Linear associations between clinically assessed upper motor neuron disease and diffusion tensor imaging metrics in amyotrophic lateral sclerosis.
To assess the relationship between clinically assessed Upper Motor Neuron (UMN) disease in Amyotrophic Lateral Sclerosis (ALS) and local diffusion alterations measured in the brain corticospinal tract (CST) by a tractography-driven template-space region-of-interest (ROI) analysis of Diffusion Tensor Imaging (DTI). This cross-sectional study included 34 patients with ALS, on whom DTI was performed. Clinical measures were separately obtained including the Penn UMN Score, a summary metric based upon standard clinical methods. After normalizing all DTI data to a population-specific template, tractography was performed to determine a region-of-interest (ROI) outlining the CST, in which average Mean Diffusivity (MD) and Fractional Anisotropy (FA) were estimated. Linear regression analyses were used to investigate associations of DTI metrics (MD, FA) with clinical measures (Penn UMN Score, ALSFRS-R, duration-of-disease), along with age, sex, handedness, and El Escorial category as covariates. For MD, the regression model was significant (p = 0.02), and the only significant predictors were the Penn UMN Score (p = 0.005) and age (p = 0.03). The FA regression model was also significant (p = 0.02); the only significant predictor was the Penn UMN Score (p = 0.003). Measured by the template-space ROI method, both MD and FA were linearly associated with the Penn UMN Score, supporting the hypothesis that DTI alterations reflect UMN pathology as assessed by the clinical examination.


[Maedi and maedi control (author's transl)].
Maedi/visna is a chronic progressive interstitial pneumonia of sheep caused by a persistent infection with a retrovirus. Approximately thirty per cent of the sheep population in the Netherlands carries antibodies to maedi virus. An experimental eradication scheme based upon serological testing with ELISA and culling of reactors every six months was started, recently. Initially, 353 (25.4 per cent) reactors were identified among 1391 sheep in sixteen flocks, whereas the second test, six months later, showed 130/1111(11.7 per cent) reactors. On 11 other farms with high infection level 382 lambs were separated from their dams immediately after birth, ovine colostrum deprived and artificially reared. The lambs were serotested at 6 months of age and 2/382 (0.5 per cent) were found positive, while naturally reared lambs on the same farms scored 39 per cent positive.


Detection of mutations in the VP7 gene of vaccine-derived strains shed by monovalent rotavirus vaccine recipients.
Strains of Rotarix, a live attenuated monovalent oral rotavirus vaccine, replicate in the intestine and are shed for about one month in immunocompetent recipients. The current study aimed to identify genetic changes of shed strains to reveal any significant mutations and their clinical impact on recipients. Stool samples of recipients of the first dose of Rotarix were sequentially collected for one month from the day of administration. Sequence analyses of the VP7 gene in eight recipients revealed five amino acid substitutions. Among them, two were observed in aa123, which is located in antigenic region 7-1a. Since there were no associated clinical symptoms, the genetic changes were unlikely to have caused reversion of pathogenicity of vaccine strain. Of interest, the virus in one case became closer to wild-type rotavirus via an amino acid change at aa123 occurring 14 days after administration, which might have resulted from multiple replications and long-term shedding of the vaccine strain.


Dyspnoea at the end of life: instrument development and validation-the CONFORTO Strategy.
To describe the construction and validation of the algorithm for Criteria for inclusion; Objective of dyspnoea; Notification of patient/family/health professionals; Facial air flow; Oxygen; Relaxion and breathing; Treating causes of dyspnoea and Opioid (CONFORTO), an instrument to guide health professionals in managing dyspnoea in patients with an advance stage of the disease at the end-of-life. The study was carried out in three stages: (1) literature review and construction of CONFORTO; (2) semantic validation; (3) application of the CONFORTO Strategy to health professionals as a test (before video lessons) and post-test (20 days after watching video lessons) methodology. The scores obtained in the pretest and post-test were compared using the Wilcoxon test. Seventy-four professionals from different internal medicine and intensive care units participated in the study. The CONFORTO Strategy involved eight acronym-forming items: Criteria for inclusion; Objective of dyspnoea; Notification of patient/family/health professionals; Facial air flow; Oxygen; Relaxion and breathing; Treating causes of dyspnoea and Opioid. The post-test indicated a significant increase in the score for the following items: facial air flow (p=0.016); oxygen (p=0.002); relaxation and breathing (p=0.002) and treating the causes of dyspnoea (p=0.011). The increase in score occurred after the training sessions with video lessons. The CONFORTO Strategy proved valid and reliable for managing dyspnoea in patients with an advanced stage of the disease at the end-of-life. Because the instrument is easy-to-use, it can be used by the entire health team at any assistance-providing location, and can, thus, contribute to improving dyspnoea management for these patients.


[Fertility mutants of the turimycin-producing Streptomyces hygroscopicus IMET JA 6599].
In a continuing search for fertility mutants of the turimycin-producer, Streptomyces hygroscopicus, strain IMET JA 6599, from more than 683 pairs of auxotrophic mutants 19 pairs were found to develop colonies after replica plating on selective media. The frequency of recombinant production in mixed cultures on complex medium varies from 10(-6) to 10(-2) in different combinations of S. hygroscopicus mutants. Typical frequencies representing the proportion of recombinant colonies (from spores and/or fragments of substrate mycelium) and a visual indication of the different fertility levels using the familial fertility test method are given in Tables and Figures. Additionally, reversion rates of markers and different types of colonies of fertility mutants used in some S. hygroscopicus crosses will be shown.


A phase I trial of 96-hour paclitaxel infusion plus accelerated radiotherapy of unrespectable head and neck cancer.
To determine the maximum tolerated dose (MTD) of paclitaxel given as a 96-hour continuous infusion during Weeks 1 and 5 of an accelerated radiotherapy schedule for the definitive treatment of advanced (nonmetastatic) unresectable squamous cell carcinoma of the head and neck (SCCHN). Thirteen patients with Stage IV SCCHN were enrolled. Radiotherapy consisted of 70-72 Gy over 6 weeks, with a fractionation scheme of 2 Gy q.d. for 4 weeks followed by 1.6 Gy b.i.d. for 2 weeks, with no planned interruptions. Paclitaxel was administered over a 96-hour continuous infusion during Weeks 1 and 5 of radiotherapy at the following dose levels: Dose Level 1: 40 mg/m(2)/96-hours (3 patients); Dose Level 2: 80 mg/m(2)/96-hrs (5 patients); Dose Level 3: 120 mg/m(2)/96-hours (2 patients); and Dose Level 2A: 100 mg/m(2)/96-hours (3 patients). The MTD of Paclitaxel was 100 mg/m(2)/96-hours. All but one patient (who experienced progressive disease after receiving 61 Gy and both cycles of paclitaxel) completed therapy as planned. Dose-limiting toxicity occurred in both patients enrolled at Dose Level 3, with one patient experiencing Grade 4 diffuse moist desquamation and the other patient experiencing Grade 4 mucositis and febrile neutropenia. Thus, Dose Level 2A was opened and no dose limiting toxicity was noted. Grade 3 non-dose limiting mucositis and dermatitis occurred at all paclitaxel dose levels. There were no treatment-related deaths. All Grade 3 and 4 toxicities were reversible. Complete responses were seen in 8 of 13 patients, 4 patients achieved partial responses, and 1 patient had no response/progressive disease. Infusional paclitaxel over 96 hours during Weeks 1 and 5 of this accelerated radiotherapy schedule is feasible. The MTD of paclitaxel in this protocol was 100 mg/m(2)/96-hours. Dose-limiting toxicities were primarily enhanced epithelial reactions, but febrile neutropenia also occurred. All patients develop non-dose limiting Grade 3 skin and mucosal reactions, reflecting the high treatment intensity. This regimen merits further investigation.


ABR and DPOAE detection of cochlear damage by gentamicin.
Auditory brainstem responses (ABR) and distortion product otoacoustic emissions (DPOAE) have been applied to the evaluation of peripheral auditory function. To date, no comparison of their relative sensitivities to aminoglycoside toxicity has been reported. The purpose of this study was to compare click evoked ABR testing and 2f1-f2 DPOAEs as detectors of cochlear damage induced by gentamicin treatment in guinea-pigs. ABR thresholds to click stimuli were recorded. DPOAE amplitude input/output functions were recorded using three different primary tone level conditions. In one condition, L1 was changed relative to a fixed L2. In the next condition, L2 was changed relative to a fixed L1. In the third condition, L1 and L2 were both changed while maintaining a consistent L1-L2 difference. Baseline L1-L2 differences were determined by adjusting L2 to produce the maximum DPOAE amplitude in each ear of each subject. Guinea-pigs were treated for a four week period with intramuscular injections of gentamicin. ABRs and DPOAEs were monitored and compared to baseline recordings or untreated control groups. DPOAE testing detected cochlear damage earlier than ABR testing. Changes in DPOAE input/output functions were noted after two weeks of treatment while changes in ABR threshold were not identified until after three weeks of treatment. The sensitivity of the DPOAE testing was related to the stimulus conditions utilized. L1-L2 differences were determined in the control group and for the initial test session by fixing L1 at 75 dB SPL and lowering L2 until the maximum DPOAE amplitude was obtained for each ear. All subsequent testing was begun using the optimal L1-L2 difference for each ear. The stimulus condition in which only L1 was changed and L2 was fixed resulted in the least sensitive DPOAE indicator of cochlear damage. The condition in which both L1 and L2 were changed, but the L1-L2 difference remained constant, resulted in the most sensitive indicator of damage. The onset and degree of cochlear damage secondary to gentamicin treatment was subject dependent. This study demonstrates that 2f1-f2 DPOAE testing is preferable to click evoked ABR testing for early detection of gentamicin toxicity of the cochlea. It also indicates that DPOAE stimulus parameters must be considered when developing test protocols. Specifically, recording the DPOAE amplitude input/output function while maintaining an effective L1-L2 difference is preferable to changing either L1 or L2 individually.


The roles of histology and immunohistology in the investigation of marsupial disease and normal lymphoid tissue.
This review acquaints scientists with current information related to the application of histology and immunohistology to the studies of normal lymphoid tissues and specific diseases in marsupials. Histological examination of tissue is a necessary prerequisite for immunohistological examination because it establishes tissue structure and detects specific areas of disease which allow the selection of smaller areas for immunohistological examination. Information is provided on the basic techniques of histology. Immunohistology (immunohistochemistry) refers to the identification of antigenic determinants of specific substances (proteins) by the application of antibodies to histological sections. Information is provided on a technique for enzyme based, avidin-biotin enhanced immunohistology, and on antibodies that can be used to mark disease agents or marsupial tissues and cells. A summary is provided of the available information on studies of the histology and immunohistology of normal marsupial lymphoid tissue (thymus, spleen, lymph nodes and mucosa associated lymphoid tissue), and of selected marsupial diseases such as chlamydiosis and lymphosarcoma in koalas.


