Enzymatic modification of pectin to increase its calcium sensitivity while preserving its molecular weight.
A commercial high-methoxy citrus pectin was treated with a purified salt-independent pectin methylesterase (PME) isozyme isolated from Valencia orange peel to prepare a series of deesterified pectins. A series of alkali-deesterified pectins was also prepared at pH 10 under conditions permitting beta-elimination. Analysis of these pectins using high-performance size exclusion chromatography (HPSEC) with on-line multiangle laser light-scattering, differential viscometer, and refractive index (RI) detectors revealed no reduction in weight-average molecular weight (M(w); 150000) in the PME-treated pectin series, whereas a 16% reduction in intrinsic viscosity (IV) occurred below a degree of esterification (DE) of 47%. In contrast, alkali deesterification rapidly reduced both M(w) and IV to less than half of that observed for untreated pectin. PME treatment of a non-calcium-sensitive citrus pectin introduced calcium sensitivity with only a 6% reduction in the DE. Triad blocks of unesterified galacturonic acid were observed in (1)H nuclear magnetic resonance spectra of this calcium-sensitive pectin (CSP). These results demonstrate that the orange salt-independent PME isozyme utilizes a blockwise mode of action. This is the first report of the preparation of a CSP by PME treatment without significant loss of the pectin's M(w) due to depolymerization.


[Analysis of patient flow by radiology information system].
HIS (hospital information system) and PACS (picture archiving and communication system) have become widely popular in clinical offices, and use of RIS (radiology information system) in the department of radiology has spread, creating networking between HIS, PACS, and diagnostic systems. RIS receives patient data and order data from HIS and sends them to the diagnostic systems. On the other hand, the RIS sends the implementation record and accounting data to HIS. When receiving and transmitting of these data are done by the RIS, the event's time is recorded in the RIS as attendant data. This paper proposes a way to analyze patient flow from the records of the event's time. The method counts the number of the accepted examinations y(i) (i = 0, 1, ... N) and the completed examinations z(i) every divided time t from the RIS work list, and computes the following three characteristic values related to patient flow. Those values are average expended time T; T = ( Sigma z(i ) i t - Sigma y(i ) i t ) / Sigma y(i) ,number of exam queue q(i); q(i) = Sigma y(i) - Sigma z(i) , and dissolved time of queue w(i); w(i) = q(i ) ( t / z(i) ). The method analyzes patient flow of radiology using these characteristic values. It also performs a simulation of the flow in cases of equipment trouble.


Left ventricular performance indices by transesophageal Doppler.
The purpose of this study was to assess whether blood flow velocity signals, obtained by esophageal continuous-wave Doppler, reflect changes in ventricular performance. Ventricular performance has previously been determined by analysis of blood flow velocity signals sampled in the ascending aorta. In this investigation velocity signals were acquired from the descending aorta, with the use of an esophageal Doppler transducer. Maximum blood flow velocity (Vm), maximum blood flow volume acceleration (Accv), and maximum linear blood flow acceleration (Acc) were the velocity signals used to evaluate left ventricular performance. Twenty-six patients scheduled for myocardial revascularization and anesthetized with fentanyl (50 micrograms/kg) and pancuronium (0.15 mg/kg) were studied. In seven patients (Group I) a good correlation (r = 0.91) was observed between Accv in the ascending and descending aorta. In 10 patients (Group 2), halothane (0.5 and 1.0 MAC end-tidal) was added to the anesthetic. At these halothane concentrations Vm, Accv, and Acc measured in the descending aorta remained unchanged. Decreases were noted in the product of mean arterial pressure (MAP) and Acc (P-Acc; decreased 20% at 0.5 MAC and 39% at 1 MAC) and the product of systemic vascular resistance and Acc (R-Acc; decreased 25% at 1 MAC). In nine patients (Group 3), phenylephrine was used to reverse the decrease in MAP induced by 1 MAC halothane. Under these conditions Vm, Accv, Acc, and P-Acc showed similar decreases (approximately 30% of baseline values), whereas R-Acc returned to baseline values. In summary, indices of blood flow in the descending aorta were easily determined with a commercial transesophageal continuous-wave Doppler device. Descending and ascending aortic blood flow Accv correlated well, and the changes in the product of MAP and Acc in the descending aorta reflected the anticipated, halothane-induced, changes in left ventricular performance. In conclusion, descending aortic blood flow acceleration contains information on left ventricular performance that can be derived by the minimally invasive transesophageal Doppler technique.


Effects of Myo-inositol Alone and in Combination with Seleno-Lmethionine on Cadmium-Induced Testicular Damage in Mice.
Cadmium (Cd) impairs gametogenesis and damages the blood-testis barrier. As the primary mechanism of Cd-induced damage is oxidative stress, the effects of two natural antioxidants, myo-inositol (MI) and seleno-L-methionine (Se), were evaluated in mice testes. Eighty-four male C57 BL/6J mice were divided into twelve groups: 0.9% NaCl (vehicle; 1 ml/kg/day i.p.); Se (0.2 mg/kg/day per os); Se (0.4 mg/kg/day per os); MI (360 mg/kg/day per os); MI plus Se (0.2 mg/kg/day); MI plus Se (0.4 mg/kg/day); CdCl2 (2 mg/kg/day i.p.) plus vehicle; CdCl2 plus MI; CdCl2 plus Se (0.2 mg/kg/day); CdCl2 plus Se (0.4 mg/kg/day); CdCl2 plus MI plus Se (0.2 mg/kg/day); and CdCl2 plus MI plus Se (0.4 mg/kg/day). After 14 days, testes were processed for biochemical, structural and immunohistochemical analyses. CdCl2 increased iNOS and TNF-α expression and Malondialdehyde (MDA) levels, lowered glutathione (GSH) and testosterone, induced testicular lesions, and almost eliminated claudin-11 immunoreactivity. Se administration at 0.2 or 0.4 mg/kg significantly reduced iNOS and TNF-α expression, maintained GSH, MDA and testosterone levels, structural changes and low claudin-11 immunoreactivity. MI alone or associated with Se at 0.2 or 0.4 mg/kg significantly reduced iNOS and TNF-α expression and MDA levels, increased GSH and testosterone levels, ameliorated structural organization and increased claudin-11 patches number. We demonstrated a protective effect of MI, a minor role of Se and an evident positive role of the association between MI and Se on Cd-induced damages of the testis. MI alone or associated with Se might protect testes in subjects exposed to toxicants, at least to those with behavior similar to Cd.


Drug profile: transdermal rivastigmine patch in the treatment of Alzheimer disease.
Cholinesterase inhibitors constitute one of the mainstays of treatment of Alzheimer disease (AD). Gastrointestinal side effects, difficulty accessing therapeutic doses and poor patient compliance have been identified as barriers to effective treatment with these substances. The rivastigmine transdermal patch provides continuous delivery of drug through the skin into the bloodstream, avoiding the fluctuations in plasma concentration associated with oral administration. This pharmacokinetic profile is associated with reduced side effects, resulting in easier access to expected target doses. These benefits, along with other practical advantages of the transdermal patch, may contribute to enhanced patient compliance. Here, we present a review of the current literature on rivastigmine patch, and offer advice based on our own collective clinical experience. Rivastigmine patch provides an efficient option for managing patients with AD, to be considered among the first line therapies for the disease.


Therapeutic effects of 1,25-dihydroxyvitamin D3 on diabetes-induced liver complications in a rat model.
It has been suggested that 1,25-dihydroxyvitamin D3 (vitamin D) plays a protective role against inflammation and insulin resistance (IR) in type 2 diabetes mellitus (T2DM). The present study investigate the hypothesis that vitamin D may exert beneficial effects on the liver in a rat model of T2DM by regulating the expression of inflammation-related cytokines and ameliorating IR induced by inflammation. Normal control group rats were fed a basic diet (NC). Experimental rats received a high-fat diet for 8 weeks and were then injected with streptozotocin (STZ) to induce T2DM. Half of the T2DM model rats received vitamin D (0.03 µg/kg/day) for 8 weeks (vitamin D-treated group; VD; n=11), while the other (T2DM group; DM; n=10) and NC group received an equivalent quantity of peanut oil. Following sacrifice, fasting plasma glucose (FPG) and fasting insulin (FINS) were recorded and homeostasis model assessment of IR (HOMA-IR) was calculated. Liver histopathology was examined using hematoxylin and eosin staining. The levels of the inflammatory cytokines C-Jun N-terminal kinase, C-Jun, tumor necrosis factor-α and interleukin-1β were measured using immunohistology, quantitative polymerase chain reaction and western blot analyses. The results revealed that treatment with vitamin D markedly alleviated the pathological alterations of liver and reduced the expression of inflammatory cytokines at the protein and mRNA levels. Furthermore, decreased levels of FPG, HOMA-IR and increased FINS were detected. In conclusion, the results of the present study indicate that vitamin D has therapeutic effects on diabetes-induced liver complications in T2DM model rats, which may involve the modulation of the inflammatory response, attenuating the crosstalk' between inflammation and IR and ameliorating hyperglycemic state.


Interactive simulator for e-Learning environments: a teaching software for health care professionals.
There is an established tradition of cardiovascular simulation tools, but the application of this kind of technology in the e-Learning arena is a novel approach. This paper presents an e-Learning environment aimed at teaching the interaction of cardiovascular and lung systems to health-care professionals. Heart-lung interaction must be analyzed while assisting patients with severe respiratory problems or with heart failure in intensive care unit. Such patients can be assisted by mechanical ventilatory assistance or by thoracic artificial lung."In silico" cardiovascular simulator was experimented during a training course given to graduate students of the School of Specialization in Cardiology at 'Sapienza' University in Rome.The training course employed CARDIOSIM©: a numerical simulator of the cardiovascular system. Such simulator is able to reproduce pathophysiological conditions of patients affected by cardiovascular and/or lung disease. In order to study the interactions among the cardiovascular system, the natural lung and the thoracic artificial lung (TAL), the numerical model of this device has been implemented. After having reproduced a patient's pathological condition, TAL model was applied in parallel and hybrid model during the training course.Results obtained during the training course show that TAL parallel assistance reduces right ventricular end systolic (diastolic) volume, but increases left ventricular end systolic (diastolic) volume. The percentage changes induced by hybrid TAL assistance on haemodynamic variables are lower than those produced by parallel assistance. Only in the case of the mean pulmonary arterial pressure, there is a percentage reduction which, in case of hybrid assistance, is greater (about 40%) than in case of parallel assistance (20-30%).At the end of the course, a short questionnaire was submitted to students in order to assess the quality of the course. The feedback obtained was positive, showing good results with respect to the degree of students' learning and the ease of use of the software simulator.


