Protection of testicular dysfunctions by MTEC, a formulated herbal drug, in streptozotocin induced diabetic rat.
Single injection of streptozotocin (STZ) resulted diabetes mellitus which was reflected here by the levels of fasting blood glucose and serum insulin. Moreover, this experimental diabetes also resulted testicular dysfunctions evaluated by count, viability and motility of sperm as well as by the activities of key enzymes for androgen synthesis. Diabetes induced testicular oxidative stress has been indicated here by the monitoring of testicular peroxidase and catalase activities as well as by quantification of TBARS and CD of testis. Testicular glucose was increased and leydig cell nuclear area was decreased in STZ induced diabetes. Treatment of herbal formulated drug named as MTEC consist of aqueous-methanol extract of Musa paradisiaca, Tamarindus indica, Eugenia jambolana and Coccinia indica to streptozotocin induced diabetic rat at the ratio of 2:2:1:1 at the dose of 60 mg/d for two times a day for 14 d resulted a significant protection in fasting blood glucose and serum insulin levels (p<0.05) along with correction of testicular above parameters towards the control level (p<0.05). This herbal formulated drug has no general toxic effects on the body weight, as well as on the activities of serum glutamate and pyruvate transaminases in serum. The results support the validity of this herbal drug for the management of testicular disorders noted in diabetic state.


Profile of extracranial cerebrovascular disease in Kelantan: a study by continuous wave Doppler ultrasonography.
The present study outlines the clinical profile and patterns of extracranial vascular abnormalities detected by continuous wave doppler ultrasonography (CWDU) in 100 patients with cerebrovascular insufficiency states. Males outnumbered females (65:35); completed stroke (CS) was a more common mode of presentation than transient ischaemic attacks (TIA); carotid strokes were more common than vertebro-basilar ones; and hypertension was the most common predisposing factor. The CWDU evaluation revealed extracranial vascular disease in 73% of patients. Vascular occlusions were more common in patients with TIA. Overall, 33% of the patients had evidence of proximal obstruction of the cerebral vessels below the neck. The clinical prediction of vascular territory (carotid or vertebro-basilar) matched with the findings on CWDU, but evidence of subclinical multiple-vessel involvement could be detected in 48% of the patients.


FNAC diagnosis of mucinous carcinoma of male breast--a case report.
Mucinous carcinoma of the male breast is a very rare tumour. So far only about 8 cases have been reported in the literature most of which were diagnosed after surgical resection. Fine-needles aspiration biopsy even though a well established procedure for the evaluation of breast masses in female there are only occasional reports of aspirates form male breast masses. We herein-present one case of mucinous carcinoma of breast in a 65 year old male diagnosed by fine needle and confirmed by histopathology.


Ultrasonic study of normal and fractured bone.
Ultrasonic velocity measurement in bone can be used as a clinical tool that will accurately and objectively monitor the progress of fracture healing. This technique may provide a rational basis for evaluating the effectiveness of various modalities in clinical treatment. The eventual goal of this technique is to determine the status of healing fractures, prescribe appropriate treatment, give the rationale for the timing and form of a rehabilitative program that would accelerate the patient's return to productivity. An instrument has been developed to measure ultrasonic velocity in the long bones of the extremities. Serial measurements of tibial fractures and the measurement of a large group of normals shows no statistically significant differences in ultrasonic measurements have been found on the basis of race, sex, or pregnancy among normals. But a numerically small but statistically significant variation with age was found. While the number of fracture cases observed was small, the evidence is clear that ultrasonic measurement in fractured tibia may give a more reliable indication of the general pattern of healing response than the clinical and roentgenographic examination.


The potential for sexual transmission to compromise control of Ebola virus outbreaks.
Recent evidence suggests that sexual contact may give rise to transmission of Ebola virus long after infection has been cleared from blood. We develop a simple mathematical model that incorporates contact transmission and sexual transmission parametrized from data relating to the 2013-2015 West African Ebola epidemic. The model explores scenarios where contact transmission is reduced following infection events, capturing behaviour change, and quantifies how these actions reducing transmission may be compromised by sexual transmission in terms of increasing likelihood, size and duration of outbreaks. We characterize the extent to which sexual transmission operates in terms of the probability of initial infection resolving to sexual infectiousness and the sexual transmission rate, and relate these parameters to the overall case burden. We find that sexual transmission can have large effects on epidemic dynamics (increasing attack ratios from 25% in scenarios without sexual transmission but with contact-transmission-reducing behaviour, up to 80% in equivalent scenarios with sexual transmission).


Fertilization effects on fineroot biomass, rhizosphere microbes and respiratory fluxes in hardwood forest soils.
Fertilizer-induced reductions in CO(2) flux from soil ((F)CO(2)) in forests have previously been attributed to decreased carbon allocation to roots, and decreased decomposition as a result of nitrogen suppression of fungal activity. Here, we present evidence that decreased microbial respiration in the rhizosphere may also contribute to (F)CO(2) reductions in fertilized forest soils. Fertilization reduced (F)CO(2) by 16-19% in 65-yr-old plantations of northern red oak (Quercus rubra) and sugar maple (Acer saccharum), and in a natural 85-yr-old yellow birch (Betula allegheniensis) stand. In oak plots, fertilization had no effects on fine root biomass but reduced mycorrhizal colonization by 18% and microbial respiration by 43%. In maple plots, fertilization reduced root biomass, mycorrhizal colonization and microbial respiration by 22, 16 and 46%, respectively. In birch plots, fertilization reduced microbial respiration by 36%, but had variable effects on root biomass and mycorrhizal colonization. In plots of all three species, fertilization effects on microbial respiration were greater in rhizosphere than in bulk soil, possibly as a result of decreased rhizosphere carbon flux from these species in fertile soils. Because rhizosphere processes may influence nutrient availability and carbon storage in forest ecosystems, future research is needed to better quantify rhizo-microbial contributions to (F)CO(2).


Basal and stress-induced differences in HPA axis, 5-HT responsiveness, and hippocampal cell proliferation in two mouse lines.
To characterize individual differences in neuroendocrine and neurochemical correlates of stress coping, two lines of wild house mice were studied. These mice are genetically selected for high and low aggression and show distinctly different behavioral strategies toward environmental stimuli. Long attack latency (LAL), low aggressive mice display a passive coping style, whereas short attack latency (SAL), high aggressive mice show an active coping style. It was hypothesized that this difference in behavioral coping style is associated with differences in stress system reactivity. This was tested by investigating the regulation of the hypothalamus-pituitary-adrenal (HPA) axis and the serotonin (5-HT) system and hippocampal cell proliferation rate in these mice under baseline and stress conditions. Baseline corticosterone output in LAL mice was found to be more sensitive to adrenocorticotropic hormone, but showed less day/night variation than in SAL mice. Furthermore, LAL mice showed lower hippocampal 5-HT(1A) receptor gene expression and function. Basal hippocampal cell proliferation rate was slightly lower in LAL than in SAL mice. Exposure to acute stress (forced swimming for 5 min) resulted in a hyper-reactive HPA response, a reduced increase in brain 5-HT metabolism, and an almost 50% reduction in hippocampal cell proliferation rate in LAL compared with SAL mice. Chronic psychosocial stress (sensory contact stress) induced long-lasting changes in the HPA axis in LAL, but not in SAL mice. In conclusion, these studies show that a genetic trait in behavioral coping style in wild house mice is associated with differences in HPA regulation, 5-HT neurotransmission, and hippocampal cell proliferation rate. The results further indicate that LAL mice have a higher stress responsivity than SAL mice. These results may have implications for a differential susceptibility for stress-related mood disorders.


Unique features of transcription termination and initiation at closely spaced tandem human genes.
The synthesis of RNA polymerase II (Pol2) products, which include messenger RNAs or long noncoding RNAs, culminates in transcription termination. How the transcriptional termination of a gene impacts the activity of promoters found immediately downstream of it, and which can be subject to potential transcriptional interference, remains largely unknown. We examined in an unbiased manner the features of the intergenic regions between pairs of 'tandem genes'-closely spaced (< 2 kb) human genes found on the same strand. Intergenic regions separating tandem genes are enriched with guanines and are characterized by binding of several proteins, including AGO1 and AGO2 of the RNA interference pathway. Additionally, we found that Pol2 is particularly enriched in this region, and it is lost upon perturbations affecting splicing or transcriptional elongation. Perturbations of genes involved in Pol2 pausing and R loop biology preferentially affect expression of downstream genes in tandem gene pairs. Overall, we find that features associated with Pol2 pausing and accumulation rather than those associated with avoidance of transcriptional interference are the predominant driving force shaping short tandem intergenic regions.


Pharmacokinetic investigations of isavuconazole in paediatric cancer patients show reduced exposure of isavuconazole after opening capsules for administration via a nasogastric tube.
To study the isavuconazole pharmacokinetics in a real-life paediatric cohort and confirm whether the isavuconazole exposures are within the adult exposure range. Furthermore, we are the first to describe unbound isavuconazole pharmacokinetics. In this prospective, observational study, the isavuconazole dosing regimen was as follows (IV/oral/nasogastric tube): 5.4 mg/kg isavuconazole (maximum 200 mg/dose) three times daily on Days 1 and 2, followed by 5.4 mg/kg isavuconazole (maximum 200 mg/dose) once daily. At least one pharmacokinetic curve was assessed. Non-linear mixed effects modelling was used for analysis. Monte Carlo simulations were performed with the above mentioned maintenance dose for IV administrations and a weight band dosing regimen for oral/nasogastric tube administrations: I) <18 kg (100 mg daily); II) 18-37 kg (150 mg daily); III)>37 kg (200 mg daily). Seventeen paediatric patients with a median age of 9 years (range 1-17) and median weight of 26.0 kg (range 8.4-78.5) were evaluated. A two-compartment model describing linear pharmacokinetics of the unbound concentrations and saturable protein binding fitted the isavuconazole concentrations best. The absolute bioavailability of isavuconazole was 41.0% (95% CI: 32.4%-50.8%). The median (IQR) simulated exposures (AUC0-24h, SS) of the total isavuconazole concentrations after IV and oral/nasogastric tube administration were 87.7 mg·h/L (70.5-105.1) and 50.3 mg·h/L (39.0-62.4), respectively. The unbound isavuconazole fraction (unbound/total) ranged from 0.5% to 2.3%. This study revealed low bioavailability after nasogastric tube administration with opened capsules. Isavuconazole exposures were in the expected range following IV administration. Total and unbound isavuconazole pharmacokinetics were reported with a 5-fold range in the unbound fraction.


