Role of miR206 in genistein-induced rescue of pulmonary hypertension in monocrotaline model.
Pulmonary hypertension (PH) is a progressive lung disease associated with proliferation of smooth muscle cells and constriction of lung microvasculature, leading to increased pulmonary arterial pressure, right ventricular failure, and death. We have previously shown that genistein rescues preexisting established PH by significantly improving lung and heart function. (Matori H, Umar S, Nadadur RD, Sharma S, Partow-Navid R, Afkhami M, Amjedi M, Eghbali M. Hypertension 60: 425-430, 2012). Here, we have examined the role of microRNAs (miRs) in the rescue action of genistein in monocrotaline (MCT)-induced PH in rats. Our miR microarray analysis on the lung samples from control, PH, and genistein-rescue group revealed that miR206, which was robustly upregulated to ∼11-fold by PH, was completely normalized to control levels by genistein treatment. Next, we examined whether knockdown of miR206 could reverse preexisting established PH. PH was induced in male rats by 60 mg/kg of MCT, and rats received three intratracheal doses of either miR206 antagomir (10 mg/kg body wt) or scrambled miR control at days 17, 21, and 26. Knockdown of miR206 resulted in significant improvement in the cardiopulmonary function, as right ventricular pressure was significantly reduced to 38.6 ± 3.61 mmHg from 61.2 ± 5.4 mmHg in PH, and right ventricular hypertrophy index was decreased to 0.35 ± 0.04 from 0.59 ± 0.037 in PH. Knockdown of miR206 reversed PH-induced pulmonary vascular remodeling in vivo and was associated with restoration of PH-induced loss of capillaries in the lungs and induction of vascular endothelial growth factor A expression. In conclusion, miR206 antagomir therapy improves cardiopulmonary function and structure and rescues preexisting severe PH in MCT rat model possibly by stimulating angiogenesis in the lung.


Physical activity and movement in children: its consequences for growth and development.
The value of physical activity to health and fitness and normal growth and development is undisputed. In contrast, lack of exercise or excesses in physical activity can be harmful to the growth and development process. Normal physical maturation represents a succession of events which appear in the same sequence in all individuals but vary in both starting point and speed of occurrence. It is often difficult to distinguish the effects of regular physical activity upon fitness from the changes associated with growth and maturation. An integral component of the relationship between health and fitness is body composition. Maintenance of a desirable body composition is an integral component in health status and in the evaluation of health, fitness and physical performance of individuals. Traditionally, discussions that have considered the benefits of regular physical activity have referenced cardiorespiratory and other components of physical fitness such as muscular strength and endurance. More recently, body composition has received considerable attention with numerous individuals of all ages preoccupied with body characteristics such as body fat and muscularity. Less recognition has been given to the role that exercise plays in the maintenance of skeletal health and the potential benefits to be gained by this component of body composition. This is gradually changing with the knowledge that osteoporosis is mediated by nutritional, physical activity and hormonal influences and that inappropriate physical activity can be potentially hazardous to the immature and mature skeleton. Regular physical activity that provides an appropriate weight bearing stimulus is critical for the maintenance of desirable body composition including normal skeletal health, irrespective of age or sex. Benefits derived for body composition are equally important to personal health as the development of other components of fitness.


Selective Neutral pH Inhibitor of Cathepsin B Designed Based on Cleavage Preferences at Cytosolic and Lysosomal pH Conditions.
Cathepsin B is a cysteine protease that normally functions within acidic lysosomes for protein degradation, but in numerous human diseases, cathepsin B translocates to the cytosol having neutral pH where the enzyme activates inflammation and cell death. Cathepsin B is active at both the neutral pH 7.2 of the cytosol and the acidic pH 4.6 within lysosomes. We evaluated the hypothesis that cathepsin B may possess pH-dependent cleavage preferences that can be utilized for design of a selective neutral pH inhibitor by (1) analysis of differential cathepsin B cleavage profiles at neutral pH compared to acidic pH using multiplex substrate profiling by mass spectrometry (MSP-MS), (2) design of pH-selective peptide-7-amino-4-methylcoumarin (AMC) substrates, and (3) design and validation of Z-Arg-Lys-acyloxymethyl ketone (AOMK) as a selective neutral pH inhibitor. Cathepsin B displayed preferences for cleaving peptides with Arg in the P2 position at pH 7.2 and Glu in the P2 position at pH 4.6, represented by its primary dipeptidyl carboxypeptidase and modest endopeptidase activity. These properties led to design of the substrate Z-Arg-Lys-AMC having neutral pH selectivity, and its modification with the AOMK warhead to result in the inhibitor Z-Arg-Lys-AOMK. This irreversible inhibitor displays nanomolar potency with 100-fold selectivity for inhibition of cathepsin B at pH 7.2 compared to pH 4.6, shows specificity for cathepsin B over other cysteine cathepsins, and is cell permeable and inhibits intracellular cathepsin B. These findings demonstrate that cathepsin B possesses pH-dependent cleavage properties that can lead to development of a potent, neutral pH inhibitor of this enzyme.


Implementation of a Standardized Data-Collection System for Comprehensive Appraisal of Cleft Care.
Our objective is to describe the process of adapting a conceptual framework into a practical toolkit for one cleft team. This is a single-arm implementation study in a single institution. Implementation took place at a mid-sized multidisciplinary clinic for patients with cleft lip and/or palate (CL/P) from urban/suburban and rural areas across North Carolina and neighboring states. Eligible participants were patients with CL/P from English-speaking families. Sixty patients entered and finished the study. The implementation of a prospective data collection system based on the International Consortium for Health Outcomes Measurement (ICHOM) standard set of outcome measures for CL/P was accomplished in multiple stages. Patient- and clinician-reported forms and protocols for gathering data were created. Team members were trained and the system was tested; finally, the system was deployed. Success was appraised using the RE-AIM framework to assess reach, effectiveness, adoption, implementation, and maintenance. Ninety-eight percent of patients and all team members agreed to participate. Ninety-four percent of required data were captured. Adaptations to friction points were made; specifically, visible reminders were affixed to charts, primary clinicians were required to assume data entry responsibility, and e-mail reminders were instituted. Development cost was US$7707; average time cost per clinician was 21 min/wk. Conceptual frameworks for outcomes studies must be tailored to their environments; otherwise, they cannot be practically implemented and sustained. We present this process for a cleft team using the ICHOM standard set. The process may help other teams implement the standard set or other conceptual frameworks.


Characterization of the distribution of spin-lattice relaxation rates of lipid spin labels in fiber cell plasma membranes of eye lenses with a stretched-exponential function.
The stretched exponential function (SEF) was used to analyze and interpret saturation recovery (SR) electron paramagnetic resonance (EPR) data obtained from spin-labeled porcine eye-lens membranes. This function has two fitting parameters: the characteristic spin-lattice relaxation rate (T 1str -1) and the stretching parameter (β), which ranges between zero and one. When β = 1, the function is a single exponential. It is assumed that the SEF arises from a distribution of single exponential functions, each described by a T 1 value. Because T 1 -1s are determined primarily by the rotational diffusion of spin labels, they are a measure of membrane fluidity. Since β describes the distribution of T 1 -1s, it can be interpreted as a measure of membrane heterogeneity. The SEF was used to analyze SR data obtained from intact cortical and nuclear fiber cell plasma membranes extracted from the eye lenses of two-year old animals and spinlabeled with phospholipid- and cholesterol-analogs. The lipid environment sensed by these probe molecules was found to be less fluid and more heterogeneous in nuclear membranes than in cortical membranes. Parameters T 1str -1 and β were also used for a multivariate K-means cluster analysis of stretched-exponential data. This analysis indicates that SEF data can be assigned accurately to clusters in nuclear or cortical membranes. In future work, the SEF will be applied to analyze data from human eye lenses of donors with differing health histories.


The importance of norepinephrine in depression.
Depression is one of the most common psychological diseases with significant potential morbidity and mortality. Although the underlying pathophysiology of depression has not been clearly defined, preclinical and clinical evidence suggest disturbances in serotonin (5-HT), norepinephrine (NE), and dopamine (DA) neurotransmission in the central nervous system. Virtually all currently available antidepressants act on one or more of the following mechanisms: inhibition of reuptake of 5-HT or NE (and DA), antagonism of inhibitory presynaptic 5-HT or NE receptors, or inhibition of monoamine oxidase. All of these mechanisms result in an enhanced neurotransmission of 5-HT and/or NE. Evidence for the involvement of NE in depression is abundant, and recent studies on neuronal pathways and symptoms highlight the specific role of NE in this disorder. NE plays a determinant role in executive functioning regulating cognition, motivation, and intellect, which are fundamental in social relationships. Social dysfunction is possibly one of the most important factors affecting the quality of life in depressed patients.


Phylogenetic reassessment of tribe Anemoneae (Ranunculaceae): Non-monophyly of Anemone s.l. revealed by plastid datasets.
Morphological and molecular evidence strongly supported the monophyly of tribe Anemoneae DC.; however, phylogenetic relationships among genera of this tribe have still not been fully resolved. In this study, we sampled 120 specimens representing 82 taxa of tribe Anemoneae. One nuclear ribosomal internal transcribed spacer (nrITS) and six plastid markers (atpB-rbcL, matK, psbA-trnQ, rpoB-trnC, rbcL and rps16) were amplified and sequenced. Both Maximum likelihood and Bayesian inference methods were used to reconstruct phylogenies for this tribe. Individual datasets supported all traditional genera as monophyletic, except Anemone and Clematis that were polyphyletic and paraphyletic, respectively, and revealed that the seven single-gene datasets can be split into two groups, i.e. nrITS + atpB-rbcL and the remaining five plastid markers. The combined nrITS + atpB-rbcL dataset recovered monophyly of subtribes Anemoninae (i.e. Anemone s.l.) and Clematidinae (including Anemoclema), respectively. However, the concatenated plastid dataset showed that one group of subtribes Anemoninae (Hepatica and Anemone spp. from subgenus Anemonidium) close to the clade Clematis s.l. + Anemoclema. Our results strongly supported a close relationship between Anemoclema and Clematis s.l., which included Archiclematis and Naravelia. Non-monophyly of Anemone s.l. using the plastid dataset indicates to revise as two genera, new Anemone s.l. (including Pulsatilla, Barneoudia, Oreithales and Knowltonia), Hepatica (corresponding to Anemone subgenus Anemonidium).