Lung antioxidant and cytokine responses to coarse and fine particulate matter from the great California wildfires of 2008.
The authors have previously demonstrated that wildfire-derived coarse or fine particulate matter (PM) intratracheally instilled into lungs of mice induce a strong inflammatory response. In the current study, the authors demonstrate that wildfire PM simultaneously cause major increases in oxidative stress in the mouse lungs as measured by decreased antioxidant content of the lung lavage supernatant fluid 6 and 24 h after PM administration. Concentrations of neutrophil chemokines/cytokines and of tumor necrosis factor (TNF)-alpha were elevated in the lung lavage fluid obtained 6 and 24 h after PM instillation, consistent with the strong neutrophilic inflammatory response observed in the lungs 24 h after PM administration, suggesting a relationship between the proinflammatory activity of the PM and the measured level of antioxidant capacity in the lung lavage fluid. Chemical analysis shows relatively low levels of polycyclic aromatic hydrocarbons compared to published results from typical urban PM. Coarse PM fraction is more active (proinflammatory activity and oxidative stress) on an equal-dose basis than the fine PM despite its lower content of polycyclic aromatic hydrocarbons. There does not seem to be any correlation between the content of any specific polycyclic aromatic hydrocarbon (or of total polycyclic aromatic hydrocarbon content) in the PM fraction and its toxicity. However, the concentrations of the oxidation products of phenanthrene and anthracene, phenanthraquinone and anthraquinone, were several-fold higher in the coarse PM than the fine fraction, suggesting a significant role for atmospheric photochemistry in the formation of secondary pollutants in the wildfire PM and the possibility that such secondary pollutants could be significant sources of toxicity in the wildfire PM.


MASP-1 of the complement system promotes clotting via prothrombin activation.
Mannan-binding lectin-associated serine protease-1 (MASP-1), a protein of the complement lectin pathway, resembles thrombin in terms of structural features and substrate specificity, and it has been shown to activate coagulation factors. Here we studied the effects of MASP-1 on clot formation in whole blood (WB) and platelet-poor plasma (PPP) by thrombelastography and further elucidated the underlying mechanism. Cleavage of prothrombin by MASP-1 was investigated by SDS-PAGE and N-terminal sequencing of cleavage products. Addition of MASP-1 or thrombin to WB and PPP shortened the clotting time and clot formation time significantly compared to recalcified-only samples. The combination of MASP-1 and thrombin had additive effects. In a purified system, MASP-1 was able to induce clotting only in presence of prothrombin. Analysis of MASP-1-digested prothrombin confirmed that MASP-1 cleaves prothrombin at three cleavage sites. In conclusion, we have shown that MASP-1 is able to induce and promote clot formation measured in a global setting using the technique of thrombelastography. We further confirmed that MASP-1-induced clotting is dependent on prothrombin. Finally, we have demonstrated that MASP-1 cleaves prothrombin and identified its cleavage sites, suggesting that MASP-1 gives rise to an alternative active form of thrombin by cleaving at the cleavage site R393.


Obesity is associated with altered lung function independently of physical activity and fitness.
Measures of obesity, especially central adiposity, have been associated with reduced lung function. However, previous studies may have been affected by confounding by physical activity and fitness. This study aimed to examine the relationship among body fatness, fat distribution, and lung function, adjusted for physical activity energy expenditure (PAEE) and aerobic fitness (VO(2)max), in a cohort of British white adults with a family history of type 2 diabetes. A total of 320 adults (mean age 40.4 +/- 6.0 years) attended for anthropometric and VO(2)max testing, and had ambulatory heart rate monitoring for 4 days to determine PAEE. Spirometry was used to measure forced expiratory volume in 1 s (FEV(1)) and forced vital capacity (FVC). The tests were repeated 12 months later, and a cross-sectional analysis using linear regression with repeated measures was performed. Measures of obesity (BMI, waist circumference (WC), fat mass (FM), body fat percentage (BF%)) were associated with lower lung function in men and women (P < 0.01), while waist-to-hip ratio (WHR) was associated with lower lung function in men only (P < 0.001). Associations remained after adjusting for age, smoking status, height, PAEE, and VO(2)max. The estimated difference in mean FEV(1) and FVC per unit increase in the exposure measures were consistently stronger in men compared to women (P for interaction <0.001). Obesity is inversely associated with lung function in adults, but central fat distribution appears to have a stronger relationship with respiratory mechanics in men than in women. These associations were independent of the degree of physical activity and aerobic fitness in this cohort.


Mobility of Vulnerable Elders (MOVE): study protocol to evaluate the implementation and outcomes of a mobility intervention in long-term care facilities.
Almost 90% of residents living in long-term care facilities have limited mobility which is associated with a loss of ability in activities of daily living, falls, increased risk of serious medical problems such as pressure ulcers, incontinence and a significant decline in health-related quality of life. For health workers caring for residents it may also increase the risk of injury. The effectiveness of rehabilitation to facilitate mobility has been studied with dedicated research assistants or extensively trained staff caregivers; however, few investigators have examined the effectiveness of techniques to encourage mobility by usual caregivers in long-term care facilities. This longitudinal, quasi-experimental study is designed to demonstrate the effect of the sit-to-stand activity carried out by residents in the context of daily care with health care aides. In three intervention facilities health care aides will prompt residents to repeat the sit-to-stand action on two separate occasions during each day and each evening shift as part of daily care routines. In three control facilities residents will receive usual care. Intervention and control facilities are matched on the ownership model (public, private for-profit, voluntary not-for-profit) and facility size. The dose of the mobility intervention is assessed through the use of daily documentation flowsheets in the health record. Resident outcome measures include: 1) the 30-second sit-to-stand test; 2) the Functional Independence Measure; 3) the Health Utilities Index Mark 2 and 3; and, 4) the Quality of Life - Alzheimer's Disease. There are several compelling reasons for this study: the widespread prevalence of limited mobility in this population; the rapid decline in mobility after admission to a long-term care facility; the importance of mobility to quality of life; the increased time (and therefore cost) required to care for residents with limited mobility; and, the increased risk of injury for health workers caring for residents who are unable to stand. The importance of these issues is magnified when considering the increasing number of people living in long-term care facilities and an aging population. This clinical trial is registered with ClinicalTrials.gov (trial registration number: NCT01474616).


Advantages of video-assisted approach in detecting epididymal anomalies and treatment of nonpalpable testis.
In children with a nonpalpable abdominal testis, preoperative localization is very helpful prior to surgical investigation both to reduce the time required and to plan the correct surgical procedure. It is no doubt that laparoscopy is useful in both diagnosis and management of nonpalpable testis. In this study, 15 patients with 17 nonpalpable testes admitted to our clinic in 2 years period were evaluated retrospectively. Ultrasound study was performed in all patients after detailed physical examination. Testicular location, size, and configuration of epididymis were determined by laparoscopy and compared with ultrasound findings. Laparoscopy, in conjunction with ultrasound, permits not only a better localization and anatomy of the testis but is also superior in planning the best choice of management. We believe that the video-assisted inguinal approach is a feasible method in the treatment of nonpalpable testis when compared to pure open surgery.


Role of decreased plasma volume in hematocrit alterations during incremental treadmill exercise in horses.
Six intact (IN) and six splenectomized (SP) mares were subjected to an incremental exercise test to examine the role of decreases in plasma volume (PV) in the changes in hematocrit (Hct) normally seen with exercise. Each horse underwent an incremental exercise test in which it ran on a treadmill up a fixed incline of 6 degrees. The test started at a speed of 4 m/s, and speed was increased 1 m/s each min until heart rate reached a plateau. Blood samples were obtained at rest and at the end of the 4, 5, 6, and 7 m/s steps of the exercise test. Resting PV was greater (P < 0.05) in the IN group (28.6 +/- 0.5 liters) compared with SP horses (22.7 +/- 2.2 liters). Exercise produced a significant increase in Hct in both groups of horses; however, the increases were greater (P < 0.05) at all exercise intensities in IN compared with SP horses. Hct increased rapidly during the first step (4 m/s) in the exercise test in the IN animals. After this, Hct increased slowly in IN horses, and values for the 5, 6, and 7 m/s steps paralleled the changes observed in the SP horses. Corrected Hct values were then used to calculate the relative change in PV. Exercise produced a significant decrease in PV in both groups of horses; however, there were no differences (P > 0.05) between the groups when IN horses (-13 +/- 3 and -18 +/- 2%) were compared with SP horses (-14 +/- 4 and -17 +/- 4%) at the 6 and 7 m/s steps of the exercise test.(ABSTRACT TRUNCATED AT 250 WORDS)


[Trends in orthodontic biomaterials: metals and ceramics].
While the beginning of orthodontics was marked by an acute scarcity in materials, the modern clinician has to face a large array of devices made of metals, plastics, ceramics and combinations thereof. Each of these materials have been developed for other purposes than orthodontics, and then transplanted "as is" in a field which has its own demands. During the years, theses devices, as well as the materials these are made of, have been modified most of time to the benefit of both the patient and the clinician, and some time to that of the manufacturer who has tried to save, or bypass limiting patients. Among the latter are the harder, but less corrosion resistant steels, the efficient but corrosion prone brazing, the inexpensive but weaker molded attachments, the aesthetic but fragile ceramics. Understanding the trends and basics of materials science should help the clinician to avoid being sued iatrogenic inflicted affections.


Profiling Cellular Processes in Adipose Tissue during Weight Loss Using Time Series Gene Expression.
Obesity is a global epidemic identified as a major risk factor for multiple chronic diseases and, consequently, diet-induced weight loss is used to counter obesity. The adipose tissue is the primary tissue affected in diet-induced weight loss, yet the underlying molecular mechanisms and changes are not completely deciphered. In this study, we present a network biology analysis workflow which enables the profiling of the cellular processes affected by weight loss in the subcutaneous adipose tissue. Time series gene expression data from a dietary intervention dataset with two diets was analysed. Differentially expressed genes were used to generate co-expression networks using a method that capitalises on the repeat measurements in the data and finds correlations between gene expression changes over time. Using the network analysis tool Cytoscape, an overlap network of conserved components in the co-expression networks was constructed, clustered on topology to find densely correlated genes, and analysed using Gene Ontology enrichment analysis. We found five clusters involved in key metabolic processes, but also adipose tissue development and tissue remodelling processes were enriched. In conclusion, we present a flexible network biology workflow for finding important processes and relevant genes associated with weight loss, using a time series co-expression network approach that is robust towards the high inter-individual variation in humans.