CT assessment of jugular foramen dominance and its association with hand preference.
Three hundred and seven normal CT scans of the head were prospectively analysed to assess jugular foramen dominance. After assessment, hand preference was elicited. Of these, 276 were right-handed and 31 were left-handed. Of the right-handed patients: 180 had a larger jugular foramen on the right; 63 had a larger jugular foramen on the left; and in 33 no difference could be discerned. Of the left-handed patients: 11 had a larger jugular foramen on the right; 16 had a larger jugular foramen on the left; and in four no difference could be discerned. The results suggested a significant association between jugular foramen dominance and hand preference.


Clinical and electrocardiographic features of complete heart block after blunt cardiac injury: A systematic review of the literature.
The underlying mechanisms and temporal course of complete heart block (CHB) after blunt cardiac injuries (BCIs) are poorly understood, and a systematic analysis of available data is lacking. In this systematic review, PubMed was searched for publications of reported cases of CHB-BCI analyzing clinical findings, electrocardiographic features, temporal course, and outcomes. Case reports on CHB-BCI were available for 50 patients, mainly secondary to traffic or sport accidents. A fatal outcome occurred in 10 of 50 (20%) of patients, while a structural damage of the atrioventricular (AV) conductive system was evident in 4 of 8 (50%) of necropsy studies. Clinical manifestation of CHB-BCI occurred within 72 hours of injury in 38 of 47 (∼80%) of patients, and 1:1 AV conduction was restored within 7-10 days in about half of early survivors. Permanent pacemaker implantation was indicated in 22 of 42 (∼50%) of early survivors because of recurrent or permanent CHB. Cardiac troponins, when analyzed, were elevated in 12 of 13 (∼90%) of patients, and electrocardiographic features of aberrancy were present in 29 of 40 (>70%) of patients. In conclusion, CHB secondary to BCI is associated with 20% mortality mainly occurring in the early posttraumatic period and most of the deaths are due to or triggered by this malignant arrhythmia. Recurrent or permanent CHB requiring pacemaker implantation occurs in ∼50% of survivors. A structural damage of the AV conductive system can be found in 50% of necropsy studies.


Interface pressure measurements of support surfaces with subjects in the supine and 45-degree Fowler positions.
In the past 20 years there has been a dramatic increase in different types of support surfaces to reduce the incidence of pressure ulcers. The purpose of this study was to determine the effect of static air overlays (Sof-Care and Tendercloud), replacement mattresses (Dermarest and Therarest), and a standard hospital mattress on tissue interface pressures in healthy subjects. A convenience sample of 25 subjects had tissue interface measurements obtained under the sacrum and heel bony prominences on the five support surfaces in the supine and 45-degree Fowler's positions. A repeated measures analysis of variance (p < 0.05) indicated that the Dermarest, Therarest, Sof-Care, and Tendercloud support surfaces reduced pressure significantly under the sacral bony prominence compared with the standard hospital mattress. Heel interface pressure measurements were significantly higher than sacral interface pressure measurements. There was no significant difference between supine and 45-degree Fowler's positions with respect to tissue interface pressures.


Multiple equilibria binding treatment of lipid and detergent interactions with membrane proteins. Application to cytochrome c oxidase solubilized in cholate.
A modified multiple binding equilibria treatment is presented that allows determination of thermodynamic parameters of the interaction of phospholipids with integral membrane proteins solubilized in excess detergent. Lipid binding is modeled as a series of exchange reactions between lipid molecules and detergent molecules at the hydrophobic protein surface. A general equation is derived which expresses a relative association constant (K) and the total number of contact sites at the lipid-protein interface (N) in terms of experimentally measurable variables. A useful simplification of the general equation occurs when the amount of detergent is high relative to the total number of lipid binding sites in the sample. Computer simulations show that in cases we have examined there appears to be an experimentally accessible range of detergent to protein molar ratios where the approximation at high detergent is useful for analyzing experimental data. This model is used to examine the competition between cholate and spin-labeled phospholipids for the hydrophobic surfaces of bovine heart cytochrome c oxidase. We find, for example, that K = 12 +/- 2 for phosphatidylcholine relative to cholate (i.e., the cholate molecules are relatively easily displaced by membrane lipids). This helps to explain the experimental observation that cholate is an effective detergent both for solubilizing cytochrome c oxidase and for reconstituting this protein into a defined lipid bilayer environment. An excess of cholate readily displaces almost all of the native phospholipids, and the protein is dispersed in cholate micelles. However, when phospholipids are added back, the cholate molecules at the protein surface are replaced because of the higher relative binding of the phospholipids. Observed differences between the behavior of phosphatidylcholine and phosphatidylglycerol suggest that reconstitution in cholate is a selective process in which detergent molecules in localized areas on the protein surface are more readily displaced by certain phospholipids.


Survey on the working, training, and research conditions of resident physicians in internistic and rheumatological continuing education-BEWUSST.
Data on the training and continuing education situation of residents in the field of internal medicine and rheumatology are not available for Germany. For this reason, the Commission for Education and Training of the German Society of Rheumatology (DGRh) initiated the BEWUSST survey on the working, training and research conditions of residents in rheumatology. A total of 102 questions on the topics of working conditions in everyday professional life, continuing medical education and training, compatibility of career and family, compatibility of work and research, perspectives as a rheumatologist and practical activities were included in an online questionnaire. A total of 102 participants took part in the survey. Of the respondents 48.1% were satisfied with their professional situation, 40.2% of the participants were supervised by a specialist mentor and 54.9% were working as scientists during their work as a physician. A compatibility of family and career was possible for 34.7%. After completion of the residency 52.9% of the respondents aspired to a combined clinical and outpatient activity. Half of the trainee rheumatologists are satisfied with their professional activities, although mentoring of the assistants in training should be further improved. With respect to the desired combined clinical and outpatient activity, the existing options should be expanded or new professional fields of activity should be established, so that the specialty remains attractive for the upcoming generations.


Evaluating health management programmes over time: application of propensity score-based weighting to longitudinal data.
Health management programmes are generally evaluated as point treatment studies in which only a baseline and outcome measurement are used in the analysis, even when multiple observations for each individual are available. By summarizing observations into two distinct measurements the evaluator loses any ability to discern patterns of change in the outcome variable over time in relation to the intervention. There are several statistical models available to evaluate longitudinal data that are typically regression-like in form and designed to adjust for clustering at the individual level. Most evaluators of longitudinal studies tend to adjust for the effect of time-dependent confounding by including these covariates as independent variables in the model. However, this standard adjustment approach is likely to provide biased estimates. In this paper we describe the application of the propensity score-based weighting technique to longitudinal data to estimate the effect of treatment on an outcome. This method reweights each treatment pattern to represent the entire population at each time point and provides an unbiased treatment effect. We illustrate the technique using data from a disease management programme and demonstrate its superiority over standard analytical adjustments in correcting for time-dependent confounding for each time period under study.


Role of Shigella infection in endometriosis: a novel hypothesis.
Endometriosis is the presence of endometrial cells and stroma at ectopic sites outside the uterine cavity. The natural history of endometriosis is uncertain, its etiology unknown, the clinical presentation inconsistent, diagnosis difficult and the treatment poorly standardized. It causes significant morbidity due to pelvic pain and infertility among 15-25% of women during their reproductive age. The benign disease causes peritoneal inflammation, fibrosis, adhesions and ovarian cysts but displays features of malignancy, like neo-vascularization, local invasion and distant metastasis. Mechanical, hormonal, immunological, environmental and genetic factors have been implicated in its etiology but provide inconclusive explanations. Present study was carried out on ectopic and eutopic endometriotic tissue specimens collected during laproscopy/laprotomy from cases of endometriosis. mRNA was isolated from the tissues and converted to cDNA by RT and subsequently subjected to differential display Polymerase Chain Reaction using seven sets of arbitrary primers. A unique band was identified only in the ectopic endometriotic tissue, which was sequenced. BLAST search results revealed sequence homology to shigella bacterial DNA leading us to hypothesize that infection may be playing a role in the etiology of endometriosis. This is the first report implicating the role of bacterial infection in the etiology of endometriosis. Shigella is known to invade the mucosa of the colon through the feco-oral route causing Shigellosis. The pathogenesis of shigellosis involves inflammation, ulceration, haemorrhage, tissue destruction and fibrosis of the colonic mucosa resulting in abdominal pain and diarrhoea/dysentery, this is similar to the pathogenesis of endometriosis which also involves inflammation, haemorrhage, tissue destruction and fibrotic adhesions of the pelvic peritoneum resulting in abdominal pain and infertility. The non-motile shigella bacteria invade the deeper mucosal layers by travelling from cell to cell of colonic epithelium, reaching the lamina propria of the colonic mucosa. We propose that, by the same mechanism, the bacteria travel across the colon wall to reach the outer peritoneal surface of the colon, which is in close proximity to the posterior uterine surface in the Pouch of Douglas, the site which incidentally happens to be the commonest site of early endometriosis. Our hypothesis therefore proposes that shigella or shigella-like organisms may be the trigger for the initiation of immunological changes in the pelvic peritoneum causing endometriosis. Once the endometrial cells are implanted at ectopic sites they are sustained by hormones and angiogenic factors. Hence "Infection hypothesis" provides a novel explanation for the etiopathogenesis of endometriosis.


Clinical analysis and long-term treatment monitoring of 3 patients with glycogen storage disease type Ib.
To investigate the clinical and genetic characteristics of patients with glycogen storage disease type Ib (GSD Ib). This report retrospectively analyzed the clinical data of 3 patients with GSD Ib admitted into our hospital, and summarized their onset characteristics, clinical manifestations, related examinations and treatment as well as mutational spectrum. After gene sequencing, the diagnosis of GSD Ib was confirmed in all 3 patients. Five variants of SLC37A4 gene were detected, of which c. 572C > T was the common variant and c. 680G > A was a novel variant. The 3 cases of GSD Ib were mainly affected by liver enlargement, growth retardation, etc., and all had a history of repeated infections. At the onset, patients mainly manifested as mildly elevated alanine-aminotransferase (ALT), accompanied by decreased absolute neutrophil count (ANC), hypertriglyceridemia, and metabolic disorders (hypoglycemia, hyperlactic acidemia, metabolic acidosis, etc.). After long-term treatment by oral uncooked cornstarch, the abnormal liver enzymes gradually returned to normal, and metabolic abnormalities were basically controlled most of the time. With increasing age, ANC of 2 patients decreased progressively, whereas the times of infections was reduced. We reported 3 cases with GSD Ib and a novel SLC37A4 variant. The possibility of GSD type Ib should be kept on alert when a patient suffers recurrent infections, accompanied by hepatomegaly, elevated liver enzymes, hypoglycemia, dyslipidemia, and metabolic disorders.