The lncRNA n340790 accelerates carcinogenesis of thyroid cancer by regulating miR-1254.
Long non-coding RNAs (lncRNAs) have been recently reported to be dysregulated and play a critical role in the progression of thyroid cancer. Here, we found that the lncRNA n340790 was highly expressed in human thyroid cancer tissues and was strongly correlated with the clinical characteristics of patients. There was a good prognostic value of n340790 for thyroid cancer. In vitro overexpression of n340790 promoted the development of thyroid cancer, while silencing n340790 inhibited this process. Additionally, n340790 accelerated the growth of thyroid cancer tumor in vivo. Furthermore, we discovered that n340790 could act as an endogenous sponge by directly binding to miR-1254 and downregulating miR-1254 expression. In addition, miR-1254 could inhibit the stimulatory effect of n340790 on the growth and invasion of thyroid cancer cells. In conclusion, n340790 promoted the development process of malignant thyroid cancer by regulating miR-1254, and targeting n340790 may be a promising strategy as a thyroid cancer therapy.


Diagnostic performance of breast ultrasonography and MRI in the prediction of lymph node status after neoadjuvant chemotherapy for breast cancer.
Background Neoadjuvant chemotherapy (NAC) is widely used to treat breast cancer. Sentinel lymph node biopsy has replaced axillary lymph node dissection in patients who convert to node-negative status after NAC. However, few studies have evaluated the diagnostic performance of ultrasonography and magnetic resonance imaging (MRI) in determining axillary lymph node status after NAC. Purpose To evaluate the diagnostic performance of breast ultrasonography and MRI in determining residual metastatic axillary lymph node status after NAC for breast cancer and to identify histopathological factors affecting radiological performance. Material and Methods This study included 157 patients who underwent initial and follow-up preoperative breast ultrasonography and MRI before NAC between January and December 2010. The sensitivity, specificity, negative and positive predictive values, and accuracy of ultrasonography, MRI, and their combinations were evaluated. Results The sensitivity of ultrasonography, MRI, and their combination in post-NAC axillary imaging was 60.00%, 57.33%, and 65.33%, respectively; the specificity was 60.47%, 72.09%, and 60.47%, respectively. The positive predictive value was highest with MRI (78.18%). On univariate analysis, positive estrogen receptor status was associated with misdiagnosis by ultrasonography ( P = 0.002), MRI ( P = 0.002), and their combination ( P = 0.001). When residual metastatic lymph nodes were present, lymph nodes with macrometastasis (>2.0 mm) were associated with correct ultrasonography-based diagnosis ( P = 0.0027). Conclusion Imaging assists in predicting axillary lymph node status in patients undergoing NAC; however, is imprudent to omit sentinel lymph node biopsy or axillary lymph node dissection for staging in women determined to be node-positive.


Health Information on Pre-Exposure Prophylaxis From Search Engines and Twitter: Readability Analysis.
Pre-exposure prophylaxis (PrEP) is proven to prevent HIV infection. However, PrEP uptake to date has been limited and inequitable. Analyzing the readability of existing PrEP-related information is important to understand the potential impact of available PrEP information on PrEP uptake and identify opportunities to improve PrEP-related education and communication. We examined the readability of web-based PrEP information identified using search engines and on Twitter. We investigated the readability of web-based PrEP documents, stratified by how the PrEP document was obtained on the web, information source, document format and communication method, PrEP modality, and intended audience. Web-based PrEP information in English was systematically identified using search engines and the Twitter API. We manually verified and categorized results and described the method used to obtain information, information source, document format and communication method, PrEP modality, and intended audience. Documents were converted to plain text for the analysis and readability of the collected documents was assessed using 4 readability indices. We conducted pairwise comparisons of readability based on how the PrEP document was obtained on the web, information source, document format, communication method, PrEP modality, and intended audience, then adjusted for multiple comparisons. A total of 463 documents were identified. Overall, the readability of web-based PrEP information was at a higher level (10.2-grade reading level) than what is recommended for health information provided to the general public (ninth-grade reading level, as suggested by the Department of Health and Human Services). Brochures (n=33, 7% of all identified resources) were the only type of PrEP materials that achieved the target of ninth-grade reading level. Web-based PrEP information is often written at a complex level for potential and current PrEP users to understand. This may hinder PrEP uptake for some people who would benefit from it. The readability of PrEP-related information found on the web should be improved to align more closely with health communication guidelines for reading level to improve access to this important health information, facilitate informed decisions by those with a need for PrEP, and realize national prevention goals for PrEP uptake and reducing new HIV infections in the United States.


Polycomb-group histone methyltransferase CLF is required for proper somatic recombination in Arabidopsis.
Homologous recombination (HR) is a key process during meiosis in reproductive cells and the DNA damage repair process in somatic cells. Although chromatin structure is thought to be crucial for HR, only a small number of chromatin modifiers have been studied in HR regulation so far. Here, we investigated the function of CURLY LEAF (CLF), a Polycomb-group (PcG) gene responsible for histone3 lysine 27 trimethylation (H3K27me3), in somatic and meiotic HR in Arabidopsis thaliana. Although fluorescent protein reporter assays in pollen and seeds showed that the frequency of meiotic cross-over in the loss-of-function mutant clf-29 was not significantly different from that in wild type, there was a lower frequency of HR in clf-29 than in wild type under normal conditions and under bleomycin treatment. The DNA damage levels were comparable between clf-29 and wild type, even though several DNA damage repair genes (e.g. ATM, BRCA2a, RAD50, RAD51, RAD54, and PARP2) were expressed at lower levels in clf-29. Under bleomycin treatment, the expression levels of DNA repair genes were similar in clf-29 and wild type, thus CLF may also regulate HR via other mechanisms. These findings expand the current knowledge of PcG function and contribute to general interests of epigenetic regulation in genome stability regulation.


Tunable Triplet-Mediated Multicolor Lasing from Nondoped Organic TADF Microcrystals.
Thermally activated delayed fluorescent (TADF) emitters have received great attention in organic light-emitting diodes and laser diodes because of high exciton utilization efficiency and low optical loss caused by triplets. However, the direct observation of lasing emission from nondoped TADF microcrystals has yet to be reported. Here, we demonstrated a three-color (green, yellow, and red) microlaser from three nondoped TADF microcrystals with well-controlled geometries. The temperature-dependent dynamic analyses testify that the regenerated singlets which originated from the reverse intersystem crossing process at room temperature are beneficial for population inversion and reduce triplet-absorption/annihilation optical loses, together resulting in thermally activated lasing actions. Thanks to single-crystalline structures of TADF emitters, the relationship between triplet-harvesting capability and the molecular structure was systematically investigated. The results not only offer rational design of pure TADF gain materials but also provide guidance for the high-performance electrically driven organic solid-state lasers and multicolor laser integration.


A hydrophobic cluster in the center of the third extracellular loop is important for thyrotropin receptor signaling.
Previous reports on the follicle-stimulating hormone receptor and choriogonadotropic/LH receptor, which belong to the glycoprotein hormone receptor family, suggest that the extracellular loop (ECL) 3 could be a key domain for ligand binding and intramolecular receptor signaling. In contrast to ECLs 1 and 2 of glycoprotein hormone receptors, the ECL3 displays high sequence homology, particularly in the central portion of the loop. Therefore, we opted to identify amino acids with functional importance within ECL3 of the TSH receptor (TSHR). Single alanine substitutions of all residues in ECL3 were generated. Functional characterization revealed the importance of five amino acids in the central portion of ECL3 and K660 at the ECL3/transmembrane helix (TMH) 7 junction for TSHR signaling. Decrease of G(s) activation and loss of G(q) activation by substitutions of K660 demonstrates a role for this position for TSHR conformation and signal transduction. By molecular modeling, we predicted potential interaction partners of K660:E409 and D410 in the N terminus of TMH1 and D573 in the ECL2. Complementary double mutants did not reconstitute G(s)/G(q)-mediated signaling, suggesting that K660 is not directly involved in a structural unit between ECL3 and the N terminus of TMH1. These results support a TSHR model in which the side chain of K660 is orientated toward the backbone of ECL2. Moreover, our findings provide evidence that a hydrophobic cluster, comprising residues 652-656 of ECL3, strongly influences intramolecular signal transduction and G protein activation of the TSHR.


Plasma adiponectin: a predictor of coronary heart disease in hemodialysis patients--a Japanese prospective eight-year study.
Plasma adiponectin may play a protective role in the pathogenesis of cardiovascular disease in hemodialysis (HD) patients. We examined the effect of plasma adiponectin levels on the prognosis of the HD patients. 68 HD patients (male:female = 38:30) were subjected to plasma adiponectin measurement in 1998 and followed up over 8 years. Plasma adiponectin concentrations differed between male and female patients (9.3 vs. 15.7 microg/ml). The plasma adiponectin concentration as a whole was positively correlated with serum high-density lipoprotein cholesterol and negatively with serum creatinine and waist circumference. During an 8-year follow-up, the cardiac events occurred in 7 of 38 men and in 10 of 30 women. Cox's proportional hazard model analysis in a stepwise manner revealed that coronary heart disease (CHD) was associated with intact parathyroid hormone concentration, age, and the presence of diabetes in men whereas plasma adiponectin concentration was the most powerful single predictor in women. The impact of the plasma adiponectin concentration was strengthened by Kaplan-Meier survival analysis. In the group with a lower plasma adiponectin concentration, CHD events were significantly increased in men (p = 0.043) and in women (p = 0.007). Plasma adiponectin concentration may predict CHD outcomes in HD patients.