Dermatological Complaints of the Elderly Attending a Dermatology Outpatient Clinic in Turkey: A Prospective Study over a One-year Period.
The geriatric population is continuously growing, which leads to more aged patients being admitted to dermatology clinics. The aim of this study is to determine the dermatological complaints of the elderly attending a dermatology outpatient clinic. All of the patients aged 65 years and older admitted to our dermatology outpatient clinic over a 1-year period were included. Patients were divided into 2 groups according to their ages as group I (65-74 years) and group II (≥75 years). The patients were asked about their dermatologic complaints. A total of 240 geriatric patients attended to the dermatology outpatient clinic over a 1-year period. Overall, the five most frequent dermatologic complaints of the patients were eczematous dermatitis (21.7%), pruritus (19.6%), fungal infections (16.7%), precancerous and malignant lesions (9.6%), and bacterial infections (7.1%). The most frequent types of eczematous dermatitis were asteatotic eczema (26.9%), neurodermatitis (26.9%), and stasis dermatitis (17.3%). Among fungal infections, the most frequent was tinea pedis (62.5%), followed by onychomycosis (32.5%) and tinea versicolor (5.0%). The most common precancerous lesion was actinic keratosis (78.3%). Bacterial infections encountered were pyoderma (58.8%), cellulitis (23.5%), and erythrasma (17.6%). Most of the skin problems in the elderly are preventable or treatable, so proper skin care and treatment of skin diseases should be emphasized in general health care for the elderly.


Intraductal papillary mucinous neoplasm of the pancreas: diagnosis and treatment.
Intraductal papillary mucinous neoplasm (IPMN) is characterized by cystic dilatation of the main and/or branch pancreatic duct. Only one-third of all patients are symptomatic, and others are diagnosed by chance. IPMNs are classified into 3 types: main duct, branch duct, and mixed IPMN. Most branch-type IPMNs are benign, while the other 2 types are frequently malignant. The presence of large mural nodules increases the possibility of malignancy in all types. Presence of a large branch-type IPMN and marked dilatation of the main duct indicate, at the very least, the existence of adenoma. Ultrasonography, endosonography, and intraductal ultrasonography clearly demonstrate ductal dilatation and mural nodules, and magnetic resonance pancreatography best visualizes the entire outline of IPMN. Not infrequently, synchronous or metachronous malignancy develops in various organs, including the pancreas. Prognosis is excellent after complete resection of benign and noninvasive malignant IPMNs. Asymptomatic branch-type IPMNs without mural nodules may be followed up without resection. Malignant IPMNs displaying acquired aggressiveness after parenchymal invasion require adequate lymph node dissection. Total pancreatectomy is needed for some IPMNs; its benefits, however, must be balanced against operative and postoperative risks because most IPMNs are slow growing and affect elderly people, and prognosis is favorable for IPMN patients with even malignant neoplasms.


Preparing for Fellowship in Internal Medicine. Steps for Success with a Focus on Pulmonary and/or Critical Care Programs.
This paper outlines specific tips for those applying to pulmonary and/or critical care medicine fellowship training in the United States using the PAIR-Match steps: preparation, application, interview, ranking, and match. Preparation for fellowship begins long before the application process with an assessment of one's long-term goals (to the extent that these are known). The cornerstone of the application is the curriculum vitae, which should highlight applicants' pulmonary and critical care-related experiences and scholarly work. Applicants should obtain letters of recommendation from faculty members who know them well and can write a letter that speaks to their strengths in clinical, scholarly, or leadership areas. The personal statement is an opportunity to share experiences not otherwise shared in the application and is an opportunity to explain any breaks in training or performance lapses. When selecting programs to which they will apply, applicants should pay close attention to the areas of education and curriculum, clinical experience, scholarly opportunity, and personal factors. Preparing for interviews should include a review of the program at which one is interviewing and development of relevant questions regarding details of the program. The interview day is the applicant's opportunity to see the "personality" of the program by meeting with the program director, faculty, and current fellows and to assess whether the program is a good fit for their goals. Applicants should only rank those programs they are willing to attend, in order of preference; they should be aware that the match process is binding.


Understanding selection bias, time-lags and measurement bias in secondary data sources: Putting the Encyclopedia of Associations database in broader context.
Secondary data gathered for purposes other than research play an important role in the social sciences. A recent data release has made an important source of publicly available data on associational interests, the Encyclopedia of Associations (EA), readily accessible to scholars (www.policyagendas.org). In this paper we introduce these new data and systematically investigate issues of lag between events and subsequent reporting in the EA, as these have important but under-appreciated effects on time-series statistical models. We further analyze the accuracy and coverage of the database in numerous ways. Our study serves as a guide to potential users of this database, but we also reflect upon a number of issues that should concern all researchers who use secondary data such as newspaper records, IRS reports and FBI Uniform Crime Reports.


Quantification of angiogenesis induced in rabbit cornea by breast carcinoma of women treated with tamoxifen.
The aim of this study was to evaluate the effect of tamoxifen on angiogenesis induced in rabbit cornea by breast carcinoma from post-menopausal women. Thirteen post-menopausal women with operable, estrogen receptor-positive breast carcinomas, treated with 20 mg of tamoxifen daily for 30 days prior to undergoing definitive surgery, participated in this study. Twenty-six virgin female New Zealand white rabbits, 3-4 months old, weighing approximately 2.5 kg each, were divided into two groups of 13 animals and received corneal implants of tumor either pre- or post-tamoxifen treatment. After 10 days, the animals were sacrificed, the region of the cornea between the tumor implant and the limbus was removed and quantification of angiogenesis was carried out by evaluating the entire hematoxylin-eosin stained slide, using a 10x objective lens (100x magnification). Student t-test was used in the statistical analysis of the data and statistical significance was established at P < 0.05. Mean microvessel count was 106.8 +/- 5.9 pre-tamoxifen treatment and 54 +/- 5.6 post-treatment. According to Student t-test, there was a significant reduction in mean microvessel density following treatment with tamoxifen (P < 0.001). Rabbit cornea proved to be an interesting experimental model for the quantification of angiogenesis. Tamoxifen, when administered for 30 days to post-menopausal women with breast cancer, significantly inhibited angiogenesis induced by tumor fragments in rabbit cornea.


Use of a continuing health history in dental practice: a survey.
The authors strongly recommend the routine use of a continual-health-update procedure at each recall appointment. The updated health-histories allow us to better evaluate the "whole" child. We have found that the parent appreciates not only the initial inquiry, but also the continuing concern about illnesses and injuries the child may have incurred since the last dental examination. The inquiries help build rapport between the families and the professional staff of our office. In addition, they upgrade the level of professional care provided.


[Vagina cancer in a young woman exposed to diethylstilbestrol: case report and literature review].
We analyzed a 20 year-old patient case exposed in utero to diethylstilbestrol, as probably predisposed factor in vaginal cancer. The histopathological report of the incisional biopsy was clear cell vaginal adenocarcinoma, stage III, widespread to the pelvic wall, with metastasis to regional lymph nodes, and lack of distant metastasis. We decided surgical management: protocolized laparotomy, peritoneal washing, retroperitoneal node biopsies and a radical hysterectomy, Piver III, with two thirds parts of vagina. By poor prognosis we decided to offer an adjuvant management, with systemic chemotherapy.


Effects of acute exercise and training on insulin binding to monocytes and insulin sensitivity in vivo.
Insulin binding to monocytes was studied in well-trained long distance runners and in sedentary control subjects in the resting state and after 3 h cycle ergometer exercise at 40% of maximal aerobic power. In addition, in previously untrained subjects we examined the effect of 6 weeks of training on insulin binding to monocytes and insulin sensitivity in vivo. In the athletes at rest, insulin binding to monocytes was 69% higher than in controls (p less than 0.01), and correlated with maximal aerobic power (r = 9.63, p less than 0.05). The rise in insulin binding in the athletes was due to an increase in binding capacity rather than a change in binding affinity. During exercise, insulin binding fell in athletes by 31% (p less than 0.025) in contrast to a 35% rise observed in control subjects (p less than 0.01). As compared to controls, the athletes had a lower respiratory exchange ratio and a smaller decline in plasma glucose during exercise. In previously untrained subjects, physical training resulted in a 35% rise in insulin binding to monocytes (p less than 0.02). The rise in binding was due mainly to an increase in binding capacity. Insulin mediated glucose uptake (as measured by insulin clamp technique) also rose by 30% after physical training (p less than 0.01). The rise in insulin sensitivity was proportional to the improvement in physical fitness (r = 0.81, p less than 0.05). These findings indicate that (a) elevated insulin binding may contribute to the enhanced insulin sensitivity observed after physical training, (b) a fall in insulin binding in athletes during acute exercise may contribute to a greater shift from carbohydrate to fat utilization during exercise in athletes as compared to sedentary controls. These data suggest that physical training may provide a means of reversing or ameliorating abnormalities in insulin binding and sensitivity in insulin resistant states, such as obesity or maturity onset diabetes.


In silico hit optimization toward AKT inhibition: fragment-based approach, molecular docking and molecular dynamics study.
Protein kinase B also known as AKT is a cardinal node in different signaling pathways that regulates diverse cell processes. AKT has three isoforms that share high homology. Hyperactivation of each isoform is related with different types of cancer. This work describes the computational search for new inhibitors using a hit optimization process of the previously reported AKT pan inhibitor, a 2,4,6-trisubstituted pyridine. A database of new molecules was proposed using a variant of fragment-based docking methodology and previous reported considerations. Molecular docking followed by molecular dynamics studies were performed to select the best compounds and analyze their behavior. Protein-ligand complexes energy was calculated using molecular mechanics Poisson-Boltzmann surface area protocol. Further, proposed molecules were compared with the ChEMBL database of compounds assayed against AKT. Data analysis leads to determine the structural requirements necessary for a favorable interaction of the proposed ligands with the AKT pocket. Molecular dynamics data suggested that the pKa of the ligands is important for the stability in the AKT pocket. Molecular similarity analysis shows that proposed ligands have not been previously reported. Thus, ligands with high docking scores and favorable behavior on molecular dynamics simulations are proposed as potential AKT inhibitors.