Inhibition of experimental asthma by indoleamine 2,3-dioxygenase.
Epidemiological evidence points to the inverse relationship between microbial exposure and the prevalence of allergic asthma and autoimmune diseases in Westernized countries. The molecular basis for this observation has not yet been completely delineated. Here we report that the administration of certain toll-like receptor (TLR) ligands, via the activation of innate immunity, induces high levels of indoleamine 2,3-dioxygenase (IDO), the rate-limiting enzyme of tryptophan catabolism in various organs. TLR9 ligand-induced pulmonary IDO activity inhibits Th2-driven experimental asthma. IDO activity expressed by resident lung cells rather than by pulmonary DCs suppressed lung inflammation and airway hyperreactivity. Our results provide a mechanistic insight into the various formulations of the hygiene hypothesis and underscore the notion that activation of innate immunity can inhibit adaptive Th cell responses.


A Matlab-based toolbox for characterizing behavior of rodents engaged in string-pulling.
String-pulling by rodents is a behavior in which animals make rhythmical body, head, and bilateral forearm as well as skilled hand movements to spontaneously reel in a string. Typical analysis includes kinematic assessment of hand movements done by manually annotating frames. Here, we describe a Matlab-based software that allows whole-body motion characterization using optical flow estimation, descriptive statistics, principal component, and independent component analyses as well as temporal measures of Fano factor, entropy, and Higuchi fractal dimension. Based on image-segmentation and heuristic algorithms for object tracking, the software also allows tracking of body, ears, nose, and forehands for estimation of kinematic parameters such as body length, body angle, head roll, head yaw, head pitch, and path and speed of hand movements. The utility of the task and software is demonstrated by characterizing postural and hand kinematic differences in string-pulling behavior of two strains of mice, C57BL/6 and Swiss Webster.


Ethanol-related traits in mice selectively bred for differential sensitivity to methamphetamine-induced activation.
Acute drug stimulation has been proposed to be an endophenotype for drug abuse. The authors previously reported the short-term selective breeding of lines of mice for low (LMACT) and high (HMACT) stimulation to methamphetamine (MA). These mice were used to examine whether common genes influence the locomotor response to MA and ethanol. Additionally, the authors tested these mice for ethanol drinking, locomotor sensitization, and clearance. LMACT mice were less stimulated by ethanol and consumed more ethanol than HMACT mice, but the lines did not differ in ethanol-induced sensitization. A small difference in ethanol clearance rate (0.1 mg/ml/h) likely had little impact on behavior. Some common genes may influence the locomotor response to MA and ethanol, as well as ethanol drinking.


Plasma level of diethylcarbamazine in jirds and hamsters.
The relation between the dosage and plasma level of diethylcarbamazine (DEC) in jirds and hamsters was examined by gas-liquid chromatography. When the drug was given intraperitoneally to jirds at 100 mg/kg body weight, the plasma level rose rapidly and reached the maximum level (20-25 micrograms/ml) at 10 minutes and afterwards fell quickly to undetectable level at 4 hours. Even if larger dosage (300 mg/kg) was given, DEC was eliminated completely from the blood circulation within 8 hours. When the same dosages of DEC were given intraperitoneally, the DEC levels remained 2-4 hours longer in the blood of hamsters than in the blood of jirds. DEC given by stomach intubation at 100 mg/kg remained detectable much longer in hamsters (8 hrs) than in jirds (2 hrs). A repeated doses schedule did not show a tendency for the drug to accumulate. DEC was excreted in the urine and feces, but the total amount of drug excreted without metabolic changes was only about 8% of the given dosage. The majority of unmetabolized DEC was excreted in the urine within 0-12 hours.


Beta-thromboglobulin in antecubital vein blood in relation to history of a stroke.
The levels of beta-thromboglobulin (BTG) have been measured in the blood of 22 male and 22 female elderly patients who gave a past history of stroke, and in 31 males and 88 females of comparable age who gave no such history. Comparisons were made within and between the groups. In the stroke patients the relationship between BTG and age was not significant for either sex, nor was there a difference between the sexes. In the BTG/time from stroke relationship the females showed significantly higher levels the longer the time that had elapsed since the stroke, and this could not be explained solely by the factor of ageing. For males, on the other hand, there was a non-significant fall in BTG with days from stroke. In 'normal' subjects the BTG/age relationship was significant in females but not in males. No significant differences were demonstrated between the BTG/age relationships between the stroke and control groups and this was true for both sexes. The potential value of estimations of BTG in the elderly is discussed.


Loss or altered subcellular localization of p27 in Barrett's associated adenocarcinoma.
The cyclin-dependent kinase inhibitor p27 is a negative regulator of the cell division cycle. It is expressed at the highest levels during the quiescent (G0) and prereplicative (G1) phases, and its degradation is required for entry into the S phase. Because lack of p27 is associated with aggressive behavior in a variety of tumors of epithelial and lymphoid origin, we used immunohistochemistry and in situ hybridization to evaluate the expression of p27 in metaplastic and dysplastic Barrett's epithelium and to assess its prognostic significance in Barrett's associated adenocarcinoma (BAA) of the esophagus. In metaplastic Barrett's epithelium, p27 protein and mRNA were restricted to the superficial third of glands in all cases and extended to the lower third in 4 cases. In contrast, expression of p27 message and protein was both increased and full-thickness, in the 23 cases with high-grade dysplasia adjacent to BAA and in carcinoma in situ. Although all invasive carcinomas had elevated levels of p27 mRNA, 45 (83%) of 54 invasive carcinomas had low p27 protein levels (<50% positive tumor cells). Low p27 protein correlated with higher histological grade (P < 0.0001), depth of invasion (P = 0.0120), presence of lymph node metastasis (P = 0.05), and survival (P = 0.0197). In addition to the nuclear staining, cytoplasmic staining of p27 was noted in 11 of 23 (48%) of cases of dysplasia and in 14 of 54 (26%) adenocarcinomas and confirmed, in a subset of cases, by subcellular fractionation of protein lysates obtained from fresh tumor tissues. Cytoplasmic localization of p27 was also associated with decreased survival (P = 0.0239). Loss of p27 conferred poor prognosis independently of proliferative index, as assessed by Ki-67 (MIB-1) immunostaining, which was not significantly different in survivors versus nonsurvivors. These results show that: (a) distribution of p27 message and protein parallel one another in metaplastic and dysplastic Barrett's epithelium, suggesting transcriptional regulation of the gene in the nonneoplastic setting; (b) p27 is inactivated in the majority of BAA as a result of either post-transcriptional modification or altered subcellular localization; and (c) loss of the cell cycle inhibitor p27 is associated with parameters of aggressive behavior and unfavorable outcome in BAA.


Using metagenomics to show the efficacy of forest restoration in the New Jersey Pine Barrens.
The Franklin Parker Preserve within the New Jersey Pine Barrens contains 5000 acres of wetlands habitat, including old-growth Atlantic white cedar (or AWC; Chamaecyparis thyoides) swamps, cranberry bogs, and former cranberry bogs undergoing restoration into AWC forests. This study showed that the C-use efficiency was greater in the old-growth AWC soils than in soils from 8-year-old mid-stage restored AWC stands, which were greater than found in soil from 4-year-old AWC stands-the latter two stands being restored from long-term cranberry bogs. A metagenomic analysis of eDNA extracted from these soils showed that the C-cycle trends were associated with increases in the relative numbers of DNA sequences from several copiotrophic bacterial groups (Bacteroidetes and Proteobacteria), complex C-decomposing fungal groups (Sordiomycetes, Mortierellales, and Thelephorales), and collembolan and formicid invertebrates. All groups are indicators of successionally more advanced soils, and critical for soil C-cycle activities. These data suggest that the restoration activities studied are enhancing critical guilds of soil biota, and increasing C-use efficiency in the soils of restored habitats, and that the use of metagenomic analysis of soil eDNA can be used in the development of assessment models for soil recovery of wetlands following restoration.


[Molecular analysis of a copy of the novel mobile element Burdock and the region of its insertion into the cut locus of Drosophila melanogaster].
Molecular analysis of a copy of the novel mobile element burdock and its insertion region into the cut locus of Drosophila was performed. The burdock was shown to be a retrotransposon containing a single open reading frame (ORF). It does not contain domens coding for protease, RNAse H, reverse transcriptase, and integrase, which are required for transposition. However, multiple insertions of this copy of the mobile element into a definite region of the cut locus (hot site) were observed earlier. The polypeptide encoded by the burdock ORF contains two successive regions homologous to the proteins encoded by the ORF1 and ORF2 of the gypsy retrotransposon in N and C regions, respectively. The burdock insertion into this region of the cut locus interrupts its ORF, since the mobile element is transcribed in the opposite direction compared with the transcription in the locus. This is presumed to account for the arising of a lethal mutation. The hot site of this element integration into the locus corresponds to the recognition site of Drosophila topoisomerase II.


Co-option of a conserved host glutamine transporter facilitates aphid/Buchnera metabolic integration.
Organisms across the tree of life colonize novel environments by partnering with bacterial symbionts. These symbioses are characterized by intimate integration of host/endosymbiont biology at multiple levels, including metabolically. Metabolic integration is particularly important for sap-feeding insects and their symbionts, which supplement nutritionally unbalanced host diets. Many studies reveal parallel evolution of host/endosymbiont metabolic complementarity in amino acid biosynthesis, raising questions about how amino acid metabolism is regulated, how regulatory mechanisms evolve, and the extent to which similar mechanisms evolve in different systems. In the aphid/Buchnera symbiosis, the transporter ApGLNT1 (Acyrthosiphon pisum glutamine transporter 1) supplies glutamine, an amino donor in transamination reactions, to bacteriocytes (where Buchnera reside) and is competitively inhibited by Buchnera-supplied arginine-consistent with a role regulating amino acid metabolism given host demand for Buchnera-produced amino acids. We examined how ApGLNT1 evolved a regulatory role by functionally characterizing orthologs in insects with and without endosymbionts. ApGLNT1 orthologs are functionally similar, and orthology searches coupled with homology modeling revealed that GLNT1 is ancient and structurally conserved across insects. Our results indicate that the ApGLNT1 symbiotic regulatory role is derived from its ancestral role and, in aphids, is likely facilitated by loss of arginine biosynthesis through the urea cycle. Given consistent loss of host arginine biosynthesis and retention of endosymbiont arginine supply, we hypothesize that GLNT1 is a general mechanism regulating amino acid metabolism in sap-feeding insects. This work fills a gap, highlighting the broad importance of co-option of ancestral proteins to novel contexts in the evolution of host/symbiont systems.