Treatment with L-citrulline in patients with post-polio syndrome: study protocol for a single-center, randomised, placebo-controlled, double-blind trial.
Post-polio syndrome (PPS) is a condition that affects polio survivors years after recovery from an initial acute infection by the Poliomyelitis virus. Most often, patients who suffered from polio start to experience gradual new weakening in muscles, a gradual decrease in the size of muscles (muscle atrophy) and fatigue years after the acute illness. L-citrulline is known to change muscular metabolism synthesis by raising nitric oxide (NO) levels and increasing protein synthesis. This investigator-initiated, randomised, placebo-controlled, double-blind, trial aims to demonstrate that L-citrulline positively influences muscle function and increases muscular energy production in patients with PPS. Thirty ambulant PPS patients will be recruited in Switzerland. Patients will be randomly allocated to one of the two arms of the study (placebo:verum 1:1). After a 24-week run-in phase to observe natural disease history and progression, participants will be treated either with L-citrulline or placebo for 24 weeks. The primary endpoint is change in the 6-min Walking Distance Test. Secondary endpoints will include motor function measure, quantitative muscle force, quantitative muscle magnetic resonance imaging and magnetic resonance spectroscopy and serum biomarker laboratory analysis DISCUSSION: The aim of this phase IIa trial is to determine if treatment with L-citrulline shows a positive effect on clinical function and paraclinical biomarkers in PPS. If treatment with L-citrulline shows positive effects, this might represent a cost-efficient symptomatic therapy for PPS patients. ClinicalTrial.gov, ID: NCT02801071 . Registered on 6 June 2016.


[Noninvasive quantitative assessment of atherosclerosis with the pulse wave velocity (PWV) and the computed tomography of the abdominal aorta].
Noninvasive quantitative assessment of atherosclerosis should be useful for the prevention of cardiovascular diseases. The pulse wave velocity is a physiological examination and one of the good tool for the determination of sclerosis. Aging and hypertension should be major risk factors to increase the PWV and the higher content of elastin in the arterial wall could make the PWV lower, but few reports exit about the influence of hyper-lipidemia on PWV. The aoPWV in diabetic patients had higher than that in non diabetic and IGT patients. Wall thickening and or calcification accumulation of the lower abdominal aorta was measured to assess the progression of atherosclerosis by using CT and the image colour analysis. We found the good correlation between the aortic calcification-stenosis indices and the coronary stenosis indices, and significant higher levels in patients with cardiovascular diseases.


Identification of a nuclear export signal in the KSHV latent protein LANA2 mediating its export from the nucleus.
LANA2 is a latent protein detected in Kaposi's sarcoma-associated herpesvirus (KSHV)-infected B cells that inhibits p53-dependent transcriptional transactivation and apoptosis and PKR-dependent apoptosis, suggesting an important role in the transforming activity of the virus. It has been reported that LANA2 localizes into the nucleus of both KSHV-infected B cells and transiently transfected HeLa cells. In this study, we show that LANA2 is a nucleocytoplasmic shuttling protein that requires a Rev-type nuclear export signal located in the C-terminus to direct the protein to the cytoplasm, through an association with the export receptor CRM1. In addition, a functional protein kinase B (PKB)/Akt phosphorylation motif partially overlapping with the nuclear export signal was identified. Nuclear exclusion of LANA2 was negatively regulated by the phosphorylation of threonine 564 by Akt. The ability of LANA2 to shuttle between nucleus and cytoplasm has implications for the function of this viral protein.


T- and B-cell function and their roles in resistance to infection.
Important alterations in T- and B-cell function affecting host defense and resistance to infection are found in critically ill patients and in experimental models of critical illness. In the setting of critical illness, injury, and blood loss, both T and B cells are affected, producing a relatively immunocompromised state where infection is more likely to occur, and where the ability to control the infection is lessened. Alterations in T-cell activation and cytokine production are frequently associated with hemorrhage and trauma. Injury and blood loss result in activation of CD8+ T-cell populations capable of altering bacterial antigen-specific B-cell repertoires and of suppressing the function of other T cells. The production of antibodies directed to bacterial antigens, and required for protection against extracellular bacterial infection, is diminished in models of critical illness, primarily because of disappearance of bacterial antigen-specific B-cell clonal precursors at systemic, pulmonary, and intestinal sites. Correction of the alterations in T- and B-cell function associated with critical illness would be expected to reduce the frequency of nosocomial infections in the ICU. In addition, maintenance of immunocompetence in critically ill patients will permit improved outcome should infection occur.


Tentorial dural arteriovenous fistula presenting as myelopathy: Case series and review of literature.
Dural arteriovenous fistula (DAVF) is a rare type of cerebral arteriovenous malformation. Common presenting symptoms are related to hemorrhage. However, rarely these patients may present with myelopathy. We present two cases of DAVF presenting as rapidly progressive myelopathy. Two treatment options are available: microsurgical interruption of the fistula and endovascular embolization. These treatment options of DAVFs have improved significantly in the last decade. The optimal treatment of DAVFs remains controversial, and there is an ongoing debate as to whether primary endovascular or primary microsurgical treatment is the optimal management for these lesions. However, despite treatment a high percentage of patients are still left with severe disability. The potential for functional ambulation in patients with DAVF is related to the time of intervention. This emphasizes the important of early diagnosis and early intervention in DAVF. The eventual outcome may depend on several factors, such as the duration of symptoms, the degree of disability before treatment, and the success of the initial procedure to close the fistula. The usage of magnetic resonance imaging and selective angiography has significantly improved the ability to characterize DAVFs, however, these lesions remain inefficiently diagnosed. If intervention is delayed even prolonged time in rehabilitation does not change the grave prognosis. This review outlines the presentation, classication and management of DAVF as well as discussing patient outcomes.


CO(2) capture and geologic storage: the possibilities.
Carbon dioxide (CO(2)) capture and geologic storage has been postulated as one possible method to stabilize the atmospheric concentration of CO(2) by injecting and storing it in deep geologic formations. This issue paper analyzes the viability of capture and geologic storage of becoming an effective method to aid in stabilizing the atmospheric concentration of CO(2). It is herein shown that such viability is contingent on overcoming major obstacles that are hydrogeological, technical, and economic in nature. Our analysis indicates that capture and geologic storage is likely to have negligible success in reducing the atmospheric buildup of CO(2) in the coming decades. The magnitude of the anthropogenic emissions of CO(2) indicates that a transition of the world economy away from reliance on fossil fuels might be the only path to stabilize its atmospheric concentration.


Modern law is composed dominantly of new fields of complex legislations such as biotechnologies laws, environmental laws or intellectual property. But a particular legal area stigmatizes more than the others this increasing complexity: the water protection laws.Due to its origins deeply established in the European culture, but also due to ethical, political, economical and social issues, water protection laws appear to be the typical representation of links between risk and complexity. The European water protection law is deeply complex on two scales. First, on the European scale: this field is characterised by a growing normative proliferation for the last thirty years, which seems to follow public opinion. Second, tools used by the European Union are dedicated to be transposed in each member state. In this way, European rules are integrated in each state legal order. But in many cases, only one transposition text is not enough. For example in France, the ?nitrates? water directive n˚91/676 required sixteen transposition texts.This complexity involves several difficulties. The natural's requirements of legal security and economical efficiency necessitate the removal of all deflections that discredit the law and threaten social cohesion. However, the multiplication of sources and authors of the law created increasingly complex situations. For example, the judge must not only apply national legislation, he also has to combine it with the texts from the European Union, international regulations, or independent administrative authorities. Moreover, despite the increased number of standards, the quality of European waters has not improved significantly since thirty years.The proliferation, the instability and the complexity of normative rules concerning water has deep consequences on the legal system and the environment. This paper presents the approach proposed by the European Union laws on water, an essential natural resource. Thus, an analysis of its social impacts will be proposed. We conclude by an analysis of the capacity of European Union law to cope with legal and environmental risks.


The role of component function in visual recognition of Chinese characters.
M. Taft and X. Zhu (1997) reported that character decision latencies to real Chinese characters containing components that entered into many combinations were faster than decision latencies to characters with components that entered into only a small number of combinations. However, this effect was restricted to components that appeared on the right side of Chinese characters. In written Chinese, phonetic components tend to appear on the right, and semantic components tend to appear on the left. Therefore, in Taft and Zhu's study, there was the possibility of a confound between position (left vs. right) and function (semantic vs. phonetic). Results of the present experiment show combinability effects for components with semantic and with phonetic functions. Counter to the claim by Taft and Zhu that component frequency effects are constrained by position, when component function was considered, character decision latencies varied with component frequency but not reliably with position.


The Emerging Oilseed Crop Sesamum indicum Enters the "Omics" Era.
Sesame (Sesamum indicum L.) is one of the oldest oilseed crops widely grown in Africa and Asia for its high-quality nutritional seeds. It is well adapted to harsh environments and constitutes an alternative cash crop for smallholders in developing countries. Despite its economic and nutritional importance, sesame is considered as an orphan crop because it has received very little attention from science. As a consequence, it lags behind the other major oil crops as far as genetic improvement is concerned. In recent years, the scenario has considerably changed with the decoding of the sesame nuclear genome leading to the development of various genomic resources including molecular markers, comprehensive genetic maps, high-quality transcriptome assemblies, web-based functional databases and diverse daft genome sequences. The availability of these tools in association with the discovery of candidate genes and quantitative trait locis for key agronomic traits including high oil content and quality, waterlogging and drought tolerance, disease resistance, cytoplasmic male sterility, high yield, pave the way to the development of some new strategies for sesame genetic improvement. As a result, sesame has graduated from an "orphan crop" to a "genomic resource-rich crop." With the limited research teams working on sesame worldwide, more synergic efforts are needed to integrate these resources in sesame breeding for productivity upsurge, ensuring food security and improved livelihood in developing countries. This review retraces the evolution of sesame research by highlighting the recent advances in the "Omics" area and also critically discusses the future prospects for a further genetic improvement and a better expansion of this crop.


Different antihypertensive and metabolic responses to rostafuroxin in undernourished and normonourished male rats: Outcomes on bodily Na+ handling.
Hypertension is a pandemic nowadays. We aimed to investigate whether chronic undernutrition modifies the response to the antihypertensive drug rostafuroxin in juvenile hypertensive rats. Chronic undernutrition was induced in male rats using a multideficient diet known as the Regional Basic Diet (RBD), mimicking alimentary habits in impoverished regions worldwide. Animals were given RBD-or a control/CTRL normal diet for rodents-from weaning to 90 days, and rostafuroxin (1 mg/kg body mass) was orally administered from day 60 onwards. For the last 2 days, the rats were hosted in metabolic cages to measure food/energy, water, Na+ ingestion, and urinary volume. Rostafuroxin increased food/energy/Na+ intake in CTRL and RBD rats but had opposite effects on Na+ balance (intake minus urinary excretion). The drug normalized the decreased plasma Na+ concentration in RBD rats, increased urinary volume in RBD but not in CTRL, and decreased and increased urinary Na+ concentration in the RBD and CTRL groups, respectively. Rostafuroxin decreased the ouabain-sensitive (Na+ +K+ )ATPase and increased the ouabain-resistant Na+ -ATPase from proximal tubule cells in both groups and normalized the systolic blood pressure in RBD without effect in CTRL rats. We conclude that chronic undernutrition modifies the response of blood pressure and metabolic responses to rostafuroxin.