Least-squares fitting of Hartmann or Shack-Hartmann data with a circular array of sampling points.
A least-squares procedure to find the tilts, curvature, astigmatism, coma, and triangular astigmatism by means of measurements of the transverse aberrations using a Hartmann or Shack-Hartmann test is described. The sampling points are distributed in a ring centered on the pupil of the optical system. The properties and characteristics of rings with three, four, five, six, or more sampling points are analyzed with more detail and better mathematical analysis than in previous publications.


Evaluation of threshold color differences using printed samples.
The performances of uniform color spaces and color-difference formulae for predicting threshold color differences were investigated based on visual assessments of 893 pairs of printed color patches under a D65 source. The average ΔE(ab,10)* of the pairs was 1.1 units. A threshold psychophysical experiment was repeated three times by a panel of 16 observers with normal color vision. The experimental data were used to evaluate nine color-difference formulae and uniform color spaces using the standardized residual sum of squares (STRESS) measure. The results indicated that all formulae and spaces performed very similarly to each other, and outperformed CIELAB for threshold color differences. The chromaticity-discrimination ellipses were used to compare with previous results from small color differences [Color Res. Appl. (2011), doi:10.1002/col.20689], and they agreed with each other, except for the purple color center.


Hepatitis C virus infection among Brazilian hemophiliacs: a virological, clinical and epidemiological study.
We determined and analyzed risk factors of hepatitis C virus (HCV)-infected Brazilian hemophiliacs according to their virological, clinical and epidemiological characteristics. A cross-sectional and retrospective study of 469 hemophiliacs was carried out at a Brazilian blood center starting in October 1997. The prevalence of HCV infection, HCV genotypes and factors associated with HCV RNA detection was determined. The seroprevalence of anti-HCV antibodies (ELISA-3.0) was 44.6% (209/469). Virological, clinical and epidemiological assessments were completed for 162 positive patients. There were seven (4.3%) anti-HCV seroconversions between October 1992 and October 1997. During the same period, 40.8% of the positive anti-HCV hemophiliacs had abnormal alanine transaminase (ALT) levels. Plasma HCV RNA was detected by nested-RT-PCR in 116 patients (71.6%). RFLP analysis showed the following genotype distribution: HCV-1 in 98 hemophiliacs (84.5%), HCV-3 in ten (8.6%), HCV-4 in three (2.6%), HCV-2 in one (0.9%), and not typeable in four cases (3.4%). Univariate analysis indicated that older age (P = 0.017) and abnormal ALT levels (P = 0.010) were associated with HCV viremia, while the presence of inhibitor antibodies (P = 0.024) and HBsAg (P = 0.007) represented a protective factor against the presence of HCV RNA. These findings may contribute to a better understanding of the relationship between HCV infection and hemophilia.


Incorporation of 1,N6-ethenoadenosine into the 3' terminus of tRNA using T4 RNA ligase. 2. Preparation and ribosome interaction of fluorescent Escherichia coli tRNAMetf.
A fluorescent derivative of tRNAMetf from Escherichia coli has been prepared which contains 1,N6-etheno-adenosine (epsilon A) in the place of adenosine 73, the fourth residue from the 3' end. The labeled tRNA, tRNAMetf epsilon A73, is fully active with respect to aminoacylation, formylation and formylmethionyl transfer to puromycin. The preparation procedure entails the chemical removal of four nucleotides from the 3' end of tRNAMetf, ligation of the truncated molecule with epsilon A 3',5'-bisphosphate by use of T4 RNA ligase and repair of the C-C-A end with nucleotidyl transferase. The fluorescence of fMet-tRNAMetf epsilon A73 has been exploited for studying tRNA-ribosome complexes. Upon binding the tRNA into the ribosomal P site, the fluorophor experiences a change of its molecular environment as indicated by an increased fluorescence intensity. On the other hand, iodide quenching experiments indicate that, in the complex, the fluorophor is not shielded against solvent access. The results suggest that (a) adenosine 73 is not involved in direct contacts with the ribosome and (b) the stacking of the 3'-terminal A-C-C-A sequence is changed upon binding to the ribosome.


Leukocyte-dependent histamine release from rabbit platelets. The role of IgE, basophils, and a platelet-activating factor.
We have studied the leukocyte-dependent mechanism of histamine release (LDHR) from rabbit platelets, a complement-independent mechanism which has been implicated in the deposition of immune complexes in acute serum sickness of rabbits. It was found by chromatography and passive transfer of serum from immunized rabbits that the antibody responsible for the LDHR was of IgE type. By electron microscope study of the reaction, the leukocyte involved in agglutination of platelets and release of their histamine content was identified as the basophil. Upon addition of antigen, basophils sensitized with IgE degranulated, released their histamine content and a platelet-activating factor (PAF) that caused aggregation of platelets and release of their histamine. Conditions of preparing and preserving PAF activity and some properties of this factor have been elucidated. LDHR must, therefore, be considered as an immediate hypersensitivity-type mechanism which may link allergic reactions with immunologic disease associated with severe structural injury.


Meta-Omics Reveals Genetic Flexibility of Diatom Nitrogen Transporters in Response to Environmental Changes.
Diatoms (Bacillariophyta), one of the most abundant and diverse groups of marine phytoplankton, respond rapidly to the supply of new nutrients, often out-competing other phytoplankton. Herein, we integrated analyses of the evolution, distribution, and expression modulation of two gene families involved in diatom nitrogen uptake (DiAMT1 and DiNRT2), in order to infer the main drivers of divergence in a key functional trait of phytoplankton. Our results suggest that major steps in the evolution of the two gene families reflected key events triggering diatom radiation and diversification. Their expression is modulated in the contemporary ocean by seawater temperature, nitrate, and iron concentrations. Moreover, the differences in diversity and expression of these gene families throughout the water column hint at a possible link with bacterial activity. This study represents a proof-of-concept of how a holistic approach may shed light on the functional biology of organisms in their natural environment.


Intercellular lamellar lipids in plantar stratum corneum.
Plantar stratum corneum was examined by means of transmission electron microscopy after conventional osmium fixation and after fixation with ruthenium tetroxide. The latter fixative was used in order to reveal the possible existence of lamelarly ordered lipids in the intercellular space, as has previously been demonstrated for non-palmo-plantar stratum corneum. A major part of the plantar stratum corneum intercellular space was occupied by extracellular parts of desmosomes. In specimens fixed with ruthenium tetroxide the intercellular space not occupied by desmosomes was found to contain multiple alternating electron dense and electron lucid bands, suggestive of membraneous structures. This pattern appeared to be similar to that previously described for non-palmo-plantar stratum corneum. It is suggested that the intercellular lipids of palmo-plantar stratum corneum may be qualitatively similar to the intercellular lipids of non-palmo-plantar stratum corneum. The lower lipid content, expressed as weight per unit weight of tissue, in palmo-plantar stratum corneum as compared to non-palmo-plantar stratum corneum may be related to the fact that a larger portion of the intercellular space of the former tissue is occupied by desmosomes. The relatively high water permeability of palmo-plantar stratum corneum implies that desmosomes, i.e. non-lipid regions of the intercellular space, may have a high water permeability and hence could establish a hydrophilic route through the stratum corneum.


Web-Based Survey Piloting Process as a Model for Developing and Testing Past Contraceptive Use and Pregnancy History: Cystic Fibrosis Case Study.
Individuals with complex, chronic diseases are now living longer, making reproductive health an important topic to address in the health care setting. Self-respondent surveys are a feasible way to collect past contraceptive use and pregnancy history to assess contraceptive safety and effectiveness. Because sensitive topics, such as contraception and pregnancy outcomes, can vary across social groups or cultures, piloting questions and evaluating survey administration procedures in the target population are necessary for precise and reliable responses before wide distribution. This study aimed to develop a precise and reliable survey instrument and related procedures among individuals with cystic fibrosis regarding contraceptive use and obstetrical history. We piloted and tested web-based questions related to contraceptive use and pregnancy history among 50 participants with and those without cystic fibrosis aged 18 to 45 years using a 3-tier process. Findings from each tier informed changes to the questionnaire before testing in the subsequent tier. Tier 1 used cognitive pretesting to assess question understanding and the need for memory prompts. In tier 2, we used test-retest self- and interviewer-administered approaches to assess question reliability, evaluate response missingness, and determine confidence between 2 types of survey administration approaches. In tier 3, we tested the questionnaire for clarity, time to complete, and whether additional prompts were necessary. In tier 1, respondents suggested improvements to the web-based survey questions and to the written and visual prompts for better recall regarding past contraceptive use. In tier 2, the test-retest reliability between self- and interviewer-administrative procedures of "ever use" contraceptive method questions was similar, with percent absolute agreement ranging between 84% and 100%. When the survey was self-administered, the percentage of missing responses was higher and respondent confidence about month and year when contraceptive methods were used was lower. Most respondents reported that they preferred the self-administered survey because it was more convenient and faster to complete. Our 3-tier process to pilot web-based survey questions related to contraceptive and obstetrical history in our complex disease population helped us tailor content and format questions before wide dissemination to our target population. Results from this pilot study informed the subsequent larger study design to include a 10% respondent test-retest self- and interviewer-administered quality control component to better inform imputation procedures of missing data.


Management of chronic kidney disease: perspectives of Brazilian primary care physicians.
To investigate primary care physicians' knowledge of and attitudes toward care for chronic kidney disease patients. In Brazil, care for chronic kidney disease, a global public health problem, is provided by the Brazilian National Health System, which is organized around primary care. The study aimed to investigate the knowledge and attitudes of primary care physicians about the management of chronic kidney disease. This research is based on quantitative and qualitative data. The participants were 92 physicians from 81 primary care units located in eight cities of the São Paulo/Brazil health region, who answered a self-administered questionnaire. Only 59% and 58% of the physicians recognized smoking and obesity, respectively, as risk factors for chronic kidney disease. Health appointments and drug therapy predominated as disease prevention strategies and less than 30% mentioned multiprofessional care and health education groups. For early diagnosis, isolated serum creatinine was the most used test and 64.6% stated they classified the disease stages. Exclusive follow-up in primary care decreased from 79% in stage 1 to 19.5% in stage 3B and the patients' monitoring in the healthcare network varied from 8.7% in stage 1 to 70.6% in stages 4 and 5ND, suggesting early referrals and lack of referral at the necessary stages. Access to information on the referred patient was, predominantly, through the patient's report and 74% of the physicians did not have matrix support regarding chronic kidney disease. The study showed that the healthcare teams need to update their knowledge and procedures to be able to provide a comprehensive and efficient approach to treating chronic kidney disease in primary care.