Behavior of flavonols and carotenoids of minimally processed kale leaves during storage in passive modified atmosphere packaging.
Minimally processed kale leaves were packed in passive modified atmosphere and stored at 3 conditions: 1 °C in the dark and 11 °C with or without light exposure. The products were evaluated during storage in terms of headspace gas composition, sensory attributes, flavonol, and carotenoid contents. The sensory quality decreased slightly during 17 d at 1 °C in the dark. At 11 °C, the vegetable shelf life was predicted to be 6 d in the dark and 3 d with light. Quercetin and kaempferol were stable during storage for 15 d at 1 °C in the absence of light. At 11 °C in the dark, quercetin was stable during 10 d, increasing slightly on the 8th day. Kaempferol decreased up to the 5th day but increased on the 8th day, decreasing again on the 10th day. After 5 d at 11 °C under light, the flavonol levels were significantly higher than those of the initial values. Neoxanthin and violaxanthin did not change significantly after 15 d at 1 °C in the dark. Lutein and β-carotene, however, decreased 7.1% and 11.3%, respectively. At 11 °C in the dark, neoxanthin, violaxanthin, lutein, and β-carotene decreased 16.1%, 13.2%, 24.1%, and 23.7% after 10 d, respectively. At 11 °C under light, neoxanthin and lutein had a slight increase while violaxanthin and β-carotene decreased 23.1% and 16.5% after 5 d. Practical Application: Passive modified atmosphere packaging together with refrigeration can extend the shelf life of minimally processed kale, retaining the health-promoting compounds, flavonols and carotenoids. Quercetin, kaempferol, neoxanthin, and violaxanthin are stable and lutein and β-carotene slightly reduced.


Demand dynamic bio-girdling in heart failure: improved efficacy of dynamic cardiomyoplasty by LD contraction during aortic out-flow.
The value of dynamic cardiomyoplasty has been brought into question by the disappointing results produced by slow contraction-relaxation cycle and possibly degeneration of the latissimus dorsi muscle (LD) secondary to temporary tenotomy and chronic daily electrical stimulation. Objective of our study is to determine whether daily periods of rest introduced by demand stimulation in the continuous contraction protocol produce systolic assistance and improve clinical results. Twelve dynamic cardiomyoplasty patients (mean age 58.2 +/- 5.8 years, M/F=11/1, sinus rhythm/atrial fibrillation=11/1) with dilated myocardiopathy were enrolled in an unrandomized trial of Demand Dynamic Heart Bio-Girdling in a public regional teaching hospital. Periods of LD inactivity, each lasting several hours, were introduced daily on a heart rate-based demand regime. To avoid full transformation of LD, fewer impulses per day were delivered, daily providing the LD with long periods of rest (Demand light stimulation). The contractile properties were measured by transcutaneous non-invasive LD tensiomyogram interrogation (LD tensiomyogram). Bio-Girdle activation was synchronized to heart beat by combining tensiomyogram and echocardiography. Clinical, echocardiographic and hemodynamic records, as well as aortic flow measurements by Doppler aortic flow wire were taken during the follow-up. Mean duration of the demand stimulation follow-up was 40.2+13.8 months. At five years, "Demand stimulation" shows: 1) no operative death; 2) 83% actuarial survival; 3) highly significant 47.4% decrease of the NYHA class (from 3.17 +/- 0.38 to 1.67 +/- 0.77, p=0.0001); 4) 41.6% improvement of LVEF (from 22.6 +/- 4.38 to 32.0 +/- 7.0, p=0.001); 5) 7.5 +/- 3.0% increase in aortic flow velocity peak in assisted vs. unassisted beats, and 6) preservation of LD from slowness (TFF value 33 +/- 7.86 at follow-up versus 15.8 +/- 11.1 Hz just before switching from continuous to demand stimulation, p=0.0001) and muscle degenerative atrophy. In dynamic cardiomyoplasty the demand light stimulation maintains LD contraction properties over time, produces effective systolic assistance, and improves clinical results. Demand dynamic bio-girdling is a safe and effective treatment for end-stage heart failure in selected patients.


Disruption of thalamocortical activity in schizophrenia models: relevance to antipsychotic drug action.
Non-competitive NMDA receptor antagonists are widely used as pharmacological models of schizophrenia due to their ability to evoke the symptoms of the illness. Likewise, serotonergic hallucinogens, acting on 5-HT(2A) receptors, induce perceptual and behavioural alterations possibly related to psychotic symptoms. The neurobiological basis of these alterations is not fully elucidated. Data obtained in recent years revealed that the NMDA receptor antagonist phencyclidine (PCP) and the serotonergic hallucinogen 1-(2,5-dimethoxy-4-iodophenyl-2-aminopropane; DOI) produce a series of common actions in rodent prefrontal cortex (PFC) that may underlie psychotomimetic effects. Hence, both agents markedly disrupt PFC function by altering pyramidal neuron discharge (with an overall increase) and reducing the power of low frequency cortical oscillations (LFCO; < 4 Hz). In parallel, PCP increased c-fos expression in excitatory neurons of various cortical areas, the thalamus and other subcortical structures, such as the amygdala. Electrophysiological studies revealed that PCP altered similarly the function of the centromedial and mediodorsal nuclei of the thalamus, reciprocally connected with PFC, suggesting that its psychotomimetic properties are mediated by an alteration of thalamocortical activity (the effect of DOI was not examined in the thalamus). Interestingly, the observed effects were prevented or reversed by the antipsychotic drugs clozapine and haloperidol, supporting that the disruption of PFC activity is intimately related to the psychotomimetic activity of these agents. Overall, the present experimental model can be successfully used to elucidate the neurobiological basis of schizophrenia symptoms and to examine the potential antipsychotic activity of new drugs in development.


Release of previously incorporated gamma-[3H]aminobutyric acid in rabbit caudate nucleus slices.
The release of gamma-aminobutyric acid (GABA) was studied in slices of the head of the rabbit caudate nucleus. The slices were preincubated with [3H]GABA and then superfused. Aminooxyacetic acid was present throughout. Both the tritium in the slices and that in the superfusate consisted practically entirely of [3H]GABA. Stimulation for 2 min by electrical field pulses of 3 ms width and 9 V/cm voltage drop (36 mA current strength) at 5 or 20 Hz elicited an overflow of [3H]GABA that amounted to 0.23 or 0.47% of the tritium content of the tissue, respectively, and was diminished by 85% in the presence of tetrodotoxin. At higher current strength, less of the stimulation-evoked overflow was tetrodotoxin-sensitive. cis-1,3-Aminocyclohexane carboxylic acid diminished the uptake of [3H]GABA into the tissue but did not change the percentage released by electrical stimulation. Ca2+ withdrawal greatly accelerated basal [3H]GABA efflux and almost abolished the response to stimulation. Nipecotic acid 10-1,000 microM enhanced both the basal and (up to eightfold) the stimulation-evoked overflow. The method described allows us to elicit electrically a quasiphysiological, i.e., Ca2+-dependent and tetrodotoxin-sensitive, neuronal release of [3H]GABA. Nipecotic acid diverts released [3H]GABA from reuptake to overflow.


Recurrence-Aware Long-Term Cognitive Network for Explainable Pattern Classification.
Machine-learning solutions for pattern classification problems are nowadays widely deployed in society and industry. However, the lack of transparency and accountability of most accurate models often hinders their safe use. Thus, there is a clear need for developing explainable artificial intelligence mechanisms. There exist model-agnostic methods that summarize feature contributions, but their interpretability is limited to predictions made by black-box models. An open challenge is to develop models that have intrinsic interpretability and produce their own explanations, even for classes of models that are traditionally considered black boxes like (recurrent) neural networks. In this article, we propose a long-term cognitive network (LTCN) for interpretable pattern classification of structured data. Our method brings its own mechanism for providing explanations by quantifying the relevance of each feature in the decision process. For supporting the interpretability without affecting the performance, the model incorporates more flexibility through a quasi-nonlinear reasoning rule that allows controlling nonlinearity. Besides, we propose a recurrence-aware decision model that evades the issues posed by the unique fixed point while introducing a deterministic learning algorithm to compute the tunable parameters. The simulations show that our interpretable model obtains competitive results when compared to state-of-the-art white and black-box models.


Integrin alpha1beta1 (VLA-1) mediates adhesion of activated intraepithelial lymphocytes to collagen.
Intraepithelial lymphocytes (IELs) from human intestinal epithelium are memory CD8+ T cells that bind to epithelial cells through human mycosal lymphocyte (HML)-1 and to mesenchymal cells through very late activation antigen-4 (VLA-4). Their binding of extracellular matrix proteins and the mechanism involved were tested. Activated 51Cr-labelled lymphocytes were incubated in protein-coated microwells with various additives. After washing, the adherent cells were detected by radioactivity. The percentages of activated IELs that bound to collagen types I and IV were 20 and 31%, respectively; fewer bound to fibronectin or laminin. Compared to interleukin-2-activated peripheral blood CD8+ T lymphocytes, more IELs bound collagen IV and fewer bound fibronectin. IEL adhesion to collagen (but not fibronectin or laminin) was up-regulated by antibody ligation of CD2 or by protein kinase C stimulation by phorbol ester; staurosporine reduced binding, while herbimycin, phytohaemagglutinin and CD3 ligation had no effect. Antibody-blocking of integrin VLA-1 subunits alpha1 (CD49a) and beta1 (CD18) inhibited adhesion to collagen type I by 82+/-6% and to type IV by 94+/-1% (P<0.001), implicating VLA-1 as the main collagen receptor for IELs. Cell adhesion was dependent on extracellular divalent cations, a characteristic event of VLA-1 never before shown for IELs: manganese and magnesium ions supported binding in a dose-dependent manner; calcium ions inhibited their effectiveness. Therefore, IELs bind collagen through integrin alpha1beta1 after protein kinase C activation. Adhesion is modulated by divalent cations.


