Regio- and Enantioselective Bromocyclization of Difluoroalkenes as a Strategy to Access Tetrasubstituted Difluoromethylene-Containing Stereocenters.
Difluoromethylene-containing compounds have attracted substantial research interest over the past decades for their ability to mimic biological functions of traditional functional groups while providing a wide variety of pharmacological benefits bestowed by the C-F bond. We report a novel strategy to access RCF2Br-containing heterocycles by regio- and enantioselective bromocyclization of difluoroalkenes enabled by chiral anion phase-transfer catalysis. The utility of this methodology was highlighted through a synthesis of an analogue of efavirenz, a drug used for treating HIV. Additionally, the synthetic versatility of the CF2Br intermediates was showcased through functionalization to a variety of enantioenriched α,α-difluoromethylene-containing products.


Corynebacteriumpollutisoli sp. nov., isolated from hexachlorocyclohexane-contaminated soil.
A Gram-stain-positive, alkaliphilic, non-spore-forming, non-motile bacterium, designated VDS11T, was isolated from a soil sample collected from the hexachlorocyclohexane dumpsite, located at Ummari Village, Lucknow, Uttar Pradesh, India. 16S rRNA gene sequence analysis indicated that strain VDS11T occupies a distinct phylogenetic position within the genus Corynebacterium, showing the highest sequence similarity with Corynebacterium humireducens MFC-5T (98.7 %) and Corynebacterium nasicanis 2673/12T (98.4 %). The DNA G+C content was 50.6 mol% and the DNA-DNA hybridization (DDH) relatedness value with C. humireducens MFC-5T and C. nasicanis 2673/12T was 49.7 and 39.6 %, respectively. Strain VDS11T contained C16 : 0 (28.3), C18 : 1ω9c (52.3), C18 : 0 (1.3) and C20 : 0 (3.0) as the major cellular fatty acids. The major isoprenoid quinone was MK-9(H2). Strain VDS11T contained diphosphatidylglycerol, phosphatidylglycerol, phosphatidylinositol, unidentified aminolipids, glycolipids, phospholipids and unidentified lipids as the major polar lipids. The peptidoglycan type was A31 (meso 2, 6-diaminopimelic acid, directly cross-linked). Based on the results of DDH studies and the biochemical and physiological data, strain VDS11T represents a novel species of the genus Corynebacteriumfor which the name Corynebacterium pollutisoli sp. nov., has been proposed. The type strain is VDS11T(=DSM 100104T=MCC 2722T=KCTC 39687T).


Abnormal Pap Smear and Diagnosis of High-Grade Vaginal Intraepithelial Neoplasia: A Retrospective Cohort Study.
The aim of this study was to analyze the correlation between the first diagnosis of high-grade Vaginal Intraepithelial Neoplasia (HG-VaIN: VaIN 2-VaIN 3) and the cytological abnormalities on the referral pap smear.All the women with histological diagnosis of HG-VaIN consecutively referred to the Gynecological Oncology Unit of the Aviano National Cancer Institute (Aviano, Italy) from January 1991 to April 2014 and with a pap smear performed in the 3 months before the diagnosis were considered, and an observational cohort study was performed.A total of 87 women with diagnosis of HG-VaIN were identified. Major cytological abnormalities (HSIL and ASC-H) on the referral pap smear were significantly more frequent than lesser abnormalities (ASC-US and LSIL) in postmenopausal women (64.9% vs 36.7%, P = 0.02) and in women with a previous diagnosis of HPV-related cervical preinvasive or invasive lesions (70.5% vs 39.5%, P = 0.01). Diagnosis of VaIN 3 was preceded by major cytological abnormalities in most of the cases (72.7% vs 27.3%, P < 0.001).The diagnosis of HG-VaIN can be preceded by different abnormalities on referral pap smear. Major abnormalities are usually reported in postmenopausal women and in women with previous cervical HPV-related disease. However, ASC-US or LSIL do not exclude HG-VaIN, especially VaIN2. An accurate examination of the whole vaginal walls (or vaginal vault) must be performed in all the women who underwent colposcopy for an abnormal pap smear, and a biopsy of all suspicious areas is mandatory.


CpG-ODN promotes phagocytosis and autophagy through JNK/P38 signal pathway in Staphylococcus aureus-stimulated macrophage.
Phagocytic and autophagic responses are critical for effective host defense against bacterial infection. Bacterial DNA which contains unmethylated Cytosine-phosphate-Guanine (CpG) motifs can trigger a variety of defense mechanisms via Toll-like receptor 9 (TLR9). Here, we aimed to investigate the underlying mechanism of TLR9-mediated phagocytosis and autophagy in Staphylococcus aureus (S.aureus)-stimulated macrophages. The macrophage cell line RAW264.7 or primary peritoneal macrophage was pretreated with CpG-ODN and then stimulated by S. aureus, where some of them were pretreated with SP600125 or SB203580 simultaneously. The protein expressions of TLR9, MyD88, SR-A, CD36, LC3, Beclin-1, and phosphorylated level of c-Jun N-terminal kinase (JNK), P38 and extracellular-regulated protein kinase (ERK) were detected by western blotting. The phagocytosis and LC3 punctate-structures of macrophage were observed by confocal laser scanning microscope. CpG-ODN significantly amplified S. aureus-induced phagocytosis and autophagy of RAW264.7 and TLR9(+/+) primary peritoneal macrophage as compared to that of Non-CpG treated cells, while such effect was abolished in TLR9(-/-) primary peritoneal macrophages. Meanwhile, CpG-ODN significantly enhanced S. aureus-induced phosphorylation of JNK and P38 but not ERK in RAW264.7. Specific inhibition of JNK or P38 by SP600125 or SB203580, dramatically down-regulated CpG-induced phagocytosis and autophagy in S. aureus-stimulated RAW264.7 and TLR9(+/+) primary peritoneal macrophage, while they showed no further down-regulation of phagocytosis and autophagy in TLR9(-/-) primary peritoneal macrophages. Our data indicated that CpG-ODN activates TLR9-JNK/P38 signaling to promote phagocytosis and autophagy in S. aureus-stimulated macrophages, these findings provide novel insights into how innate immune cells defend bacterial infection via TLR9.


Increase of bone marrow macrophages and CD8+ T lymphocytes predict graft failure after allogeneic bone marrow or cord blood transplantation.
Graft failure (GF) remains an obstacle to survival after allogeneic hematopoietic stem cell transplantation. However, differentiating GF from delayed engraftment (DE) can be difficult. Host CD8+ lymphocytes have been reported to mediate graft rejection, but the impact of macrophages on DE or GF is yet to be clarified. Peri-engraftment bone marrow (BM) specimens of 32 adult patients with normal engraftment, DE or GF were retrospectively evaluated to identify the potential associations of CD163+ macrophage and CD8+ lymphocyte infiltration into BM. The macrophage or CD8+ lymphocyte number/total nucleated cell number was defined as the Mac ratio and CD8 ratio, respectively. Both DE and GF groups had significantly higher Mac ratios at day 14 than the normal group (P<0.0001), but no significant difference was observed between the DE and GF groups (P=1.000). The CD8 ratio at day 14 was significantly higher in the GF than in the normal group (P=0.005), whereas the CD8 ratios of the DE and normal groups were similar (P=0.07). A high Mac ratio at day 14 was associated with a risk of DE or subsequent GF. Patients with increased CD8 ratio at day 14 had a further risk of GF. The Mac ratio and the CD8 ratio appear to be well suited for predicting engraftment status.


Quantitative oil spill risk from offshore fields in the Bohai Sea, China.
The oil spill risk in the environments surrounding the Bohai Sea is aggravated by increasing marine petroleum exploitation. There is a growing need to assess the risk of oil pollution in sensitive marine areas and coastlines. Both the recurrence frequency of spill accidents and the duration of exposure in marine areas and coastal shorelines are considered in our statistical model, which consists of a probabilistic oil spill model used to simulate various oil spill scenarios at twenty oil fields in the Bohai Sea based on high-resolution oceanographic, meteorological, and geomorphological data. The statistical results of the risk to marine areas integrate the probability of pollution in marine areas, oil slick thickness, and duration of water surface covered by a floating slick. The coastal risk index includes the probability of a shoreline hit, average mass of stranding oil, and time of oil beaching. The spatial distributions of environmental triggering factors and coastal/marine vulnerability are merged, and a map of the oil spill risk in the Bohai Sea is presented, which is useful for contingency planning and the assessment of environmental risk of marine petroleum exploitation.


Formation of polyol-fatty acid esters by lipases in reverse micellar media.
The synthesis of polyol-fatty acid esters has strong implications in such industries as foods, cosmetics, and polymers. We have investigated these esterification reactions employing the polyols ethylene glycol, 2-monoglyceride, and sugars and their derivatives with the biocatalyst lipase in water/AOT/isooctane reverse micellar media. For the first reaction, 50-60% conversion was achieved and product selectivity toward the monoester over the diester shown possible by employing lipase from Rhizopus delemar. A simple kinetic model based on the formation of acyl-enzyme intermediate accurately predicted the effect of polyol concentration but not the effect of fatty acid or water concentration probably due to the model exclusion of partitioning effects. The success of this reaction in reverse micellar media is due greatly to its capacity to solubilize large quantities of glycol despite the media's overall hydrophobicity. The second reaction, investigated for its potential for production of "mixed" glycerides, also achieved about 50% conversion but had only a small portion of triglyceride in its product distribution. Also, isomerization of the 2-monoglyceride to 1-monoglyceride, followed by hydrolysis of the latter, unfortunately occurred to a significant extent. Attempts at esterification with hexoses and their derivatives such as glucose and mannitol produced no conversion.


Serum uric acid is associated with increased risk of idiopathic venous thromboembolism in high HDL-C population: A case-control study.
Many studies have indicated that metabolic disorders are positively correlated with idiopathic venous thromboembolism (VTE), whereas the risk factor serum uric acid (SUA) for idiopathic VTE has yet to be investigated. In this retrospective case-control study, 276 idiopathic VTE patients and 536 gender- and age-matched control subjects were included. The subjects in the case and control groups exhibiting common known VTE risk factors and the patients with a first VTE onset in one month were excluded. For the control group, primary and secondary VTE patients were excluded. High-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol, total cholesterol, fasting blood glucose, and current smoking were significantly associated with idiopathic VTE in the univariate analysis. Hyperuricemia was detected in 56/276 (20.29%) idiopathic patients compared with 71/536 (13.25%) in the control group. HDL-C was considered the most prominent interactive factor for SUA in idiopathic VTE by the interaction analysis. After testing for the interaction terms, SUA was closely associated with idiopathic VTE in the high HDL-C population (P=0.0026 for interaction), while there was no such correlation in the low HDL-C group. The results indicated no obvious correlation between triglyceride and hypertension to idiopathic VTE. In conclusion, SUA is closely associated with an increased risk of idiopathic VTE in the high HDL-C population. The abnormality of SUA may act as an important linkage between atherosclerosis and idiopathic VTE through HDL-C.