Neuroimaging of rapidly progressive dementias, part 1: neurodegenerative etiologies.
Most dementias begin insidiously, developing slowly and generally occurring in the elderly age group. The so-called rapidly progressive dementias constitute a different, diverse collection of conditions, many of which are reversible or treatable. For this reason, prompt identification and assessment of acute and subacute forms of dementia are critical to effective treatment. Numerous other entities within this category of presenile rapid-onset dementias are untreatable such as the prion-related diseases. Neuroimaging aids in the diagnosis and evaluation of many of these rapidly progressive dementias, which include myriad conditions ranging from variations of more common neurodegenerative dementias, such as Alzheimer disease, dementia with Lewy bodies, and frontotemporal dementia; infectious-related dementias such as acquired immune deficiency syndrome dementia; autoimmune and malignancy-related conditions; to toxic and metabolic forms of encephalopathy. This first of a 2-part review will specifically address the ability of MR imaging and ancillary neuroimaging strategies to support the diagnostic evaluation of rapidly progressive dementias due to neurodegenerative causes.


Predicting Corynebacterium glutamicum promoters based on novel feature descriptor and feature selection technique.
The promoter is an important noncoding DNA regulatory element, which combines with RNA polymerase to activate the expression of downstream genes. In industry, artificial arginine is mainly synthesized by Corynebacterium glutamicum. Replication of specific promoter regions can increase arginine production. Therefore, it is necessary to accurately locate the promoter in C. glutamicum. In the wet experiment, promoter identification depends on sigma factors and DNA splicing technology, this is a laborious job. To quickly and conveniently identify the promoters in C. glutamicum, we have developed a method based on novel feature representation and feature selection to complete this task, describing the DNA sequences through statistical parameters of multiple physicochemical properties, filtering redundant features by combining analysis of variance and hierarchical clustering, the prediction accuracy of the which is as high as 91.6%, the sensitivity of 91.9% can effectively identify promoters, and the specificity of 91.2% can accurately identify non-promoters. In addition, our model can correctly identify 181 promoters and 174 non-promoters among 400 independent samples, which proves that the developed prediction model has excellent robustness.


[The silent disappearance of PADHUE doctors: the end of a State injustice or a new form of exclusion?]
Up until recently in France, physicians who obtained their degrees outside the European Union had a specifically disadvantaged status, that was supposed to be eliminated by the end of 2016. Until that date, a selective qualification process authorized foreign physicians to "full practice". The deadline has been postponed to 2017 to resolve the complicated situations of certain doctors and to avoid tensions in hospital wards. These developments raise questions about the working conditions and motivations for migration of foreign medical doctors, particularly African doctors, who participate in the French healthcare system, and the obstacles to their integration. Does the disappearance of unequal working conditions constitute progress, or does suspension of access to full practice for PADHUE doctors from 2018 constitute a step backwards? Recent social science analyses, particularly on the motivations of African doctors for migration, show complex stakes. In a protectionist French healthcare system willing to maintain health coverage, out of phase with globalization that promotes transnational mobility, the closure of borders for medical doctors who obtained their degrees outside of Europe, that replaces inequality by exclusion, constitutes a subject of debate.


Tumor necrosis factor-alpha (TNF-alpha)-induced optic neuropathy in rabbits.
Both in vitro and in vivo studies have implicated a role for tumor necrosis factor-alpha (TNF alpha) in various demyelinating diseases, including HIV-related encephalopathy. To investigate whether intravitreal TNF alpha can induce optic nerve axonal damage in a rabbit eye model, fifteen rabbit eyes were initially injected with TNF alpha (final concentrations: 2U, 20U, and 200U respectively) and studied at varying time intervals for up to 24 weeks post-injection, using light and electron microscopy. Control optic nerves (no injection or diluent injection only) had normal myelinated axons and glia; the myelinated regions, neural retina, retinal glia and vasculature of control retinas were normal. In TNF alpha-exposed optic nerves, intact, degenerating and demyelinated axons were interspersed. Astrogliosis was present, particularly from 8 weeks p.i. and was noted up to 24 weeks. Oligodendrocytes were not severely affected in TNF alpha-exposed optic nerves, and activated macrophages or microglia were not obvious. Axonal degeneration was visible among the more superficial myelinated fibers in TNF alpha-exposed retinas however the neural retina glia were unaffected. These observations suggest that the axonal degeneration induced in TNF alpha-exposed rabbit optic nerves over a 24 week period was most likely related to direct effects of TNF alpha on optic nerve axons, and not primarily due to anterograde degeneration from retinal lesions. In-so-far as neurological pathology in general, and optic nerve degeneration in particular, has been described in AIDS, and TNF alpha levels may be elevated in this disease, it is of great clinical significance that TNF alpha has the capacity to mediate neuronal or axonal injury. If so, strategies to block or inhibit TNF alpha can be pursued for treatment for the neurological symptoms of AIDS.


Treatment options for brain metastases from melanoma.
Brain metastases are a common complication of metastatic malignant melanoma, conferring an exceedingly poor prognosis. Diagnosis of brain metastasis often has significant implications for duration and quality of life, and management can be difficult due to rapid progression of disease and resistance to conventional therapies. This review focuses primarily on the published evidence for treatment modalities for brain metastases from melanoma, emerging technologies and outlines future directions for research. In summary, external-beam radiation alone appears effective in palliating symptoms. Surgical management of solitary or acutely symptomatic lesions appears to alleviate symptoms and provide the possibility of local control of disease. Stereotactic radiosurgery is an increasingly utilized technique for patients with a limited number of metastases and presents a less-invasive alternative to craniotomy. Chemotherapy alone is relatively ineffective, although combined chemotherapy with external-beam radiation is being investigated. Future directions include combined modality therapy, the incorporation of novel agents and careful consideration of the structure of clinical trials for this disease.


Racehorse welfare across a training season.
Racehorse welfare is gaining increasing public attention, however scientific evidence in this area is lacking. In order to develop a better understanding of racehorse welfare, it must be measured and monitored. This is the first study to assess racehorse welfare using scientific objective methods across a training season. The aim of this study was threefold, firstly to investigate welfare measures which could be used in the first welfare assessment protocol for racehorses. Secondly, to understand the effect that a racing and training season had on individual racehorses and thirdly to identify risk factors for both good and poor welfare. Thirteen racehorse training yards were visited at the beginning and the peak of the racing season in England. Behavioral observations along with individual environmental and animal-based welfare measures were carried out on 353 horses in 13 training yards selected for variability. In our sample the horses were generally in good physical health: 94% of horses recorded as an ideal body condition score, no horses had signs of hoof neglect and 77.7% had no nasal discharge. The overall prevalence of external Mouth Corner Lesions was 12.9% and was significantly higher for Flat racing than Jump racing horses. The majority of horses (67.5%) showed positive horse human interactions. When stabled 54.1% horses had physical social contact and nasal discharge was not associated with increased physical contact. The training season significantly affected Human Reactivity Tests, Horse Grimace Scale scores and time spent resting and feeding. A total of 14.5% of horses displayed stereotypic behavior on at least two occasions. Horses with windows in their stables spent more time surveying their surroundings. Overall, in this population of racehorses, horses spent around a third of their daytime feeding (33.7%) followed by time spent standing resting (22.6%). The welfare assessment protocol used in this study is suitable for use in industry to collect welfare data on racehorses.


Effect of dietary fat on the initiation of hepatocarcinogenesis by diethylnitrosamine or 2-acetylaminofluorene in rats.
The purpose of this study was to determine if increasing dietary fat, either as saturated fat or polyunsaturated fat, would alter initiation of hepatocarcinogenesis by diethylnitrosamine (DEN) or 2-acetylaminofluorene (AAF). Rats were fed one of three purified diets: a low-fat (LF) diet (containing 5% of calories as safflower oil), a high saturated fat (HSF) diet (containing 48% of calories as palm oil) and a high polyunsaturated fat (HPUF) diet (containing 48% of calories as safflower oil). Four weeks later, all rats were subjected to partial hepatectomy (PH). Rats were then divided into four groups and received no carcinogen, DEN (10 mg/kg, p.o., 24 h after PH) or AAF (25 or 100 mg/kg, p.o., 12 h after PH). Five days later, all rats were fed an unrefined diet, and 9 weeks later, all rats were fed phenobarbital in the diet for 26 weeks as a tumor promoter. In rats initiated with DEN, the number of gamma-glutamyl transpeptidase-positive and ATPase-negative foci was higher in the rats fed the HPUF diet, but not the HSF diet, as compared to rats fed the LF diet. The incidence of neoplastic nodules, the mean focal volume and the volume fraction, however, were not significantly altered by dietary fat in DEN-injected rats. The dietary fat content of the diet did not affect the induction of altered hepatic foci or neoplastic nodules in rats initiated with AAF or receiving no initiation. This study shows that initiation of hepatocarcinogenesis can be influenced by dietary fat, but that the effect may be carcinogen-specific.