A dual autoencoder and singular value decomposition based feature optimization for the segmentation of brain tumor from MRI images.
The brain tumor is the growth of abnormal cells inside the brain. These cells can be grown into malignant or benign tumors. Segmentation of tumor from MRI images using image processing techniques started decades back. Image processing based brain tumor segmentation can be divided in to three categories conventional image processing methods, Machine Learning methods and Deep Learning methods. Conventional methods lacks the accuracy in segmentation due to complex spatial variation of tumor. Machine Learning methods stand as a good alternative to conventional methods. Methods like SVM, KNN, Fuzzy and a combination of either of these provide good accuracy with reasonable processing speed. The difficulty in processing the various feature extraction methods and maintain accuracy as per the medical standards still exist as a limitation for machine learning methods. In Deep Learning features are extracted automatically in various stages of the network and maintain accuracy as per the medical standards. Huge database requirement and high computational time is still poses a problem for deep learning. To overcome the limitations specified above we propose an unsupervised dual autoencoder with latent space optimization here. The model require only normal MRI images for its training thus reducing the huge tumor database requirement. With a set of normal class data, an autoencoder can reproduce the feature vector into an output layer. This trained autoencoder works well with normal data while it fails to reproduce an anomaly to the output layer. But a classical autoencoder suffer due to poor latent space optimization. The Latent space loss of classical autoencoder is reduced using an auxiliary encoder along with the feature optimization based on singular value decomposition (SVD). The patches used for training are not traditional square patches but we took both horizontal and vertical patches to keep both local and global appearance features on the training set. An Autoencoder is applied separately for learning both horizontal and vertical patches. While training a logistic sigmoid transfer function is used for both encoder and decoder parts. SGD optimizer is used for optimization with an initial learning rate of .001 and the maximum epochs used are 4000. The network is trained in MATLAB 2018a with a processor capacity of 3.7 GHz with NVIDIA GPU and 16 GB of RAM. The results are obtained using a patch size of 16 × 64, 64 × 16 for horizontal and vertical patches respectively. In Glioma images tumor is not grown from a point rather it spreads randomly. Region filling and connectivity operations are performed to get the final tumor segmentation. Overall the method segments Meningioma better than Gliomas. Three evaluation metrics are considered to measure the performance of the proposed system such as Dice Similarity Coefficient, Positive Predictive Value, and Sensitivity. An unsupervised method for the segmentation of brain tumor from MRI images is proposed here. The proposed dual autoencoder with SVD based feature optimization reduce the latent space loss in the classical autoencoder. The proposed method have advantages in computational efficiency, no need of huge database requirement and better accuracy than machine learning methods. The method is compared Machine Learning methods Like SVM, KNN and supervised deep learning methods like CNN and commentable results are obtained.


Technical note: Calculation of standard errors of estimates of genetic parameters with the multiple-trait derivative-free restricted maximal likelihood programs.
The multiple-trait derivative-free REML set of programs was written to handle partially missing data for multiple-trait analyses as well as single-trait models. Standard errors of genetic parameters were reported for univariate models and for multiple-trait analyses only when all traits were measured on animals with records. In addition to estimating (co)variance components for multiple-trait models with partially missing data, this paper shows how the multiple-trait derivative-free REML set of programs can also estimate SE by augmenting the data file when not all animals have all traits measured. Although the standard practice has been to eliminate records with partially missing data, that practice uses only a subset of the available data. In some situations, the elimination of partial records can result in elimination of all the records, such as one trait measured in one environment and a second trait measured in a different environment. An alternative approach requiring minor modifications of the original data and model was developed that provides estimates of the SE using an augmented data set that gives the same residual log likelihood as the original data for multiple-trait analyses when not all traits are measured. Because the same residual vector is used for the original data and the augmented data, the resulting REML estimators along with their sampling properties are identical for the original and augmented data, so that SE for estimates of genetic parameters can be calculated.


Esthetic management of congenitally missing lateral incisors with single-tooth implants: a case report.
Achievement of an esthetic single-tooth restoration in the anterior segment is a difficult task for the restorative dentist. A case is described in which two congenitally missing maxillary lateral incisors were replaced with single-tooth implants. A new technique was used to restore the teeth provisionally with a polyethylene ribbon and resin replacement. Light-cured staining systems for acrylic resins and ceramics were employed to customize both the provisional and final restorations.


Separated response function ratios in exclusive, forward π(±) electroproduction.
The study of exclusive π(±) electroproduction on the nucleon, including separation of the various structure functions, is of interest for a number of reasons. The ratio RL=σL(π-)/σL(π+) is sensitive to isoscalar contamination to the dominant isovector pion exchange amplitude, which is the basis for the determination of the charged pion form factor from electroproduction data. A change in the value of RT=σT(π-)/σT(π+) from unity at small -t, to 1/4 at large -t, would suggest a transition from coupling to a (virtual) pion to coupling to individual quarks. Furthermore, the mentioned ratios may show an earlier approach to perturbative QCD than the individual cross sections. We have performed the first complete separation of the four unpolarized electromagnetic structure functions above the dominant resonances in forward, exclusive π(±) electroproduction on the deuteron at central Q(2) values of 0.6, 1.0, 1.6 GeV(2) at W=1.95 GeV, and Q(2)=2.45 GeV(2) at W=2.22 GeV. Here, we present the L and T cross sections, with emphasis on RL and RT, and compare them with theoretical calculations. Results for the separated ratio RL indicate dominance of the pion-pole diagram at low -t, while results for RT are consistent with a transition between pion knockout and quark knockout mechanisms.


Contribution of cerebrospinal fluid thymosin β4 levels to the clinical differentiation of Creutzfeldt-Jakob disease.
To asses thymosin β4 specificity as relevant to the diagnosis of Creutzfeldt-Jakob disease (CJD). A matrix-assisted laser desorption ionization time-of-flight mass spectrometry protein profiling analysis was applied to several neurological disorders that are known to lead to dementia. The relative peak area (percentage of area) of the thymosin β4 MS signal was taken into account. National Research Council, Cosenza, Italy. Cerebrospinal fluid analysis was performed on 21 patients with neuropathologically confirmed CJD; 15 patients with frontotemporal dementia; 18 patients with probable Alzheimer disease; and 9 patients with a rapid-onset progressive dementia. A non-cognitively impaired control group consisted of 25 individuals without CJD or dementia. The thymosin β4 test results in CJD and other dementia. The thymosin β4 cerebrospinal fluid levels appeared to be markedly increased in CJD samples compared with frontotemporal cases (P = 10(-7)) and patients with Alzheimer disease (P = 10(-7)). A lower significance was observed vs the group with rapid-onset progressive dementia (P = .0004). Thus, at a cutoff value of 1.2% of the thymosin β4 relative peak area, we estimated 100% sensitivity with 98.5% specificity. These findings indicate that cerebrospinal fluid levels of thymosin β4 protein measured by matrix-assisted laser desorption ionization time-of-flight mass spectrometry may effectively contribute to discriminate CJD from other forms of dementia.


Nosocomial outbreaks: the Centers for Disease Control's Hospital Infections Program experience, 1980-1990. Epidemiology Branch, Hospital Infections Program.
From January 1980 to July 1990, the Hospital Infections Program of the Centers for Disease Control conducted 125 on-site epidemiologic investigations of nosocomial outbreaks. Seventy-seven (62%) were caused by bacterial pathogens, 11 (9%) were caused by fungi, 10 (8%) were caused by viruses, five (4%) were caused by mycobacteria, and 22 (18%) were caused by toxins or other organisms. The majority of fungi and mycobacterial outbreaks occurred since July 1985. Fourteen (11%) outbreaks were device related, 16 (13%) were procedure related, and 28 (22%) were product related. The proportion of outbreaks involving products, procedures, or devices increased from 47% during 1980-1985 to 67% between 1986 and July 1990. Recent outbreaks have shown that packed red blood cell transfusion-associated Yersinia enterocolitica sepsis results from contamination of the blood by the asymptomatic donor; that povidone-iodine solutions can become intrinsically contaminated and cause outbreaks of infection and/or pseudoinfection; and that rapidly growing mycobacteria can cause chronic otitis media, surgical wound infection, and hemodialysis-associated infections. These and other outbreaks demonstrate how epidemiologic and laboratory investigations can be combined to identify new pathogens and sources of infection and ultimately result in disease prevention.


Fluorinated MIL-101 for carbon capture utilisation and storage: uptake and diffusion studies under relevant industrial conditions.
Carbon capture utilisation and storage (CCUS) using solid sorbents such as zeolites, activated carbon and Metal-Organic Frameworks (MOFs) could facilitate the reduction of anthropogenic CO2 concentration. Developing efficient and stable adsorbents for CO2 capture as well as understanding their transport diffusion limitations for CO2 utilisation plays a crucial role in CCUS technology development. However, experimental data available on CO2 capture and diffusion under relevant industrial conditions is very limited, particularly for MOFs. In this study we explore the use of a gravimetric Dynamic Vapour Sorption (DVS) instrument to measure low concentration CO2 uptake and adsorption kinetics on a novel partially fluorinated MIL-101(Cr) saturated with different water vapour concentrations, at ambient pressure and temperature. Results show that up to water P/P 0 = 0.15 the total CO2 uptake of the modified material improves and that the introduction of small amounts of water enhances the diffusion of CO2. MIL-101(Cr)-4F(1%) proved to be a stable material under moist conditions compared to other industrial MOFs, allowing facile regeneration under relevant industrial conditions.


The Diagnosis of Urinary Tract Infection in Young Children (DUTY) Study Clinical Rule: Economic Evaluation.
To estimate the cost-effectiveness of a two-step clinical rule using symptoms, signs and dipstick testing to guide the diagnosis and antibiotic treatment of urinary tract infection (UTI) in acutely unwell young children presenting to primary care. Decision analytic model synthesising data from a multicentre, prospective cohort study (DUTY) and the wider literature to estimate the short-term and lifetime costs and healthcare outcomes (symptomatic days, recurrent UTI, quality adjusted life years) of eight diagnostic strategies. We compared GP clinical judgement with three strategies based on a 'coefficient score' combining seven symptoms and signs independently associated with UTI and four strategies based on weighted scores according to the presence/absence of five symptoms and signs. We compared dipstick testing versus laboratory culture in children at intermediate risk of UTI. Sampling, culture and antibiotic costs were lowest in high-specificity DUTY strategies (£1.22 and £1.08) compared to clinical judgement (£1.99). These strategies also approximately halved urine sampling (4.8% versus 9.1% in clinical judgement) without reducing sensitivity (58.2% versus 56.4%). Outcomes were very similar across all diagnostic strategies. High-specificity DUTY strategies were more cost-effective than clinical judgement in the short- (iNMB = £0.78 and £0.84) and long-term (iNMB =£2.31 and £2.50). Dipstick tests had poorer cost-effectiveness than laboratory culture in children at intermediate risk of UTI (iNMB = £-1.41). Compared to GPs' clinical judgement, high specificity clinical rules from the DUTY study could substantially reduce urine sampling, achieving lower costs and equivalent patient outcomes. Dipstick testing children for UTI is not cost-effective.