The use of think-aloud protocols to identify a decision-making process of community pharmacists aimed at improving CMS Star Ratings scores.
The Center for Medicare and Medicaid Services (CMS) created the Star Rating system based on multiple measures that indicate the overall quality of health plans. Community pharmacists can impact certain Star Ratings measure scores through medication adherence and patient safety interventions. To explore methods, needs, and workflow issues of community pharmacists to improve CMS Star Ratings measures. Think-aloud protocols (TAPs) were conducted with active community retail pharmacists in Oklahoma. Each TAP was audio recorded and transcribed to documents for analysis. Analysts agreed on common themes, illuminated differences in findings, and saturation of the data gathered. Methods, needs, and workflow themes of community pharmacists associated with improving Star Ratings measures were compiled and organized to exhibit a decision-making process. Five TAPs were performed among three independent pharmacy owners, one multi-store owner, and one chain-store administrator. A thematically common 4-step process to monitor and improve CMS Star Ratings scores among participants was identified. To improve Star Ratings measures, pharmacists: 1) used technology to access scores, 2) analyzed data to strategically set goals, 3) assessed individual patient information for comprehensive assessment, and 4) decided on interventions to best impact Star Ratings scores. Participants also shared common needs, workflow issues, and benefits associated with methods used in improving Star Ratings. TAPs were useful in exploring processes of pharmacists who improve CMS Star Ratings scores. Pharmacists demonstrated and verbalized their methods, workflow issues, needs, and benefits related to performing the task. The themes and decision-making process identified to improving CMS Star Ratings scores will assist in the development of training and education programs for pharmacists in the community setting.


Self-reference plasmonic sensors based on double Fano resonances.
High-sensitivity plasmonic refractive index sensors show great applications in the areas of biomedical diagnostics, healthcare, food safety, environmental monitoring, homeland security, and chemical reactions. However, the unstable and complicated environments considerably limit their practical applications. By employing the independent double Fano resonances in a simple metallic grating, we experimentally demonstrate a self-reference plasmonic sensor, which significantly reduces the error contributions of the light intensity fluctuations in the long-distance propagation and local temperature variations at the metallic grating, and the detection accuracy is guaranteed. The numerical simulation shows that the two Fano resonances have different origins and are independent of each other. As a result, the left Fano resonance is quite sensitive to the refractive index variations above the metal surface, while the right Fano resonance is insensitive to that. Experimentally, a high figure of merit (FOM) of 31 RIU-1 and a FOM* of 860 RIU-1 are realized by using the left Fano resonance. More importantly, by using the right Fano resonance as a reference signal, the influence of the light intensity fluctuations and local temperature variations is monitored and eliminated in the experiment. This simple self-reference plasmonic sensor based on the double Fano resonances may find important applications in highly-sensitive and accurate sensing under unstable and complicated environments, as well as multi-parameter sensing.


Diagnosis of alpha-1 antitrypsin deficiency: a population-based study.
Alpha-1 antitrypsin deficiency (AATD) remains an underdiagnosed condition despite initiatives developed to increase awareness. The objective was to describe the current situation of the diagnosis of AATD in primary care (PC) in Catalonia, Spain. We performed a population-based study with data from the Information System for Development in Research in Primary Care, a population database that contains information of 5.8 million inhabitants (80% of the population of Catalonia). We collected the number of alpha-1 antitrypsin (AAT) determinations performed in the PC in two periods (2007-2008 and 2010-2011) and described the characteristics of the individuals tested. A total of 12,409 AAT determinations were performed (5,559 in 2007-2008 and 6,850 in 2010-2011), with 10.7% of them in children. As a possible indication for AAT determination, 28.9% adults and 29.4% children had a previous diagnosis of a disease related to AATD; transaminase levels were above normal in 17.7% of children and 47.1% of adults. In total, 663 (5.3%) individuals had intermediate AATD (50-100 mg/dL), 24 (0.2%) individuals had a severe deficiency (<50 mg/dL), with a prevalence of 0.19 cases of severe deficiency per 100 determinations. Nine (41%) of the adults with severe deficiency had a previous diagnosis of COPD/emphysema, and four (16.7%) were diagnosed with COPD within 6 months. The number of AAT determinations in the PC is low in relation to the prevalence of COPD but increased slightly along the study period. The indication to perform the test is not always clear, and patients detected with deficiency are not always referred to a specialist.


Using social choice theory and acceptability analysis to measure the value of health systems.
The Future Health Index (FHI) is developed by the Royal Philips to help determine the readiness of countries to address global health challenges and build sustainable, fit-for-purpose national health systems. The FHI 2018 presents the Value Measure to measure the value of 16 health systems, which is formulated by taking the arithmetic average of Access, Satisfaction and Efficiency. However, this scheme is not the Pareto optimal and loses association with weights. For these reasons, this paper proposes to apply the social choice theory and Stochastic Multicriteria Acceptability Analysis for group decision making (SMAA-2) to measure the value of health systems, by means of re-constructing the Value Measure. Specifically, we begin with considering all possible individual preferences among Access, Satisfaction and Efficiency, which is mathematically represented by ranked weights of them; the pessimistic and optimistic outcomes under certain individual preference are derived in a closed-form manner, according to which an interval decision matrix is then formulated; the SMAA-2 is then lastly applied to compute the holistic acceptability index, which is considered as a revised Value Measure. An empirical study using the data of 16 health systems is conducted to show the effectiveness and superiority of our method. It is demonstrated that our method always outperforms the Value Measure, by means of comparing the Spearman's rank correlation coefficients.


Contraceptive use following spontaneous and induced abortion and its association with family planning services in primary health care: results from a Brazilian longitudinal study.
Although it is well known that post-abortion contraceptive use is high when family planning services are provided following spontaneous or induced abortions, this relationship remains unclear in Brazil and similar settings with restrictive abortion laws. Our study aims to assess whether contraceptive use is associated with access to family planning services in the six-month period post-abortion, in a setting where laws towards abortion are highly restrictive. This prospective cohort study recruited 147 women hospitalized for emergency treatment following spontaneous or induced abortion in Brazil. These women were then followed up for six months (761 observations). Women responded to monthly telephone interviews about contraceptive use and the utilization of family planning services (measured by the utilization of medical consultation and receipt of contraceptive counseling). Generalized Estimating Equations were used to analyze the effect of family planning services and other covariates on contraceptive use over the six-month period post-abortion. Women who reported utilization of both medical consultation and contraceptive counseling in the same month had higher odds of reporting contraceptive use during the six-month period post-abortion, when compared with those who did not use these family planning services [adjusted aOR = 1.93, 95 % Confidence Interval: 1.13-3.30]. Accessing either service alone did not contribute to contraceptive use. Age (25-34 vs. 15-24 years) was also statistically associated with contraceptive use. Pregnancy planning status, desire to have more children and education did not contribute to contraceptive use. In restrictive abortion settings, family planning services offered in the six-month post-abortion period contribute to contraceptive use, if not restricted to simple counseling. Medical consultation, in the absence of contraceptive counseling, makes no difference. Immediate initiation of a contraceptive that suits women's pregnancy intention following an abortion is recommended, as well as a wide range of contraceptive methods, including long-acting reversible methods, even in restrictive abortion laws contexts.


Common variable immunodeficiency-associated granulomatous and interstitial lung disease.
Common variable immunodeficiency (CVID) is the most common primary immunodeficiency characterized by a deficiency of immunoglobulins. Approximately 30% of the patients develop autoimmune and granulomatous disease. Similar to sarcoidosis, granulomatous disease in CVID can potentially affect all organs, but the lung is the most common. Interstitial lung disease (ILD) manifests in 5-15% of CVID patients, and is present already at the initial diagnosis in the majority of patients. The number of published studies addressing ILD in CVID is limited. However, recently, several studies added substantial knowledge to the field and are discussed within this review in the context of the literature. Histologically, ILD in CVID presents within the known patterns of sarcoid-like granuloma, organizing pneumonia, lymphocytic interstitial pneumonitis and nonspecific interstitial pneumonia. Often, these patterns are concomitantly found in the same patients. Three new articles were published which analyzed high-resolution computed tomography findings and response to treatment. In a considerable number of patients, ILD is stable over years and patients may not need any immunosuppressive treatment. Prednisone treatment is often used as the first-line treatment and studies suggest response to treatment in 50-66% of cases. In progressive disease with lung function impairment, combined immunosuppressive treatment is recommended.


Fat-filled postoperative renal cortical defects: sonographic and CT appearance.
Surgical filling of renal cortical wedge resection defects with vascularized retroperitoneal fat resulted in postoperative sonographic and CT appearances that simulated focal renal masses in four patients. Correct identification of this abnormality is important in order to avoid unnecessary further evaluation to exclude renal neoplasm.


Testosterone for peri- and postmenopausal women.
: The value of adding testosterone to hormone therapy (HT) for the management of peri- and postmenopausal women is controversial and has not been systematically reviewed. : To determine the benefits and risks of testosterone therapy for peri- and postmenopausal women taking hormone therapy. : We searched the Cochrane Menstrual Disorders and Subfertility Group Trials Register (1st November 2003), The Cochrane Library (Issue 2, 2003), MEDLINE (1966 to 1st November 2003), EMBASE (1980 to 1st November 2003), Biological Abstracts (1969 to 2002), PsycINFO (1972 to 1st November 2003), CINAHL (1982 to 1st November 2003), and reference lists of articles. We also contacted pharmaceutical companies and researchers in the field. : Studies that were randomized comparisons of testosterone plus hormone therapy versus hormone therapy alone in peri- or postmenopausal women. : Two review authors assessed the quality of the trials and extracted data independently. Where it was necessary, the corresponding authors of eligible trials were contacted for additional information. For dichotomous outcomes Peto odds ratios and 95% confidence intervals were calculated. For continuous outcomes non-skewed data from valid scales were synthesized using a weighted mean difference or standardized mean difference. If statistical heterogeneity was found, a random-effects model was used and reasons for the heterogeneity were explored and discussed. : Twenty-three trials with 1957 participants were included in the review. The median study duration was 6 months (range 1.5 to 24 months). Most of the trials were of adequate quality with regard to randomization and concealment of allocation sequence. The major methodological limitations were attrition bias and lack of a washout period in the cross-over studies. The pooled estimate from the studies suggested that the addition of testosterone to HT regimens improved sexual function scores for postmenopausal women. A significant adverse effect was a decrease in high-density lipoprotein (HDL) cholesterol levels. The discontinuation rate was not significantly greater with testosterone therapy (Peto odds ratio 1.01, 95% confidence interval 0.76 to 1.33) than with HT alone. There was insufficient evidence of a treatment effect for perimenopausal women or for other outcomes. : Only a limited number of studies could be pooled in the meta-analyses. This limited the power of the meta-analysis to provide conclusions about efficacy and safety. However, there is evidence that adding testosterone to HT has a beneficial effect on sexual function in postmenopausal women. There was a reduction in HDL cholesterol associated with the addition of testosterone to the HT regimens. The meta-analysis combined studies using different testosterone regimens. It is, therefore, difficult to estimate the effect of testosterone on sexual function in association with any individual hormone treatment regimen.