Urinary 8-Oxo-7,8-Dihydro-2'-Deoxyguanosine in Tunisian Electric Steel Foundry Workers Exposed to Polycyclic Aromatic Hydrocarbons.
In this study, urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), as biomarker of oxidative DNA damage, was evaluated in Tunisian electric steel foundry workers and was associated with polycyclic aromatic hydrocarbon (PAH) exposure. Ninety-three healthy male workers were enrolled in the study; 8-oxodG was assessed by liquid chromatography-triple quadrupole mass spectrometry. Exposure to PAHs was evaluated by measuring 16 urinary PAHs (U-PAHs) and 8 monohydroxylated metabolites (OHPAHs). The median 8-oxodG level for all subjects was 3.20 µg l-1 (1.85 µg g-1 creatinine). No correlation between 8-oxodG and 1-hydroxypyrene or any other OHPAH was found. Significant linear correlations between 8-oxodG and some U-PAHs were found, particularly urinary acenaphthylene (r = 0.249), phenanthrene (r = 0.327), anthracene (r = 0.357), fluoranthene (r = 0.248), and pyrene (r = 0.244). Multiple regression analyses confirmed that urinary phenanthrene, anthracene, and naphthalene (the latter with a non-linear relationship) were predictors of 8-oxodG; job title, but not smoking, was a determinant of 8-oxodG; the variance explained by these models was up to 20%. The oxidative DNA damage assessed by urinary 8-oxodG was moderate and in the range of values reported in other occupational fields or in the general population. The results of this study indicate that the investigated biomarkers of PAH exposure were only minor contributors to urinary 8-oxodG.


Alcohol-Tolerant Platinum Electrocatalyst for Oxygen Reduction by Encapsulating Platinum Nanoparticles inside Nitrogen-Doped Carbon Nanocages.
Pt-based electrocatalysts are the most popular for direct alcohol fuel cells, but their performances easily deteriorate for the oxygen reduction reaction (ORR) at the cathode because of the alcohol crossover effect. Herein, we report the novel Pt electrocatalyst encapsulated inside nitrogen-doped carbon nanocages (Pt@NCNC), which presents excellent alcohol-tolerant ORR activity and durability in acidic media, far superior to the Pt counterpart immobilized outside the nanocages (Pt/NCNC). The superb performance is correlated with the molecule-sieving effect of the micropores penetrating through the shells of the nanocages, which admit the small-sized oxygen and ions but block the large-sized alcohols into the nanocages. This mechanism is confirmed by examining the size dependence of ORR and alcohol oxidation activities by regulating the micropores sizes. This study provides a promising strategy to develop the superior alcohol-tolerant Pt-based ORR electrocatalyst in acidic media.


Improving the accuracy of interpolated potential energy surfaces by using an analytical zeroth-order potential function.
We present a method for improving the accuracy and efficiency of interpolation methods, in which an analytical zeroth-order potential-energy surface is employed as a reference surface. To investigate and test the method, we apply it to hydrogen peroxide where there exists an accurate analytical surface which we take as the "exact" surface for obtaining the energies and derivatives for fitting and assessing the accuracy. Examples are given for four-dimensional and six-dimensional surfaces interpolated by using either the modified Shepard or second-degree interpolating moving least-squares approach, with comparisons for cases with and without using the zeroth-order potential.


Sampling of quantum dynamics at long time.
The principle of energy conservation leads to a generalized choice of transition probability in a piecewise adiabatic representation of quantum(-classical) dynamics. Significant improvement (almost an order of magnitude, depending on the parameters of the calculation) over previous schemes is achieved. Perspectives for theoretical calculations in coherent many-body systems are opened.


[Rheumatologists' current tasks].
The main tasks for contemporary rheumatology include finding methods for the early identification of patients with inflammatory arthropathy, the use and development of prognostic indicators of the degree of aggressiveness required in treatment, and well structured and comprehensive follow-up treatment modalities administered in new ways and of the many new modalities that are under development. Success in these respects will entail close liaison with primary care and with other related disciplines. Dynamic developments are to be expected concerning the introduction of new generations of immunoregulatory agents.


Antiplatelet agents for secondary prevention of stroke.
Patients with recent ischemic stroke or transient ischemic attack (TIA) face a high risk of recurrent stroke as well as an increased risk of myocardial infarction and sudden cardiac death. In the absence of a clearly established indication for long-term anticoagulation, such as atrial fibrillation, antiplatelet agents are the antithrombotic drugs of choice for preventing recurrent vascular events. For many years, aspirin (ASA) has been the first-line therapy for patients at high risk of vascular ischemic events. Two large clinical trials have established the superiority of the combination of ASA and extended-release dipyridamole (ASA/ERDP) over ASA alone in patients with recent noncardioembolic ischemic stroke or TIA. Clopidogrel, another antiplatelet agent, is a reasonable alternative to ASA, but its superiority to ASA in patients with a history of stroke has not been as clearly established. The combination of ASA and clopidogrel, which is effective in patients with acute coronary syndrome, has not been shown to be either effective or safe, compared with either agent alone, in stroke patients, although there may be some benefit to this combination in patients with acute TIA. The results from a large randomized trial comparing ASA/ERDP with clopidogrel, anticipated soon, will further assist clinicians in choosing among available antiplatelet agents.


Follicle-stimulating hormone receptor polymorphism (G-29A) is associated with altered level of receptor expression in Granulosa cells.
Polymorphisms of the FSHR gene are associated with variable ovarian response to FSH stimulation in subjects undergoing in vitro fertilization (IVF) treatment. The type of ovarian response is correlated with the level of FSH receptor (FSHR) expression on granulosa cells. We investigated whether the polymorphism at position -29 in the promoter of the FSHR gene may contribute in altered receptor expression. FSHR polymorphism at position -29 was studied in 100 subjects undergoing IVF treatment. Association of this polymorphism with level of FSHR expression was retrospectively analyzed. The study was conducted at an academic research institute and private IVF clinic. The genotype at position -29 of the FSHR gene was studied in IVF subjects by PCR-restriction fragment length polymorphism. Total RNA and protein was extracted from granulosa cells. The relative FSHR mRNA expression was carried out by real-time PCR. The receptor protein expression was evaluated by Western blot and confocal microscopy. The clinical and endocrinological parameters revealed that almost 72% of subjects with the AA genotype at position -29 of FSHR gene were poor ovarian responders (odds ratio 8.63, 95% confidential interval 1.84-45.79; P = 0.001). The lower cleavage intensity predicted by in silico analysis for A allele as compared with the G allele suggest the difference in the DNA-protein binding affinity. The relative expression of FSHR at mRNA and protein level was significantly reduced in subjects with AA genotype as compared with the GG genotype. Poor ovarian response observed in subjects with the AA genotype at position -29 of the FSHR gene is due to reduced receptor expression.


A naturalistic study of clinical use of risperidone.
Follow-up data on 97 of the 101 patients at a university-based psychiatric hospital for whom risperidone had been prescribed between February 1994, when the medication was introduced, and October 1996 were reviewed an average of 102 weeks after the start of the medication. Only 28.9 percent of the patients were still on risperidone at follow-up. Patients who were maintained on risperidone were able to tolerate a higher dose with fewer side effects. The most common reasons for discontinuation were failure to achieve a therapeutic effect, noncompliance, and adverse side effects. The findings of this naturalistic study represent a cautionary consideration for the remarkable enthusiasm that surrounded the introduction of risperidone.


New cascade processes on group 6 Fischer-type carbene complexes: cyclopropanation and metathesis reactions.
Alkynyl Fischer carbene complexes 1, which feature a pendant olefin group, undergo novel cascade processes triggered by [2+2], [3+2], and [4+2] cycloadditions. Competition between cyclopropanation and olefin metathesis is controlled by the substitution at the double bond. The method described can be used to obtain different kind of polycarbo- and -heterocycles. A mechanistic explanation by means of DFT computational modeling is provided.


Health-Related Quality of Life, Treatment Satisfaction and Adherence Outcomes of Haemophilia Patients Living in a German Rural Region.
In the context of the 'Mobile Haemophilia Outpatient Care (MHOC)' project we aimed to gather insights into the health-related quality of life (HRQoL), treatment satisfaction (TS) and adherence of persons with haemophilia (PWHs) who get treated at the Saarland University Hospital Haemophilia Treatment Centre (HTC). PWHs were visited at home at least twice (baseline, follow-up) by trained medical staff. Individual interviews were performed to measure patients' HRQoL and TS with validated questionnaires (Haem-A-QoL/Haemo-QoL and Hemo-SatA/Hemo-SatP). Socio-demographic and clinical data were collected. In total, 79 PWHs were enrolled; 56 adults with a mean age of 37.4 ± 16.4 years (17-78) and 23 children [mean age of 9.8 ± 4.2 years (3-16)]. In total, 62% were severely affected; 48.1% received prophylaxis. Patients reported good HRQoL (adults: 23.1 ± 17.1; kids: 24.3 ± 11.1). Patients (M = 11.2 ± 9.5) and parents (M = 14.3 ± 7.4) were very satisfied with their provided treatment. The majority of study participants were evaluated to have a good treatment adherence. After 1-year follow-up of the MHOC, a significant improvement in HRQoL was seen in adults (p < 0.033) and in proxy ratings of parents (p < 0.0001); TS remained high with no change by MHOC intervention. Patients reported good HRQoL and TS. Most of them were evaluated as having a good treatment adherence. After implementation of the MHOC, adult patients reported a better HRQoL. Such a mobile medical care service is considered beneficial for patients, especially with limited access to a HTC.


Examining the effect of affective commitment to the supervisor on nurses' psychological health as a function of internal locus of control.
This research aimed to examine how affective commitment to the supervisor related to nurses' well- and ill-being, and to explore the moderating function of internal locus of control in these relationships. Little is known about the effects of affective commitment to the supervisor on well- and ill-being, even less so in the nursing profession. Moreover, previous studies suggested that nurses' psychological reactions to their work environment might vary as a function of their individual characteristics. This cross-sectional research used a questionnaire survey to explore the hypothesised relationships in a sample of 100 female certified nursing assistants. The results revealed that affective commitment to the supervisor was most strongly related to job satisfaction and well-being, and associated with lower levels of emotional exhaustion, when the internal locus of control was high. The present study emphasises the importance of a high quality relationship between nurses and their supervisors in order to promote their psychological health, and underscores the importance of individual characteristics. This research indicates how nurses' psychological health could be promoted by fostering their affective commitment to the supervisor. It also emphasises that managers' relationships with their subordinates should be adjusted as a function of nurses' individual characteristics.