Accuracy of pixel-based classification: application of different algorithms to landscapes of Western Iran.
Scenarios for monitoring land cover on a large scale, involving large volumes of data, are becoming more prevalent in remote sensing applications. The accuracy of algorithms is important for environmental monitoring and assessments. Because they performed equally well throughout the various research regions and required little human involvement during the categorization process, they appear to be resilient and accurate for automated, big area change monitoring. Malekshahi City is one of the important and at the same time critical areas in terms of land use change and forest area reduction in Ilam Province. Therefore, this study aimed to compare the accuracy of nine different methods for identifying land use types in Malekshahi City located in Western Iran. Results revealed that the artificial neural network (ANN) algorithm with back-propagation algorithms could reach the highest accuracy and efficiency among the other methods with kappa coefficient and overall accuracy of approximately 0.94 and 96.5, respectively. Then, with an overall accuracy of about 91.35 and 90.0, respectively, the methods of Mahalanobis distance (MD) and minimum distance to mean (MDM) were introduced as the next priority to categorize land use. Further investigation of the classified land use showed that good results can be provided about the area of the land use classes of the region by applying the ANN algorithm due to high accuracy. According to those results, it can be concluded that this method is the best algorithm to extract land use maps in Malekshahi City because of high accuracy.


Positive factors on survival of head and neck cancer of unknown primary: what the clinician can do.
Management of patients with head and neck cancer of unknown primary (HNCUP) is challenging. To provide a long-term analysis focusing on protective survival factors for clinical decision-making. Furthermore, the prognostic value of the current N classification system was evaluated. We retrospectively analyzed patients with HNCUP between 2003 and 2016. Univariate and multivariate analyses were used to investigate predictors of overall survival (OS). A primary tumor was found in 67 of 290 patients with suspected HNCUP, leaving after exclusion 141 HNCUP cases for analysis, who received multi-step therapy (MST) (n = 108) or single therapy (n = 28). Chemotherapy (CT) (n = 101), curative MST, ≤3 positive lymph nodes (LN) (n = 33), squamous cell carcinoma (SCC) (n = 123), HPV+ (n = 21), M0 (n = 70) increased OS by 21.8%, 24.4%, 12.7%, 6.8%, 18.7%, 29.6%, respectively. 5- and 10-year OS was 78.1%/66.6%. The number of metastatic LNs predicted OS is better than N classification. Aspects for clinical decision-making: Curative MST and SCC histology were the most significant predictors for improved OS. Categorizing LN into 1, 2-3, and >3 LNs was more significant than the traditional N classification. The addition of CT to curative MST has a stronger impact on survival than HPV and N classifications.


A standardized nomenclature for endogenous mouse mammary tumor viruses.
We propose a revised standardized nomenclature for endogenous mouse mammary tumor viruses based on characterization by molecular cloning techniques and genetic segregation data.


Legionnaires' disease diagnosed by bronchoalveolar lavage.
A 51-year-old woman who had been on steroid therapy for systemic lupus erythematosus (SLE) developed a high fever 3 days after visiting a hot spring resort. Chest X-ray films revealed an interstitial, pneumonia-like shadow in the left lung field, which increased rapidly with a worsening of her symptoms. She died of multiple organ failure one week after the onset of the pneumonia. Although the serum antibody titer was negative, Legionella pneumophila was recovered from her bronchoalveolar lavage (BAL) fluid. BAL seems to be a useful method to diagnose Legionnaires' disease.


Striatal mechanisms underlying movement, reinforcement, and punishment.
Direct and indirect pathway striatal neurons are known to exert opposing control over motor output. In this review, we discuss a hypothetical extension of this framework, in which direct pathway striatal neurons also mediate reinforcement and reward, and indirect pathway neurons mediate punishment and aversion.


The challenge of the approach to oral cancer in primary health care.
The aim of this study was to understand the performance of dentists in public health about mouth cancer. A cross-sectional study was performed whit 121 dentists from Fortaleza Health Department, interviewed through a semi-structured questionnaire. The study did not identify statistically significant difference regarding the ability to perform biopsy by gender, year of graduation, expertise or time of public service. Only 22 professionals (18.2%) reported being able to perform biopsies and 13 (10.7%) would do so at the Family Health Unit. The reference and counter-reference system, by including another stage in patient care, increase the possibility of absenteeism from patient to health service. Although clearly identify the relevance of oral cancer mortality in the population, the vast majority of dentists is not equipped to perform the biopsy as a routine activity. Whereas the vast majority of biopsies of the oral tissues is performed as an outpatient, low technological complexity to perform the procedure and the effectiveness of biopsy in the early diagnosis of oral cancer, it is essential to hold this procedure in primary care, what can effectively contribute to decreasing mortality from oral cancer.


Empty sella turcica in intracranial sarcoidosis. Pituitary insufficiency, primary polydipsia, and changing neuroradiologic findings.
A 37-year-old man with visual loss was found to have hypopituitarism and primary polydipsia associated with sarcoidosis. Neuroradiologic studies demonstrated a dramatic evolution of CNS lesions, including a left thalamic infarct, an enhancing suprasellar mass, and ultimately an empty sella turcica. The patient has been clinically stable in spite of these changes. This case is likely to be the first reported of CNS sarcoidosis with an empty sella turcica documented by computed tomography.


Vitamin C deficiency: rare cause of severe anemia with hemolysis.
Historically known to be a disease of sailors and soldiers in the seventeenth and eighteenth century, scurvy is a rare nutritional deficiency in the developed world, but it can still be seen among the alcoholics and the malnourished. We present a case of a 39-year-old alcoholic male who presented with progressive fatigue and diffuse purpuric rash with scattered ecchymosis for 2 months. Blood work was remarkable for hemoglobin of 9.1 g/dl, which further dropped to 7 g/dl over the next few days. He was then found to have hemolysis on lab work. After an extensive workup, the common causes of hemolytic anemia were ruled out, vitamin C level was checked, which interestingly resulted as 0 mg/dl. Supplementation with oral vitamin C resulted in the gradual resolution of hemolytic anemia and rash. Hemoglobin improved to 15 g/dl in 4 weeks, with normalization of vitamin C level. The clinical features of scurvy can easily be confused with conditions such as vasculitis, deep venous thrombosis, and systemic bleeding disorders. Therefore, comprehensive workup up is required prior to the diagnosis. Although rare, being a reversible condition, early diagnosis and treatment of scurvy in high-risk populations cannot be stressed enough.


Chronic pain, body mass index and cardiovascular disease risk factors: tests of moderation, unique and shared relationships in the Study of Women's Health Across the Nation (SWAN).
Chronic pain may be related to cardiovascular disease (CVD) risk. The current study examined whether persistent bodily pain was related to cardiovascular disease risk factors, whether these effects were moderated by body mass index (BMI), and, if not, whether chronic pain accounted for unique variance in CVD risk factors. Participants were women (N = 2,135) in the Study of Women's Health Across the Nation. A high pain frequency variable (high pain in 0 through 4 assessments) was coded to reflect the frequency of high levels of bodily pain across the first 3 years of the study. Six CVD risk factors and BMI were measured at follow-up year 3. High pain frequency and BMI were correlated significantly with risk factors, although effects for the former were small. Hierarchical multiple regressions revealed high pain frequency × BMI interactions for 5 of 6 CVD risk factors. Dissecting the interactions revealed a similar pattern across 4 risk factors: for women with normal BMI, there was a "dose-response" in which increasing frequency of high pain revealed increasingly worse CVD risk factor levels, whereas for women with obese BMI, high pain frequency was unrelated to risk factors. For obese women, increasing frequency of high pain was associated with higher blood glucose. Although BMI is a well-established CVD risk factor, evaluation of CVD risk level may be improved by considering the incidence of persistent pain, particularly in normal weight women (BMI < 25 kg/m(2)) lower BMI.


Intracellular mediators of JAM-A-dependent epithelial barrier function.
Junctional adhesion molecule-A (JAM-A) is a critical signaling component of the apical junctional complex, a structure composed of several transmembrane and scaffold molecules that controls the passage of nutrients and solutes across epithelial surfaces. Observations from JAM-A-deficient epithelial cells and JAM-A knockout animals indicate that JAM-A is an important regulator of epithelial paracellular permeability; however, the mechanism(s) linking JAM-A to barrier function are not understood. This review highlights recent findings relevant to JAM-A-mediated regulation of epithelial permeability, focusing on the role of upstream and downstream signaling candidates. We draw on what is known about proteins reported to associate with JAM-A in other pathways and on known modulators of barrier function to propose candidate effectors that may mediate JAM-A regulation of epithelial paracellular permeability. Further investigation of pathways highlighted in this review may provide ideas for novel therapeutics that target debilitating conditions associated with barrier dysfunction, such as inflammatory bowel disease.


Knowledge, attitudes, and likelihood of pre-exposure prophylaxis (PrEP) use among US women at risk of acquiring HIV.
Although the Food and Drug Administration (FDA) approved oral Truvada for pre-exposure prophylaxis (PrEP) for women at risk of HIV infection in the US in July 2012, and the Centers for Disease Control and Prevention (CDC) issued guidance for clinicians to provide PrEP to women "at substantial risk of HIV acquisition" in May 2014, there remain no clinical trial data on efficacy among US women, and there is a dearth of research on knowledge, attitudes, and likelihood of use of PrEP among them. We conducted a qualitative focus group (FG) study with 144 at-risk women in six US cities between July and September 2013, including locations in the Southern US, where HIV infections among women are most prevalent. FG questions elicited awareness of PrEP, attitudes about administration and uptake, and barriers to and facilitators of use. Women expressed anger at the fact that they had not heard of PrEP prior to the study, but once informed most found it attractive. PrEP was seen as additional, not substitute protection to condoms, and participants suggested several dissemination strategies to meet the diverse needs of women. Key barriers to PrEP uptake included distrust of the medical system, stigma, and cost. Findings suggest that US women view PrEP as an important prevention option, assuming side effects and the cost to the consumer are minimal, the efficacy of the drug is reasonable, and PrEP is delivered by trusted providers in trusted venues.