Optimal location for a helicopter in a rural trauma system: prediction using discrete-event computer simulation.
A discrete-event computer simulation was developed using the C programming language to determine the optimal base location for a trauma system helicopter in Maine, a rural area with unevenly distributed population. Ambulance run reports from a one-year period provided input data on the times and places where major injuries occurred. Data from a statewide trauma registry were used to estimate the percentage of cases which would require trauma center care and the locations of functional trauma centers. Climatic data for this region were used to estimate the likelihood that a helicopter could not fly due to bad weather. The incidence of trauma events was modeled as a nonstationary Poisson process, and location of the events by an empirical distribution. For each simulated event, if the injuries were sufficiently severe, if weather permitted flying, if the occurrence were not within 20 miles of a center or outside the range of the helicopter, and if the helicopter were not already in service, then it was used for transportation. 35 simulated years were run for each of 4 proposed locations for the helicopter base. One of the geographically intermediate locations was shown to produce the most frequent utilization of the helicopter. Discrete-event simulation is a potentially useful tool in planning for emergency medical services systems. Further refinements and validation of predictions may lead to wider utilization.


Prevention of sudden death using beta-blockers. Review of possible contributory actions.
Coronary artery disease is the most serious complication of hypertension; therefore, the treatment of hypertension should be directed toward reducing the mortality from this disease. Since the majority of deaths occurring in post-myocardial infarction patients and hypertensive patients are sudden, the key objective is coronary artery disease treatment that will reduce the risk of sudden death. Several pharmacological interventions have been tested to determine whether they reduce the risk of sudden death. So far, only treatment with beta-adrenoceptor antagonists has been proven effective. Since most sudden cardiac deaths are due to ventricular fibrillation, an antifibrillatory effect on beta-adrenoceptor blockade has been invoked and demonstrated in clinical as well as animal experimental studies. Apart from an antifibrillatory effect, other effects of beta-blockade may also be involved. In the present review, different effects of beta-blockers that may contribute to the observed beneficial effects are discussed. The reduction in the risk of sudden death during active beta-adrenoceptor blockade reported in clinical studies is probably related to the summation of different effects, since cardiovascular drugs with a more limited mode of action (i.e., pure anti-ischemic effect or pure antiarrhythmic effect) have not shown similar impressive results.


Delayed closure of persistent postpneumonectomy bronchopleural fistula.
A 73-year-old man with a history of postpneumonectomy empyema and a long-term chest tube since 1979 presented with fever, chills, leukocytosis, and purulent fluid from the left tube thoracostomy. CT scan and bronchoscopy demonstrated a right lower lobe pneumonia and a left mainstem dehiscence with direct communication to the left tube thoracostomy. He underwent primary closure of the bronchopleural fistula with latissimus dorsi muscle flap coverage after antibiotic therapy for right lower lobe pneumonia.


A review of dental microwear and diet in modern mammals.
Recent work has shown that microscopic wear patterns on teeth may yield insights into variations in diet and tooth use in modern and prehistoric mammals. This paper presents a review of dental microwear and diet in modern mammals, plus a discussion of topics for further research. To date, incisor and molar microwear have been examined, although there are far fewer studies of the former. Facilitated by the use of high-resolution casts and scanning electron microscopy, analyses have ranged from: qualitative to quantitative, low magnification to high magnification, and experimental studies to comparative studies of museum collections. Results are encouraging and may lead to further insights into a variety of topics including food processing and dental microstructure.


Effects of friction massage of the popliteal fossa on blood flow velocity of the popliteal vein.
[Purpose] Friction massage (friction) of the popliteal fossa is provided for the purpose of relieving pain related to circulatory disorders by improving venous flow in the lower legs. The purpose of this study is to verify the effects of enhancing the venous flow based on measuring the blood flow velocity of the popliteal vein before and after providing friction to the patients. [Subjects and Methods] Fifteen healthy male university students participated in the study. The Doppler ultrasonography (DU) was used to measure the blood flow velocity of the popliteal vein, in order to verify the effects of enhancing the venous flow by comparing the measured values before and after a friction massage. [Results] The result of comparing the blood flow velocity before and after providing friction showed that there was a significant increase after friction. [Conclusion] This study proved that friction to the popliteal fossa is effectively enhances venous flow by increasing the blood flow velocity in the popliteal vein.


Comparison of the susceptibility of chicks of different ages to infection with nephrosis/nephritis-causing strain of infectious bronchitis virus.
Two- and 6-week-old chicks were inoculated with the Kagoshima-34 strain of avian infectious bronchitis virus. Serum, bile, Harderian gland, lachrymal fluid, saliva and tracheal washings were collected and their antibody content determined using neutralisation tests. The neutralising antibody (NA) in the serum and bile was detected earlier and in slightly higher concentration in the 6-week-old chicks. Although there was no marked difference in the levels of NA in other body fluids, it was detected earlier in the 6-week-old chicks. In both experiments, the clinical signs were more severe in the 2-week-old chicks. Recovery of virus from the trachea of both ages was not different but virus was recovered for longer in the lungs, kidneys and colon of the 2-week-old chicks. This is the first report wherein IBV-neutralising antibody in the bile is described.


Accessing the Columbia Clinical Repository.
The Columbia Clinical Repository is the foundation of the Clinical Information System at the Columbia Presbyterian Medical Center (CPMC). The Repository is implemented as a relational database on an IBM mainframe, using a generic design that employs a small number of tables. Client applications on remote platforms send and receive data through Database Access Modules (DAMs), which support the HL7 protocol, while applications on the mainframe manipulate data through DAMs supporting a locally defined "query template". Implementation using static (compiled) SQL is compared to dynamic (ad hoc) SQL in terms of efficiency and flexibility.


A new species of Sweltsa (Plecoptera: Chloroperlidae) from Sichuan Province of southwestern China.
A new chloroperlid stonefly species, Sweltsa brevihamula sp. nov. from Sichuan Province of southwestern China is described and illustrated. We also provide a provisional key to the known Sweltsa males of China.


Granular cell tumor (myoblastoma) of the eyebrow.
Granular cell tumor (Myoblastoma) is a tumor of controversial nature that rarely appears in the ocular adnexa. A 37-year-old man with such a tumor in his right eyebrow is reported, and the relevant literature is reviewed.


Analysis of production, purification, and cytolytic potential of bi-specific antibodies reactive with ovarian-carcinoma-associated antigens and the T-cell antigen CD3.
OV-TL3 and MOv 18 MAbs, due to their restricted specificity, have been successfully used to visualize ovarian cancer in patients and might therefore be used to develop therapies for ovarian cancer. The bi-specific MAbs alpha T3/OC2 and alpha OC/TR (both being combinations of MOv18 and alpha CD3) have been shown to lyse ovarian tumor cells in vitro. To evaluate the relative merits of MOv18/CD3 and OV-TL 3/CD3, the present study was undertaken in which the bi-specific MAbs alpha T3/OC2 and alpha OC/TR, and a newly developed bi-specific MAb, OV-TL 3/CD3, were highly purified and compared for specificity, stability, purification and cytolytic potential. The dual specificity of the hybrid-hybridoma supernatants was analyzed by immunohistochemistry, and by testing bi-specific MAb-mediated cytotoxicity against relevant target cells in the presence of effector cells. Stability testing of bi-specific MAb-producing hybridomas showed that, after sub-cloning, clones stably produced up to 40% bi-specific MAb even after prolonged in vitro culture. The purification of the bi-specific fractions was performed with protein A and by ion-exchange high-pressure liquid chromatography, depending on the sub-class combination of the bi-specific MAb. The purified bi-specific MAbs were tested for their ability to mediate target-cell lysis with the use of cytotoxic T-cell clones and activated peripheral-blood lymphocytes. The purified alpha T3/OC2, alpha OC/TR, and OV-TL3/CD3 were all able to mediate highly specific lysis of various ovarian-carcinoma cell lines. No correlation was found between the level of antigen expression and bi-specific MAb-mediated cytolysis.


CD80/CD86 costimulation regulates acute vascular rejection.
Xenotransplantation may provide the only solution to the shortage of human donor organs. Although hyperacute rejection associated with xenotransplantation can now be overcome, acute vascular rejection (AVR) remains a primary barrier to xenotransplantation. To date, standard immunosuppressive agents fail to block AVR or prolong xenograft survival. The present study was undertaken to determine the role of CD80/CD86 costimulatory molecules in regulating AVR. Lewis rat hearts were transplanted heterotopically into wild-type or IL-12, CD80- or CD86-deficient C57BL/6 mice. Wild-type recipients were treated with CD80 or CD86 neutralizing Ab with and without daily cyclosporin A (CsA, 15 mg/kg). Transplanted hearts in untreated wild-type recipients were rejected on postoperative days (POD) 17-21 and showed cell-mediated rejection (CMR) and AVR pathologies. In contrast, transplanted hearts in IL-12 and CD80 recipients or wild-type recipients treated with CD80 neutralizing Ab were rapidly rejected on POD 5 and 6 with AVR pathology. Interestingly, hearts transplanted into CD86 knockout recipients or wild-type recipients treated with CD86 neutralizing Ab underwent CMR on POD 17. Finally, blockade of CD86 but not CD80 rendered xenograft recipients sensitive to daily CsA therapy, leading to indefinite xenograft survival. To conclude, we demonstrate that AVR can be overcome by blocking the CD86 costimulatory pathway. Furthermore, we demonstrate that CD80 and CD86 have opposing roles in regulation of xenotransplantation rejection, where CD80 drives CMR and attenuates AVR while CD86 drives AVR. Most strikingly, indefinite xenograft survival can be achieved by suppressing AVR with CD86 neutralization in combination of CsA therapy, which inhibits CMR.