Second malignancies following treatment in non-Hodgkin's lymphoma.
Second malignancies represent an important iatrogenic complication of the treatment of hematologic and other neoplasms. In this review we summarize the literature relating specifically to malignancies developing in the wake of treated non-Hodgkin's lymphoma (NHL). In these patients, the risk of myelodysplastic syndrome (MDS) and acute non lymphocytic leukemia (ANLL) is reported to be increased 10-105 fold over that of the general population. Factors in the development of MDS and ANLL include basic defects in cellular immunity in NHL patients as well as treatment with alkylating agents and low dose total body irradiation. Biologically these secondary MDS and ANLLs are characterized by specific cytogenetic abnormalities and results of treatment are poor. Currently bone marrow transplantation offers the only potential cure. There is no clear statistical evidence that solid tumors occur more frequently after NHL. However, bladder carcinoma, in cyclophosphamide treated patients, and lung cancer have been reported by some to occur with an increased incidence. Further investigation of the molecular events leading to the occurrence of second malignancies in NHL patients and the role played by oncogenes and tumor suppressor genes in this process is still needed.


Effect of spironolactone on the renin-aldosterone system in rats.
PRA, PRC and the plasma concentration of aldosterone (Aldo) were measured in rats (Sp-rats) receiving a daily sc injection of Spironolactone, (Sp, 20 mg in olive oil) and in control rats (C-rats) receiving olive oil only. Animals were studied one day after starting treatment, 5 days on treatment or after 5 weeks on the study. PRA, PRC and Aldo were significantly increased in Sp-rats as compared to C-rats throughout all the study. In additional Sp-rats and C-rats, the urine volume, serum Na+ and K+ concentration, Na+ and K+ intake and the urinary excretion of Na+, K+ and aldosterone-18-glucuronide (UAldV) were serially measured during 5 weeks. The total radioactivity plasma clearance after an i.v. bolus injection of 3H-aldosterone was subsequently measured in (5 Sp-rats and 5 C-rats). No significant differences in serum Na+ and K+ concentration and in Na+ and K+ balance were observed between Sp-rats and C-rats. UAldV was significantly higher in Sp-rats than in C-rats during all the study. After 5 weeks on treatment the total radioactivity plasma clearance was significantly higher in Sp-rats than in C-rats. These results indicate that Sp, at high dosage, stimulates renin release and aldosterone secretion by a mechanism unrelated to alterations in Na+ and K+ balance.


Epidemiology, disease burden, and treatment challenges of ulcerative colitis in Africa and the Middle East.
Ulcerative colitis is an idiopathic, chronic, inflammatory bowel disorder characterized by an unpredictable course of alternating cycles of relapse and remission. Traditionally viewed as a disease of Western countries, the prevalence of ulcerative colitis is reported to be increasing in the developing world. In these regions, there is the potential to further explore the etiology of the disease, mainly through genetic studies. With this in mind, we consider available data relating to the epidemiology, clinical manifestations, and disease course of ulcerative colitis in Africa and the Middle East. Current treatment approaches in these countries are also reviewed and discussed in the context of new, small molecule, orally administered therapies. Areas covered: Available data on the epidemiology, clinical manifestations, and risk factors of ulcerative colitis in Africa and the Middle East are reviewed using a PubMed database search. Expert commentary: Epidemiologic studies from African and Middle Eastern countries suggest disease trends similar to the West, and an important health and economic burden. The management of ulcerative colitis within these developing countries is challenging, with the need to improve early diagnosis, access to healthcare, and patient education, along with facilitation of access to treatment options and improvement of medication adherence.


A prospective randomized double-blind crossover study comparing the antiemetic activity of alizapride and metoclopramide in patients receiving cisplatin chemotherapy.
We designed a double-blind randomized crossover study to compare the antiemetic activity and toxicity of high-dose intravenous alizapride (3.5 mg/kg) versus high-dose intravenous metoclopramide (1 mg/kg) both combined with intravenous methylprednisolone in 40 untreated cancer patients submitted to cisplatin chemotherapy alone. The mean number of vomiting episodes (3.6 vs. 1.0), length of vomiting (209.8 vs. 80.9 min), and rate of complete prevention of vomiting (25% vs. 68.4%) at first cycle were in favor of metoclopramide, with a statistically significant difference. This difference was not statistically significant in the second cycle after crossover. Toxicity of both treatments was mild and diarrhea was more frequent in the alizapride-treated patients. Preference expressed by the patients was also in favor of metoclopramide. We conclude that alizapride offers less antiemetic protection than metoclopramide in patients receiving cisplatin chemotherapy. Further use of alizapride in such patients is not recommended.


EEG-based single-trial detection of errors from multiple error-related brain activity.
A key ability of the human brain is to monitor erroneous events and adjust behaviors accordingly. Electrophysiological and neuroimaging studies have demonstrated different brain activities related to errors. Meanwhile, the recognition of error-related brain activity as one aspect of performance monitoring has been reported for potential applications in clinical neuroscience and brain-machine interface, where single-trial analysis and classification would provide novel insights on dynamic brain responses to errors. However, procedures of selecting features, as well as procedures of single-trial classification, are not fully investigated for optimal performance. In the present study, we investigated the performance of different configurations of feature extractions in both temporal and frequency domains, for discriminating response errors in a color-word matching Stroop task. Motivated by our previous investigations, we evaluated both temporal and frequency features with component signals, which were obtained from EEG signals via an independent component analysis (ICA). Five component signals (independent components, ICs), originated from the frontal, motor, parietal, and occipital areas, were included in detecting error-related brain activity from single-trial EEG data. The results showed that better performance can be achieved by optimizing time window and frequency range of selected features, sampling scheme of feature-related data, and training of classifiers. However, a simple combination of features from multiple component signals can only slightly improve the detection performance of errors in single-trial data as compared to the frontal IC only. More importantly, it is indicated that four ICs other than the frontal one also carry similar discriminative information about errors in both temporal and frequency domains. The fact suggests flexible means in detecting errors from EEG beyond the frontal brain areas, which might be very valuable in practical applications such that the frontal area is not accessible.


Perception of stochastically undersampled sound waveforms: a model of auditory deafferentation.
Auditory deafferentation, or permanent loss of auditory nerve afferent terminals, occurs after noise overexposure and aging and may accompany many forms of hearing loss. It could cause significant auditory impairment but is undetected by regular clinical tests and so its effects on perception are poorly understood. Here, we hypothesize and test a neural mechanism by which deafferentation could deteriorate perception. The basic idea is that the spike train produced by each auditory afferent resembles a stochastically digitized version of the sound waveform and that the quality of the waveform representation in the whole nerve depends on the number of aggregated spike trains or auditory afferents. We reason that because spikes occur stochastically in time with a higher probability for high- than for low-intensity sounds, more afferents would be required for the nerve to faithfully encode high-frequency or low-intensity waveform features than low-frequency or high-intensity features. Deafferentation would thus degrade the encoding of these features. We further reason that due to the stochastic nature of nerve firing, the degradation would be greater in noise than in quiet. This hypothesis is tested using a vocoder. Sounds were filtered through ten adjacent frequency bands. For the signal in each band, multiple stochastically subsampled copies were obtained to roughly mimic different stochastic representations of that signal conveyed by different auditory afferents innervating a given cochlear region. These copies were then aggregated to obtain an acoustic stimulus. Tone detection and speech identification tests were performed by young, normal-hearing listeners using different numbers of stochastic samplers per frequency band in the vocoder. Results support the hypothesis that stochastic undersampling of the sound waveform, inspired by deafferentation, impairs speech perception in noise more than in quiet, consistent with auditory aging effects.


Metastatic adenocarcinoma of the prostate: presentation as a pleural-based mass.
We have presented an unusual case of metastatic prostate carcinoma simulating a primary bone tumor. Although previous reports have described periosteal and "pseudosarcomatous" prostate metastases, no report makes reference to rib involvement. Furthermore, the large soft tissue component is highly unusual. This case illustrates that although such lesions are rare, in the older patient, metastases should be included along with primary tumors in the differential diagnosis of a spiculated bone lesion with prominent soft tissue involvement.


Probing RNA structures and functions by solvent accessibility: an overview from experimental and computational perspectives.
Characterizing RNA structures and functions have mostly been focused on 2D, secondary and 3D, tertiary structures. Recent advances in experimental and computational techniques for probing or predicting RNA solvent accessibility make this 1D representation of tertiary structures an increasingly attractive feature to explore. Here, we provide a survey of these recent developments, which indicate the emergence of solvent accessibility as a simple 1D property, adding to secondary and tertiary structures for investigating complex structure-function relations of RNAs.