Cordyceps sinensis (a traditional Chinese medicine) for treating chronic kidney disease.
Cordyceps sinensis (Cordyceps, Dong Chong Xia Cao), a herbal medicine also known as Chinese caterpillar fungus, is one of the most commonly used ingredients in traditional Chinese medicine for the treatment of people with chronic kidney disease (CKD). This review aimed to evaluate the therapeutic effects and potential adverse effects of Cordyceps sinensis for the treatment of people with CKD. We searched the Cochrane Renal Group's Specialised Register to 14 April 2014 through contact with the Trials' Search Co-ordinator using search terms relevant to this review. We also searched CINAHL, AMED, Current Controlled Trials, OpenSIGLE, and Chinese databases including CBM, CMCC, TCMLARS, Chinese Dissertation Database, CMAC and Index to Chinese Periodical Literature. Randomised and quasi-randomised trials comparing Cordyceps or its products with placebo, no treatment, or conventional treatment were considered for inclusion in the review. Two authors independently assessed data quality and extracted data. Statistical analyses were performed using the random-effects model and the results expressed as risk ratio (RR) for dichotomous outcomes or mean difference (MD) for continuous data with 95% confidence intervals (CI). We included 22 studies that involved 1746 participants. Among people with CKD who were not receiving dialysis, Cordyceps preparations were found to significantly decrease serum creatinine (14 studies, 987 participants): MD -60.76 μmol/L, 95% CI -85.82 to -35.71); increase creatinine clearance (6 studies, 362 participants): MD 9.22 mL/min, 95% CI 3.10 to 15.34) and reduce 24 hour proteinuria (4 studies, 211 participants: MD -0.15 g/24 h, 95% CI -0.24 to -0.05). However, suboptimal reporting and flawed methodological approaches meant that risk of bias was assessed as high in four studies and unclear in 18 studies, and hence, these results need to be interpreted with caution. We found that Cordyceps preparation, as an adjuvant therapy to conventional medicine, showed potential promise to decrease serum creatinine, increase creatine clearance, reduce proteinuria and alleviate CKD-associated complications, such as increased haemoglobin and serum albumin. However, definitive conclusions could not be made because of the low quality of evidence.


α-Ketoglutarate Promotes Pancreatic Progenitor-Like Cell Proliferation.
A major source of β cell generation is pancreatic progenitor-like cell differentiation. Multiple studies have confirmed that stem cell metabolism plays important roles in self-renewal and proliferation. In the absence of glucose, glutamine provides the energy for cell division and growth. Furthermore, α-ketoglutarate (αKG), a precursor for glutamine synthesis, is sufficient for enabling glutamine-independent cell proliferation. We have demonstrated that αKG contributes to the large-scale proliferation of pancreatic progenitor-like cells that can provide an ample amount of clinically relevant β cells. We compared the mRNA expression of a subset of genes, the abundance of ATP, reactive oxide species, mitochondrial number, and the colony-forming frequency between mouse pancreatic CD133⁺ and CD133- cells. We employed Real-Time PCR, immunostaining and passage assays to investigate self-renewal and proliferation of pancreatic progenitor-like cells in a 3D culture system in the presence and absence of αKG. The energy metabolism of CD133⁺ cells was more prone to oxidative phosphorylation. However, in the 3D culture system, when αKG was supplemented to the culture medium, the proliferation of the pancreatic progenitor-like cells was significantly elevated. We confirmed that the presence of αKG correlated with the up-regulation of Ten-Eleven Translocation (Tet). αKG can promote the proliferation of pancreatic progenitor-like cells via the up-regulation of Tet.


CBCT for the assessment of second mesiobuccal (MB2) canals in maxillary molar teeth: effect of voxel size and presence of root filling.
To compare detection of the second mesiobuccal (MB2) canal in maxillary molar teeth using cone-beam computed tomography (CBCT) with different voxel sizes against conventional radiographic examination when the MB1 was unprepared, prepared and filled. Radiographic examination and 0.2-, 0.25- and 0.3-mm CBCT (n = 89) were performed in 3 stages: S1, no first mesiobuccal (MB1) canal preparation or filling; S2, after MB1 preparation and filling; and S3, after MB1 root canal filling removal and canal repreparation. Images were analysed using the i-Cat software. After RE and CBCT acquisition in S3, all the samples were clarified to directly visualize the presence of the MB2 canal. All images were analysed by a blinded, previously calibrated examiner. Accuracy, specificity and sensitivity were compared using analysis of variance (P < 0.05 level of significance). MB2 root canals were detected in 67% of the samples. Overall, radiographic examination was associated with lower mean accuracy values for detecting MB2 than CBCT regardless of the MB1 condition. The MB1 root canal condition did not influence MB2 detection in 0.2-mm voxel images. The presence of root fillings in the MB1 canals reduced the detection of MB2 canals, especially in the 0.3- and 0.25-mm voxel-size images (P < 0.05). CBCT was associated with higher mean values of specificity and sensibility than radiographic examination for the detection of MB2 canals. When endodontic retreatment is necessary removal of the root filling prior to the CBCT examination eliminates artefacts, thereby permitting the use of the 0.3-mm voxel protocol that has good diagnostic performance and lower radiation dose.


Prph2 initiates outer segment morphogenesis but maturation requires Prph2/Rom1 oligomerization.
The retinal disease gene peripherin 2 (PRPH2) is essential for the formation of photoreceptor outer segments (OSs), where it functions in oligomers with and without its homologue ROM1. However, the precise role of these proteins in OS morphogenesis is not understood. By utilizing a knock-in mouse expressing a chimeric protein comprised of the body of Rom1 and the C-terminus of Prph2 (termed RRCT), we find that the Prph2 C-terminus is necessary and sufficient for the initiation of OSs, while OS maturation requires the body of Prph2 and associated large oligomers. Importantly, dominant-negative physiological and biochemical defects in RRCT heterozygous rods are rescued by removing Rom1, suggesting Rom1 is a regulator for OS formation. Our experiments evaluating Prph2 trafficking show that Rom1 is a key determinant of whether Prph2 complexes utilize conventional versus unconventional (Golgi bypass) secretory pathways to reach the OS. These findings significantly advance our understanding of the molecular underpinnings of OS morphogenesis and particularly the role of Rom1.


Genetic changes in a novel breeding population of Brassica napus synthesized from hundreds of crosses between B. rapa and B. carinata.
Introgression of genomic variation between and within related crop species is a significant evolutionary approach for population differentiation, genome reorganization and trait improvement. Using the Illumina Infinium Brassica 60K SNP array, we investigated genomic changes in a panel of advanced generation new-type Brassica napus breeding lines developed from hundreds of interspecific crosses between 122 Brassica rapa and 74 Brassica carinata accessions, and compared them with representative accessions of their three parental species. The new-type B. napus population presented rich genetic diversity and abundant novel genomic alterations, consisting of introgressions from B. rapa and B. carinata, novel allelic combinations, reconstructed linkage disequilibrium patterns and haplotype blocks, and frequent deletions and duplications (nonrandomly distributed), particularly in the C subgenome. After a much shorter, but very intensive, selection history compared to traditional B. napus, a total of 15 genomic regions with strong selective sweeps and 112 genomic regions with putative signals of selective sweeps were identified. Some of these regions were associated with important agronomic traits that were selected for during the breeding process, while others were potentially associated with restoration of genome stability and fertility after interspecific hybridization. Our results demonstrate how a novel method for population-based crop genetic improvement can lead to rapid adaptation, restoration of genome stability and positive responses to artificial selection.


An anesthesia information system designed to provide physician-specific feedback improves timely administration of prophylactic antibiotics.
Surgical site infections are a frequent cause of morbidity and mortality and add significantly to the cost of care. One component of the national Surgical Infection Prevention (SIP) program is to ensure timely administration of prophylactic antibiotics, a key factor to reduce postoperative infection. Our anesthesia department decided to assume the responsibility for timing and administration of antibiotic prophylaxis and we initiated a multitiered approach to remind the anesthesiologist to administer the prophylactic antibiotics. We used our anesthesia clinical information system to implement practice guidelines for timely antibiotic administration and to generate reports from the database to provide specific feedback to individual care providers with the goal of ensuring that patients receive antibiotic prophylaxis within 1 h of incision. Before the initiation of this project, 69% of eligible patients received antibiotics within 60 min of the incision. After the program began, there was a steady increase in compliance to 92% 1 yr later. Provider-specific feedback increases compliance with practice guidelines related to timely administration of prophylactic antibiotics. Anesthesia information systems hold promise for implementing and monitoring new practice guidelines and the anesthesiologist may play a key role in influencing surgical outcomes by ensuring appropriate therapy that may not be directly related to anesthesia care.


A scoping review of interventions to mitigate common non-communicable diseases among people with TB.
BACKGROUND: Recommendations have been made to integrate screening for common non-communicable diseases (NCDs) within TB programs. However, we must ensure screening is tied to evidence-based interventions before scale-up. We aimed to map the existing evidence regarding interventions that address NCDs that most commonly affect people with TB.METHODS: We systematically searched PubMed, Medline, and Embase for studies that evaluated interventions to mitigate respiratory disease, cardiovascular disease, alcohol and substance use disorder, and mental health disorders among people with TB. We excluded studies that only screened for comorbidity but resulted in no further intervention. We also excluded studies focusing on smoking cessation interventions for which evidence-based guidelines are well established.RESULTS: The search identified 20 studies that met our inclusion criteria. The most commonly evaluated intervention was referral for diabetes care (6 studies). Other interventions included pulmonary rehabilitation (5 studies), care programs for alcohol use disorder (4 studies), and psychosocial support or individual counselling (5 studies).CONCLUSION: There is limited robust evidence to support identified interventions in changing individual outcomes, and a significant knowledge gap remains on the long-term durability of the interventions´ clinical benefit, reach, and effectiveness. Implementation research demonstrating feasibility and effectiveness is needed before scaling up.