Diffuse panbronchiolitis: report of a rare disease from India.
Initially described by a group of Japanese clinicians and pulmonary pathologists to distinguish it from other chronic obstructive lung diseases, diffuse panbronchiolitis (DPB) is an uncommon disorder which has been reported largely from the eastern world. It is imperative to recognise this condition because of its potentially treatable nature. Recently, long-term macrolide therapy has revolutionised its management. Herein, we describe a 65-year-old male who was being managed as a case of chronic bronchitis before this diagnosis was suspected and proved.


Reprint of "Affective picture processing as a function of preceding picture valence: an ERP analysis".
Event-related brain potential (ERP) studies consistently revealed that a relatively early (early posterior negativity; EPN) and a late (late positive potential; LPP) ERP component differentiate between emotional and neutral picture stimuli. Two studies examined the processing of emotional stimuli when preceded either by pleasant, neutral, or unpleasant context images. In both studies, distinct streams of six pictures were shown. In Study 1, hedonic context was alternated randomly across the 180 picture streams. In Study 2, hedonic context sequences were blocked, resulting in 60 preceding sequences of pleasant, neutral, and unpleasant context valence, respectively. The main finding was that the valence of the preceding picture sequence had no significant effect on the emotional modulation of the EPN and LPP components. However, previous results were replicated in that emotional stimulus processing was associated with larger EPN and LPP components as compared to neutral pictures. These findings suggest that the prioritized processing of emotional stimuli is primarily driven by the valence of the current picture.


Preparation of siRNA-PLGA/Fab'-PLGA mixed micellar system with target cell-specific recognition.
Small interfering RNAs (siRNAs) are susceptible to nucleases and degrade quickly in vivo. Moreover, siRNAs demonstrate poor cellular uptake and cannot cross the cell membrane because of its polyanionic characteristics. To overcome these challenges, an intelligent gene delivery system that protects siRNAs from nucleases and facilitates siRNA cellular uptake is required. We previously reported the potential of siRNA-poly(D,L-lactic-co-glycolic acid; PLGA) micelles as an effective siRNA delivery tool in a murine peritoneal dissemination model by local injection. However, there was no effective formulation for siRNA delivery to target cells via intravenous injection. This study aimed to prepare siRNA-PLGA/Fab'-PLGA mixed micelles for siRNA delivery to target floating cells and evaluate its formulation in vitro. As the target siRNA protein in CEMx174, CyclinB1 levels were significantly reduced when siRNA-PLGA/Fab'-PLGA mixed micelles were added to cells compared with siRNA-PLGA micelles. siRNA-PLGA/Fab'-PLGA mixed micelles have high cell permeability and high target cell accumulation by endocytosis because flow cytometry detected labeling micelles in target cells. This study supports siRNA-PLGA/Fab'-PLGA mixed micelles as an effective siRNA delivery tool. This formulation can be administered systemically in dosage form against target cells, including cancer metastasis or blood cancer.


1-DE MS and 2-D LC-MS analysis of the mouse bronchoalveolar lavage proteome.
Bronchoalveolar lavage fluid (BALF) is a complex mixture of proteins, which represents a unique clinically useful sampling of the lower respiratory tract. Many proteomic technologies can be used to characterize complex biological mixtures; however, it is not yet clear which technology(s) provide more information regarding the number of proteins identified and sequence coverage. In this study, we initially compared two common proteomic approaches, 2-D LC microESI MS/MS and 1-DE followed by gel slice digestion, peptide extraction and peptide identification by MS in characterization of the mouse BALF proteome; secondly, we identified 297 unique proteins from the mouse BALF proteome, greatly expanded the BALF proteome by about threefold regardless of species.


Solid Nanocrystals of Rebamipide Promote Recovery from Indomethacin-Induced Gastrointestinal Bleeding.
Indomethacin (IMC)-induced gastrointestinal (GI) injuries are more common in rheumatoid arthritis (RA) patients than in other IMC users, and the overexpression of nitric oxide (NO) via inducible NO synthase (iNOS) is related to the seriousness of IMC-induced GI injuries. However, sufficient strategies to prevent IMC-induced GI injuries have not yet been established. In this study, we designed dispersions of rebamipide (RBM) solid nanocrystals (particle size: 30-190 nm) by a bead mill method (RBM-NDs), and investigated whether the oral administration of RBM-NDs is useful to prevent IMC-induced GI injuries. The RBM nanocrystals were spherical and had a solubility 4.71-fold greater than dispersions of traditional RBM powder (RBM-TDs). In addition, the RBM-NDs were stable for 1 month after preparation. The RBM contents in the stomach, jejunum, and ileum of rats orally administered RBM-NDs were significantly higher than in rats administered RBM-TDs. Moreover, the oral administration of RBM-NDs decreased the NO levels via iNOS and area of the GI lesions in IMC-stimulated RA (adjuvant-induced arthritis rat) rats in comparison with the oral administration of RBM-TDs. Thus, we show that the oral administration of RBM-NDs provides a high drug supply to the GI mucosa, resulting in a therapeutic effect on IMC-induced GI injuries. Solid nanocrystalline RBM preparations may offer effective therapy for RA patients.


Childbirth Pain, Attachment Orientations, and Romantic Partner Support During Labor and Delivery.
Attachment anxiety is associated with greater perceived physical pain, whereas social support is associated with lower pain perceptions. Few studies, however, have examined the joint effects of attachment and support on acute physical pain in a dyadic context. In this study, first-time expectant mothers (N=140) and their male partners completed romantic attachment measures (prenatally) and postnatal assessments of women's pain and men's emotional support during labor and delivery. More securely attached women benefited from emotional support in terms of reduced pain, more avoidantly attached women reported greater pain when given more support, and more anxiously attached women reported greater pain, regardless of their partner's support. These results advance our understanding of which women are most vulnerable to painful childbirth.


Mediator-Microorganism Interaction in Microbial Solar Cell: a Fluo-Electrochemical Insight.
Microbial solar cells that mainly rely on the use of photosynthesic organisms are a promising alternative to photovoltaics for solar electricity production. In that way, we propose a new approach involving electrochemistry and fluorescence techniques. The coupled setup Electro-Pulse-Amplitude-Modulation ("e-PAM") enables the simultaneous recording of the produced photocurrent and fluorescence signals from the photosynthetic chain. This methodology was validated with a suspension of green alga Chlamydomonas reinhardtii in interaction with an exogenous redox mediator (2,6-dichlorobenzoquinone; DCBQ). The balance between photosynthetic chain events (PSII photochemical yield, quenching) and the extracted electricity can be monitored overtime. More particularly, the nonphotochemical quenching induced by DCBQ mirrors the photocurrent. This setup thus helps to distinguish the electron harvesting from some side effects due to quinones in real time. It therefore paves the way for future analyses devoted to the choice of the experimental conditions (redox mediator, photosynthetic organisms, and so on) to find the best electron extraction.


Skyrmion-Bubble Bundles in an X-Type Sr2 Co2 Fe28 O46 Hexaferrite above Room Temperature.
Magnetic skyrmions are spin swirls that possess topological nontriviality and are considered particle-like entities. They are distinguished by an integer topological charge Q. The presence of skyrmion bundles provides an opportunity to explore the range of values for Q, which is crucial for the advancement of topological spintronic devices with multi-Q properties. In this study, a new material candidate, Sr2 Co2 Fe28 O46 hexaferrite of the X-type, which hosts small dipolar skyrmions at room temperature and above is presented. By exploiting reversed magnetic fields from metastable skyrmion bubbles at zero fields, skyrmion-bubble bundles with different interior skyrmion/bubble numbers, topological charges, and morphologies at room temperature are incorporated. These experimental findings are consistently supported by micromagnetic simulations. These results highlight the versatility of topological spin textures in centrosymmetric uniaxial magnets, thereby paving the way for the development of room-temperature topological spintronic devices with multi-Q characteristics.


Effect of olive mill wastewaters on the oxygen consumption by activated sludge microorganisms: an acute toxicity test method.
The test for inhibition of oxygen consumption by activated sludge (ISO 8192-1986 (E)) was evaluated as a tool for assessing, the acute toxicity of olive mill wastewaters (OMW). According to the ISO test, information generated by this method may be helpful in estimating the effect of a test material on bacterial communities in the aquatic environment, especially in aerobic biological treatment systems. However, the lack of standardized bioassay methodology for effluents imposed that the test conditions were modified and adapted. The experiments were conducted in the presence or absence of an easily biodegradable carbon source (glucose) with different contact times (20 min and 24 h). The results obtained showed a remarkable stimulatory effect of this effluent to the activated sludge microorganisms. In fact, the oxygen uptake rate values increase with increasing effluent concentrations and contact times up to 0.98 microl O(2) h(-1) mg(-1) dry weight for a 100% OMW sample, 24 h contact time, with blanks exhibiting an oxygen uptake rate of ca. 1/10 of this value (0.07-0.10). It seems that the application of the ISO test as an acute toxicity test for effluents should be reconsidered, with convenient adaptation for its utilization as a method of estimating the effect on bacterial communities present in aerobic biological treatment systems.


Rebound nystagmus in olivocerebellar atrophy: a clinicopathological correlation.
Rebound nystagmus was recorded in a patient with cerebellar dysfunction. Neuropathological examination showed degeneration of the inferior olivary nuclei and the cerebellar cortex. The basis pontis and the brainstem tegmentum were spared. Rebound nystagmus is attributed to a smooth eye movement bias that is generated within intact vestibuloocular pathways to oppose gaze-evoked centripetal drift of the eyes. The source of the rebound bias was not visual, because rebound nystagmus normally occurs in darkness, smooth pursuit was paretic, and the olivocerebellar visual relay pathway was degenerated. An extraretinal, efference copy signal of the eye position error must detect the ocular drift and generate the rebound bias. The neuropathological findings indicate that rebound nystagmus can be a sign of involvement confined to the olivocerebellar circuit and that nonvisual signals of eye position are monitored independently of this cerebellar system.