[Efficacy and safety of infliximab in the treatment of pediatirc Crohn's disease].
Objective: To analyze the efficacy and safety of the biological agent infliximab (IFX) in the treatment of pediatric Crohn's disease. Methods: A total of 86 children with Crohn's disease who had received IFX in three hospitals (Ruijin Hospital, Ruijin Hospital North and Shanghai Children's Hospital) in Shanghai from January 2007 to December 2017 were included in this retrospective study. The efficacy of IFX was assessed by comparing clinical and laboratory data before and after IFX treatment. Student t test, Mann-Whitney U test or chi-square test were used to analyze the data of the two groups. Logistic reggression analysis were used to analyze the effects of variables such as age, clinical characteristics, disease behavior and combined medications on the efficacy and safety of IFX. Results: Among the 86 children with Crohn's disease in the study, 50 were males and 36 females. The IFX treatment was initiated at 12.0 (7.1, 13.6) years of age, and the follow-up period was 94.1 (47.8, 185.5) weeks. Efficacy analysis showed that in the induction remission phase, the clinical response rate was 97% (79/81) and the remission rate was 74% (60/81). In the maintenance remission phase, the clinical response rate was 75% (51/68) and the remission rate was 68% (46/68). After 34 weeks of treatment with IFX, pediatric Crohn's disease activity index (PCDAI) (5 (0, 10) vs. 36 (26, 45)), C-reactive protein (3 (1, 8) vs. 8 (3, 31) mg/L), erythrocyte sedimentation rate (10 (6, 10) vs. 35 (20, 50) mm/1 h), platelet ( (327±107)×109 vs. (438±159) ×109/L), albumin ((37±6) vs. (30±6) g/L), hemoglobin ((116±16) vs. (103±18) g/L), change of body weight (-0.5±1.2 vs. -1.0±0.9), anemia (29% (20/68) vs. 75% (51/68)), and perianal disease (13/21 vs. 0) were significantly improved (all P<0.05). By the end of 34 weeks of IFX treatment, 25% (17/68) of children experienced secondary loss of response to IFX. Logistic reggression analysis showed that PCDAI>30 was positively correlated with secondary loss of response (OR=3.823, 95%CI 1.015-15.328, P=0.048), and combined with azathioprine was conducive to maintaining efficacy of IFX (OR=0.440, 95%CI 0.106-1.033, P=0.044). The IFX-related adverse events included infusion reactions in 17% (15/86) and infections in 42% (36/86) of children. Analysis showed that age<6 years was a risk factor for infusion reactions (χ2=6.556, P=0.010), and combined use of steroids (χ2=5.230, P=0.022) may increase the incidence of infection. Conclusions: IFX is effective in the treatment of pediatric Crohn's disease with favorable safety. Reducing secondary loss of response to IFX is an urgent issue that need to be addressed. At the same time, it is necessary to pay close attention to the adverse events during IFX treatment.


Accurate determination of complex χ(2) spectrum of the air/water interface.
Discussion on the structure of the water surface relies on accurate determination of the χ(2) spectrum. For obtaining accurate χ(2) spectrum of the air/water interface in the OH stretch region, we performed heterodyne-detected vibrational sum-frequency generation measurements with a high phase accuracy, and also examined the validity of the phase and amplitude calibration using different non-resonant materials. In contrast to the previous reports, it was concluded that the imaginary part of the χ(2) spectrum of the air/water interface does not exhibit noticeable positive resonance in the low frequency region within the experimental error. This result urges us to reconsider the structure of the air/water interface based on the accurate χ(2) spectrum.


Neurobiology of anxiety disorders and implications for treatment.
The neurobiology of the anxiety disorders, which include panic disorder, post-traumatic stress disorder (PTSD), and specific phobias, among others, has been clarified by advances in the field of classical or Pavlovian conditioning, and in our understanding of basic mechanisms of memory and learning. Fear conditioning occurs when a neutral conditioned stimulus (such as a tone) is paired with an aversive, or unconditioned stimulus (such as a footshock), and then in the absence of the unconditioned stimulus, causes a conditioned fear response. Preclinical studies have shown that the amygdala plays a key role in fear circuitry, and that abnormalities in amygdala pathways can affect the acquisition and expression of fear conditioning. Drugs such as glutamate N-methyl-D-aspartate (NMDA) antagonists, and blockers of voltage-gated calcium channels, in the amygdala, may block these effects. There is also preliminary evidence for the use of centrally acting beta-adrenergic antagonists, like propranolol, to inhibit consolidation of traumatic memories in PTSD. Finally, fear extinction, which entails new learning of fear inhibition, is central to the mechanism of effective anti-anxiety treatments. Several pharmacological manipulations, such as D-cycloserine, a partial NMDA agonist, have been found to facilitate extinction. Combining these medication approaches with psychotherapies that promote extinction, such as cognitive behavioral therapy (CBT), may offer patients with anxiety disorders a rapid and robust treatment with good durability of effect.


Investigations into the metabolism of two-dimensional colony and suspended microcarrier cultures of human embryonic stem cells in serum-free media.
Metabolic studies of human embryonic stem cells (hESCs) can provide important information for stem cell bioprocessing. To this end, we have examined growth and metabolism of hESCs in both traditional 2-dimensional (2D) colony cultures and 3-dimensional microcarrier cultures using a conditioned medium and 3 serum-free media. The 2D colony cultures plateaued at cell densities of 1.1-1.5 × 10⁶ cells/mL at day 6 due to surface limitation. Microcarrier cultures achieved 1.5-2 × 10⁶ cells/mL on days 8-10 before reaching a plateau; this growth arrest was not due to surface limitation, but probably due to metabolic limitations. Metabolic analysis of the cultures showed that amino acids (including glutamine) and glucose are in excess and are not limiting cell growth; on the other hand, the high levels of waste products (25 mM lactate and 0.8 mM ammonium) and low pH (6.6) obtained at the last stages of cell propagation could be the causes for growth arrest. hESCs cultured in media supplemented with lactate (up to 28 mM) showed reduced cell growth, whereas ammonium (up to 5 mM) had no effect. Lactate and, to a lesser extent, ammonia affected pluripotency as reflected by the decreasing population of cells expressing pluripotent marker TRA-1-60. Feeding hESC cultures with low concentrations of glucose resulted in lower lactate levels (∼10%) and a higher pH level of 6.7, which leads to a 40% increase in cell density. We conclude that the high lactate levels and the low pH during the last stages of high-density hESC culture may limit cell growth and affect pluripotency. To overcome this limitation, a controlled feed of low levels of glucose and online control of pH can be used.


Prophylaxis against opportunistic infections in persons infected with human immunodeficiency virus.
This article outlines the current official recommendations for the prevention of opportunistic disease in adults and adolescents infected with human immunodeficiency virus, including specific guidelines for discontinuing primary and secondary prophylaxis when immune reconstitution has occurred as a result of highly active antiretroviral therapies. The recommendations, developed by the U. S. Public Health Service and the Infectious Diseases Society of America for clinicians and healthcare providers, were originally published in 1995 and revised in 1997, 1999, and 2002. The 2002 recommendations are summarized in this article.


[Beta2 microglobulin, antibeta2 microglobulin activity and circulating immune complexes in rheumatoid arthritis. Serum and synovial study].
In this work, the authors found significantly raised serum Beta2m microglobulin values in a group of 120 cases of rheumatoid arthritis, without any difference between the serum positive group (55 cases) and the serum negative group (65 cases). Such a rise was found in the synovial fluids with a beta2 serum synovial fluid greater than unity in 81 % of cases of rheumatoid arthritis as against 6 % in a control group. The comparative study and the main immunological disorders permits one to note a correlation between the levels of circulating immune complexes (CIC) fixing the Clq and the serum beta2m in serum negative cases of rheumatoid arthritis (RA) (r = 0.52 p < 0.001) whereas this link does not exist in the serum positive group (r = 0.08). These conclusions led the authors to an anti-serum beta2m activity in the serum positive and negative groups of RA, which were very significantly different from the control groups. Furthermore, a study of complement activation, by titration of C3d showed a significant correlation between the levels of CIC and of C3d in RA -, but not in RA +. The authors discuss the participation of beta2m in the formatiton of CIC during RA and its role in the activation of complement.


Reliability of blood test results in samples obtained using a 2-mL discard volume from the proximal lumen of a triple-lumen central venous catheter in the critically ill patient.
Intensive care patients require a high frequency of blood testing, which results in a significant amount of blood loss. When blood is obtained from a central venous catheter (CVC), a large volume is usually discarded to obtain an unaltered sample for testing. To determine the reliability of complete blood test results in blood samples obtained from the proximal lumen of a triple-lumen CVC using a 2-mL discard volume DESIGN: Observational study with the prospective collection of data METHODS: The subjects enrolled were all patients with a subclavian triple-lumen CVC, older than 17 years and consecutively admitted to intensive care over a 2-year period. In each of the 54 participants, one blood sample was drawn from the proximal lumen of the catheter, discarding 1·61 mL of blood plus 0·39 mL of catheter deadspace (2 mL) and without interrupting infusion in the middle and distal lumens. A second sample was then obtained by direct venous puncture. The reliability of blood test results was determined by comparing sets of variables recorded for the two sampling methods through intraclass correlation coefficients in the Bland-Altman method. Inter-method reliability for the variables examined was excellent, >0·75; range (0·868-0·998). Mean differences between the two sample types for the variables most often determined in critically ill patients were leukocytes: 0·200 × 103 /µL, 95% confidence interval (CI) (0·025 to 0·375); erythrocytes: 0·045 × 106 /uL, 95% CI (-0·003 to 0·094); sodium: 0·074 mEq/L, 95% CI (-0·369 to 0·517); potassium: -0·002mEq/L, 95% CI (-0·065 to 0·061) and glucose: 2·426 mg/dL, 95% CI (0·498-4·354). The sampling method proposed minimizes blood loss while offering reliable blood test results. The main benefit of the method proposed is reduced blood loss, improving the care of a critically ill patient.


Dissecting carbohydrate-Cyanovirin-N binding by structure-guided mutagenesis: functional implications for viral entry inhibition.
The HIV-inactivating protein Cyanovirin-N (CV-N) is a cyanobacterial lectin that exhibits potent antiviral activity at nanomolar concentrations by interacting with high-mannose carbohydrates on viral glycoproteins. To date there is no molecular explanation for this potent virucidal activity, given the experimentally measured micromolar affinities for small sugars and the problems encountered with aggregation and precipitation of high-mannose/CV-N complexes. Here, we present results for two CV-N variants, CV-N(mutDA) and CV-N(mutDB), compare their binding properties with monomeric [P51G]CV-N (a stabilized version of wtCV-N) and test their in vitro activities. The mutations in CV-N(mutDA) and CV-N(mutDB) comprise changes in amino acids that alter the trimannose specificity of domain A(M) and abolish the sugar binding site on domain B(M), respectively. We demonstrate that carbohydrate binding via domain B(M) is essential for antiviral activity, whereas alterations in sugar binding specificity on domain A(M) have little effect on envelope glycoprotein recognition and antiviral activity. Changes in A(M), however, affect the cross-linking activity of CV-N. Our findings augment and clarify the existing models of CV-N binding to N-linked glycans on viral glycoproteins, and demonstrate that the nanomolar antiviral potency of CV-N is related to the constricted and spatially crowded arrangement of the mannoses in the glycan clusters on viral glycoproteins and not due to CV-N induced virus particle agglutination, making CV-N a true viral entry inhibitor.