Podoplanin and CLEC-2 drive cerebrovascular patterning and integrity during development.
Mice with a constitutive or platelet-specific deletion of the C-type-lectin-like receptor (CLEC-2) exhibit hemorrhaging in the brain at mid-gestation. We sought to investigate the basis of this defect, hypothesizing that it is mediated by the loss of CLEC-2 activation by its endogenous ligand, podoplanin, which is expressed on the developing neural tube. To induce deletion of podoplanin at the 2-cell stage, we generated a podoplanin(fl/fl) mouse crossed to a PGK-Cre mouse. Using 3-dimensional light-sheet microscopy, we observed cerebral vessels were tortuous and aberrantly patterned at embryonic (E) day 10.5 in podoplanin- and CLEC-2-deficient mice, preceding the formation of large hemorrhages throughout the fore-, mid-, and hindbrain by E11.5. Immunofluorescence and electron microscopy revealed defective pericyte recruitment and misconnections between the endothelium of developing blood vessels and surrounding pericytes and neuro-epithelial cells. Nestin-Cre-driven deletion of podoplanin on neural progenitors also caused widespread cerebral hemorrhaging. Hemorrhaging was also seen in the ventricles of embryos deficient in the platelet integrin subunit glycoprotein IIb or in embryos in which platelet α-granule and dense granule secretion is abolished. We propose a novel role for podoplanin on the neuro-epithelium, which interacts with CLEC-2 on platelets, mediating platelet adhesion, aggregation, and secretion to guide the maturation and integrity of the developing vasculature and prevent hemorrhage.


Phosphatidylinositol 3'-kinase, mTOR, and glycogen synthase kinase-3β mediated regulation of p21 in human urothelial carcinoma cells.
The PTEN/Phosphatidylinositol 3'-kinase (PI3-kinase) growth factor signaling pathway plays a critical role in epithelial tumor development in a multitude of tissue types. Deletion of the Pten tumor suppressor gene in murine urothelial cells in vivo results in upregulation of cyclin-dependent kinase inhibitor p21. We have previously shown in mice that p21 expression blocks an increase in urothelial cell proliferation due to Pten deletion. In this study, we utilized human urothelial carcinoma cells UMUC-3 and UMUC-14 to identify the signaling pathways downstream of PI3-kinase that regulate p21. Cells were treated with a combination of PI3-kinase stimulating growth factors and kinase inhibitors, or transfected with exogenous genes in order to identify the signaling events that are necessary for p21 induction. Mice with conditional deletion of Pten in bladder urothelium were also examined for evidence of PI3-kinase pathway signaling events that affect p21 expression. When cells were treated with PI3-kinase activating growth factors EGF or PDGF, we found that p21 levels increased, in a manner similar to that observed in mice. We used the inhibitors LY294002, Akti-1/2, and rapamycin, to show that p21 induction is dependent upon PI3-kinase and AKT activity, and partially dependent on mTOR. We treated the cells with proteasome inhibitor MG-132 and found that p21 may be degraded in the proteasome to regulate protein levels. Importantly, our findings show that GSK-3β plays a role in diminishing p21 levels in cells. Treatment of cells with the GSK-3β inhibitor SB-216763 increased p21 levels, while exogenous expression of GSK-3β caused a decrease in p21, indicating that GSK-3β actively reduces p21 levels. We found that a combined treatment of LY294002 and SB-216763 improved the cytotoxic effect against UMUC-3 and UMUC-14 carcinoma cells over LY294002 alone, suggesting potential therapeutic uses for GSK-3β inhibitors. Immunohistochemical staining in bladders from wild-type and Pten-deleted mice indicated that GSK-3β inhibitory phosphorylation increases when Pten is deleted. PI3-kinase and AKT cause an upregulation of p21 by suppressing GSK-3β activity and activating mTOR in both cultured human urothelial carcinoma cells and mouse urothelial cells in vivo.


The development of a biotin deficiency in domestic fowl given wheat-based diets.
1. Studies were done of the possible development of a biotin deficiency in domestic fowl of various ages as a result of feeding with diets composed mainly of wheat, and meat-and-bone meal. The degree of deficiency was estimated from physical symptoms, liver and kidney composition and hepatic enzyme activities. 2. Only a mild biotin deficiency developed in 3-week-old chickens and no adverse metabolic effect were found for chickens reared to 7 or 15 weeks of age or maintained for 9 months in lay on these diets, which were suspected of producing fatty liver and kidney disease in young chickens. At 3 weeks of age the deficiency was more severe the heavier the strain of chicken and the greater the rate of body-weight gain. 3. The present results question the supposition that biotin deficiency is the sole factor responsible for the development of fatty liver and kidney syndrome in young chickens.


Panax notoginseng saponins prevent senescence and inhibit apoptosis by regulating the PI3K‑AKT‑mTOR pathway in osteoarthritic chondrocytes.
Panax notoginseng saponins (PNS) are active extracts obtained from the P. notoginseng plant. PNS exhibit various anti‑inflammatory, anti‑oxidant and anti‑aging pharmacological properties in some cells. However, the effects of PNS on senescence and apoptosis in chondrocytes have not been studied to date. In the present study, whether PNS could limit tumor necrosis factor (TNF)‑α‑induced senescence and apoptosis in chondrocytes and whether they could slow down cartilage degeneration in a surgery‑induced rat osteoarthritis (OA) model by regulating the phosphatidyl inositol 3 kinase (PI3K)‑protein kinase B (AKT)‑mammalian target of rapamycin (mTOR) signaling pathway was examined. A potential mechanism underlying these effects was further elucidated. The present in vitro experiments showed that PNS significantly inhibited senescence and apoptosis in OA chondrocytes and prevented a decrease in the mitochondrial membrane potential and excessive mitochondrial permeability. In addition, the expression levels of autophagy‑related proteins and the anti‑apoptotic protein Bcl‑2 were significantly increased in PNS‑treated OA chondrocytes, but the expression levels of Bax and caspase‑3 were decreased; these effects were concentration‑dependent. TNF‑α significantly increased the expression of p‑PI3K/p‑AKT/p‑mTOR in OA chondrocytes, whereas PNS reduced PI3K, AKT and mTOR phosphorylation. The results of the in vivo experiments demonstrated that PNS significantly inhibited the PI3K‑AKT‑mTOR signaling pathway and collagen II degradation, as well as reduced matrix metalloproteinase (MMP)‑3 and MMP‑13 expression in chondrocytes in a rat OA model, thus attenuating cartilage destruction in OA. The results obtained in the rat model were consistent with the in vitro experimental results. Furthermore, histological analyses and ultrastructural observations confirmed these results. Taken together, the results of the present study demonstrated that PNS may protect osteoarthritic chondrocytes from senescence and apoptosis by inhibiting the PI3K‑AKT pathway, thus delaying the degradation of articular cartilage.


Effects of Clockwise and Counterclockwise Job Shift Work Rotation on Sleep and Work-Life Balance on Hospital Nurses.
Rotational shift work is associated with sleep disturbances, increased risk of cardiovascular and psychological disorders, and may negatively impact work⁻life balance. The direction of shift rotation (Clockwise, CW or counterclockwise, CCW) and its role in these disorders are poorly understood. The aim of the study was to investigate the effect of the shift schedule direction on sleep quantity and quality, alertness and work performance, and on work⁻life balance on hospital nurses. One-hundred female nurses, working a continuous rapid shift schedule in hospitals in the north of Italy, participated in this cross-sectional study. Fifty worked on CW rotation schedule (Morning: 6 a.m.⁻2 p.m., Afternoon: 2 p.m.⁻10 p.m., Night: 10 p.m.⁻6 a.m., 2 rest days) and fifty on CCW rotation (Afternoon, Morning, Morning, Night, 3 rest days). Data were collected by ad hoc questionnaire and daily diary. During the shift cycle CW nurses slept longer (7.40 ± 2.24 h) than CCW (6.09 ± 1.73; p < 0.001). CW nurses reported less frequently than CCW awakening during sleep (40% vs. 80%; p < 0.001), attention disturbance during work (20% vs. 64%; p < 0.001), and interference with social and family life (60% vs. 96% and 20% vs. 70%, respectively; p < 0.001). CCW rotating shift schedule seems to be characterized by higher sleep disturbances and a worse work⁻life balance.


Using an observation tool (Parent-Infant Interaction Observation Scale) to assess parent-infant interaction in the first 2 weeks of life: A feasibility study.
Emotional maltreatment (EM) has profound effects on the developing brain but is hardest to identify in infancy. Early observations of parent-infant interactions may provide opportunities to identify babies at risk of neglect and EM. This prospective study tests, in the first fortnight of life, the feasibility of using an observation tool previously validated for use at 2 to 7 months of age. Women awaiting induction of labour were recruited in South Wales in July 2016. Women consented to being contacted postnatally and video recordings of mother-infant interaction at two home visits between 7 and 10 days (T1) and 8-12 weeks old (T2). Demographic details, information on the pregnancy, delivery, and infant condition were obtained at T1. A questionnaire was completed at T2 to capture any significant events affecting the parent-infant relationship. The Parent-Infant Interaction Observation Scale (PIIOS) was used to score the videos. Exclusion criteria included admission to neonatal unit. Recruitment of suitable participants and full research data completion were feasible. Of 60 women who consented to be contacted post-delivery, 30 women (31 infants) participated at T1 and T2. Three babies were excluded. Women accepted being observed in their homes with their babies, with no attrition between T1 and T2. Using the PIIOS 10 of the 13 items could be scored with an awake infant under 2 weeks. These encouraging findings can inform exploration of an observation tool to identify high-risk dyads for targeted support. A trial and test of a modified scoring system (based on the PIIOS) should be developed for a future study using a larger sample size. Further research should assess if this approach reliably produces a consistent valid screening tool to assess parental sensitive responsiveness and resilience promoting behaviours at this early stage of life.


Impact of sludge thickening on energy recovery from anaerobic digestion.
This paper presents energy balances for various digestion systems, which include single mesophilic digestion, single thermophilic digestion, two-stage thermophilic-mesophilic digestion system and systems at elevated solids content in sludge. On the basis of a sludge flow containing 30 tons TS/day (equivalent to a 100 ML/d WWTP plant) it was shown that a two-stage thermophilic-mesophilic digestion system generated more available energy than single mesophilic digestion and single thermophilic digestion systems. Sludge thickening offered the greatest amount of available energy; however that energy surplus was offset by the cost of thickening. After the cost of thickening was converted into equivalent energy units it was shown that the price of energy is important in calculation of equivalent energy units related to operation of the thickening plant. Sludge thickening may be beneficial from energy view point compared to conventional mesophilic digestion when price of energy exceeds dollars 0.08 CAN kW-hr.