Soil chemistry and meteorological conditions influence the elemental profiles of West European wines.
Elemental profiles of wines have been used successfully to distinguish their geographical provenience around the world; however, underlying mechanisms are poorly understood. In this study, Ba, Ca, Mg, Mn and Sr contents were determined in 215 wines from several West European wine-growing areas using an easy-to-perform analysis based on ICP-OES. Major environmental and wine-making parameters (soil type as "calcareous" or not, rainfall, temperature and wine color) were used to explain variations within the dataset. The combined effects of wine-making processes (expressed by wine color) and soil type explained 28.5% of total variance. The effect of climatic conditions explained 24.1% of variance and could be interpreted as intensity of drought stress. Finally, carbonate occurrence in soils and climatic conditions systematically influenced the elemental composition of the wines. These findings provide insights into the mechanisms underlying elemental fingerprinting and allow prediction of which wine-growing regions can easily be distinguished based on elemental profiles as a marker of the terroir in viticulture.


Chemoselective reduction of α,β-unsaturated aldehydes using an unsupported nanoporous gold catalyst.
The remarkable effect of an unsupported nanoporous gold catalyst (AuNPore) on chemoselective hydrogenation of α,β-unsaturated aldehydes using silane has been described. Enals can be reduced with excellent selectivity, giving the corresponding allylic alcohols in good to high chemical yields.


Central line-associated bloodstream infection rate elevation: Attributable to National Healthcare Safety Network surveillance definition changes, ongoing opportunities for infection prevention, or both?
Calendar year 2015 intensive care unit (ICU) central line-associated bloodstream infections (CLABSIs) from 1 hospital were reviewed using 2014 CLABSI surveillance definitions to assess the relative impact of definition changes and infection control practices on CLABSI rates. Increased ICU primary CLABSI rates were found to be a result of both surveillance definition changes and infection control practices.


Cytomegalovirus antigenemia and outcome of patients treated with pre-emptive ganciclovir: retrospective analysis of 241 consecutive patients undergoing allogeneic hematopoietic stem cell transplantation.
CMV disease remains a major infectious complication after allogeneic hematopoietic stem cell transplantation (HSCT). To investigate the relationship between CMV antigenemia, treatment with ganciclovir (GCV), and outcome, we retrospectively analyzed 241 consecutive patients at risk for CMV infection who underwent allogeneic HSCT. Antigenemia-guided pre-emptive strategy with GCV was used for all patients. CMV antigenemia developed in 169 patients (70.1%), and CMV disease in 18 patients (7.5%). Multivariate analysis showed that acute GVHD (grades II-IV) was the only risk factor for developing antigenemia, and acute GVHD and advanced age for CMV disease. GCV use, as well as acute GVHD and advanced age, significantly increased the risk for bacterial and fungal infection after engraftment. Those who developed CMV antigenemia had a poorer outcome than those who did not (log-rank, P=0.0269), although the development of CMV disease worsened the outcome with only borderline significance (log-rank, P=0.0526). In conclusion, detection of antigenemia proved to be a poor prognostic factor for HSCT patients, which may be attributed to a combination of factors, including CMV disease itself, the effect of treatment, and a host status that allows for reactivation of CMV. Optimal pre-emptive strategy needs to be determined.


Oxidative stress increases A1 adenosine receptor expression by activating nuclear factor kappa B.
The A1 adenosine receptor (A1AR) contributes to the cytoprotective action of adenosine under conditions known to generate reactive oxygen species (ROS). Pharmacological manipulation of A1AR expression has been shown to modulate this cytoprotective role. In this study, we provide evidence that ROS generated could increase the expression of the A1AR and thereby offset the detrimental effects of ROS. Incubation of DDT1MF-2 smooth muscle cells with ROS-generating chemotherapeutic agents, such as cisplatin (2.5 microM) or H2O2 (10 microM), elicited an increase in A1AR expression within 24 hr. The induction by H2O2 was reduced by the ROS scavenger catalase but not superoxide dismutase. Inhibition of nuclear factor kappa B (NF kappa B) by pyrrolidine dithiocarbamate (200 microM), dexamethasone (100 nM), or genistein (1 microM) abrogated the cisplatin-mediated increase in A1AR. Cisplatin promoted rapid translocation of NF kappa B (but not AP-1) to the nucleus, as detected by electrophoretic mobility shift assays and by Western blotting. A putative NF kappa B sequence in the A1AR promoter effectively competed with labeled kappa B probe for binding in nuclear preparations derived from DDT1MF-2 cells. Transient transfection of DDT1MF-2 cells with the A1AR promoter coupled to firefly luciferase reporter gene led to cisplatin-inducible and pyrrolidine dithiocarbamate-sensitive luciferase activity, suggesting the presence of functional NF kappa B binding site(s) in the A1AR promoter sequence. Treatment of cells with (R)-phenylisopropyladenosine (1 microM), an agonist of the A1AR, reduced cisplatin-mediated lipid peroxidation, which was reversed after blockade of the A1AR. These data suggest that ROS can increase the expression of the A1AR by activating NF kappa B regulatory site(s) on this gene and thereby enhance the cytoprotective role of adenosine.


Pharmacological Modulation of Host Immunity with Hen Egg White Lysozyme (HEWL)-A Review.
In the 100 years since its discovery, lysozyme has become an important molecule, both as model for studies in different fields and as a candidate for the therapy of various pathological conditions. Of the dozens of known lysozymes, in this review we focus on one in particular, lysozyme extracted from hen egg white (HEWL), and its interaction with the immune system when it is administered orally. Experimental data show that there is an axis that directs immune system activation from GALT (gut-associated lymphoid tissue) and the intestinal lymphocyte clusters. Although a contribution of peptidoglycans from digestion of the bacterial cell wall in the intestinal lumen cannot be excluded, immune stimulation is not dependent on the enzymatic activity of HEWL. The immune responses suggest that HEWL is able to recover from immunodepression caused by tumor growth or immunosuppressants, and that it also improves the success of chemotherapy. The positive results obtained in a small Phase 2 study in patients, the ease of oral administration of this protein, and the absence of adverse effects suggest that HEWL may play an important role in all diseases where the immune system is weakened or where its enhancement plays a critical role in the resolution of the pathology.


[Alcohol, criminality, and personality].
It seems to be possible to affirm the existence of correlations between abuse of alcoholic drinks and the different forms of criminality. However other facts do exist in the determinism of the criminal acts. The psychological factors are important. The author wants to try to understand the role of alcohol in the passage of criminal acts of different types of personality.


Prognostic typing in breast cancer.
Infiltrating breast carcinomas in which recurrence takes place 10 years or more after operation are reported to contain tumour cells of characteristic morphology. The cytological features of these tumour cells form the basis of the system of classification described here. Three cytological types are recognized, prognosis being best in type III. Typing is carried out on specimens stained with haematoxylin and eosin. The results of typing were reproducible in over 90% of cases and independent of the histology of the lesion. Correlation to survival time was shown in a total of 222 cases.


Standardised 3D-CT lung volumes for patients with acute exacerbation of rheumatoid arthritis-associated interstitial lung disease.
Fibrotic interstitial lung disease (ILD) is a progressive lung disease characterised by loss of lung volume, resulting in a leading cause of death in patients with rheumatoid arthritis (RA). Crucially, acute exacerbation (AE) of ILD shows higher morbidity and mortality with rapid deterioration of the lungs. However, a quantitative assessment for physiological changes at AE has yet to be performed. This study hypothesised that quantitative assessments of lung volume (LV) accurately indicate disease severity and mortality risk in patients with AE-RA-ILD. This multicentre cohorts study quantitatively assessed physiological changes of RA-ILD at diagnosis (n = 54), at AE (Discovery-cohorts; n = 20, and Validation-cohort; n = 33), and controls (n = 35) using 3D CT (3D-CT) images. LV was quantitatively measured using 3D-CT and standardised by predicted forced vital capacity. Patients with RA-ILD at diagnosis showed decreased LV, predominantly in lower lobes, compared with controls. Further substantial volume loss was found in upper- and lower lobes at AE compared with those at diagnosis. During AE, decreased standardised 3D-CT LV was associated with a worse prognosis in both cohorts. Subsequently, standardised 3D-CT LV was identified as a significant prognostic factor independent of age, sex, and the presence of UIP pattern on CT by multivariate analyses. Notably, a composite model of age and standardised 3D-CT LV successfully classified mortality risk in patients with AE-RA-ILD. Volume loss at AE in patients with RA-ILD was associated with increased mortality. Assessing physiological change using standardised 3D-CT might help evaluate disease severity and mortality risk in patients with AE-RA-ILD.


Optimal haemoglobin during treatment with recombinant human erythropoietin.
The optimal target haemoglobin during treatment with recombinant human erythropoietin (r-HuEPO) is still controversial. The impact of haemoglobin on cardiovascular function or survival, on physical performance and on medical rehabilitation have to be taken into consideration. Although currently there is no solid evidence to show that haemoglobin beyond that recommended by the ad hoc committee of the National Kidney Foundation improves survival, sound theoretical arguments can be offered for this proposition, particularly in cardiac patients. It is sensible to individualize the target haemoglobin and to avoid rapid correction of anaemia.


An approach to pathogenesis of male infertility with anti-sperm antibodies.
To determine subsets and functional characteristics of peripheral blood lymphocytes in men with infertility associated with anti-sperm antibodies. Blood from 28 infertile men with anti-sperm antibodies and 34 fertile control males were tested for the lymphocyte subsets by indirect immunofluorescence and also for lymphocyte transformation responses to phytohemagglutinin (PHA), ConA, and pokeweed mitogen (PWM). Also studied were effects of seminal plasma on the lymphocyte transformation responses. Percentages of CD3, -4, and -8 cells and lymphocyte blastogenic responses to PHA and ConA were significantly lowered in patients. Percentage of B-cells, CD4/CD8 ratio, and blastogenic response to PWM were increased. All seminal plasmas suppressed lymphocyte blastogenesis induced by PHA, PWM, and ConA, but the suppressive effect on PHA and PWM by patients' plasma was less than that of controls. The results suggest that number and function of T-lymphocytes, especially CD8 cells, are lessened and those of CD4 and B-cells enhanced in the infertile patients. These factors would be conducive to development of an immunologic response to sperm.


Collective cell migration: a physics perspective.
Cells have traditionally been viewed either as independently moving entities or as somewhat static parts of tissues. However, it is now clear that in many cases, multiple cells coordinate their motions and move as collective entities. Well-studied examples comprise development events, as well as physiological and pathological situations. Different ex vivo model systems have also been investigated. Several recent advances have taken place at the interface between biology and physics, and have benefitted from progress in imaging and microscopy, from the use of microfabrication techniques, as well as from the introduction of quantitative tools and models. We review these interesting developments in quantitative cell biology that also provide rich examples of collective out-of-equilibrium motion.