The Effect of Sitagliptin on the Regression of Carotid Intima-Media Thickening in Patients with Type 2 Diabetes Mellitus: A Post Hoc Analysis of the Sitagliptin Preventive Study of Intima-Media Thickness Evaluation.
Background. The effect of dipeptidyl peptidase-4 (DPP-4) inhibitors on the regression of carotid IMT remains largely unknown. The present study aimed to clarify whether sitagliptin, DPP-4 inhibitor, could regress carotid intima-media thickness (IMT) in insulin-treated patients with type 2 diabetes mellitus (T2DM). Methods. This is an exploratory analysis of a randomized trial in which we investigated the effect of sitagliptin on the progression of carotid IMT in insulin-treated patients with T2DM. Here, we compared the efficacy of sitagliptin treatment on the number of patients who showed regression of carotid IMT of ≥0.10 mm in a post hoc analysis. Results. The percentages of the number of the patients who showed regression of mean-IMT-CCA (28.9% in the sitagliptin group versus 16.4% in the conventional group, P = 0.022) and left max-IMT-CCA (43.0% in the sitagliptin group versus 26.2% in the conventional group, P = 0.007), but not right max-IMT-CCA, were higher in the sitagliptin treatment group compared with those in the non-DPP-4 inhibitor treatment group. In multiple logistic regression analysis, sitagliptin treatment significantly achieved higher target attainment of mean-IMT-CCA ≥0.10 mm and right and left max-IMT-CCA ≥0.10 mm compared to conventional treatment. Conclusions. Our data suggested that DPP-4 inhibitors were associated with the regression of carotid atherosclerosis in insulin-treated T2DM patients. This study has been registered with the University Hospital Medical Information Network Clinical Trials Registry (UMIN000007396).


Movement-related modulation in mouse auditory cortex is widespread yet locally diverse.
Neurons in the mouse auditory cortex are strongly influenced by behavior, including both suppression and enhancement of sound-evoked responses during movement. The mouse auditory cortex comprises multiple fields with different roles in sound processing and distinct connectivity to movement-related centers of the brain. Here, we asked whether movement-related modulation might differ across auditory cortical fields, thereby contributing to the heterogeneity of movement-related modulation at the single-cell level. We used wide-field calcium imaging to identify distinct cortical fields followed by cellular-resolution two-photon calcium imaging to visualize the activity of layer 2/3 excitatory neurons within each field. We measured each neuron's responses to three sound categories (pure tones, chirps, and amplitude modulated white noise) as mice rested and ran on a non-motorized treadmill. We found that individual neurons in each cortical field typically respond to just one sound category. Some neurons are only active during rest and others during locomotion, and those that are responsive across conditions retain their sound-category tuning. The effects of locomotion on sound-evoked responses vary at the single-cell level, with both suppression and enhancement of neural responses, and the net modulatory effect of locomotion is largely conserved across cortical fields. Movement-related modulation in auditory cortex also reflects more complex behavioral patterns, including instantaneous running speed and non-locomotor movements such as grooming and postural adjustments, with similar patterns seen across all auditory cortical fields. Our findings underscore the complexity of movement-related modulation throughout the mouse auditory cortex and indicate that movement-related modulation is a widespread phenomenon.


Facts on the fragmentation of antigens in presenting cells, on the association of antigen fragments with MHC molecules in cell-free systems, and speculation on the cell biology of antigen processing.
The processing of a protein antigen is a multi-step event taking place in antigen-presenting cells. Processing is a prerequisite for the recognition of most antigens by T lymphocytes. The antigen is ingested by endocytosis, transported to an acid cellular compartment and subjected to proteolytic fragmentation. Some of the antigen fragments bind to MHC class II molecules and are transported to the surface of the antigen-presenting cell where the actual presentation to T lymphocytes occurs. The nature of the processed antigen, how and where it is derived and subsequently becomes associated with MHC molecules are the questions discussed in this review. To us, the entire concept of processing has appeal not only because it explains some hitherto well-established, but poorly understood, phenomena such as the fact that T lymphocytes focus their attention entirely upon antigens on other cells. It has appeal also because processing allows for a thorough scrutiny of all the proteins of a cell including both the proteins which have been taken up from the environment (mostly MHC class II-restricted) and the cell's own proteins (mostly MHC class I-restricted). Through the mechanism of processing fragments of all these proteins including "internal" fragments which are not present on the globular protein's surface are brought out on the cell surface in association with MHC molecules and displayed to the T-lymphocyte system. This allows for the identification and, if necessary, the destruction of cells which in their interior harbor abnormal proteins, be they derived from virus-encoded genes or other abnormal genes.


Competing evaporation and condensation processes during the boiling of methane.
The atomistic mechanism of the boiling of methane is explored from molecular dynamics simulations. The liquid --> vapor transition is initiated by local density fluctuations resulting in a nanometer-sized domain that exhibits both liquid and vapor characteristics. Though the rates of evaporation and condensation events increase dramatically in this area, the overall balance exhibits only a marginal net rate of evaporation. Growth of the precritical domain leads to the nucleation of a vapor phase in which isolated methane molecules are confined by a liquid-vapor interface. After crossing the transition state, the system experiences progressive destabilization of the liquid phase and the evaporation processes clearly outnumber the condensation events.


Intrahepatic cholestasis after liver transplantation.
Cholestasis is a common sequela of liver transplantation. Although the majority of cases remain subclinical, severe cholestasis may be associated with irreversible liver damage, requiring retransplantation. Therefore, it is essential that clinicians be able to identify and treat the syndromes associated with cholestasis. In this review, we consider causes of intrahepatic cholestasis. These may be categorized by time of occurrence, namely, within 6 months of liver transplantation (early) and thereafter (late), although there may be an overlap in their causes. The causes of intrahepatic cholestasis include ischemia/reperfusion injury, bacterial infection, acute cellular rejection, cytomegalovirus infection, small-for-size graft, drugs for hepatotoxicity, intrahepatic biliary strictures, chronic rejection, hepatic artery thrombosis, ABO blood group incompatibility, and recurrent disease. The mechanisms of cholestasis in each category and the clinical presentation, diagnosis, treatment, and outcome are discussed in detail.


[A comparison of the serological effects of classical cholera vaccine and of purified fraction vaccine, with or without simultaneous yellow fever vaccine (author's transl)].
In order to test whether simultaneously administered cholera vaccine has a depressive effect on yellow fever vaccine, a controlled trial was undertaken on school-age children in the South-Central Province of Cameroun. In addition to this principle objective, the study also permitted a comparison of the serological response in subjects vaccinated with classical cholera vaccine and in those vaccinated with a purified fraction vaccine, either with or without simultaneous yellow fever vaccine. The evaluation was measured by changes in vibriocidal antibodies and cholera agglutinins 30 days after vaccination. Only subjects without cholera antibodies prior to the study, were included. 1) Results obtained by assay of vibriocidal antibodies. It was confirmed that, no matter which cholera vaccine was used, the simultaneous administration of yellow fever vaccine had no influence on the percentage of subjects showing a significant rise in vibriocidal antibodies (4-fold increase in titre) following vaccination. In addition, in this study the purified fraction vaccine resulted in a significantly higher rate of seroconversion than did the classical vaccine. However, in comparison to other studies using classical cholera vaccine, our figures for seroconversion after purified fraction vaccine show very little, if any, differences. 2) Results obtained by assay of agglutinating antibodies. When measured by this method, there was a high frequency of non-reactors to the vaccines. This may be attributed to the date of the post vaccination blood speciment (30th day after vaccination). It has been shown that agglutinins decay rapidly after the 15th day following clinical cholera. Thus, the late date of the second speciment after vaccination could explain why we were unable to show any difference in the level of agglutinin after either classical or purified cholera vaccination. The simultaneous administration of the yellow fever vaccine did not influence the titre of agglutinins induced by the classic cholera vaccine. On the other hand, using the association, the seroconversion rate as observed on the 30th day post vaccination was significantly higher than that observed when the fraction was administered alone. If one accepts the generally admitted specificity of the agglutination reaction after clinical disease, two hypotheses can be considered: a) the yellow fever vaccine has an adjuvant effect for the production of antibodies induced by the purified fraction vaccine, or b) the addition of yellow fever vaccine has a retarding effect on the elimination of the agglutinins which, in the natural disease, are rapidly eliminated. Further studies to verify these hypothesis should be undertaken.


Interactions of selenate with copper(I) oxide particles.
The chemical mechanisms responsible for the immobilization of selenate (SeO4(2-) from aqueous solutions on cuprite (Cu2O) particles were determined from batch experiments. This was achieved by performing both solution-phase analyses and characterization of solid particles by X-ray photoelectron spectroscopy and transmission electron microscopy techniques, after equilibration of cuprite particles with selenate-containing solutions at various pH values, solid-to-solution ratios, and ionic strengths. Two distinct mechanisms have been pointed out. In the acidic medium, where the acid-catalyzed dissolution of cuprite into CuI species occurs, the immobilization of selenate implies a redox reaction with transient CuI leading to the precipitation of copper(II) selenite, CuSeO3. In the absence of protons added in the medium, Cu2O is chemically stable and immobilization of SeO4(2-) is essentially due to adsorption in the form of an outer-sphere surface complex. The uptake level of selenate by Cu2O is markedly lower than that observed for selenite species in the same conditions.


[Influence of functional status of ovaries on results of controlled ovarian hyperstimulation].
The controlled ovarian hyperstimulation is an integral part of infertility treatment. Its main objective is to obtain oocytes with a highest developmental potential. The stimulation protocols involving the gonadotropin-releasing hormone analogues and gonadotropins are considered as the most efficient. Despite many years of use, some aspects of controlled ovarian stimulation has not yet been clarified, especially the role of the functional status of ovaries before hormonal stimulation. The aim of study was to assess the influence of the functional status of ovaries on the results of the controlled ovarian hyperstimulation. The retrospective study included female patients suffering from infertility The patients were divided into two groups depending on ultrasonographic appearance of ovaries before controlled ovarian hyperstimulation. The patients with small antral follicles < 6 mm in diameter were selected into group I. The patients with five or more antral follicles > or = 8 mm in diameter in each ovary were included into group II. The patients from both groups underwent similar treatment process. The major area of interest was the number, type and quality of oocytes obtained from patients from both groups after ovarian puncture. A retrospective study was conducted on 635 infertile patients (group I 382, group II 253). Altogether, 4055 oocytes were obtained in the group I and 2555 oocytes in the group II. The mean number of MII oocytes in group I was 9,2 and 8,7 in group II; p < 0.05. There were significantly more MI oocytes in group I than II. The mean numbers of immature oocytes were comparable between groups. The athretic and dysmorphic oocytes were more prevalent in group II. The results of the present study indicates that the functional status of ovaries before controlled ovarian hyperstimulation plays pivotal role for the treatment outcome.