Modulation of Epstein-Barr virus release from cells by components of normal human serum.
By filtration of normal human serum through a Sephadex G-200 column, an anti-virus release factor (AVRF), which is capable of inhibiting the release of Epstein-Barr virus (EBV) from cells cultured in vitro, was found in the fractions corresponding to IgM. Another component, antagonistic to the activity of AVRF, was found in the fractions close to those of albumin. Both AVRF and anti-AVRF were found in all sera from four EBV seropositive and three sero-negative adults tested. EBV-release inhibition by AVRF was reversible. AVRF did not neutralize virus infectivity or inhibit intracellular virus growth. Virus adsorption on to cells was not prevented by AVRF but cap formation of EBV antigens on cells was augmented by it.


Zero methane emission bogs: extreme rhizosphere oxygenation by cushion plants in Patagonia.
• Vascular wetland plants may substantially increase methane emissions by producing root exudates and easily degradable litter, and by providing a low-resistance diffusion pathway via their aerenchyma. However, model studies have indicated that vascular plants can reduce methane emission when soil oxygen demand is exceeded by oxygen released from roots. Here, we tested whether these conditions occur in bogs dominated by cushion plants. • Root-methane interactions were studied by comparing methane emissions, stock and oxygen availability in depth profiles below lawns of either cushion plants or Sphagnum mosses in Patagonia. • Cushion plants, Astelia pumila and Donatia fascicularis, formed extensive root systems up to 120 cm in depth. The cold soil (< 10°C) and highly decomposed peat resulted in low microbial activity and oxygen consumption. In cushion plant lawns, high soil oxygen coincided with high root densities, but methane emissions were absent. In Sphagnum lawns, methane emissions were substantial. High methane concentrations were only found in soils without cushion plant roots. • This first methane study in Patagonian bog vegetation reveals lower emissions than expected. We conclude that cushion plants are capable of reducing methane emission on an ecosystem scale by thorough soil and methane oxidation.


[Contemporary opinion about anticholinergics use in premedication].
The article deals with the analysis of publications which discuss anticholinergics use in premedication. The article briefly says about the use history and characteristics of anticholinergics. In conclusion the article stresses the need to abandon the routine anticholinergics use. Intravenous anticholinergics application is preferable if there are indications for its use. New inhalation and intravenous anaesthetics promote to prescribe the anticholinergics individually


Transcriptomic and Network Analysis of Minor Salivary Glands of Patients With Primary Sjögren's Syndrome.
Primary Sjögren's syndrome (pSS) is a systemic autoimmune disease characterized primarily by immune-mediated destruction of exocrine tissues, such as those of the salivary and lacrimal glands, resulting in the loss of saliva and tear production, respectively. This disease predominantly affects middle-aged women, often in an insidious manner with the accumulation of subtle changes in glandular function occurring over many years. Patients commonly suffer from pSS symptoms for years before receiving a diagnosis. Currently, there is no effective cure for pSS and treatment options and targeted therapy approaches are limited due to a lack of our overall understanding of the disease etiology and its underlying pathology. To better elucidate the underlying molecular nature of this disease, we have performed RNA-sequencing to generate a comprehensive global gene expression profile of minor salivary glands from an ethnically diverse cohort of patients with pSS. Gene expression analysis has identified a number of pathways and networks that are relevant in pSS pathogenesis. Moreover, our detailed integrative analysis has revealed a primary Sjögren's syndrome molecular signature that may represent important players acting as potential drivers of this disease. Finally, we have established that the global transcriptomic changes in pSS are likely to be attributed not only to various immune cell types within the salivary gland but also epithelial cells which are likely playing a contributing role. Overall, our comprehensive studies provide a database-enriched framework and resource for the identification and examination of key pathways, mediators, and new biomarkers important in the pathogenesis of this disease with the long-term goals of facilitating earlier diagnosis of pSS and to mitigate or abrogate the progression of this debilitating disease.


Lagrangian tracking of long-lasting plastic tags: From lobster fisheries in the USA and Canada to Macaronesia.
Plastic waste from the fishing industry, particularly lobster trap identification tags from the USA and Canada, poses a significant threat to marine ecosystems due to its resilience. This study unveils a novel link between North American fisheries and the appearance of these plastic tags in Macaronesia. Collected in the Azores and Canary Islands, these tags offer a unique insight into the sources and spatio-temporal scales of marine plastic pollution. Ocean model data indicates the Labrador Current and Gulf Stream as key forces transporting these tags. Virtual particle simulations show a small fraction reaching Macaronesia (4.12 % in the Azores, 0.76 % in the Canary Islands), suggesting real ocean drift. The Azores, with more collected tags, are more susceptible, and tags can reach Macaronesia in under a year. These findings underscore the urgency of better waste management and emphasize the role of citizen science in monitoring and combating marine pollution.


Comparison of self-reported pain and the PAINAD scale in hospitalized cognitively impaired and intact older adults after hip fracture surgery.
The purpose of this study was a psychometric evaluation of the PAINAD to assess pain in hospitalized cognitively impaired and intact older adults admitted for surgical repair of a hip fracture. A descriptive correlational design was used. A convenience sample of older patients hospitalized for surgical repair of a hip fracture was used. Twelve of the patients had cognitive impairment and 13 were cognitively intact. All were assessed for pain using both the self-report numeric rating scale and an observational assessment tool, the PAINAD. A positive correlation was found between the PAINAD and a self-report pain scale, providing evidence of concurrent validity. PAINAD scores were higher when patients were likely to experience pain than when unlikely, providing evidence of discriminant validity. The results of this study provide evidence supporting the validity and reliability of the PAINAD in the pain assessment of hospitalized post-orthopaedic surgical older adults who are unable or reluctant to self-report pain.


Empirical assessment of whether moderate payments are undue or unjust inducements for participation in clinical trials.
Paying patients to participate in clinical trials is ethically controversial. However, there has been no empirical documentation regarding whether payment represents an undue or unjust inducement. To evaluate these questions, we described hypothetical placebo-controlled trials of a new antihypertensive drug to 126 patients with mild-to-moderate hypertension recruited from hypertension and general medicine clinics at a university hospital. Using a 3 x 3, within-subjects design, we altered a risk to participation (either adverse effect rate or rate of randomization to placebo) and the payment participants would receive ($100, $1000, and $2000) and asked patients to indicate their willingness to participate (WTP) in each trial using a 6-point scale. Clustered ordinal logistic regression models revealed that patients' WTP decreased with higher risk of adverse effects (P<.001), higher risk of being assigned to placebo (P =.02), and lower payment level (P<.001). There were no significant interactions between payment level and either risk variable, suggesting that increasing payments do not alter peoples' perceptions of risk. There was a trend toward a positive interaction between income and the influence of payment on WTP (P =.09), suggesting that payment more strongly influences WTP among wealthier people. Wealthier patients were more likely to state that payment was important in their participation decision (37% vs 20%, P =.05). Although higher payment motivates research participation, we found no evidence that commonly used payment levels represent undue or unjust inducements.


Traumatic pathology of the thoracic aorta. Personal experience based on 42 cases.
Between 1974 and 1989, 42 patients have been operated on at the Istituto di Chirurgia Generale e Cardiovascolare of University of Milan, for traumatic pathology of the thoracic aorta: in 14 cases it occurred an acute rupture at the level of aortic isthmus and in 28 cases a posttraumatic fals aneurysm. We had an operative mortality of 28% (4 cases) in the acute rupture: 3 patients died for neurological complications which were present at hospitalization. In one case appeared a serious ARDS. We had no surgical deaths in patients operated on for the posttraumatic false aneurysm. In 15 cases, the patients suffered for a postoperative paraplegia. Surgical indications are discussed, overall for the posttraumatic false aneurysms. The authors consider the advantage and the risks of the use of ECC and of total heparinization of the patients.


Expressed sequence tags from poplar wood tissues--a comparative analysis from multiple libraries.
Xylogenesis involves successive developmental processes--cambial division, cell expansion and differentiation, cell death--each occurring along a gradient from the cambium to the pith of the stem. Taking advantage of the high level of organisation of wood tissues, we isolated cambial zone (CZ), differentiating xylem (DX) and mature xylem (MX) from both tension wood (TW) and opposite wood (OW) of bent poplars. Four different cDNA libraries were then constructed and used to generate 10,062 EST, reflecting the genes expressed in the different wood tissues. For the most abundant clusters, the EST distributions were compared between libraries in order to identify genes specific or over-represented at some specific developmental stages. They clearly showed a developmental shift between CZ and DX, whereas there is a continuity of development between DX and MX. CZ was mainly characterized by clusters of genes involved in cell cycle, protein synthesis and fate. Interestingly, two clusters with no assigned function were found specific to the cambial zone. In DX and MX, clusters were mostly involved in methylation of lignin precursors and microtubule cytoskeleton. In addition, in DX, EST from TW and OW were compared: five clusters of arabinogalactan proteins, one for sucrose synthase and one for fructokinase were specific or over-represented in TW. Moreover, a putative transcription factor and a cluster of unknown function were also identified in DX-TW. The informative comparison of multiple libraries prepared from wood tissues led to the identification of genes--some with still unknown functions--putatively involved in xylogenesis and tension wood formation.


Bioinformatics Analysis of the Expression of Key Long Intergenic Non-Protein Coding RNA Genes in Bladder Cancer.
BACKGROUND Evidence indicates that there is an important role for long non-coding RNAs (lncRNA) in numerous cellular processes and that lncRNAs dysregulation contributes to tumor progression. Improved insight into the molecular characteristics of bladder cancer is required to predict outcomes and to develop a new rationale for targeted therapeutic strategies. Bioinformatics methods, including functional enrichment and network analysis combined with survival analysis, are required to process a large volume of data to obtain further information about differentially expressed genes (DEGs) in bladder cancer. This study aimed to explore the role of lncRNAs and their regulation network in bladder cancer. MATERIAL AND METHODS We analyzed bladder cancer data by The Cancer Genome Atlas profiling to identify differentially expressed lncRNAs in bladder cancer. The genes involved in the circlncRNAnet database were evaluated using Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Ontology (GO), evolutionary relationship analysis, and protein-protein interaction (PPI) networks. RESULTS Two new lncRNAs, ADAMTS9-AS1 and LINC00460, were shown to be differentially expressed in bladder cancer. Patients were divided into 2 groups (high expression and low expression) according to their median expression values. The overall survival and disease-free survival of patients with high ADAMTS9-AS1 bladder cancer were significantly shorter; the expression of LINC00460 had no significant correlation with survival. GO and KEGG analysis of the 2 lncRNA-related genes revealed that these lncRNAs played a vital role in tumorigenesis. Bioinformatics analysis showed that key genes related to LINC00460, including CXCL, CCL, and CSF2, may be related to the development of bladder cancer. The low expression of ADAMTS9-AS1 may influence the survival rate of bladder cancer with the hub gene as a target. CONCLUSIONS LncRNA, including LINC00460 and ADAMTS9-AS1, might play a crucial role in the biosynthesis network of bladder cancer. Differential expression results of ADAMTS9-AS1 suggests it may be correlated with a worse prognosis and a shorter survival time. We outlined the biosynthesis network that regulates lncRNAs in bladder cancer. Further experimental data is needed to validate our results.