Adipose-derived stem cells ameliorate colitis by suppression of inflammasome formation and regulation of M1-macrophage population through prostaglandin E2.
Inflammatory bowel disease (IBD) is an idiopathic disease caused by a dysregulated immune response to intestinal microbes in an individual with a genetic predisposition. Therefore, alleviation of inflammation is very important to treat IBD. Mesenchymal stem cells (MSCs) have been highlighted as new candidates for treating autoimmune disease based on their immunomodulatory properties. In this study, we investigated the anti-inflammatory mechanism and therapeutic effects of adipose tissue-derived MSCs (ASCs) using THP-1 macrophages and dextran sodium sulfate (DSS)-induced mice with chronic colitis. LPS-treated THP-1 cells expressed mRNA of CD11b, an M1 macrophage marker, at day 2. However, THP-1 co-cultured with ASCs expressed mRNA of CD206, CD68, CCL18, legumain, and IL-10, markers of M2 macrophages. In THP-1 cells co-cultured with ASCs, precursor (pro)-IL-1β, Cox-2, and NLRP3 increased dramatically compared to LPS-treated THP-1 cells. Secretion of IL-1β and IL-18 was significantly inhibited by ASCs, but PGE2 production was highly increased in co-culture conditions of THP-1 and ASCs. IL-18 secretion was inhibited by PGE2 treatment, and PGE2 inhibited inflammasome complex (ASC/Cas-1/NLRP3) formation in THP-1 cells. In the DSS-induced chronic colitis model, ASCs ameliorated colitis by decreasing the total number of macrophages and the M1 macrophage population. Our results suggest that ASCs can suppress the inflammatory response by controlling the macrophage population, and ASCs may be therapeutically useful for the treatment of IBD.


Preliminary design of laser-induced breakdown spectroscopy for proto-Material Plasma Exposure eXperiment.
Laser-induced breakdown spectroscopy (LIBS) is a technique for measuring surface matter composition. LIBS is performed by focusing laser radiation onto a target surface, ablating the surface, forming a plasma, and analyzing the light produced. LIBS surface analysis is a possible diagnostic for characterizing plasma-facing materials in ITER. Oak Ridge National Laboratory has enabled the initial installation of a laser-induced breakdown spectroscopy diagnostic on the prototype Material-Plasma Exposure eXperiment (Proto-MPEX), which strives to mimic the conditions found at the surface of the ITER divertor. This paper will discuss the LIBS implementation on Proto-MPEX, preliminary design of the fiber optic LIBS collection probe, and the expected results.


Buerger's disease in Hong Kong: a review of 89 cases.
A retrospective analysis of 103 case records from 1978 to 1996 with a provisional diagnosis of Buerger's disease was undertaken at the Department of Surgery, University of Hong Kong, Queen Mary Hospital. The aim of the study was to elucidate the clinical course and evaluate the results of surgical intervention of Buerger's disease in Hong Kong Chinese people. Fourteen patients were subsequently excluded from the study because of inability of fulfil our diagnostic criteria. Data on clinical presentation, investigations, indications and results of surgical intervention were reviewed. Sympathectomies and arterial reconstructions were performed on 42 and four patients, respectively, for critical ischaemia or rest pain. Outcome was analysed with respect to the rate of ulcer healing, pattern of recurrence and limb loss. The patients were all young male heavy smokers with a mean age of 36.5 years. The majority of patients (80%) presented with ischaemic ulceration or gangrene. Vascular reconstruction was undertaken in four patients and satisfactory long-term results were obtained in three patients. Sympathectomy was able to relieve symptoms in 87% of operated patients and ischaemic ulceration healed in 2.6 (mean) +/- 1.7 (SD) months after the operation. If the patient continued to smoke, surgical intervention did not exempt the patient from a relapse or amputation. Sympathectomy provides short-term pain relief and promotes ulcer healing in patients with Buerger's disease but carries no long-term benefit. Complete abstinence from smoking is the only means of arresting the progression of the disease.


Microporous Organic Network: Superhydrophobic Coating to Protect Metal-Organic Frameworks from Hydrolytic Degradation.
Despite the rapid development of versatile metal-organic frameworks (MOFs), the synthesis of water-stable MOFs remains challenging, which significantly limits their practical applications. Herein, a novel engineering strategy was developed to prepare superhydrophobic MOFs by an in situ fluorinated microporous organic network (FMON) coating. Through controllable modification, the resulting MOF@FMON retained the porosity and crystallinity of the pristine MOFs. Owing to the superhydrophobicity of the FMON and the feasibility of MOF synthesis, the FMON coating could be in situ integrated with various water-sensitive MOFs to provide superhydrophobicity. The coating thickness and hydrophobicity of the MOF@FMON composites were easily regulated by changing the FMON monomer concentration. The MOF@FMON composites exhibited excellent oil/water separation and catalytic activities and enhanced durability in aqueous solutions. This study provides a general approach for the synthesis of superhydrophobic MOFs, expanding the application scope of MOFs.


Neural Pathways of Craniofacial Muscle Pain: Implications for Novel Treatments.
Craniofacial muscle pain is highly prevalent in temporomandibular disorders but is difficult to treat. Enhanced understanding of neurobiology unique to craniofacial muscle pain should lead to the development of novel mechanism-based treatments. Herein, we review recent studies to summarize neural pathways of craniofacial muscle pain. Nociceptive afferents in craniofacial muscles are predominantly peptidergic afferents enriched with TRPV1. Signals from peripheral glutamate receptors converge onto TRPV1, leading to mechanical hyperalgesia. Further studies are needed to clarify whether hyperalgesic priming in nonpeptidergic afferents or repeated acid injections also affect craniofacial muscle pain. Within trigeminal ganglia, afferents innervating craniofacial muscles interact with surrounding satellite glia, which enhances the sensitivity of the inflamed neurons as well as nearby uninjured afferents, resulting in hyperalgesia and ectopic pain originating from adjacent orofacial tissues. Craniofacial muscle afferents project to a wide area within the trigeminal nucleus complex, and central sensitization of medullary dorsal horn neurons is a critical factor in muscle hyperalgesia related to ectopic pain and emotional stress. Second-order neurons project rostrally to pathways associated with affective pain, such as parabrachial nucleus and medial thalamic nucleus, as well as sensory-discriminative pain, such as ventral posteromedial thalamic nuclei. Abnormal endogenous pain modulation can also contribute to chronic muscle pain. Descending serotonergic circuits from the rostral ventromedial medulla facilitate activation of second-order neurons in the trigeminal nucleus complex, which leads to the maintenance of mechanical hyperalgesia of inflamed masseter muscle. Patients with temporomandibular disorders exhibit altered brain networks in widespread cortical and subcortical regions. Recent development of methods for neural circuit manipulation allows silencing of specific hyperactive neural circuits. Chemogenetic silencing of TRPV1-expressing afferents or rostral ventromedial medulla neurons attenuates hyperalgesia during masseter inflammation. It is likely, therefore, that further delineation of neural circuits mediating craniofacial muscle hyperalgesia potentially enhances treatment of chronic muscle pain conditions.


Instituting Racial Equity: The Allegheny County Racial and Ethnic Approaches to Community Health Initiative.
In 2018, The Live Well Allegheny: Lifting Wellness for African Americans (LWA2) Initiative was developed to support six priority, Black communities in Allegheny County, Pennsylvania to address health equity in chronic disease. The LWA2 coalition members participated in ongoing anti-racism and racial equity sessions with a nationally recognized anti-racist facilitation team. The sessions included a 2-days experience in January 2020 along with follow up meetings throughout 2020. Surveys were administered to understand their perceptions related to anti-racism and oppression and subsequent actions as a result of the sessions. Additionally, we conducted nine in-depth interviews with organizational partners (January -May 2020) to evaluate the overall effectiveness of the coalition and inform future activities. Ten participants completed the post session surveys. Seven out of 10 survey respondents felt they had a good understanding of how oppression (racism, sexism, capitalism) influenced their life and work. However, the majority indicated needing the tools to implement anti-racist strategies in their work. The in-depth interviews with organizational partners revealed that racial equity was of concern to all partners but there was variability in intentionality around racial equity as a core element of each organization's mission, goals and subsequent actions. As a result of the interviews, coalition members developed a racial equity statement and theory of change for implementation in the coalition work and within individual organizations along with a plan for implementing an equity audit of the coalition. Coalitions of this kind should be intentional about implementing continuous strategies related to anti-racism for structural changes toward achieving racial equity in their overall work.


Anxiety and performance in two ego threatening situations.
The relationship between trait and state anxiety and performance was studied in two ego threatening situations among 312 subjects. Candidates with high scores in trait and state anxiety measured just prior to a selection interview for medical school were predicted to receive poorer interview ratings than those candidates with low scores. High trait anxiety, but not state anxiety, measured prior to selection interviews was predicted to be negatively related to academic performance measured up to 1 year later. Neither trait nor state anxiety was found to be significantly related to interview performance ratings. Trait anxiety, but not state anxiety, was found to be significantly related to academic performance: low trait anxious subjects performed better than medium and high trait anxious subjects. This relationship was found to be sustained when controlled for academic aptitude.


Comparison of dyspnea ratings during submaximal constant work exercise with incremental testing.
The purpose of this study was to determine whether dyspnea ratings would be similar during submaximal (as used for training) and incremental (as used in testing) exercise at specific intensities in patients with chronic obstructive pulmonary disease (COPD). We studied 20 patients with COPD. Age was 66 +/- 9 yr (mean +/- SD); FEV1 was 43 +/- 14% pred. At Visit 1 patients provided dyspnea ratings (0 to 10 scale) each minute during incremental exercise on the cycle ergometer. At Visit 2 patients rated dyspnea during production of submaximal exercise for 10 min at two intensities. Peak oxygen consumption (VO2) was 13.9 +/- 3.2 mL.kg-1.min-1. At visit 2 VO2 was stable, but dyspnea ratings increased slightly. Dyspnea ratings (2.0 +/- 1.2) during submaximal exercise were higher than during incremental exercise (1.1 +/- 0.7) at 55 +/- 8% of peak VO2 (P = 0.02) but were similar (4.3 +/- 1.5 vs 3.9 +/- 1.5) at 77 +/- 8% of peak VO2 (P = 0.40). In patients with COPD, dyspnea ratings were similar during steady state compared with equivalent levels of incremental exercise at a "high" intensity, but were slightly higher at the "low" exercise intensity. These data support the potential use of dyspnea ratings obtained during incremental exercise as a target for exercise training in patients with respiratory disease.