In vivo and in vitro characteristics of eccrine sweating in patas and rhesus monkeys.
Biopsy specimens from the chest, palm, back, and lateral calf were obtained from three patas (4-6 kg) and two rhesus monkeys (6 and 8 kg) tranquilized with ketamine hydrochloride (10 mg/kg). The eccrine sweat glands of the specimens were subsequently isolated under a stereomicroscope and prepared for analysis. In both palmar and hairy skin (chest, lateral calf) patas eccrine glands were larger than those isolated from corresponding sites obtained from the rhesus specimens. In vitro stimulation of the patas' glands with methacholine (MCH) chloride produced a dose-dependent increase in sweating rate that was blocked by atropine. Maximal palmar sweating was comparable between the two species of monkey. Mean maximal in vitro sweating rates on the chest and lateral calf of the three patas monkeys were 3.79 and 4.6 nl. gl-1.min-1, respectively. In contrast, the in vitro sweating rate of the rhesus chest glands was negligibly small, i.e., 0.05 nl.gl-1. min-1. Maximal in vivo sweating rates measured by resistance hygrometry during exercise in a hot (40 degrees C) environment were usually synchronous, cyclic, and only slightly below maximal in vitro rates. When the monkey (patas) was already sweating, the onset and cessation of exercise produced an immediate rise and decline in sweating, respectively. At any given rectal or mean skin temperature, sweating was two- to sixfold higher in the patas compared with that of the rhesus monkey. These results indicate that the patas monkey is an excellent model for studying the physiology of sweating in humans.


Chronic high-frequency stimulation of the subthalamic nucleus and L-DOPA treatment in experimental parkinsonism: effects on motor behaviour and striatal glutamate transmission.
Hyperactivity of striatal glutamatergic synaptic transmission in response to dopamine depletion plays a major role in the pathogenesis of parkinsonian motor symptoms. In the present study we investigated the impact, on this hyperactivity, of chronic dyskinesiogenic L-DOPA treatment, combined or not with high-frequency stimulation (HFS) of the subthalamic nucleus (STN). In vitro patch-clamp recordings were performed from striatal spiny neurons of hemiparkinsonian rats (intranigral 6-OHDA injection). Here we show that dyskinesiogenic L-DOPA treatment exacerbated striatal glutamatergic hyperactivity induced by 6-OHDA lesion. Chronic 5-day STN HFS had the opposite effect, reducing striatal glutamatergic transmission in both parkinsonian and dyskinetic animals. Consistently, chronic HFS stimulation could progressively ameliorate motor parkinsonian signs (akinesia) but, conversely, did not improve L-DOPA-induced dyskinesia (LID). Thus, the effects of L-DOPA and HFS on corticostriatal transmission seem to be dissociated. These data show for the first time that dyskinesiogenic L-DOPA treatment and chronic STN HFS with antiakinetic effects induce opposite plastic rearrangements in the striatum. The interaction between these two treatments provides further evidence that striatal glutamatergic hyperactivity is a pathophysiological correlate of akinesia rather than LID.


Implementation of a regulatory food policy to reduce availability of energy-dense foods in Costa Rican high schools.
To assess the extent to which mandatory Guidelines to improve the school food environment were being implemented in Costa Rican high schools and to explore the perspectives of key policy actors towards the Guidelines. Semi-structured interviews and site observations. Interviews were recorded, transcribed verbatim and imported to NVivo 12 for analysis. Inductive and deductive themes were identified, and elements of the RE-AIM framework and the social process framework were used when classifying these themes. Sixteen public high schools in San José, Costa Rica. High school principal and kiosk concessionaires. Products that did not adhere to the Guidelines were still widely available in schools, and amongst the most prevalent challenges to implementation that emerged from our interviews, were a lack of understanding of the policy content, a lack of monitoring and accountability, and competing values amongst actors which affected their views on the role that the school must have in offering a healthy food environment. Most products offered in high schools did not meet the criteria required by the mandatory Guidelines, and several contextual factors were found to influence implementation. Strengthening the implementation of the Costa Rican Guidelines will require further actions at the governmental and school levels.


Effects of aging and caloric restriction on bone structure and mechanical properties.
This study examined the effects of caloric restriction on structural and material properties of tibiae and sixth lumbar vertebrae in F344BN male rats. Rats were divided into two dietary groups, ad libitum or calorie restricted. Caloric restriction commenced at 14 weeks of age, with 40% restriction and micronutrient supplementation by 16 weeks maintained until death. Rats were studied at 100% (8 months), 70% (30-35 months), and 35% (35-40 months) survival rates. Specimens were assessed using microcomputed tomography, mechanical testing, and ash analysis. A calorically restricted diet resulted in a significant decrease in total body mass when compared to ad libitum diet. Generally, direct comparisons between same-aged groups showed no significant changes in material properties, with significantly greater normalized-to-body-mass structural properties under caloric restriction. These results suggested a possible beneficial response to the calorically restricted diet where bone quality was maintained with bone quantity improved per unit body mass.


A promoter polymorphism of the alpha2-HS glycoprotein gene is associated with its transcriptional activity.
alpha2-Heremans Schmid glycoprotein (AHSG), also designated fetuin-A, is an abundant plasma protein that is expressed in hepatocytes. AHSG/fetuin-A has diverse biological functions including regulation of calcium homeostasis and inhibition of insulin receptor tyrosine kinase activity. The aim of this study was to detect single nucleotide polymorphisms (SNPs) of the AHSG gene that can be involved in regulation of AHSG/fetuin-A expression. By a cycle sequencing method, two common SNPs in the promoter region of AHSG gene, -799A/T (rs2248690, dbSNP ID) and -425G/T (rs2077119), were identified. A reporter gene assay using HepG2 cells showed that the -799A allele had significantly higher promoter activity compared with the -799T allele. The overexpression of c-Fos/c-Jun significantly repressed transcriptional activity and a gel shift assay showed that the -799T DNA fragment had a greater affinity for transcription factor AP-1 than the -799A. In 40 unrelated healthy subjects, serum AHSG/fetuin-A levels increased with the following order of genotypes: -799TT<-799AT<-799AA (mean+/-S.E.M.; 222.1+/-11.0, 291.8+/-8.1, and 349.0+/-13.0 microg/ml, respectively, P<0.001). In conclusion, SNP rs2248690 in the promoter region of the AHSG gene affects the AHSG gene transcription, possibly by producing different association with AP-1.


[A Case of Androgen Insensivity Syndrome with a Seminoma in the Abdominal Undescended Testis].
A 48-year-old female was referred to our hospital for further urological examination of primary amenorrhea. She had been suffering from amenorrhea since 12 years old. Although she had normal female external genitalia, she had a blind-ended vagina with complete absence of the uterus.Laboratory tests showed high testosterone level and the 46 XY karyotype. Thus, our diagnosis was androgen insensivity syndrome. Magnetic resonance imaging showed bilateral intra-abdominal testes. We performed laparoscopic bilateral gonadalectomy. Pathological diagnosis was seminoma in the right gonad. She is free of recurrence 6 months after operation.


A filtering method for signal equalization in region-of-interest fluoroscopy.
A method to significantly reduce the exposure area product in fluoroscopy using a pre-patient region-of-interest (ROI) attenuator is presented. The attenuator has a thin central region and a gradually increasing thickness away from the center. It is shown that the unwanted brightening artifact caused by the attenuator can be eliminated by attenuating the low spatial frequencies in the detected image using digital image processing techniques. An investigation of the best image processing method to correct for the presence of the attenuator is undertaken. The correction procedure selected is suitable for use with real-time image processors and the ROI attenuator can be permitted to move during image acquisition. Images of an anthropomorphic chest phantom acquired in the presence of the ROI attenuator using an x-ray image intensifier/video chain are corrected to illustrate the clinical feasibility of our approach.


A simple combined floating and anchored collagen gel for enhancing mechanical strength of culture system.
In this study, a simple combined method consisting of floating and anchored collagen gel in a ligament or tendon equivalent culture system was used to produce the oriented fibrils in fibroblast-populated collagen matrices (FPCMs) during the remodeling and contraction of the collagen gel. Orientation of the collagen fibrils along single axis occurred over the whole area of the floating section and most of the fibroblasts were elongated and aligned along the oriented collagen fibrils, whereas no significant orientation of fibrils was observed in normally contracted FPCMs by the floating method. Higher elasticity and enhanced mechanical strength were obtained using our simple method compared with normally contracted floating FPCMs. The Young's modulus and the breaking point of the FPCMs were dependent on the initial cell densities. This simple method will be applied as a convenient bioreactor to study cellular processes of the fibroblasts in the tissues with highly oriented fibrils such as ligaments or tendons.


The Impact of Hypothyroidism on Diabetes Mellitus and Its Complications: A Comprehensive Review.
Diabetes mellitus (DM) is one of the most prevalent metabolic disorders in the world and is characterized by excessive blood glucose levels, which lead to deranged carbohydrate, protein, and lipid metabolisms. At its core, DM is an impairment of insulin metabolism, leading to a plethora of clinical features. The thyroid gland is another vital cog in the wheel of the endocrine system, and the hormones synthesized by it are heavily involved in the control of the body's metabolism. Hypothyroidism is a state in which thyroid hormones are deficient due to various factors and is characterized by a metabolically hypoactive state. Together, insulin, implicated in DM, and thyroid hormones engage in an intricate dance and serve to regulate the body's metabolism. It is imperative to explore the relationship between these two common endocrine disorders to understand their clinical association and mold treatments specific to patients in which they coexist. Both type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) have been shown to have an increased association with hypothyroidism, especially in patients with risk factors including female sex, hyperlipidemia, obesity, and anemia. This review also explores DM's macrovascular and microvascular complications and their association with hypothyroidism. It is of great use to screen for hypothyroidism in diabetic patients. Specific protocols, especially for patients at an elevated risk, provide improved quality of life to patients affected by this highly prevalent disease.


Localized pure ground-glass opacity on high-resolution CT: histologic characteristics.
The aim of this study is to assess the histologic characteristics in cases of localized pure ground-glass opacity (LPGGO) that do not exhibit consolidation on high-resolution CT (HRCT) images. Twenty surgically resected lesions from 20 consecutive cases were retrospectively investigated. Each of the 20 lesions had exhibited LPGGO on HRCT images. The HRCT images and histopathologic findings were examined for correlations. The areas of LPGGO had a maximum diameter of 2.0-24 mm on the HRCT images. Histopathology of the LPGGO lesions resulted in diagnosis of fibrosis (n = 3; 15%), atypical adenomatous hyperplasia (n = 5; 25%), bronchioloalveolar carcinoma (n = 10; 50%), and adenocarcinoma with stromal invasion (n = 2; 10%). Nonaerogenous components corresponding to solid components without normal alveolar septal destruction were pathologically observed in 15 of the 20 lesions. The diameter of the nonaerogenous components varied between 0.2 and 2.0 mm. Because 10% of LPGGO lesions include invasive disease, patients with LPGGO should undergo pathologic examination for confirmation.