Cd, Cu, Zn, Se, and metallothioneins in two amphibians, Necturus maculosus (Amphibia, Caudata) and Bufo bufo (Amphibia, Anura).
The accumulation of cadmium, its affinity for metallothioneins (MTs), and its relation to copper, zinc, and selenium were investigated in the experimental mudpuppy Necturus maculosus and the common toad Bufo bufo captured in nature. Specimens of N. maculosus were exposed to waterborne Cd (85 μg/L) for up to 40 days. Exposure resulted in tissue-dependent accumulation of Cd in the order kidney, gills > intestine, liver, brain > pancreas, skin, spleen, and gonads. During the 40-day exposure, concentrations increased close to 1 μg/g in kidneys and gills (0.64-0.95 and 0.52-0.76; n = 4), whereas the levels stayed below 0.5 in liver (0.14-0.29; n = 4) and other organs. Cd exposure was accompanied by an increase of Zn and Cu in kidneys and Zn in skin, while a decrease of Cu was observed in muscles and skin. Cytosol metallothioneins (MTs) were detected as Cu,Zn-thioneins in liver and Zn,Cu-thioneins in gills and kidney, with the presence of Se in all cases. After exposure, Cd binding to MTs was clearly observed in cytosol of gills as Zn,Cu,Cd-thionein and in pellet extract of kidneys as Zn,Cu,Cd-thioneins. The results indicate low Cd storage in liver with almost undetectable Cd in liver MT fractions. In field trapped Bufo bufo (spring and autumn animals), Cd levels were followed in four organs and found to be in the order kidney > liver (0.56-5.0 μg/g >0.03-0.72 μg/g; n = 11, spring and autumn animals), with no detectable Cd in muscle and skin. At the tissue level, high positive correlations between Cd, Cu, and Se were found in liver (all r > 0.80; α = 0.05, n = 5), and between Cd and Se in kidney (r = 0.76; n = 5) of autumn animals, possibly connected with the storage of excess elements in biologically inert forms. In the liver of spring animals, having higher tissue level of Cd than autumn ones, part of the Cd was identified as Cu,Zn,Cd-thioneins with traces of Se. As both species are special in having liver Cu levels higher than Zn, the observed highly preferential Cd load in kidney seems reasonable. The relatively low Cd found in liver can be attributed to its excretion through bile and its inability to displace Cu from MTs. The associations of selenium observed with Cd and/or Cu (on the tissue and cell level) point to selenium involvement in the detoxification of excessive cadmium and copper through immobilization.


A SIMPLE AND-SENSITIVE STABILITY-INDICATING UHPLC-DAD METHOD FOR THE DETERMINATION OF CEFETAMET PIVOXIL HYDROCHLORIDE.
A fast and sensitive UHPLC-DAD method was developed and subsequently validated for determination of cefetamet pivoxil hydrochloride in the presence of its degradation products. The chromatographic separation was carried out on a Waters Acquity BEH C18, (2.1 x 100 mm, 1.7 µm) column. The mobile phase was composed of 0.1% formic acid and acetonitrile (40 : 60, v/v) at the flow rate 0.7 mL/min. The detection wavelength was 265 nm and the temperature was 30 °C. Cefetamet pivoxil hydrochloride was susceptible to degradation under the influence of sodium hydroxide, hydrochloric acid and in the conditions of increased temperature and relative humidity. However, it was stable after irradiation, in increased temperature in dry air and in the presence of oxidizing agent. The developed UHPLC-DAD method was linear over the concentration range of 10-240 µg/mL (r2 = 0.9999; n = 12). The obtained RSD values were less than 2%, demonstrating that the described procedure is precise. The accuracy was also confirmed (mean recoveries were 97.79-102.08%). Under applied chromatographic conditions LOD and LOQ values were 2.08 mg/mL and 6.29 mg/mL, respectively. The proposed method was successfully applied in determination of cefetamet pivoxil hydrochloride in aqueous solutions as well as in the solid state.


Preparation of donor lamellar tissue for deep lamellar endothelial keratoplasty using a microkeratome and artificial anterior chamber system: endothelial cell loss and predictability of lamellar thickness.
To measure endothelial cell loss and predictability of lamellar thickness after preparing donor tissue for deep keratoplasty with an artificial anterior chamber and microkeratome. A microkeratome set at a depth of 350 microm and a diameter of 9 mm was used to obtain ten lamellar lenticules from corneoscleral rims mounted in an artificial chamber. A punch trephine then was used to cut the donor tissue 7 mm in diameter. Specular microscopy was performed to evaluate endothelial cell density before the procedure, after cutting with the microkeratome, and after trephination. Pachymetry was performed to determine the predictability of lenticule thickness, before the procedure and after microkeratome incision. Mean post-microkeratome endothelial cell loss was 79 +/- 88 cells/mm2 and post-punch trephination was 85 +/- 94 cells/mm2. This represented a mean percentage loss of 3.2% and 3.5% for the respective steps of this procedure. Nine of the ten lenticules were cut within +/- 75 microm of the intended 350-microm thickness. Preparing donor lenticules for deep lamellar endothelial keratoplasty with a microkeratome with artificial chamber system caused a relatively small loss of endothelial cells (6.7% of the total) and a reproducible thickness. This may have advantages over manual preparation techniques.


Dose to the shielded thymic region of irradiated mouse cadavers.
Frozen mouse cadavers were exposed to 220 kV roentgen irradiation with the thymic area covered with a lead plate sized 18 mm X 24 mm X 4 mm oe 18 mm X 12 mm X 4 mm. Lif-Telfon rods were used for dose measurements. With larger plate the mean dose from scattered radiation, in percent of that in the uprotected abdomen, was 12.77 (thymic lobes) and 18.34 (vertebra). With the smaller shield the figures were markedly increased, 16.70 and 23.77, respectively. Since the percentage dose is relatively high, the amount of scattered radiation may have biologic significance.


Cutaneous collision tumors. An analysis of 69 cases and review of the literature.
The association of two different neoplasms in the same biopsy specimen is not uncommon and has been reported by numerous authors. Some associations may result from involvement of related cell types, however, most are serendipitous. Our study attempted to investigate the nature and types of contiguous or "collision" tumors seen in our dermatopathology service. A retrospective evaluation of approximately 40,000 cutaneous biopsies was performed, yielding 69 examples of collision tumors. Excluded were biphasic lesions of the same cell type (e.g., basosquamous carcinomas or combined nevi). Results were as follows: The most common combinations included basal cell carcinoma and nevus (14), basal cell carcinoma and seborrheic keratosis (8), nevus and seborrheic keratosis (14), actinic keratosis and nevus (7), and basal cell carcinoma and neurofibroma (4). Adnexal tumors were found combined with other neoplasms in four patients and blue nevi were noted in three additional tumors. We believe that most of these represent the presence of two or more common lesions juxtaposed by coincidence. However, certain combinations are of similar cell lineages or contain a relatively uncommon tumor and may indicate a possible link between the different cell types.


Visualization of protein compartmentation within the plasma membrane of living yeast cells.
Different distribution patterns of the arginine/H+ symporter Can1p, the H+ plasma membrane ATPase Pma1p, and the hexose transport facilitator Hxt1p within the plasma membrane of living Saccharomyces cerevisiae cells were visualized using fluorescence protein tagging of these proteins. Although Hxt1p-GFP was evenly distributed through the whole cell surface, Can1p-GFP and Pma1p-GFP were confined to characteristic subregions in the plasma membrane. Pma1p is a well-documented raft protein. Evidence is presented that Can1p, but not Hxt1p, is exclusively associated with lipid rafts, too. Double labeling experiments with Can1p-GFP- and Pma1p-RFP-containing cells demonstrate that these proteins occupy two different nonoverlapping membrane microdomains. The size of Can1p-rich (Pma1p-poor) areas was estimated to 300 nm. These domains were shown to be stable in growing cells for >30 min. To our knowledge, this is the first observation of a cell polarization-independent lateral compartmentation in the plasma membrane of a living cell.


Inflammatory Biomarker and Response to Antidepressant in Major Depressive Disorder: a Systematic Review and Meta-Analysis.
Inadequate response to antidepressant treatment, in a significant proportion of patients diagnosed with Major Depressive Disorder, contributes to the large burden of disability associated with the disease; thus, predicting treatment response is one of the most important challenge for clinicians who deal with depressed patients. The cytokine hypothesis of depression suggests that altered pheripheral cytokine levels are involved in the pathophysiology of depressive disorder and in modulating response to treatment. Present meta-analysis aimed to investigate the association between cytokine levels at baseline and response to antidepressant therapies. Authors performed a systematic search of PubMed and Embase databases for studies published between 2010 and January 2021: of 3345 identified records, 31 studies met the inclusion criteria for the qualitative synthesis, whereas 19 studies were eligible for quantitative analysis. Patients who failed to respond to antidepressant had aberrant inflammatory process, namely higher baseline levels of C-Reactive Protein and Interleukine-8, which is associated with treatment outcome in Major Depressive Disorder. Despite these promising results, further investigations are needed in order to replicate the data and to examine the potential role of inflammatory marker as a novel predictive tool for pharmacological treatment of depressive disorder.


Particulated Costal Allocartilage With Microfracture Versus Microfracture Alone for Knee Cartilage Defects: A Multicenter, Prospective, Randomized, Participant- and Rater-Blinded Study.
Microfracture is the first-line treatment for cartilage defects; however, the suboptimal quality of the repaired cartilage remains an issue. The aim of this first in-human study was to compare the clinical efficacy and safety of a combination of particulated costal allocartilage and microfracture versus microfracture alone in treating knee cartilage defects. We hypothesized that the particulated costal allocartilage with microfracture would result in superior cartilage repair quality and better clinical outcomes at 48 weeks postoperatively. Randomized controlled trial; Level of evidence, 1. Patients with cartilage defects were allocated randomly to the treatment group (particulated costal allocartilage with microfracture) and control group (microfracture alone). Magnetic resonance imaging (MRI) outcomes of cartilage repair (the primary outcome measure) were evaluated at the 48-week follow-up using the Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) score. Patient-reported clinical outcomes (visual analog scale [VAS] pain score, Knee injury and Osteoarthritis Outcome Score [KOOS], and International Knee Documentation Committee score) and adverse events were evaluated at 12, 24, and 48 weeks postoperatively. Overall, 88 patients were included (44 patients each in the treatment and control groups). The total MOCART score at 48 weeks postoperatively was significantly higher in the treatment group than in the control group (P < .001). Among the 9 MOCART variables, 6 were significantly superior in the treatment versus the control group: degree of repair and defect filling (P < .001), integration to the border zone (P < .001), surface (P = .006), structure (P = .011), signal intensity of the repair tissue (P < .001), and subchondral lamina (P = .005). There were significant between-group differences in KOOS-Pain (P = .014), KOOS-Activities of Daily Living (P = .010), KOOS-Sports (P = .029), and KOOS-Symptoms (P = .039) at 12 weeks postoperatively and in VAS pain (P = .012) and KOOS-Pain (P = .005) at 24 weeks postoperatively. At 48 weeks postoperatively, clinical outcomes were comparable between the groups. Microfracture augmented with particulated costal allocartilage resulted in superior cartilage repair quality compared with microfracture alone in terms of MRI evaluation of the knee joint cartilage defect at the 48-week follow-up. Functional outcomes were favorable for both treatments at final follow-up. KCT0004936 (Clinical Research Information Service [CRiS] of the Republic of Korea).