Birth order and risk of hepatocellular carcinoma in chronic carriers of hepatitis B virus: a case-control study in The Gambia.
Early age at infection with Hepatitis B virus (HBV) increases the risk of chronic infection. Moreover, early HBV infection may further independently increase the risk of hepatocellular carcinoma (HCC) beyond its effect on chronicity. The distribution of birth order, a proxy for mode and timing of HBV transmission, was compared in The Gambia between hepatitis B surface antigen (HBsAg)-positive HCC cases recruited from hospitals (n = 72) and two HBsAg-positive control groups without HCC: population-based controls from a community HBV screening (n = 392) and hospital-based controls (n = 63). HCC risk decreased with increasing birth order in the population-based case-control analysis. Using first birth order as the reference, the odds ratios were 0.52 (95% CI: 0.20-1.36), 0.52 (0.17-1.56), 0.57 (0.16-2.05) and 0.14 (0.03-0.64) for second, third, fourth and greater than fourth birth order respectively (P = 0.01). A similar inverse association was observed in the hospital-based case-control comparison (P = 0.04). Compared to controls, HCC cases had earlier birth order, a proxy for young maternal age and maternal HBV viraemia at birth. This finding suggests that in chronic HBV carriers perinatal mother-to-infant transmission may increase HCC risk more than horizontal transmission. Providing HBV vaccine within 24 h of birth to interrupt perinatal transmission might reduce the incidence of HCC in The Gambia.


Molecular dynamics and free energy studies on the wild-type and mutated HIV-1 protease complexed with four approved drugs: mechanism of binding and drug resistance.
The current strategy to improve the quality of life of Human Immunodeficiency Virus (HIV) infected individuals through suppressing viral replication and maintaining the virus at low to undetectable levels is based on highly active antiretroviral therapy (HAART). Protease inhibitors are essential components of most HAART protocols and are often used as the first line of treatment. However, a considerable percentage of new HIV-1 infections are caused by viruses carrying antiretroviral drug-resistant mutations. In this paper molecular dynamics, docking simulations, and free energy analysis of mutated HIV protease complexes were used to estimate the influence of different drug resistance-associated mutations in lopinavir, amprenavir, saquinavir, and atazanavir protease recognition. In agreement with virological and clinical data, the structural analysis showed that the single mutations V82A, I84V, and M46I are associated with higher energetic values for all analyzed complexes with respect to wild-type, indicating their decreased stability. Interestingly, in atazanavir complexes, in the presence of the L76V substitution, the drug revealed a more productive binding affinity, in agreement with hypersusceptibility data.


Growth and energetics of Leuconostoc mesenteroides NRRL B-1299 during metabolism of various sugars and their consequences for dextransucrase production.
The metabolic and energetic properties of Leuconostoc mesenteroides have been examined with the goal of better understanding the parameters which affect dextransucrase activity and hence allowing the development of strategies for improved dextransucrase production. Glucose and fructose support equivalent specific growth rates (0.6 h-1) under aerobic conditions, but glucose leads to a better biomass yield in anaerobiosis. Both sugars are phosphorylated by specific hexokinases and catabolized through the heterofermentative phosphoketolase pathway. During sucrose-grown cultures, a large fraction of sucrose is converted outside the cell by dextransucrase into dextran and fructose and does not support growth. The other fraction enters the cell, where it is phosphorylated by an inducible sucrose phosphorylase and converted to glucose-6-phosphate (G-6-P) by a constitutive phosphoglucomutase and to heterofermentative products (lactate, acetate, and ethanol). Sucrose supports a higher growth rate (0.98 h-1) than the monosaccharides. When fructose is not consumed simultaneously with G-1-P, the biomass yield relative to ATP is high (16.8 mol of ATP.mol of sucrose-1), and dextransucrase production is directly proportional to growth. However, when the fructose moiety is used, a sink of energy is observed, and dextransucrase production is no longer correlated with growth. As a consequence, fructose catabolism must be avoided to improve the amount of dextransucrase synthesized.


SYCP2 and SYCP3 are required for cohesin core integrity at diplotene but not for centromere cohesion at the first meiotic division.
Much of the organization of the meiotic prophase-I chromosome axis is attributed to two groups of proteins: the axial element proteins, SYCP2 and SYCP3; and the cohesin-complex proteins. Although the cohesin-complex proteins ensure that sister chromatids remain paired during meiosis, the role of SYCP2 and SYCP3 is not clear. Interestingly, it has been shown that SYCP3 and SYCP2 associate with the centromere regions of male, but not female, metaphase-I chromosomes, suggesting a sex-specific function for the two proteins. We have analysed the spatial distribution of cohesin-complex proteins associated with meiotic chromosomes in germ cells derived from Sycp3-deficient female and male mice. We show that, in the absence of SYCP3, the cohesin cores associated with the female meiotic chromosomes disassemble prematurely at the diplotene stage of meiosis. We also show that SYCP3 and SYCP2 are not required for centromere cohesion at the metaphase-I stage in male germ cells. We conclude that SYCP3 has a temporally restricted role in maintaining, but not establishing, cohesin-core organization during prophase I. This finding supports a model in which the removal of bulk cohesin from paired sister chromatids at late prophase in both meiotic and mitotic cells ensures proper chromosome compaction and segregation.


[Progressive multifocal leukoencephalopathy in patients with AIDS: is there a change in patients treated with highly active antiretroviral therapies?].
Progressive multifocal leukoencephalopathy (PML) develops in up to 4-8% of all AIDS patients. Before highly active antiretroviral therapies (HAART) the median survival was only 4-6 months. In this study we analyzed epidemiological parameters in AIDS-related LMP patients in search for differences in the incidence and prognosis between before and after HAART era. Retrospective review of clinical histories of patients diagnosed of AIDS and PML at Hospital Meixoeiro in Vigo, Spain, between 01/01/94-31/05/97 (Before-HAART period) and 01/06/97-30/04/00 (After-HAART period). PML was diagnosed by clinical and neuroimaging criteria, with biopsy in 2 cases and positive JC virus hibridation in CSF in another case. We identified 12 patients (global prevalence of 3.8%, without differences between periods): 11 males, 10 intravenous drugs users (IDU), mean age of 38 years (31-43). In 6, LMP was the first opportunistic infection. When PML was diagnosed, 6 patients had a HIV viral load (VL) > 250.000 copies of RNA/ml (range, 254.003-3.170.000), and overall a mean CD4 lymphocytes counts of 89 x 10(6)/ml (40-134). Three patients received cytarabine + Interferon with zidovudine (2 patients) and zidovudine + lamivudine (1 patient) and other patient HAART + cidofovir, but no improvement was observed. The median survival was 10 months in before-HAART group and 17 months in after-HAART group, with a survival > 48 months in 2 patients in the last group. LMP is observed in severely immunosuppressed IDU men (VL > log 5 copies RNA/ml and CD4 < 150 x 106/ml). Complementary treatments were ineffective and only in patients with HAART a prolonged survival was observed.


Learning disability and oligodendrocyte myelin glycoprotein (OMGP) gene in neurofibromatosis type 1.
Neurofibromatosis type 1 (NF1) is an autosomal dominant disease where phenotypic heterogeneity is explained by the effect of modifier genes. Thirty to 65% of patients have learning disability. The oligodendrocyte myelin glycoprotein (OMGP) gene located within the neurofibromatosis type 1 (NF1) gene might affect the phenotype of learning disability because it is expressed in the brain, and OMGP gene mutations have been associated with cognitive disturbances. We analyzed the OMGP gene in NF1 patients with and without learning disability (n = 50 each) and healthy controls (n = 100). The allele distribution of OMGP62 polymorphism was not significantly different between the groups (p = 0.447). These results do not support a relationship between the OMGP gene and the learning disability phenotype observed in NF1. Other modifying genes, post-translational modifications or receptor interactions might be involved in the phenotypic variability of NF1.


A comparison of three fermentation methods for the confirmation of Neisseria gonorrhoeae.
When confirming suspected isolates of Neisseria gonorrhoeae, laboratories use a fluorescent antibody method or a fermentation technique, usually the cystine-trypticase agar (CTA) semisolid. Suspected N. gonorrhoeae from sites such as the throat, rectum, and blood require this confirmation. The modified rapid fermentation test (MRFT) was compared with the standard CTA and the Mueller-Hinton agar (MHA) slant methods. The MRFT appeared to have greater sensitivity than the other two methods, and results could be obtained within a 4-hour period as compared with overnight for the other two methods. The MRFT gave quicker results with greater sensitivity than either the MHA slant or the CTA semi-solid techniques.


Educational Video Addition to the Bariatric Surgery Informed Consent Process: a Randomized Controlled Trial.
Bariatric surgery is not a risk-free procedure and requires lifelong patient compliance in the postoperative period. Although the risks involved in bariatric surgery and the importance of lifelong follow-ups in the postoperative period are explained to patients in detail through verbal and written informed consent, the strong desire for weight loss can sometimes cause patients and their families to be ignorant of the mentioned issues preoperatively. The objective of this study is to evaluate the effectiveness of preoperative informational videos at improving the comprehension of informed consent content in bariatric surgery candidates. A total of 74 bariatric surgery candidates were randomized into two groups. The first group was given a usual verbal-written informed consent. The second group got an additional informing video presentation informed consent, in addition to the usual verbal-written informed consent. Then, both groups got a questionnaire evaluating their knowledge of bariatric surgery informed consent. The correct response scores and their relationship with patient demographics were analyzed. Both groups had similar demographic features. Video-presented group had higher scores in questionnaire (11.3 ± 2.3 versus 9.4 ± 1.7, p = 0.001). Subgroup analysis showed that health care workers (12.5 ± 1.9 versus 10.3 ± 2.2, p = 0.005) and university graduates (11.6 ± 2.4 versus 10.1 ± 2.1, p = 0.03) got better results in the questionnaire. In multivariate analysis, video-assisted informing was found to be the only independent variable for high questionnaire scores (p = 0.0001). This study showed that video-assisted informed consent improves patients' comprehension prior to bariatric surgery. We recommend routine preoperative video-assisted informing for bariatric surgery candidates in addition to usual verbal-written informed consent.