The role of cytokines in physiological sleep regulation.
Several growth factors (GFs) are implicated in sleep regulation. It is posited that these GFs are produced in response to neural activity and affect input-output relationships within the neural circuits where they are produced, thereby inducing a local state shift. These GFs also influence synaptic efficacy. All the GFs currently identified as sleep regulatory substances are also implicated in synaptic plasticity. Among these substances, the most extensively studied for their role in sleep regulation are interleukin-1beta (IL-1) and tumor necrosis factor alpha (TNF). Injection of IL-1 or TNF enhances non-rapid eye movement sleep (NREMS). Inhibition of either IL-1 or TNF inhibits spontaneous sleep and the sleep rebound that occurs after sleep deprivation. Stimulation of the endogenous production of IL-1 and TNF enhances NREMS. Brain levels of IL-1 and TNF correlate with sleep propensity; for example, after sleep deprivation, their levels increase. IL-1 and TNF are part of a complex biochemical cascade regulating sleep. Downstream events include nitric oxide, growth hormone releasing hormone, nerve growth factor, nuclear factor kappa B, and possibly adenosine and prostaglandins. Endogenous substances moderating the effects of IL-1 and TNF include anti-inflammatory cytokines such as IL-4, IL-10, and IL-13. Clinical conditions altering IL-1 or TNF activity are associated with changes in sleep, for example, infectious disease and sleep apnea. As our knowledge of the biochemical regulation of sleep progresses, our understanding of sleep function and of many clinical conditions will improve.


Endotracheal lactate reflects lower respiratory tract infections and inflammation in intubated patients.
The aim of this study was to assess L-lactate and D-lactate in endotracheal aspirate from intubated patients hospitalized at the intensive care unit and explore their use as diagnostic biomarkers for inflammation and lower respiratory tract infections (LRTI). Tracheal aspirates from 91 intubated patients were obtained at time of intubation and sent for microbiological analyses, neutrophil count, and colorimetric lactate measurements. We compared the concentration of lactate from patients with microbiological verified LRTI or clinical/radiological suspicion of LRTI with a control group. In addition, associations between inflammation and the lactate isomers were examined by correlating L-lactate and D-lactate with sputum neutrophils and clinical assessments. The concentration of L-lactate was increased in aspirates with verified or suspected LRTI (p < 0.001) relative to the control group at Day 0. Connections between L-lactate and inflammation were indicated by the correlation between neutrophils and L-lactate (p < 0.001). We found no increase in sputum D-lactate from patients with verified or suspected LRTI relative to the control group and D-lactate was not correlated with neutrophils. L-lactate was found to be a potential indicator for inflammation and LRTI at the time of intubation. An association was found between neutrophil count and L-lactate. Interestingly, the increase of L-lactate in the control group after intubation may suggest that intubation challenges the host response by inflicting tissue damage or by introducing infectious microbes.


Nickel-Catalyzed Trifluoromethylselenolation of Aryl Halides Using the Readily Available [Me4N][SeCF3] Salt.
A convenient and efficient method for the construction of aryl trifluoromethyl selenoethers from the corresponding aryl halides in the presence of Ni(COD)2 and an appropriate ligand is reported. Various aryl iodides, bromides, and chlorides were smoothly converted in this reaction by simply varying the ligand, which afforded aryl and heteroaryl trifluoromethyl selenoethers in good to almost quantitative yields. The reaction was also applicable to the synthesis of druglike molecules. This work is the first report for trifluoromethylselenolation of aryl chlorides. Advantages of the present Ni-catalyzed approach include mild reaction conditions, good functional group tolerance, inexpensive reagents, easy operation, and no use of additional additives. This protocol allows for a straightforward and reliable access to trifluoromethyl selenides that are latent screening candidates for new pharmaceuticals and agrochemicals.


Edaravone ameliorates experimental autoimmune thyroiditis in rats through HO-1-dependent STAT3/PI3K/Akt pathway.
Autoimmune thyroiditis is among the most prevalent of all the autoimmunities in population. It is characterized as both cellular immune responses with T, B cells infiltrating to the thyroid gland followed by hypothyroidism as a result of destruction of the thyroid follicles and fibrous replacement of the parenchymal tissue, as well as immune response for TPO and Tg-antibody production. Experimental autoimmune thyroiditis (EAT) has been proven to be an ideal model to study autoimmune thyroiditis. In the present study, we induced an EAT model in rats and examined the effect of edaravone, a hydroxyl radical scavenging agent, on EAT severity and explored the mechanism. The results showed that edaravone reduced the severity score of thyroiditis dose-dependently and the levels of serum TPOAb, TgAb, T3 and T4. Edaravone significantly decreased the mRNA level of IL-17, but increased the mRNA level of IL-10, IL-4, TNF-α and IFN-γ. EAT model significantly induced oxidative stress, which was inhibited by the treatment of 10 mg/kg, 20 mg/kg or 40 mg/kg of edaravone. The EAT model significantly increased the Akt and STAT3 phosphorylation, but when rats were treated with 20 mg/kg or 40 mg/kg edaravone, they were significantly inhibited. The HO-1 expression was greatly increased by 20 mg/kg or 40 mg/kg edaravone. The PI3K inhibitor LY294002, Akt inhibitor triciribine or STAT3 inhibitor WP1066 all significantly decreased the severity score of thyroiditis in the EAT model group, while the HO-1 inhibitor ZnPP-IX increased the severity score of thyroiditis. These results confirm the invlovment of ROS and HO-1-dependent STAT3/PI3K/Akt pathway in the process of Hashimoto's thyroiditis and suggest the potential usage of edaravone in the therapy of it.


Utilizing logistic regression to compare risk factors in disease modeling with imbalanced data: a case study in vitamin D and cancer incidence.
Imbalanced data, a common challenge encountered in statistical analyses of clinical trial datasets and disease modeling, refers to the scenario where one class significantly outnumbers the other in a binary classification problem. This imbalance can lead to biased model performance, favoring the majority class, and affecting the understanding of the relative importance of predictive variables. Despite its prevalence, the existing literature lacks comprehensive studies that elucidate methodologies to handle imbalanced data effectively. In this study, we discuss the binary logistic model and its limitations when dealing with imbalanced data, as model performance tends to be biased towards the majority class. We propose a novel approach to addressing imbalanced data and apply it to publicly available data from the VITAL trial, a large-scale clinical trial that examines the effects of vitamin D and Omega-3 fatty acid to investigate the relationship between vitamin D and cancer incidence in sub-populations based on race/ethnicity and demographic factors such as body mass index (BMI), age, and sex. Our results demonstrate a significant improvement in model performance after our undersampling method is applied to the data set with respect to cancer incidence prediction. Both epidemiological and laboratory studies have suggested that vitamin D may lower the occurrence and death rate of cancer, but inconsistent and conflicting findings have been reported due to the difficulty of conducting large-scale clinical trials. We also utilize logistic regression within each ethnic sub-population to determine the impact of demographic factors on cancer incidence, with a particular focus on the role of vitamin D. This study provides a framework for using classification models to understand relative variable importance when dealing with imbalanced data.


[Predictive factors of intestinal necrosis in acute mesenteric vascular occlusive diseases].
To explore the predictive factors of intestinal necrosis in acute mesenteric vascular occlusive diseases and its significance for the timing of exploratory laparotomy. This retrospective study enrolled 63 patients diagnosed as acute mesenteric vascular occlusive diseases at Peking University People's Hospital between July 1995 and June 2015. Univariate analysis and multivariate logistic regression analysis were used to identify predictive factors for intestinal necrosis. Of 63 patients, 39 were male and 24 were female, with a mean age of (58.8±12.7)(31 to 82) years. The overall rate of intestinal necrosis was 46.0%(29/63). Patients with intestinal necrosis had a poorer prognosis than those who did not develop intestinal necrosis (χ2=5.908, P=0.015). In univariate analysis, the predictive factors of intestinal necrosis were systemic inflammatory reactive syndrome (SIRS) (χ2=18.535, P=0.000), shock (χ2=7.775, P=0.007), peritoneal irritation sign (χ2=11.533, P=0.001), changes of intestinal wall and blood signals on ultrasound or CT scans (χ2=14.344, P=0.000), international normalized ratio(INR) (prothrombin time) ≥1.2 (χ2=4.498, P=0.034), D-dimer ≥1 000 g/L(χ2=6.680, P=0.010), low-density lipoprotein ≥270 U/L (χ2=6.513, P=0.011), serum albumin <35 g/L (χ2=3.914, P=0.048), blood urea nitrogen ≥6.2 mmol/L (χ2=11.377, P=0.000), pH values <7.35 (χ2=15.887, P=0.000), blood lactate ≥2 mmol/L(χ2=17.134, P=0.000), base excess <-1.0 mmol/L (χ2=6.674, P=0.010). According to multivariate logistic regression analysis, SIRS(OR=28.945, 95%CI:2.294 to 365.199, P=0.009), pH values <7.35(OR=13.174, 95%CI:1.157 to 150.027, P=0.038), changes of intestinal wall and blood signals on ultrasound or CT scans(OR=4.857, 95%CI:1.110 to 21.253, P=0.036) were independent predictive factors of intestinal necrosis in patients with acute mesenteric vascular occlusive diseases. Intestinal necrosis in acute mesenteric vascular occlusive diseases prompts a poor prognosis. When patients with acute mesenteric vascular occlusive diseases are found to have acidosis, SIRS and changes of intestinal wall and blood signals on ultrasound or CT scans, surgeons should be alert to the occurrence of intestinal necrosis and should perform laparotomy promptly in order to take suitable management.