Memory for emotional stories in high and low depressed children.
Cognitive theories of depression emphasise a vicious circle linking depressed mood and biased recall towards negative information. In line with this, depressed adults show selectively enhanced recall for negative information. This recall bias is held to be mediated by increased accessibility of negative self-referent schemas formed as a result of adverse early experiences. Given this, surprisingly few studies have examined depression-related recall biases from a developmental perspective. Clinically depressed children have been found to show enhanced recall of negative adjectives, particularly when self-referent, but to date there is no evidence for similar recall biases in non-clinically depressed groups. The current study addressed this by investigating high and low non-clinically depressed children's (aged 5-11 years) recall of emotional stories. High depressed children showed enhanced recall of negative stories, relative to positive stories, compared to the low depressed group. This did not vary with age group. We conclude that, when child-oriented materials are used, depression-related biases in recall towards negative information are observable even in a non-clinical sample of children from 5 years of age.


The development of students' perceptions of effective teaching: the ideal, best and poorest clinical teacher in nursing.
This article attempts to study students' perceptions of effective clinical teacher in nursing. To do this, 123 students from three schools with different curricula identified the important characteristics of a clinical teacher, using a modified NCTEI instrument. Then each respondent assessed to what extent her or his best and poorest clinical teachers possess these characteristics. The profile of an effective clinical teacher which emerged places the highest weight on the nursing competencies of the teacher and downplays both interpersonal relationships and personality traits. Differences between 2nd and 3rd year students were found in the placement of teaching skills and evaluation characteristics. No differences were disclosed among the compared schools. Conflicting research findings are analyzed. The results strongly suggest that the image of the ideal clinical teacher is not rooted in an existing teacher figure. The possible implications of the findings on the role model function of the clinical teacher are discussed.


In Vivo Molecular Insights into Syntrophic Geobacter Aggregates.
Direct interspecies electron transfer (DIET) has been considered as a novel and highly efficient strategy in both natural anaerobic environments and artificial microbial fuel cells. A syntrophic model consisting of Geobacter metallireducens and Geobacter sulfurreducens was studied in this work. We conducted in vivo molecular mapping of the outer surface of the syntrophic community as the interface of nutrients and energy exchange. System for Analysis at the Liquid Vacuum Interface combined with time-of-flight secondary ion mass spectrometry was employed to capture the molecular distribution of syntrophic Geobacter communities in the living and hydrated state. Principal component analysis with selected peaks revealed that syntrophic Geobacter aggregates were well differentiated from other control samples, including syntrophic planktonic cells, pure cultured planktonic cells, and single population biofilms. Our in vivo imaging indicated that a unique molecular surface was formed. Specifically, aromatic amino acids, phosphatidylethanolamine components, and large water clusters were identified as key components that favored the DIET of syntrophic Geobacter aggregates. Moreover, the molecular changes in depths of the Geobacter aggregates were captured using dynamic depth profiling. Our findings shed new light on the interface components supporting electron transfer in syntrophic communities based on in vivo molecular imaging.


A qualitative analysis of patient and family perspectives of palliative care.
To provide truly patient-centered palliative care services, there is a need to better understand the perspectives and experiences of patients and families. Increased understanding will provide insight into the development of health care team competencies and organizational changes necessary to improve patient care. Our aim was to explore patient and family perceptions of palliative care services at the end of life or during serious illness and to identify facilitators and barriers to receipt of palliative care services. In-depth, semi-structured patient and family interviews were conducted, transcribed, and independently reviewed using grounded theory methodology and preliminary interpretations. A combined deductive and inductive iterative qualitative approach was used to identify recurring themes. The study was conducted in a physician-led, not-for-profit, multispecialty integrated health system serving three large, western, rural states. A purposive sample of 14 individuals who received palliative care services were interviewed alone or with their families for a total of 12 interviews. Presence, Reassurance, and Honoring Choices emerged as central themes linked to satisfaction with palliative care services. Themes were defined as including health care professional attributes of respect, approachability, genuineness, empathy, connectedness, compassion, sensitivity, an ability to listen, good communication, provision of information, empowerment, and timeliness. Honoring Choices included those pertaining to treatment, spirituality, and family needs. At end of life or during times of serious illness, patients and families identified behaviors of Presence, Reassurance, and Honoring Choices as important. According to patients/families, health care providers must be compassionate and empathetic and possess skills in listening, connecting, and interacting with patients and families.


Inhibiting effects of serotonin and serotonin antagonists on the migration of mononuclear leucocytes.
The effect of serotonin and the serotonin antagonists ketanserin, methiotepine and ICS-205-930 on the migration of leucocytes was studied by using the sealed capillary migration technique. The migration of mononuclear leucocytes was inhibited by serotonin at 10(-4) and 10(-6)-10(-10)mol/l. An inhibition of the mononuclear leucocyte migration was also caused by ICS-205-930 at 10(-4)mol/l, ketanserin at 10(-4) and 10(-8)-10(-10)mol/l and methiotepine at 10(-4) and 10(-6)-10(-8)mol/l. No inhibiting effects of serotonin or the serotonin antagonists were found on the migration of polymorphonuclear leucocytes. Thus, both serotonin and serotonin antagonists may inhibit mononuclear leucocyte migration.


A Novel Process to Recruit and Select Community Partners for a Hybrid Implementation-Effectiveness Study.
Creating strong partnerships with community organizations is essential to test implementation of evidence-based interventions. However, partners are often chosen based on convenience rather than capacity or diversity. Streamlined processes are needed to identify qualified, diverse, and invested partners to conduct community-based research. There is a gap in the literature on effective and efficient processes for recruiting partners. This paper aims to fill that gap by describing a novel approach for identifying a diverse group of community organizations to participate in research. We used a Request for Partners (RFP) approach to recruit partners to participate in a hybrid implementation-effectiveness study of the Veggie Van mobile market model. The process included formative work to inform RFP development, creation of an external advisory committee, an intent-to-apply round, a full application round, and an inperson training and selection process. Data was collected to characterize applicant size, location, and experience; pre-post surveys were conducted to understand the training's utility. We received 59 intent-to-apply submissions and invited 28 organizations to apply: 17 submitted applications and 12 organizations were chosen as finalists. The process took approximately 8 months to recruit 9 organizations and 32 community sites across 5 states and increased understanding of the intervention and partner responsibilities. An RFP process is familiar to many community organizations that compete for grant funding but may not have prior research experience. This process streamlined recruitment timelines, increased diversity, and cultivated community among organizations. It may also improve research transparency, study completion, and intervention fidelity.


Preparation of ADM/PRP freeze-dried dressing and effect of mice full-thickness skin defect model.
Acellular dermal matrix (ADM) and platelet-rich plasma (PRP) have each been used in wound healing. There are a few reports on the application of ADM with PRP in skin full-thickness defect models. In this study, the microstructure of ADM/PRP freeze-dried dressing was observed by scanning electron microscope. The PRP, ADM and PRP/ADM samples were recorded by Fourier transform infrared (FTIR) spectrometer by the KBr methods. The concentration of growth factor was measured by enzyme-linked immunosorbent assay. Then, we made a mice full-thickness defect model and treated it with saline, PRP, ADM and PRP/ADM, respectively. The wound size was measured and calculated on days 3, 5, 7, 10 and 14. The obtained results demonstrated that the ADM/PRP freeze-dried dressing resulted in earlier collagen development. FTIR analysis confirmed the integration of ADM and PRP in the prepared PRP/ADM scaffold. The concentration of bFGF, EGF, TGF-β1 and PDGF-BB in the ADM/PRP group was lower than that in the PRP group. The wound healing rate of the ADM/PRP group was significantly promoted. Furthermore, the ADM/PRP group had significant revascularization, rapid epithelialization and a well-differentiated epidermis. The collagen fibers were regularly arranged. Accordingly, ADM/PRP freeze-dried dressing promotes wound healing and can be used in the skin full-thickness wound.


RSM-based Model to Predict Optimum Fermentation Conditions for Soluble Expression of the Antibody Fragment Derived from 4D5MOC-B Humanized Mab in SHuffle™ T7 E. coli.
Overexpression of the EpCAM in epithelial-derived neoplasms makes this receptor a promising target in antibody-based therapy. Due to the lack of N-glycosylation, Escherichia coli (E. coli) seems to be the most appropriate choice for the expression of antibody fragments. However, developing a robust and cost-effective process that produces consistent therapeutic proteins from inclusion bodies is a major challenge. Undoubtedly, it can be circumvented by the soluble expression of these proteins. Utilization of numerous genetically modified hosts and optimization of cultivation conditions are two effective approaches widely used to overcome the insolubility problem. Due to the cytoplasmic expression of DsbC and the ability to the correct formation of disulfide bonds, the Shuffle™ T7 strain can be a suitable host for the soluble production of recombinant proteins. Here, Box-Behnken design (BBD)- Response surface methodology (RSM) modeling was employed to develop optimized culture conditions for 4D5MOC-B scFv fragment production in SHuffle™ T7 strain while solubility and production level were considered as responses. Although both responses were significantly influenced by post-induction temperature, cell density at induction time, and IPTG concentration, the temperature had the largest effect. The maximum experimental soluble protein obtained by adding 1 mM of IPTG into the M9 medium when the cell density reached 0.7 at 23 ᵒC was 693.56 µg/mL which was in good correlation with the predicted value of 720.742 µg/mL. Predictable total expression value was also experimentally verified. This strategy can be scaled-up for the production of large amounts of scFvs from SHuffle™ T7 E. coli to facilitate their potential applications as therapeutic and diagnostic agents.