The cellular basis of allograft rejection in vivo. III. Restoration of first-set rejection of heart grafts by T helper cells in irradiated rats.
An adoptive transfer model was used to examine the subpopulations of lymphocytes required to effect first-set rejection of directly vascularized heart allografts. PVG heart grafts are not rejected in irradiated DA hosts for at least 50 days. The adoptive transfer of 5 X 10(7) syngeneic lymph node cells (LNC) restores rejection to 14.4 +/- 2.4 days (mean +/- SD). Subpopulations of LNC, were separated by an indirect "panning" technique using the mouse antirat monoclonal antibodies W3/13, MRC OX8, or W3/25 to deplete the unwanted subsets of cells. Each subpopulation was tested, in a number equivalent to the number present in 5 X 10(7) normal LNC, for its ability to cause the rejection of heart grafts. Whole T cells (W3/13+) or helper/inducer T cells (W3/25+) restored graft rejection to 16.4 +/- 3.8 d and 16.0 +/- 2.4 days, respectively. Neither cytotoxic/suppressor T cells (MRC OX8+) nor B cells (Ig+) restored rejection. Indirect immunoperoxidase stains of the grafts showed that although W3/25+ cells predominated in the rejected tissue, MRC OX8+ cells were also present even in grafts from rats restored with inocula that contained less than 1% MRC OX8+ cells. Examination of lymphoid tissues suggested that the MRC OX8+ cells might be of host origin. By the time the grafts were rejected in irradiated hosts, significant thymic regeneration had occurred and there were large numbers of MRC OX8+ cells present in the thymus, as well as some in lymph nodes and spleen.


Low prevalence of BK virus nephropathy on nonprotocol renal biopsies in Iranian kidney transplant recipients: one center's experience and review of the literature.
BK virus-associated nephropathy in renal transplant recipients has been increasing in frequency in recent years. This rise is probably because of widespread use of highly potent immunosuppressive regimens, and increased immunosuppression load leads to inability of the recipients to increase a successful antiviral immune response. The incidence of BK virus-associated nephropathy in different reports is between 1% and 10%, with an allograft loss in significant numbers of patients, especially when timely diagnosis and treatment is not restored. We report our experience on BK virus nephropathy in our institute. All renal transplant biopsies performed at our center between 2001 and 2006 were immunohistochemically screened for the presence of PV-specific protein (SV40 Ag). The histologic diagnosis of BK virus-associated nephropathy was made upon the observation of morphologic changes in tubular epithelium and confirmation with immunohistochemical staining. We reviewed the clinical records of the subjects for demographic, clinical, and laboratory data. BK virus nephropathy was found in 0.93% of all investigated allograft biopsies (1/108) and in 1.04% of all recipients (1/96; mean age of recipients, 36.48±14.10 years; age range, 13-74 years); 54 of them were male (57%). Type of kidney transplant was living-unrelated donor 76 (79%), living-related donor 13 (14%), and deceased donor 7. Seventeen patients (18%) were transplanted for a second time. Immunosuppressive drugs in 87 of recipients (90%) were cyclosporine, mycophenolate mofetil, and prednisolone. Our patient who developed BK virus-associated nephropathy 9 months after transplant was a 37-year-old man on prednisone, cyclosporine, and azathioprine immunosuppresion. He lost his graft 4 months after diagnosis. Although BK virus nephropathy after renal transplant is uncommon, it is a serious complication causing loss of the allograft. It should be included in the clinical differential diagnosis of transplant dysfunction.


Marmoset pulmonary cytochrome P450 2F1 oxidizes biphenyl and 7-ethoxycoumarin and hepatic human P450 substrates.
1. A potentially useful animal model for preclinical studies is the common marmoset (Callithrix jacchus). In this study, using reverse-transcription polymerase chain reaction from marmoset livers, we identified a novel cytochrome P450 (P450) 2F1 cDNA with an open reading frame of 1473 bp. 2. High sequence identities of 92-94% with primate P450 2 F amino acid sequences were indicated by deduced amino acid sequences of P450 2F1 cDNA. Phylogenetic analysis indicates that marmoset P450 2F1 is more congruent with primate P450 2 F forms than those of other species such as rodents. 3. Among five tissue types examined, abundant expression of marmoset P450 2F1 mRNA and P450 2F1 protein in lungs was shown. Cynomolgus monkey P450 2F1 mRNA was abundantly expressed in lungs as well as testes and ovaries in 10 tissue types. 4. Similar to those of humans and cynomolgus monkeys, marmoset P450 2F1 heterologously expressed in Escherichia coli membranes efficiently catalyzed 7-ethoxycoumarin O-deethylation and biphenyl hydroxylation, however unlike human P450 2F1, marmoset P450 2F1 exhibited hydroxylation activity toward coumarin and chlorzoxazone. 5. These findings indicated that P450 2F1 enzyme expressed in marmoset lungs and also catalyzed metabolism of xenobiotics, suggesting the importance of P450 2 F-dependent drug metabolism in marmoset lungs.


Antidepressant-like effects and possible mechanisms of amantadine on cognitive and synaptic deficits in a rat model of chronic stress.
The aim of this study was to examine whether amantadine (AMA), as a low-affinity noncompetitive N-methyl-d-aspartate (NMDA) receptor antagonist, is able to improve cognitive deficits caused by chronic stress in rats. Male Wistar rats were divided into four groups: control, control + AMA, stress and stress + AMA groups. The chronic stress model combined chronic unpredictable stress (CUS) with isolated feeding. Animals were exposed to CUS continued for 21 days. AMA (25 mg/kg) was administrated p.o. for 20 days from the 4th day of CUS to the 23rd. Weight and sucrose consumption were measured during model establishing period. Spatial memory was evaluated using the Morris water maze (MWM) test. Following MWM testing, both long-term potentiation (LTP) and depotentiation were recorded in the hippocampal CA1 region. NR2B and postsynaptic density protein 95 (PSD-95) proteins were measured by Western-blot analysis. AMA increased weight and sucrose consumption of stressed rats. Spatial memory and reversal learning in stressed rats were impaired relative to controls, whereas AMA significantly attenuated cognitive impairment. AMA also mitigated the chronic stress-induced impairment of hippocampal synaptic plasticity, in which both the LTP and depotentiation were significantly inhibited in stressed rats. Moreover, AMA enhanced the expression of hippocampal NR2B and PSD-95 in stressed rats. The data suggest that AMA may be an effective therapeutic agent for depression-like symptoms and associated cognitive disturbances.


Applications of NMR to membrane proteins.
Membrane proteins present a challenge for structural biology. In this article, we review some of the recent developments that advance the application of NMR to membrane proteins, with emphasis on structural studies in detergent-free, lipid bilayer samples that resemble the native environment. NMR spectroscopy is not only ideally suited for structure determination of membrane proteins in hydrated lipid bilayer membranes, but also highly complementary to the other principal techniques based on X-ray and electron diffraction. Recent advances in NMR instrumentation, spectroscopic methods, computational methods, and sample preparations are driving exciting new efforts in membrane protein structural biology.


Genomic characterisation of Eμ-Myc mouse lymphomas identifies Bcor as a Myc co-operative tumour-suppressor gene.
The Eμ-Myc mouse is an extensively used model of MYC driven malignancy; however to date there has only been partial characterization of MYC co-operative mutations leading to spontaneous lymphomagenesis. Here we sequence spontaneously arising Eμ-Myc lymphomas to define transgene architecture, somatic mutations, and structural alterations. We identify frequent disruptive mutations in the PRC1-like component and BCL6-corepressor gene Bcor. Moreover, we find unexpected concomitant multigenic lesions involving Cdkn2a loss and other cancer genes including Nras, Kras and Bcor. These findings challenge the assumed two-hit model of Eμ-Myc lymphoma and demonstrate a functional in vivo role for Bcor in suppressing tumorigenesis.


Knowledge, non-use, use and source of information on contraceptive methods among women in various stages of reproductive age in rural Lagos, Southwest Nigeria.
Contraceptives are advocated to be used against unwanted pregnancy and sexually transmitted diseases as unsafe abortion contributes to high maternal mortality in Nigeria while unwanted pregnancies have terminated the educational development of many females. This questionnaire-based survey aimed to describe the knowledge, nonuse, and use of various contraceptive methods among women in different child-bearing age groups in rural Lagos, Nigeria. Between 2012 and 2013, 816 females in rural communities within Lagos State were surveyed for their knowledge, source of information, and use of contraceptives. They were grouped into early, mid, and late reproductive age. Statistical analysis of data harvested from respondents was carried out using STATA 13 software. In all, 816 females in different stages of reproductive age were involved in the study, among whom 19% were single, 78% married, 3% divorced, and 0.5% widowed. About 6% had no formal education, while the majority (81%) were of the Yoruba ethnic group. Married respondents were approximately thrice more likely to know of contraceptives than single respondents (χ2 =29.9, P=0.000, odds ratio =2.9, 95% confidence interval =1.9, 4.2). Condom use was the most widely known and used method of contraceptive regardless of marital status and reproductive age status. Information about contraceptives was mainly from health facilities among married and divorced women and from school or educational institution among singles. Overall prevalence of contraceptive use was 51.9%. Nonuse of contraceptives was 43% among married women and 67% among singles. Knowledge of contraceptive method was negatively associated with marital status (t=-2.24, P=0.025) but positively associated with source of information on contraceptives (t=20.00, P=0.000). Use of contraceptives was positively associated with stage of reproductive age (t=1.94, P=0.05) and source of information on contraceptives (t=11.22, P=0.000), but negatively associated with marital status (t=-2.79, P=0.005) and religious belief (t=-1.89, P=0.05). Knowledge and use or nonuse of contraceptives could be pivotal in designing adequate prenatal care to prevent unwanted pregnancy and consequently illegal abortion or possible adverse pregnancy outcomes such as low birth weight, preterm birth, and conditions such as small for gestational age. Data from this study can also be used to design penetrating health education on making pregnancy safer or living a healthy female reproductive life.


Nuclear identity specifies transcriptional initiation in plant mitochondria.
Alterations in mitochondrial gene expression and abnormal floral phenotypes, such as male sterility, characterize alloplasmic plants having the nucleus from Nicotiana tabacum combined with the cytoplasm from Nicotiana repanda. In all Nicotiana species investigated the mitochondrial atpl gene is co-transcribed with the upstream orf274; however, unique for alloplasmic plants is a marked accumulation of these mitochondrial co-transcripts. In the present work, we show that a major component of the transcript difference is that in the alloplasmic male-sterile plants transcription initiates from novel sites internal to orf274. The sequences surrounding these initiation sites lack the CRTA consensus motif for plant mitochondrial promoters as well as similarity to other known plant mitochondrial promoters. Thus, initiation of transcription is under control of a mitochondrial promoter of a novel non-consensus type. This non-consensus promoter is inactivated when the fertility restoring heritable fragment chromosome from N. repanda is present in the N. tabacum nucleus of the alloplasmic plants. Our data suggest that the fertility-restoring fragment chromosome encodes a factor that represses initiation from this unusual promoter.


