appeared overexpressed in ruptured aneurysms when compared to unruptured aneurysms. Our study is the first, to our knowledge, that compares gene expression profiles (genoma-wide) in intracranial aneurysms. The results of our study suggest that the inhibitor of the metalloproteinase, the pathway of nitric oxide and the apoptotic process play a key-role in reducing the resistance of the arterial wall, that can result in formation and rupture of the intracranial aneurysms.


Depression, Anxiety, and Anger in Patients with Polycystic Ovary Syndrome.
Polycystic Ovary Syndrome (PCOS) is a syndrome of heterogeneous nature, affecting multiple systems, particularly the endocrine system. We propose to investigate the possible relationships among hormonal changes, levels of anxiety, depression, and anger in patients with PCOS. Forty-four female patients with PCOS and 44 body mass index (BMI )-matched healthy women participated in this study. We measured the sociodemographic features, some serum hormonal levels (insulin, gonadotropins, prolactin, dehydroepiandrosterone sulfate (DHEAS), thyroid-stimulating hormone (TSH), triiodothyronine (T3), thyroxine (T4), 17 OH-progesterone, and total and free testosterone), and some other biochemical parameters of the participants. Also, all participants completed the Trait Anger-Anger Expression Scale (STAS), Beck Depression, and Beck Anxiety Inventories. We evaluated the psychiatric scale scores obtained from PCOS patients and control subjects. We used the independent-samples t-test for parametric data to evaluate normal distribution, and Mann-Whitney U-test was used for both abnormally distributed and nonparametric data. We used Pearson correlation analysis to evaluate the potential connection between the two groups' data. The mean ages of the patients with PCOS and control subjects who participated in this study were 27.3±5.6 and 27.4±6.1 years, respectively. The measures of BMI, insulin, luteinizing hormone (LH), DHEAS, and total testosterone serum levels in the patient group were significantly higher than in the control group (p<.05). There was a statistically significant positive correlation between Beck anxiety scores and serum DHEAS levels (Pearson r=.4366, P=.0001). We found significant differences between the two groups in terms of trait anger, anger control, outward and inward anger, anxiety level, and depression scores (P<.05). Anxiety symptoms indicate a stronger relationship compared to depression with DHEAS serum levels via the autonomic nervous system, considering the gamma-aminobutyric acid (GABA)-antagonistic effect of DHEAS. Obesity, hirsutism, and infertility may reduce self-confidence and create depressive symptoms in patients with PCOS. In addition, changes in hormonal levels may lead to anxiety directly. Possibly, depressive symptoms are a secondary reflection of these changes.


Composition, structure, morphology and physicochemical properties of lablab bean, navy bean, rice bean, tepary bean and velvet bean starches.
The composition, morphology, structure and physicochemical properties of starches from lablab bean, navy bean, rice bean, tepary bean and velvet bean were examined. Starch yield (on a whole seed basis), total lipid, apparent amylose (AM) and starch damage were in the range 20.6-29.9%, 0.48-0.62%, 22.1-32.1% and 0.004-0.011%, respectively. Difference in amylopectin chain length distribution amongst the starches was marginal. The starches differed significantly with respect to granule morphology, molecular order, molecular orientation, double helical content, gelatinization parameters, swelling factor, AM leaching, thermal stability and enzyme hydrolysis. The results showed that interplay amongst differences in molecular order, double helical content, relative crystallinity, AM content, granule morphology and the extent of interaction between and amongst starch chains within the amorphous and crystalline domains, influenced thermal, rheological and digestibility properties.