Isocyanate exposures in autobody shop work: the SPRAY study.
Isocyanates, known to cause respiratory sensitization and asthma, are widely used in automotive refinishing where exposures to aliphatic polyisocyanates occur by both inhalation and skin contact. The work reported here, the characterization of isocyanate exposure in the autobody industry, was part of an epidemiologic study of workers in 37 autobody shops in Connecticut. This article describes workplaces, tasks, and controls, and outlines the frequency, duration, and intensity of isocyanate exposures. Personal air samples taken outside of respirators had median concentrations of 66.5 microg NCO/m3 for primer, 134.4 microg (NCO)/m3 for sealer, and 358.5 microg NCO/m3 for clearcoat. Forty-eight percent of primer, 66% of sealer, and 92% of clearcoat samples exceeded the United Kingdom Health and Safety Executive guideline for isocyanate, though none exceeded the National Institute for Occupational Safety and Health (NIOSH) recommended exposure limit for monomer. Nonisocyanate-containing primers and sealers are used in more than half the shops, but nonisocyanate clearcoats are rare. Eighty-two percent of personal samples taken within a spray booth exceeded the U.K. guideline: 81% of those in downdraft spray booths, 74% in semidowndraft booths, and 92% in crossdraft booths. Only 8% of shops reported that spraying is done exclusively in spray booths. All painters wore some type of respirator. In 30% of shops, painters used supplied air respirators; the rest relied on half face organic vapor cartridge respirators with N95 overspray pads. All shops provided some type of gloves, usually latex, not recommended for isocyanate protection. Despite improvements in autobody shop materials, practices, and controls, there are still opportunities for substantial exposures to isocyanates.


Development of a prognostic scoring system to predict risk of reoperation for contralateral hematoma growth after unilateral evacuation of bilateral chronic subdural hematoma.
Bilateral chronic subdural hematoma (bCSDH) is frequently drained unilaterally when the contralateral CSDH is small and asymptomatic. However, reoperation rates for contralateral CSDH growth can be high. We aimed to develop a prognostic scoring system to guide the selection of suitable patients for unilateral drainage of bCSDH. Data were collected retrospectively across three tertiary hospitals from 2010 to 2017 on all consecutive bCSDH patients aged 21 or above. Predictors of reoperation were identified using multivariable logistic regression. A prognostic score was developed and internally validated. 240 bCSDH patients were analyzed. 98 (40.8%) underwent unilateral and 142 (59.2%) underwent bilateral evacuation. Clinical outcomes were comparable between the unilateral and bilateral evacuation groups. Within the unilateral evacuation group, 4 (4.1%) had a reoperation for contralateral CSDH growth. Reoperation for contralateral CSDH was predicted by preoperative use of anticoagulants (OR = 15.0, 95% CI: 1.49-169.15, p = 0.017). Complete resolution of contralateral CSDH was predicted by its preoperative maximum width, with a cut-off of 9 mm producing the highest sensitivity and specificity (OR = 4.17 for ≤9 mm, 95% CI: 1.54-11.11, p = 0.004). Using our prognostic score, reoperation rate for contralateral CSDH was 1.6%, 3.6%, 16.7%, and 50.0% in low-risk, moderate-risk, high-risk and very high-risk patients, respectively. With each increase of 1 in the prognostic score, patients were 4 times as likely to undergo reoperation for contralateral CSDH (OR = 3.98, 95% CI: 1.36-13.53, p = 0.013). Our proposed risk score may be used as an adjunct in clinical decision making for bCSDH patients undergoing unilateral evacuation.


Characterization of the first tenuivirus naturally infecting dicotyledonous plants.
A mechanically transmissible virus tentatively named "melon chlorotic spot virus" (MeCSV) was isolated in southeastern France from a melon plant showing chlorotic spots and yellowing of the older leaves. Its complete sequence was obtained by Illumina and Sanger sequencing. The genome comprises eight RNAs for a total size of 20,079 nt and is distantly related to Ramu stunt virus and maize yellow stunt virus, two tentative tenuiviruses. MeCSV differs from other tenuiviruses by its number of genomic fragments, by being readily mechanically transmissible, and by infecting only dicotyledonous hosts. MeCSV should thus be considered a member of a tentative new species related to tenuiviruses.


The influence of PUVA treatment on the substructure of nevocellular nevi in psoriatic patients.
The influence of PUVA treatment on junction A-cell nevi in psoriatic patients has been analysed. After long-term PUVA therapy the nevocytes display an obvious increase in melanosome synthesis. The melanosomes are clearly polymorphous, without any predominant configuration. The structural organization of the melanosomes is profoundly aberrant. Formation of autophagosomes is conspicuous. The cytoplasmic filaments are displaced peripherally. No convincing signs of malignancy are observed electron microscopically. Light microscopical findings of a bridging proliferation of nevocytes between junction nests is a precautionary observation, however.


Efficient enantioselective reduction of ketones with Daucus carota root.
A novel and efficient reduction of various prochiral ketones such as acetopehones, alpha-azido aryl ketones, beta-ketoesters, and aliphatic acyclic and cyclic ketones to the corresponding optically acive secondary alcohols with moderate to excellent chemical yield was achieved by using Daucus carota, root plant cells under extremely mild and environmentally benign conditions in aqueous medium, has been described. Many of these optically active alcohols are the potential chiral building blocks for the synthesis of pharmaceutically important molecules and asymmetric chiral ligands. Hence, this biocatalytic approach is found to be the most suitable for the preparation of a wide range of chiral alcohols and gave inspiration for the development of a new biotechnological process.


Coronary thrombolysis with clot-selective plasminogen activators.
Coronary thrombolysis is at present intensively investigated in the treatment of acute myocardial infarction. One line of research focuses on the development of new, fibrin-specific agents which might induce more clot-selective thrombolysis than streptokinase and urokinase. Clot-selective thrombolytic agents preferentially activate fibrin-bound plasminogen and, thereby, minimize the generation of free circulating plasmin which is responsible for the hemostatic breakdown and bleeding risk. Intravenous administration of fibrin-specific thrombolytic agents has two major advantages over intracoronary administration: firstly, infusion is more easily and widely applicable and secondly, therapy may be initiated more rapidly, which is important for the early restoration of nutritional blood flow and salvage of functional myocardial tissue. Three clot-selective thrombolytic agents are presently investigated for coronary thrombolysis. Impressive reopening rates have been reported with acylated streptokinase-plasminogen complex, but unfortunately, its use was associated with extensive systemic fibrinolytic activation and bleeding complications. Pro-urokinase, the single chain precursor of urokinase, exhibited intrinsic, fibrin-specific thrombolytic activity in vitro and in animal models but no human trials have yet been reported. At present, the largest clinical experience has been obtained with tissue-type plasminogen activator (t-PA). After small-scale pilot studies with t-PA obtained from cell culture media, larger clinical trials have now been performed using t-PA obtained by recombinant DNA technology (rt-PA). In the first study, intravenous infusion of rt-PA in patients with acute myocardial infarction yielded a recanalization rate of about 75% without clinically relevant systemic activation of the fibrinolytic system in most patients.(ABSTRACT TRUNCATED AT 250 WORDS)


A Review of Landfill Microbiology and Ecology: A Call for Modernization With 'Next Generation' Technology.
Engineered and monitored sanitary landfills have been widespread in the United States since the passage of the Clean Water Act (1972) with additional controls under RCRA Subtitle D (1991) and the Clean Air Act Amendments (1996). Concurrently, many common perceptions regarding landfill biogeochemical and microbiological processes and estimated rates of gas production also date from 2 to 4 decades ago. Herein, we summarize the recent application of modern microbiological tools as well as recent metadata analysis using California, USEPA and international data to outline an evolving view of landfill biogeochemical/microbiological processes and rates. We focus on United States landfills because these are uniformly subject to stringent national and state requirements for design, operations, monitoring, and reporting. From a microbiological perspective, because anoxic conditions and methanogenesis are rapidly established after daily burial of waste and application of cover soil, the >1000 United States landfills with thicknesses up to >100 m form a large ubiquitous group of dispersed 'dark' ecosystems dominated by anaerobic microbial decomposition pathways for food, garden waste, and paper substrates. We review past findings of landfill ecosystem processes, and reflect on the potential impact that application of modern sequencing technologies (e.g., high throughput platforms) could have on this area of research. Moreover, due to the ever evolving composition of landfilled waste reflecting transient societal practices, we also consider unusual microbial processes known or suspected to occur in landfill settings, and posit areas of research that will be needed in coming decades. With growing concerns about greenhouse gas emissions and controls, the increase of chemicals of emerging concern in the waste stream, and the potential resource that waste streams represent, application of modernized molecular and microbiological methods to landfill ecosystem research is of paramount importance.


Shaping the mammalian auditory sensory organ by the planar cell polarity pathway.
The human ear is capable of processing sound with a remarkable resolution over a wide range of intensity and frequency. This ability depends largely on the extraordinary feats of the hearing organ, the organ of Corti and its sensory hair cells. The organ of Corti consists of precisely patterned rows of sensory hair cells and supporting cells along the length of the snail-shaped cochlear duct. On the apical surface of each hair cell, several rows of actin-containing protrusions, known as stereocilia, form a "V"-shaped staircase. The vertices of all the "V"-shaped stereocilia point away from the center of the cochlea. The uniform orientation of stereocilia in the organ of Corti manifests a distinctive form of polarity known as planar cell polarity (PCP). Functionally, the direction of stereociliary bundle deflection controls the mechanical channels located in the stereocilia for auditory transduction. In addition, hair cells are tonotopically organized along the length of the cochlea. Thus, the uniform orientation of stereociliary bundles along the length of the cochlea is critical for effective mechanotransduction and for frequency selection. Here we summarize the morphological and molecular events that bestow the structural characteristics of the mammalian hearing organ, the growth of the snail-shaped cochlear duct and the establishment of PCP in the organ of Corti. The PCP of the sensory organs in the vestibule of the inner ear will also be described briefly.


Origin of Enriched Regulatory T Cells in Patients Receiving Combined Kidney-Bone Marrow Transplantation to Induce Transplantation Tolerance.
We examined tolerance mechanisms in patients receiving HLA-mismatched combined kidney-bone marrow transplantation (CKBMT) that led to transient chimerism under a previously published nonmyeloablative conditioning regimen (Immune Tolerance Network study 036). Polychromatic flow cytometry and high-throughput sequencing of T cell receptor-β hypervariable regions of DNA from peripheral blood regulatory T cells (Tregs) and CD4 non-Tregs revealed marked early enrichment of Tregs (CD3+ CD4+ CD25high CD127low Foxp3+ ) in blood that resulted from peripheral proliferation (Ki67+ ), possibly new thymic emigration (CD31+ ), and, in one tolerant subject, conversion from non-Tregs. Among recovering conventional T cells, central memory CD4+ and CD8+ cells predominated. A large proportion of the T cell clones detected in posttransplantation biopsy specimens by T cell receptor sequencing were detected in the peripheral blood and were not donor-reactive. Our results suggest that enrichment of Tregs by new thymic emigration and lymphopenia-driven peripheral proliferation in the early posttransplantation period may contribute to tolerance after CKBMT. Further, most conventional T cell clones detected in immunologically quiescent posttransplantation biopsy specimens appear to be circulating cells in the microvasculature rather than infiltrating T cells.