Phosphoenolpyruvate carboxylase prevalent in maize roots: isolation of a cDNA clone and its use for analyses of the gene and gene expression.
In search of the gene family for phosphoenolpyruvate carboxylase (PEPC) [EC 126.96.36.199] in C4 plants, we isolated from a maize root cDNA library a new cDNA clone that cross-hybridized with a cDNA for PEPC involved in the C4 photosynthesis (Yanagisawa et al. (1988) FEBS Lett. 229, 107-110). Alignment of the nucleotide sequence with that of the probe cDNA revealed the absence of sequence homology in the 3' non-coding region between the two cDNAs. Southern blot hybridization probed with this specific sequence indicated that the corresponding gene is unique in the maize genome. Northern blot hybridization using the same probe showed that this gene-family member was expressed most strongly in roots and also in green leaves to a lesser extent, but not significantly in etiolated leaves.


Reaction-subdiffusion and reaction-superdiffusion equations for evanescent particles performing continuous-time random walks.
Starting from a continuous-time random-walk (CTRW) model of particles that may evanesce as they walk, our goal is to arrive at macroscopic integrodifferential equations for the probability density for a particle to be found at point r at time t given that it started its walk from r_{0} at time t=0 . The passage from the CTRW to an integrodifferential equation is well understood when the particles are not evanescent. Depending on the distribution of stepping times and distances, one arrives at standard macroscopic equations that may be "normal" (diffusion) or "anomalous" (subdiffusion and/or superdiffusion). The macroscopic description becomes considerably more complicated and not particularly intuitive if the particles can die during their walk. While such equations have been derived for specific cases, e.g., for location-independent exponential evanescence, we present a more general derivation valid under less stringent constraints than those found in the current literature.


The cohesion establishment factor Esco1 acetylates α-tubulin to ensure proper spindle assembly in oocyte meiosis.
Esco1 has been reported to function as a cohesion establishment factor that mediates chromosome cohesion and segregation in mitotic cells. However, its exact roles in meiosis have not been clearly defined. Here, we document that Esco1 is expressed and localized to both the nucleus and cytoplasm during mouse oocyte meiotic maturation. Depletion of Esco1 by siRNA microinjection causes the meiotic progression arrest with a severe spindle abnormality and chromosome misalignment, which is coupled with a higher incidence of the erroneous kinetochore-microtubule attachments and activation of spindle assembly checkpoint. In addition, depletion of Esco1 leads to the impaired microtubule stability shown by the weakened resistance ability to the microtubule depolymerizing drug nocodazole and the decreased level of acetylated α-tubulin. Conversely, overexpression of Esco1 causes hyperacetylation of α-tubulin and spindle defects. Moreover, we find that Esco1 binds to α-tubulin and is required for its acetylation. The reduced acetylation level of α-tubulin in Esco1-depleted oocytes can be restored by the ectopic expression of exogenous wild-type Esco1 but not enzymatically dead Esco1-G768D. Purified wild-type Esco1 instead of mutant Esco1-G768D acetylates the synthesized peptide of α-tubulin in vitro. Collectively, our data assign a novel function to Esco1 as a microtubule regulator during oocyte meiotic maturation beyond its conventional role in chromosome cohesion.


Mission-driven priorities: public health in health information exchange.
Developing state- and nationwide health information exchange (HIE) is one of the health priorities defined in the American Recovery and Reinvestment Act. States are expected to take leadership in statewide planning and implementation. To balance limited resources among mandated responsibilities and emerging HIE accountability, we maintain that state public health practitioners must integrate HIE into our mission-driven practice in five priority areas: 1) connecting real-time disease surveillance and notifiable case reporting through HIE to better protect citizens; 2) sharing public health-managed clinical information through HIE for preventive services, 3) conduct health education for targeted populations via HIE to promote healthy lifestyles; 4) leverage public health informatics with Medicaid information system to provide quality healthcare; and 5) serve as a regulator for standardized HIT to participate in healthcare reform. We summarize public health's broad practice into "Five P's" and link each domain's historical foundation, current and proposed practices to sustain success.


[Current status and prospects of laboratory tests for inflammatory bowel disease].
Inflammatory bowel disease (IBD) is a chronic inflammatory disease affecting the gastrointestinal tract, with a global incidence increasing year by year, and the incidence of IBD in developing countries has been increasing since the end of the last century. The pathogenesis of IBD remains unclear, which is the combined result of genetic, immune, diet, environmental and other factors. There is no gold standard for the diagnosis of IBD. Colonoscopy and mucosal biopsy are the preferred clinical tests, but these invasive and time-consuming methods are not conducive to early screening and frequent monitoring. Therefore, convenient, fast, non-invasive and reliable methods are urgently needed to assist the clinical diagnosis and evaluation of IBD. This paper aims to elaborate the laboratory diagnosis and monitoring methods of IBD based on fecal and blood indicators, which can provide ideas for the prevention, screening, diagnosis and monitoring of IBD, and help reduce its burden on people's living standards, public health and society.


Attitude towards Antipsychotic Medications in Patients Diagnosed with Schizophrenia: A Cross-Sectional Study at Amanuel Mental Specialized Hospital, Addis Ababa, Ethiopia.
Poor attitude towards antipsychotic drugs is high, and it is a factor for non-adherence to treatment. This increases the risk of relapse, associated healthcare utilization, and costs. This study aimed to assess attitude towards antipsychotic medication among patients with schizophrenia. The aim of this institution based cross-sectional study was to assess attitude towards antipsychotic medications and associated factors among patients with schizophrenia who attend the outpatient clinics at Amanuel Mental Specialized Hospital, 2018. In a cross-sectional study, 393 schizophrenic patients from Amanuel Mental Specialized Hospital were recruited by a systematic random sampling technique. Drug Attitude Inventory (DAI-10) was used to assess attitude, experience, and belief about antipsychotics. Glasgow antipsychotic side effect scale modified version, positive and negative syndrome scale, and Birch wood's insight scale for psychosis were the instruments used to assess the associated factors. Simple and multiple linear regression analysis models were fitted, and the adjusted unstandardized beta (β) coefficient at 95% confidence interval was used. The mean score of attitude towards antipsychotic medications was 6.51 with standard deviation (SD) of 2.22. In multiple linear regression, positive symptoms (β= -0.07, 95% CI: (-0.09, -0.05)), negative symptoms (β= -0.04, 95% CI: (-0.06,-0.02)), shorter (≤5 years) duration of illness (β= -0.39, 95% CI: (-0.63, -0.15)), first generation antipsychotics (β = -0.35, 95% CI: (-0.55,-0.14)), having sedation (β= -0.28, 95% CI: (-0.52, -0.02)), and extra-pyramidal side effects (β= -0.34, 95% CI: (-0.59,-0.09)) were factors negatively associated with attitude towards antipsychotic medication treatment. Insight to illness (β= 0.24, 95% CI: (0.20, 0.27) was a factor positively associated with attitude towards antipsychotic medications. The result suggests that the mean score of participants' attitude towards antipsychotic medications was good. Prevention of side effects particularly due to first generation antipsychotics is necessary.


Effects of intermittent pneumatic compression on venous haemodynamics and fibrinolytic activity.
Pneumatic intermittent compression is an effective method to prevent postoperative venous thromboembolism. Its efficacy has been ascribed to both a haemodynamic action (increase of blood flow velocity) and a stimulation of endogenous fibrinolytic activity [via the production of tissue-type plasminogen activator (t-PA) by the vascular endothelium]. The relative contribution of these two effects is still debated. In a randomized, cross-over study in ten healthy volunteers, we compared the haemodynamic and fibrinolytic effects of two different pneumatic intermittent compression devices: a classical, low-pressure, whole-leg boots system, and a novel, high-pressure, plantar compression system. The study was performed at rest, to compare haemodynamics and fibrinolytic activity modifications, and under induced venous leg stasis, in order to compare the two compression systems in experimental conditions mimicking laparoscopic surgery. Our data show that (1) a pneumatic compression device that exerts its compression on the plantar venous plexus only induced an increase of venous blood peak velocity and flow in the common femoral vein that is very similar to that induced by the classical whole-leg boots compression system; (2) the venous stasis induced by an external pressure mimicking the conditions of laparoscopic surgery further increased the absolute velocity and flow increase, with the two intermittent compression systems tested; (3) no changes of t-PA or plasminogen activator-inhibitor 1 antigens were observed with either pneumatic compression device. In conclusion, the present study indicates that the antithrombotic effect of mechanical prophylaxis is probably mainly due to its ability to increase venous peak velocity and flow, especially under venous stasis conditions.


Structural mining: self-consistent design on flexible protein-peptide docking and transferable binding affinity potential.
A flexible protein-peptide docking method has been designed to consider not only ligand flexibility but also the flexibility of the protein. The method is based on a Monte Carlo annealing process. Simulations with a distance root-mean-square (dRMS) virtual energy function revealed that the flexibility of protein side chains was as important as ligand flexibility for successful protein-peptide docking. On the basis of mean field theory, a transferable potential was designed to evaluate distance-dependent protein-ligand interactions and atomic solvation energies. The potential parameters were developed using a self-consistent process based on only 10 known complex structures. The effectiveness of each intermediate potential was judged on the basis of a Z score, approximating the gap between the energy of the native complex and the average energy of a decoy set. The Z score was determined using experimentally determined native structures and decoys generated by docking with the intermediate potentials. Using 6600 generated decoys and the Z score optimization criterion proposed in this work, the developed potential yielded an acceptable correlation of R(2) = 0.77, with binding free energies determined for known MHC I complexes (Class I Major Histocompatibility protein HLA-A(*)0201) which were not present in the training set. Test docking on 25 complexes further revealed a significant correlation between energy and dRMS, important for identifying native-like conformations. The near-native structures always belonged to one of the conformational classes with lower predicted binding energy. The lowest energy docked conformations are generally associated with near-native conformations, less than 3.0 Angstrom dRMS (and in many cases less than 1.0 Angstrom) from the experimentally determined structures.


Therapeutic Targeting of microRNAs in Cancer: Future Perspectives.
Preclinical Research The discovery of microRNAs (miRNAs) and their link with cancer has opened a new era in cancer therapeutics. Approximately, 18 - 24 nucleotides long, miRNAs can up-regulate or down-regulate gene expression in many cancer types and are respectively categorized as oncogenes (oncomirs) or tumor suppressors. Expression profiles of miRNAs with biomarker potential can be used for the classification, diagnosis, therapeutic treatment, and prognosis of different cancer types. miRNA mimics and miRNA antagonists are the two main approaches to miRNA-based cancer therapies that respectively inhibit oncomirs or restore the expression of tumor suppressive miRNAs. This review serves to provide some general insight into miRNA biogenesis, cancer related miRNAs, and miRNA therapeutics.