Purification, sequence analysis, and biological characterization of a second bovine monocyte chemotactic protein-1 (Bo MCP-1B).
Madin Darby bovine kidney (MDBK) cells were used as a source to identify novel bovine chemotactic factors for granulocytes and monocytes. A major bovine granulocyte chemotactic protein (GCP-2) has previously been isolated. A novel bovine monocyte chemotactic protein (bo MCP) was produced on MDBK cells stimulated with phorbol ester. The 14-kDa protein was purified to homogeneity by adsorption to controlled pore glass, heparin affinity chromatography, cation-exchange FPLC, and RP-HPLC. The amino acid sequence of the NH2-terminally blocked protein was determined by Edman degradation using proteolytic fragments. The primary structure of the bo MCP, characterized by four conserved cysteines, allowed classification of the protein within the C-C chemokine family. Bo MCP-1B was most related to known human and bovine MCPs. Compared to bovine MCP-1 and MCP-2, the protein consists of 84% and 53% identical amino acids, respectively. Since this bo MCP was also most homologous to human and animal MCP-1, it was designated bo MCP-1B. The minimal effective dose of bo MCP-1B for monocyte chemotactic activity was 0.2 mM. The maximal migration index, reached at 2 nM, was comparable to that of natural human MCP-1. Furthermore, bo MCP-1B was found to be capable of stimulating beta-glucuronidase release from monocytes. In contrast, bo MCP-1B was not chemotactic for neutrophilic and eosinophilic granulocytes. By its biological and biochemical characteristics, bo MCP-1B has to be considered as an authentic additional MCP-1 chemokine. The existence of a possible human counterpart for this novel MCP-1B still needs to be elucidated.


Temporary vascular catheters for hemodialysis: a 3-year prospective study.
Temporary hemodialysis catheters are necessary in patients with uremia, but complications associated with these catheters represent one of the most important sources of morbidity among ESRD patients. There is no general agreement about the optimal venous access for insertion of a central venous catheter, while risk factors of catheter related complications have not been entirely elucidated. One hundred and seven consecutive patients who required a temporary hemodialysis catheter were prospectively examined. Catheters were placed in 107 consecutive patients (66 right jugular (JC), 41 right femoral (FC)) and maintained in situ for a cumulative total of 2101 days. Early complications (puncture site hemorrhage, hematoma formation, artery puncture) were infrequent, without clinical sequelae. The main late complication was catheter related bacteremia (CRB). There were 16 episodes of CRB (JC-10; FC-6) and Staphylococcus aureus was the most frequently isolated cause of CRB. The mean catheter duration before the onset of CRB was 19.9 and 18.2 days for JC and FC, respectively. Duration of catheter use, and the number of hemodialyses significantly increased the risk for CRB. Actuarial survival for FC was significantly worse than for JC, while Cox proportional hazard models revealed that the femoral site, chronic renal failure and kidney transplantation increased the risk of catheter failure significantly. CRB was the most common late complication. Its frequency was similar in JC and FC. The main risk factors for development of CRB were duration of catheter use and the number of performed dialyses. Cumulative hazard of CRB was significantly magnified 3 weeks after insertion for both JC and FC, but actuarial survival with JC was significantly longer.


Effect of prenatal exposure to ethanol on the development of cerebral cortex: I. Neuronal generation.
Prenatal exposure to ethanol causes profound disruptions in the development of the cerebral cortex. Therefore, the effect of in utero ethanol exposure on the generation of neurons was determined. Pregnant rats were fed a liquid diet in which ethanol constituted 37.5% of the total caloric content (Et) or pair-fed an isocaloric control diet (Ct) from gestational day (GD) 6 to the day of birth. The time of origin of cortical neurons was determined in the mature pups of females injected with [3H]thymidine on one day during the period from GD 10 to the day of birth. The brains were processed by standard autoradiographic techniques. Ethanol exposure produced multiple defects in neuronal ontogeny. The period of generation was 1-2 days later for Et-treated rats than for rats exposed prenatally to either control diet. Moreover, the generation period was 1-2 days longer in Et-treated rats. The numbers of neurons generated on a specific day was altered; from GD 12-19 significantly fewer neurons were generated in Et-treated rats than in Ct-treated rats, whereas after GD 19 more neurons were born. The distribution of neurons generated on a specific day was disrupted; most notable was the distribution of late-generated neurons in deep cortex of Et-treated rats rather than in superficial cortex as they are in controls. Cortical neurons in Et-treated rats tended to be smaller than in Ct-treated rats, particularly early generated neurons in deep cortex. The late-generated neurons in Et-treated rats were of similar size to those in Ct-treated rats despite their abnormal position in deep cortex. Neurons in Ct-treated rats tended to be rounder than those in Et-treated rats which were more polarized in the radial orientation. A proliferation index, which was based on the amount of autoradiographic signal over each labeled neuron, indicated that an additional, late surge in proliferative activity occurred in Et-treated rats on GD 20-21. The amount of [3H]thymidine incorporated each day was determined by biochemical analyses. In Ct-treated rats, incorporation increased to a maximum on GD 17 and decreased thereafter. In Et-treated rats, there were two maxima, the first on GD 18 and the second on GD 20. These data fully support the findings of the autoradiographic analyses. The present data show that neuronal generation is profoundly affected by ethanol. Such disturbances result from ethanol-induced abnormalities in neuronal proliferation and migration.


[Development of the facial and periodontal approach to the maxillary sinus].
The nasal approach for operations of the maxillary sinus is becoming increasingly popular. The oral approach provides the best access for demonstration of the orbital floor, for ligation of the maxillary artery, for drainage of resistant rhinogenic sinusitis, and for removal of foreign bodies, tooth roots, dislocated teeth, odontogenic cysts and benign tumours of the maxillary sinus. Formerly the anterior wall of the maxillary sinus was removed, but nowadays procedures preserving the bone are chosen. The classical otorhinolaryngological incision lies in the limbus of the vestibule. Maxillofacial surgeons prefer an incision at the junction of the attached to the unattached gingiva because scars in the limbus of the vestibule create problems during later fitting of a denture. A follow-up of 40 patients shows that the gingival marginal incision causes no problems. This incision, introduced by Peter in 1930, is therefore preferred. The marginal incision does not leave any visible scars. It corresponds to an incision on the alveolar ridge in the edentulous patient.


Vibrotactilometry as a diagnostic tool in ulnar nerve entrapment at the elbow.
Vibrotactilometry with testing of the thresholds of the vibration sense at seven frequencies between 8-500 Hz in different intensities has been correlated with nerve conduction studies of the ulnar nerve to evaluate its diagnostic power in neuropathies at the elbow. Thirty-nine patients with entrapment symptoms were studied. Vibrotactilometry was abnormal in 33 patients (85%) and nerve conduction studies were abnormal in 19 (49%). The sensitivity of vibrotactilometry in relation to nerve conduction studies was 89%, and in relation to the patients' symptoms was 85%. We conclude that vibrotactilometry is a sensitive test that correlates well with the patients' symptoms, while nerve conduction studies are less sensitive (49%) in relation to the patients' symptoms. Vibrotactilometry in the frequency area of 8-500 Hz is recommended in the screening of ulnar nerve entrapment. Nerve conduction studies are recommended in clinically doubtful cases to localise the entrapment to the elbow region.


Exploring the Adjudication of Methamphetamine-related Housing Contamination Cases in New Zealand.
Residential methamphetamine contamination in New Zealand has resulted in substantial clean-up costs and evictions. Disputes between tenants and landlords have been adjudicated by the New Zealand Tenancy Tribunal (NZTT). However, the adjudication processes applied are not covered in specific legislation, and scientific advice and related regulatory standards have evolved over time, leading to uncertainty about the consistency of decisions. This study explores the factors that have influenced adjudicators' decisions by thematically analysing 685 NZTT orders from 2014 to 2019. Landlords filed 84% of applications and tenants were deemed liable for 96% of the NZ$2.8 million damages awarded. The Tribunal's decisions were unevenly influenced by baseline testing, presence of children, experience of health issues, police intervention, and neighbours' reports. Several factors contributed to inconsistent decisions, including the contamination threshold applied, sampling methodology, establishing liability for contamination, and assessing "cleanliness". This study suggests more judicial guidance and legislation is required to resolve these cases more equitably.


Randomized controlled trial: effect of nutritional counselling in general practice.
To investigate the effectiveness of a non-structured 15-min educational intervention by general practitioners (GPs) on modifications of daily diet among healthy adults. Two arms randomized trial lasting 12 months. Italian general practitioner wards. Subjects A total of 3,186 men and women aged 18-65 years recruited in the medical ward by their GPs. An educational intervention and a brochure on the basics of a healthy diet based on the Italian Guidelines for a Correct Nutrition, 1998. The main study goal was to attain an intake of fruits and vegetables >5 servings per day. Follow-up visit every 6 months. Main outcome measures Weight, blood pressure, and a 40-items Food Frequency Questionnaire. The intervention group showed a slightly reduced net intake of meat and a slightly increased net intake of fruits and vegetables, fish products, and olive oil. Body mass index (BMI) changed only in the treatment arm [-0.41 95% confidence interval (95% CI) -0.11 to -0.53]. The net change at 1 year in the intervention arm was +1.31 (CI 0.90-4.39) for fruits and vegetables, and -0.22 (-0.11 to -0.69) for meat (portions per week). We also computed a 'healthy diet score' reflecting compliance with recommended dietary habits. In the intervention group, the mean score at recruitment was significantly lower than the mean score at the end of follow-up (Crude score change = 0.29; CI 0.19-0.48). No differences were observed in the control group (Crude score change = -0.04; CI -0.22-0.02). The difference in score from baseline to the final visit, comparing the intervention vs the control group, was statistically significant (P < 0.001) (MANOVA adjusted by sex, BMI, education, and time). A brief educational intervention by GPs can induce multiple diet changes that may lower BMI and potentially reduce chronic disease risk in generally healthy adults.