Arbuscular mycorrhizal fungal communities differ in neighboring vineyards of different ages.
Arbuscular mycorrhizal fungi (AMF) are key organisms in viticultural ecosystems as they provide many ecosystem services to soils and plants. Data about AMF community dynamics over time are relatively scarce and at short time scales. Many factors such as the soil, climate, and agricultural practices could modify the dynamics and functions of microbial communities. However, the effects on microbial communities of plant phenology and changes in plant physiology over time largely have been overlooked. We analyzed the diversity of AMF in three geographically close vineyards with similar soil parameters for 2 years. The plots differed in grapevine age (11, 36, and 110 years), but had the same soil management practice (horse tillage). Diversity analyses revealed a difference in the composition of AMF communities between the soil and grapevine roots and among roots of grapevines of different ages. This underlines AMF adaptation to physiological changes in the host which can explain the development of different AMF communities. The dynamics of AMF communities can highlight their resilience to environmental changes and agricultural practices.


Recurrence of frozen shoulder after manipulation under anaesthetic (MUA): the results of repeating the MUA.
Manipulation under anaesthetic (MUA) is a recognised form of treatment for patients with a frozen shoulder. However, not all patients benefit. Some have persistent or recurrent symptoms. There are no clear recommendations in the literature on the optimal management of recurrent frozen shoulder after a MUA. We aimed to address this issue in this study. We analysed a prospectively collected, single-surgeon, consecutive series of patients who underwent MUA for frozen shoulder between January 1999 and December 2015. The Oxford Shoulder Scores (OSS) and range of movement were the outcome measures. A total of 730 patients (792 shoulders) underwent MUA during the study period. A further MUA was undertaken in 141 shoulders (17.8%), for which we had complete data for 126. The mean improvement in OSS for all patients undergoing MUA was 16 (26 to 42), and the mean post-operative OSS in those requiring a further MUA was 14 (28 to 42; t-test, no difference between mean improvements, p = 0.57). Improvement was seen after a further MUA, regardless both of the outcome of the initial MUA, and of the time of recurrence. Patients with type-1 diabetes mellitus were at a 38% increased risk of requiring a further MUA, compared with the 18% increased risk of the group as a whole (p < 0.0001). Patients with a poor outcome or recurrent symptoms of a frozen shoulder after a MUA should be offered a further MUA with the expectation of a good outcome and a low complication rate. Cite this article: Bone Joint J 2017;99-B:812-17.


Debridement and wound bed preparation.
Debridement can play a vital role in wound bed preparation and the removal of barriers that impair wound healing. In accordance with the TIME principles, debridement can help remove nonviable tissue, control inflammation or infection, decrease excess moisture, and stimulate a nonadvancing wound edge. There are many types of debridement, each with a set of advantages and disadvantages that must be clearly understood by the healthcare team. Failure to use the correct debridement method for a given type of wound may lead to further delays in healing, increase patient suffering, and unnecessarily increase the cost of care. This review article discusses the various methods of debridement, describes currently available debriding agents, evaluates the clinical data regarding their efficacy and safety, and describes strategies for the management of problematic nonhealing wounds.


Mechanisms of sterol uptake and transport in yeast.
Sterols are essential lipid components of eukaryotic membranes. Here we summarize recent advances in understanding how sterols are transported between different membranes. Baker's yeast is a particularly attractive organism to dissect this lipid transport pathway, because cells can synthesize their own major sterol, ergosterol, in the membrane of the endoplasmic reticulum from where it is then transported to the plasma membrane. However, Saccharomyces cerevisiae is also a facultative anaerobic organism, which becomes sterol auxotroph in the absence of oxygen. Under these conditions, cells take up sterol from the environment and transport the lipid back into the membrane of the endoplasmic reticulum, where the free sterol becomes esterified and is then stored in lipid droplets. Steryl ester formation is thus a reliable readout to assess the back-transport of exogenously provided sterols from the plasma membrane to the endoplasmic reticulum. Structure/function analysis has revealed that the bulk membrane function of the fungal ergosterol can be provided by structurally related sterols, including the mammalian cholesterol. Foreign sterols, however, are subject to a lipid quality control cycle in which the sterol is reversibly acetylated. Because acetylated sterols are efficiently excreted from cells, the substrate specificity of the deacetylating enzymes determines which sterols are retained. Membrane-bound acetylated sterols are excreted by the secretory pathway, more soluble acetylated sterol derivatives such as the steroid precursor pregnenolone, on the other hand, are excreted by a pathway that is independent of vesicle formation and fusion. Further analysis of this lipid quality control cycle is likely to reveal novel insight into the mechanisms that ensure sterol homeostasis in eukaryotic cells. Article from a special issue on Steroids and Microorganisms.


Enhancing reciprocity between mother and neonate.
Thirty mothers of newborn infants were assigned to one of three equal-sized treatment groups to assess the effects on maternal responsiveness of an early intervention designed to familiarize mothers with the capabilities and individual characteristics of their infants. Mothers in one treatment group observed the administration of the Brazelton Neonatal Behavior Assessment Scale to their infants, were given an explanation of each item on the scale, and were told their infants' responses. Mothers in a second group were given the same individualized explanations about the scale items and their infants' responses, but did not observe the events. A third group of mothers, which served as control group, received individual instruction on infant furnishings. Maternal responsiveness was enhanced significantly in the "show-and-tell" group but not in the "tell-only" group. Parallel effects on infant responsiveness were also observed. '


Reversal of phenylpropanolamine anorexia in rats by the alpha-1 receptor antagonist benoxathian.
Phenylpropanolamine (PPA) is a phenethylamine anorectic drug that exerts direct agonist effects predominantly on alpha-1 adrenergic receptors, with some alpha-2 adrenergic activity. Direct injections of PPA as well as the alpha-1 agonist 1-phenylephrine into rat paraventricular nucleus (PVN) suppress feeding. In the present study, we evaluate the hypothesis that systemic PPA acts within the PVN on an alpha-1 receptor population to suppress feeding. Accordingly, adult male rats were prepared with a unilateral guide cannula aimed at the PVN. Microinjection of the alpha-1 adrenergic receptor antagonist benoxathian (0, 2.5, 5.0 or 10.0 nmol) into the PVN was found to have no effect on baseline feeding behavior. Microinjection of 10.0 nmol benoxathian into the PVN completely reversed the anorexia induced by 2.5, 5.0 or 10.0 mg/kg PPA (IP), yet did not alter the hypodipsia produced by PPA. These data strongly suggest that PPA anorexia is mediated by an alpha-1 adrenergic satiety mechanism within the PVN.


Alterations of dopaminergic and noradrenergic innervations in motor cortex in Parkinson's disease.
The motor areas of the cerebral cortex contain dense dopaminergic and noradrenergic innervation in humans. We looked for changes of these innervations in cases with Parkinson's disease (PD). The density of fibers immunolabeled with tyrosine hydroxylase or dopamine-beta-hydroxylase was evaluated in the primary motor, premotor, and prefrontal cortical regions in 6 cases with PD and 7 control cases. Reductions of both noradrenergic and dopaminergic cortical innervations were observed, with similar magnitudes of reduction found in the motor and prefrontal regions of the cortex. Depletion of noradrenergic innervation was diffuse, involving all cortical laminae. Depletion of dopaminergic innervation was laminar specific, with the most significant reductions in layers I and II; reductions in layers V and VI were either less marked (prefrontal cortex) or not detectable (primary motor). The results suggest the existence of two separate mesocortical dopaminergic systems in humans, with the one distributing to upper cortical layers being preferentially involved in PD.


Mitochondrial Sirtuins in cardiometabolic diseases.
Mitochondria are heterogeneous and essentially contribute to cellular functions and tissue homeostasis. Mitochondrial dysfunction compromises overall cell functioning, tissue damage, and diseases. The advances in mitochondrion biology increase our understanding of mitochondrial dynamics, bioenergetics, and redox homeostasis, and subsequently, their functions in tissue homeostasis and diseases, including cardiometabolic diseases (CMDs). The functions of mitochondria mainly rely on the enzymes in their matrix. Sirtuins are a family of NAD+-dependent deacylases and ADP-ribosyltransferases. Three members of the Sirtuin family (SIRT3, SIRT4, and SIRT5) are located in the mitochondrion. These mitochondrial Sirtuins regulate energy and redox metabolism as well as mitochondrial dynamics in the mitochondrial matrix and are involved in cardiovascular homeostasis and CMDs. In this review, we discuss the advances in our understanding of mitochondrial Sirtuins in mitochondrion biology and CMDs, including cardiac remodeling, pulmonary artery hypertension, and vascular dysfunction. The potential therapeutic strategies by targetting mitochondrial Sirtuins to improve mitochondrial function in CMDs are also addressed.


Inhibition of NADPH oxidase activation by 4-(2-aminoethyl)-benzenesulfonyl fluoride and related compounds.
The elicitation of an oxidative burst in phagocytes rests on the assembly of a multicomponental complex (NADPH oxidase) consisting of a membrane-associated flavocytochrome (cytochrome b559), representing the redox element responsible for the NADPH-dependent reduction of oxygen to superoxide (O-2), two cytosolic components (p47(phox), p67(phox)), and the small GTPase Rac (1 or 2). We found that 4-(2-aminoethyl)-benzenesulfonyl fluoride (AEBSF), an irreversible serine protease inhibitor, prevented the elicitation of O-2 production in intact macrophages and the amphiphile-dependent activation of NADPH oxidase in a cell-free system, consisting of solubilized membrane or purified cytochrome b559 combined with total cytosol or a mixture of recombinant p47(phox), p67(phox), and Rac1. AEBSF acted at the activation step and did not interfere with the ensuing electron flow. It did not scavenge oxygen radicals and did not affect assay reagents. Five other serine protease inhibitors (three irreversible and two reversible) were found to lack an inhibitory effect on cell-free activation of NADPH oxidase. A structure-function study of AEBSF analogues demonstrated that the presence of a sulfonyl fluoride group was essential for inhibitory activity and that compounds containing an aminoalkylbenzene moiety were more active than amidinobenzene derivatives. Exposure of the membrane fraction or of purified cytochrome b559, but not of cytosol or recombinant cytosolic components, to AEBSF, in the presence of a critical concentration of the activating amphiphile lithium dodecyl sulfate, resulted in a marked impairment of their ability to support cell-free NADPH oxidase activation upon complementation with untreated cytosol or cytosolic components. Kinetic analysis of the effect of varying the concentration of each of the three cytosolic components on the inhibitory potency of AEBSF indicated that this was inversely related to the concentrations of p47(phox) and, to a lesser degree, p67(phox). AEBSF also prevented the amphiphile-elicited translocation of p47(phox) and p67(phox) to the membrane. These results are interpreted as indicating that AEBSF interferes with the binding of p47(phox) and/or p67(phox) to cytochrome b559, probably by a direct effect on cytochrome b559.