Computer Simulations of Static and Dynamical Properties of Weak Polyelectrolyte Nanogels in Salty Solutions.
We investigate the chemical equilibria of weak polyelectrolyte nanogels with reaction ensemble Monte Carlo simulations. With this method, the chemical identity of the nanogel monomers can change between neutral or charged following the acid-base equilibrium reaction HA ⇌ A- + H⁺. We investigate the effect of changing the chemical equilibria by modifying the dissociation constant K a . These simulations allow for the extraction of static properties like swelling equilibria and the way in which charge-both monomer and ionic-is distributed inside the nanogel. Our findings reveal that, depending on the value of K a , added salt can either increase or decrease the gel size. Using the calculated mean-charge configurations of the nanogel from the reaction ensemble simulation as a quenched input to coupled lattice-Boltzmann molecular dynamics simulations, we investigate dynamical nanogel properties such as the electrophoretic mobility μ and the diffusion coefficient D.


StatAlign 2.0: combining statistical alignment with RNA secondary structure prediction.
Comparative modeling of RNA is known to be important for making accurate secondary structure predictions. RNA structure prediction tools such as PPfold or RNAalifold use an aligned set of sequences in predictions. Obtaining a multiple alignment from a set of sequences is quite a challenging problem itself, and the quality of the alignment can affect the quality of a prediction. By implementing RNA secondary structure prediction in a statistical alignment framework, and predicting structures from multiple alignment samples instead of a single fixed alignment, it may be possible to improve predictions. We have extended the program StatAlign to make use of RNA-specific features, which include RNA secondary structure prediction from multiple alignments using either a thermodynamic approach (RNAalifold) or a Stochastic Context-Free Grammars (SCFGs) approach (PPfold). We also provide the user with scores relating to the quality of a secondary structure prediction, such as information entropy values for the combined space of secondary structures and sampled alignments, and a reliability score that predicts the expected number of correctly predicted base pairs. Finally, we have created RNA secondary structure visualization plugins and automated the process of setting up Markov Chain Monte Carlo runs for RNA alignments in StatAlign. The software is available from http://statalign.github.com/statalign/.


Statistical selector of the best multiple ICD-coding method.
The International Classification of Diseases 10th version (ICD-10) is one of the standard and most important disease classifications. Since computerized ICD-10 coding systems have drawn a great deal of attention in the medical field, a great number of different coding systems have been proposed. This paper proposes a hybrid architecture of different coding systems. First, given an input disease name, three coding systems output codes with their confidence scores. A C4.5-based system selector then selects the best output by using both input statistics and the confidence score from each system. The experimental results demonstrated that the selector significantly boosts the overall performance (+3.4 points).


Strong strain hardening in nanocrystalline nickel.
Low strain hardening has hitherto been considered an intrinsic behavior for most nanocrystalline (NC) metals, due to their perceived inability to accumulate dislocations. In this Letter, we show strong strain hardening in NC nickel with a grain size of approximately 20 nm under large plastic strains. Contrary to common belief, we have observed significant dislocation accumulation in the grain interior. This is enabled primarily by Lomer-Cottrell locks, which pin the lock-forming dislocations and obstruct dislocation motion. These observations may help with developing strong and ductile NC metals and alloys.


Differential distribution of a potassium current in immunocytochemically identified supraoptic magnocellular neurones of the rat.
Magnocellular hypothalamo-neurohypophysial neurones display characteristic firing patterns, related to the hormone they release. To identify the membrane currents that may underlie these firing patterns, we performed whole-cell recording of freshly dissociated magnocellular neurones from the supraoptic nucleus. After recording, cells were immunocytochemically identified by using highly selective monoclonal antibodies raised respectively against vasopressin (AVP) and oxytocin (OT) neurophysin. In 64 out of 131 neurones (48.8%), we detected the presence of a transient potassium current whose kinetic properties were characteristic of an A-current. The A-current was activated by depolarisation over -40 mV, and inactivated rapidly with a monoexponential decay (tau = 28 +/- 2.7 ms; n = 33 at 0 mV). Using conditioning prepulses of 50 ms, the voltage dependence of the inactivation was determined, and the data were adequately fit with a Boltzman equation (half-maximal inactivation: -42.5 mV). The steady-state time-dependent inactivation curve was determined using a prepulse potential at -40 mV, and data were best described with a mono-exponential equation (tau = 89.7 ms). The sensitivity to 1 mM 4-amino-pyridine (63 +/- 9% inhibition, n = 6), and a reversal potential close to the theoretical Nernst equilibrium for potassium (-56.3 +/- 1 mV, n = 6, vs. -58 mV) confirmed that the transient current studied was indeed an A-type potassium current. Immunocytochemical identification revealed that the A-current was selectively expressed in OT-neurophysin-positive cells. As previous work in hypothalamic slice preparations suggests that the A-current is expressed by both AVP cells and OT cells, the present data suggest that whereas the A-current is expressed in the soma of OT cells, it may be expressed only on the dendritic tree of AVP cells, which is truncated in the dispersed cell preparation used here. This distribution may play a role in the specific firing characteristics of magnocellular neurones.


Expression and function of the human calcitonin/alpha-CGRP gene in health and disease.
Studies on the structure and expression of the rat and human calcitonin gene provide a remarkable example by which a combination of molecular, immunocytochemical and pharmacological techniques have led to the identification of a novel gene product, the calcitonin gene-related peptide, a peptide of unexpected tissue distribution and biological activity. Future studies at the molecular level will provide insight into post-transcriptional mechanisms by which a single gene can give rise to discrete mRNAs in a tissue-specific manner. The isolation and characterization of the CGRP receptor, and hence the site(s) and mechanism(s) of action of the CGRP family within the vasculature, will also add significantly to our understanding of molecular mechanisms involved in the modulation of cardiovascular function in man. Furthermore, the role and mechanism of action of the CGRP peptide family in the central and peripheral nervous systems remains to be elucidated. It is also apparent that measurement of circulating plasma levels of CGRP may be of diagnostic and prognostic value, providing information concerning the onset and progression of lung and thyroid carcinoma. Our analysis of the structure and expression of the calcitonin/alpha-CGRP gene also demonstrates, for the first time, the molecular basis of large calcitonin secretion by lung carcinoma cells. Whether the expression of this gene in lung carcinoma cell-lines can truly be described as 'ectopic' is however questionable, in the light of recent immunocytochemical evidence which demonstrates that the lung is a major source of CGRP producing cells in the rat (see Springall et al., 1984).


Epilepsy and stigma in Africa: Viewpoint of healthcare professionals and combat strategies.
Epilepsy is a major public health problem in developing countries where eighty percent (80%) of people with epilepsy (PWE) live. Stigma has psychological consequences as well as serious repercussions on patients' quality of life. This study assesses the perception of health professionals in Africa regarding the stigmatization of PWE. This is a multicenter descriptive, cross-sectional study, from 1st August 2020 to 1st September 2021. Medical practitioners from African countries involved in the management of epilepsy and who agreed to fill out forms were included in the study. Sampling was nonrandom and based on respondent choice. The data were analyzed using the EPI INFO 7 software. A total of two hundred and twenty-nine (229) health workers from twenty-six (26) African countries participated in this survey. 24.89% of the respondents were specialists and 46.72% were neurologists. Ninety-one percent (91%) of practitioners felt that PWE were stigmatised. The main forms of stigma were isolation (68.56%), celibacy (60.70%), unemployment (53.28%), divorce (44.54%) and exclusion (37.99%)%). Community, school and family were recognized as the main places of stigmatization. The fight against this stigma was carried out mainly in hospitals and in isolation in 58.4% and 55.8% of cases, respectively. Only 0.4% of practitioners opted for mass awareness. PWE are victims of various forms of stigmatization, particularly in community settings. Measures aimed at raising awareness of the public are essential to reduce this stigma and improve patients' quality of life.


Leisure-time physical activity among US adults 60 or more years of age: results from NHANES 1999-2004.
We examined leisure-time physical activity (LTPA) in US adults 60 or more years of age. After determining the prevalence of 3 levels of LTPA (no LTPA, <150 minutes LTPA/wk, and > or =150 minutes of LTPA/ wk), we examined the association of demographic variables and current health status with LTPA. Self-reported LTPA was examined by gender, age, race/ethnicity, education, family poverty income ratio, marital status, and self-reported health. Multiple logistic regression methods were used in the adjusted model. Walking was the most frequently reported LTPA. Overall, 27% of adults achieved LTPA levels of 150 minutes or more per week. Male gender, younger age, non-Hispanic white race/ethnicity, higher education attainment, higher income status, being married, and excellent self-reported health were associated with higher LTPA. The prevalence of no LTPA (52.5%) exceeded the Healthy People 2010 objective target of 20%. Our findings show that more than half of adults 60 or more years of age reported no LTPA and that levels of LTPA in the older population vary by demographic and health characteristics.


Association of mast cell, eosinophil leucocyte and microvessel densities in actinic cheilitis and lip squamous cell carcinoma.
To determine the contributions of mast cells (MC), eosinophil leucocytes (EL) and microvessel density (MVD) in lip carcinogenesis, and to establish the relationships between these biomarkers and their possible prognostic value in lip squamous cell carcinoma (LSCC). Archived specimens of lip mucosa (n=13), actinic cheilitis (n=29) and LSCC (n=29) were formalin-fixed, paraffin-embedded, sectioned and stained with toluidine blue and haematoxylin and eosin (H&E) in order to identify MC and EL and to measure their densities. Tumour angiogenesis was estimated by determining, with the use of CD31 antibody MVD in areas with the highest number of stained microvessels ('hot spots'). Progressive increases of MC, EL and MVD were observed during lip tumour development. Correlation analysis revealed positive associations between the biomarkers during tumour progression. In LSCC samples, significant associations were found between MVD values and metastatic disease. On multivariate analysis, MVD was a predictor of risk of cervical metastasis. The densities of MC, EL and microvessels increase during lip carcinogenesis, and for MC and EL this may be related to the stimulation of tumour angiogenesis. MVD could be a useful predictor of cervical metastasis in LSCC.