Post-transplant lymphoproliferative disorders: T-cell lymphoma following cardiac transplant.
Post-transplant lymphoproliferative disorders (PTLD) are a frequently fatal complication occurring after transplant. The majority of cases are of B-cell origin but a smaller percentage of cases are of T-cell origin. The etiology of these disorders is unclear, however, EBV (Epstein-Barr virus) in the context of immunosuppression is thought to play a role, particularly in B-cell PTLD. We report a case of T-cell PTLD limited to the bone marrow occurring eight years post-cardiac transplantation and review the literature on T-cell PTLD after heart transplant.


Increased systemic and regional coagulation activity in patients with mitral stenosis and sinus rhythm.
A hypercoagulable state has been reported in patients with mitral stenosis (MS) and sinus rhythm (SR). However it has been suggested that the coagulation activity may be increased only within the left atrium in MS, with normal peripheral blood levels. The aim of the present study was to assess regional left atrial and systemic coagulation activities by measuring PF1+2 in patients with severe mitral stenosis and sinus rhythm, normal blood clotting times, and no left atrial thrombus. The study was conducted in 25 consecutive patients with moderate-to-severe MS and sinus rhythm who underwent percutaneous balloon mitral valvuloplasty. Transesophageal echocardiography was performed before the valvuloplasty procedure in all patients to exclude the presence of left atrial thrombus and left atrial spontaneous echo contrast (LASEC). There were no statistically significant differences between LASEC-positive and LASEC-negative patients with respect to age, gender, fibrinogen levels, prothrombin time, mitral valve area, mean mitral gradient, pulmonary artery pressure (in all p > 0.05). Regional (left atrial) PF1+2 levels of both LASEC-positive and LASEC-negative patients were significantly elevated when compared to control subjects (p < 0.01). Statistically significant elevated systemic level of PF1+2 was observed only in LASEC-positive patients when compared to control subjects (p < 0.01, p > 0.05, respectively). In conclusion patients with severe mitral stenosis and SR have increased regional coagulation activity in both LASEC-negative and LASEC-positive groups. Although this increased regional coagulation activity has been reflected in peripheral blood of LASEC-positive patients, it has not been reflected in peripheral blood of LASEC-negative patients.


Detection of neuronal loss using T(1rho) MRI assessment of (1)H(2)O spin dynamics in the aphakia mouse.
The loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNc) is well characterized in Parkinson's disease (PD). Recent developments in magnetic resonance imaging (MRI) techniques have provided the opportunity to evaluate for changes in cellular density. Longitudinal relaxation measurements in the rotating frame (T(1rho)) provide a unique magnetic resonance imaging contrast in vivo. Due to the specificity of T(1rho) to water-protein interactions, the T(1rho) MRI method has strong potential to be used as a non-invasive method for quantification of neuronal density in the brain. Recently introduced adiabatic T(1rho) magnetic resonance imaging mapping methods provide a tool to assess molecular motional regimes with high sensitivity due to utilization of an effective magnetic field sweep during adiabatic pulses. In this work, to investigate the sensitivity of T(1rho) to alterations in neuronal density, adiabatic T(1rho) MRI measurements were employed in vivo on Pitx3-homeobox gene-deficient aphakia mice in which the deficit of DA neurons in the SNc is well established. The theoretical analysis of T(1rho) maps in the different areas of the brain of aphakia mouse suggested variation of the (1)H(2)O rotational correlation times, tau(c). This suggests tau(c) to be a sensitive indicator for neuronal loss during neurological disorders. The results manifest significant dependencies of the T(1rho) relaxations on the cell densities in the SNc, suggesting T(1rho) MRI method as a candidate for detection of neuronal loss in neurological disorders.


Evaluation of response to immune checkpoint inhibitors: Is there a role for positron emission tomography?
Strategies targeting intracellular negative regulators such as immune checkpoint inhibitors (ICPIs) have demonstrated significant antitumor activity across a wide range of solid tumors. In the clinical practice, the radiological effect of immunotherapeutic agents has raised several more relevant and complex challenges for the determination of their imaging-based response at single patient level. Accordingly, it has been suggested that the conventional Response Evaluation Criteria in Solid Tumors assessment alone, based on dimensional evaluation provided by computed tomography (CT), tends to underestimate the benefit of ICPIs at least in a subset of patients, supporting the need of immune-related response criteria. Different from CT, very few data are available for the evaluation of immunotherapy by means of 18F-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET). Moreover, since the antineoplastic activity of ICPIs is highly related to the activation of T cells against cancer cells, FDG accumulation might cause false-positive findings. Yet, discrimination between benign and malignant processes represents a huge challenge for FDG-PET in this clinical setting. Consequently, it might be of high interest to test the complex and variegated response to ICPIs by means of PET and thus it is worthwhile to ask if a similar introduction of immune-related PET-based criteria could be proposed in the future. Finally, PET might offer a new insight into the biology and pathophysiology of ICPIs thanks to a growing number of non-invasive immune-diagnostic approaches based on non-FDG tracers.


Effect of Caraway Seed Extract on the Blood Biochemistry and Antioxidant Capacity among the Hyperoxidative Stress-Induced Rats.
Carum carvi (Carium) or caraway is traditionally used for the treatment of several metabolic and non-metabolic disorders. In the current study, extracted oil, flavonoids, and alkaloids from the Carium were used to evaluate the effects of these components on blood lipid profile and heart regeneration from oxidative damages caused by hydrogen peroxide consumption. A total of 50 male BALB/c mice were used in this study with a body weight of 23-32 g. The animals were randomly divided into 5 groups (n=10). Group 1: The animals in this group were considered the control group and fed with a normal diet. Group 2: Hyperoxidative stress was induced in this group by giving hydrogen peroxide at a concentration of 1% into the drinking water for 6 weeks. After this period, they did not receive any treatments and only received saline solution by intraperitoneal (IP) injection once a day for 4 weeks. Group 3: Hyperoxidative stress was induced by hydrogen peroxide at a concentration of 1% for 6 weeks. All the animals in this group received 1.25 mg/kg body weight (B.W.) extracted oil from Caraway seeds for 4 weeks by IP injection once a day each week. Group 4: Hyperoxidative stress was induced by hydrogen peroxide at a concentration of 1% for 6 weeks. All the animals in this group received 61.28 mg/kg B.W. extracted flavonoids from Caraway seeds for 4 weeks by IP injection once a day each week. Group 5: Hyperoxidative stress was induced by hydrogen peroxide at a concentration of 1% for 6 weeks. All the animals in this group received 7.8 mg/kg B.W. extracted alkaloids from Caraway seeds for 4 weeks by IP injection once a day each week. The levels of glutathione and malondialdehyde were estimated in the liver and kidneys in the animals with cardiovascular disorders induced by hydrogen peroxide at a concentration of 1%. The results of the current study showed that the alkaloids had the greatest effect in reducing harmful total cholesterol and a complete recovery of the heart and aorta from atherosclerotic lesions through viewing the tissue sections.


Proteome Profiling of Mycobacterium tuberculosis Cells Exposed to Nitrosative Stress.
Reactive nitrogen species (RNS) are secreted by human cells in response to infection by Mycobacterium tuberculosis (Mtb). Although RNS can kill Mtb under some circumstances, Mtb can adapt and survive in the presence of RNS by a process that involves modulation of gene expression. Previous studies focused primarily on stress-related changes in the Mtb transcriptome. This study unveils changes in the Mtb proteome in response to a sub-lethal dose of nitric oxide (NO) over several hours of exposure. Proteins were identified using liquid chromatography coupled with electrospray ionization mass spectrometry (LC-MS/MS). A total of 2911 Mtb proteins were identified, of which 581 were differentially abundant (DA) after exposure to NO in at least one of the four time points (30 min, 2 h, 6 h, and 20 h). The proteomic response to NO was marked by two phases, with few DA proteins in the early phase and a multitude of DA proteins in the later phase. The efflux pump Rv1687 stood out as being the only protein more abundant at all the time points and might play a role in the early protection of Mtb against nitrosative stress. These changes appeared to be compensatory in nature, contributing to iron homeostasis, energy metabolism, and other stress responses. This study thereby provides new insights into the response of Mtb to NO at the level of proteomics.


Interdigital vs Transarticular Lateral Release With Scarf Osteotomy.
We compare the clinical and radiographic outcomes of the interdigital approach vs the medial transarticular approach for lateral release combined with scarf osteotomy. Seventy-seven feet with moderate to severe hallux valgus underwent scarf osteotomy and lateral soft tissue release, using an interdigital approach (n = 36) vs medial transarticular approach (n = 41). The clinical measurements (range of motion, American Orthopaedic Foot & Ankle Society [AOFAS] score) and radiographic data were evaluated preoperatively and at final follow-up (93-124 months postoperatively). Additionally, the numeric pain rating scale and Foot and Ankle Outcome score [FAOS] were assessed postoperatively. The AOFAS score improved from 60 (q1 = 54, q3 = 70) to 93 (q1 = 85, q3 = 98) in the transarticular group, and from 59 (q1 = 50, q3 = 64) to 95 (q1 = 85, q3 = 100) in the interdigital group. The hallux valgus angle improved from 35.7±6.5 degrees to 15.5±7.6 degrees in the transarticular group, and from 36.0±6.8 degrees to 12.9±13.0 degrees in the interdigital group. The intermetatarsal angle improved from 16.5±2.5 degrees to 6.5±2.7 degrees within the transarticular group and from 17.2±2.5 degrees to 7.3±4.3 degrees in the interdigital group. None of the clinical or radiographic parameters showed any significant differences between the treatment groups. Comparison of outcomes between the interdigital approach and the transarticular approach for lateral soft-tissue release with scarf osteotomy are equally successful. The transarticular approach can thus be considered safe and effective, with the additional benefits of just one scar as opposed to 2. Level III, therapeutic.