Protective Effect of Combined Moxibustion and Decoction Therapy on Bleomycin-Induced Pulmonary Fibrosis in Rats under Nuclear Factor-κB/Transforming Growth Factor-β1/Smads Signaling Pathway.
it was aimed to discuss the effect of moxibustion (Mox) combined with Bu Fei Qu Yu (BFQY) decoction under the nuclear factor-κB (NF-κB)/transforming growth factor-β1 (TGF-β1)/Smads signaling pathway in the treatment of pulmonary fibrosis (PF). The PF rat models were prepared with bleomycin (BLM). They were divided into the normal (Nor) group, the PF model group (BLM puncture perfusion), the Mox group (grain-sized Mox at the back-shu points and Xuxiao points), the BFQY group (intragastrical BFQY decoction), and the Mox combined with BFQY decoction (Mox+BFQY) group. Lung tissue sections were prepared, and the hematoxylin-eosin (HE) staining and Masson staining were performed to observe the inflammatory response and the degree of PF. The contents of hydroxyproline (HYP), glutathione (GSH), and malondialdehyde (MDA), and the expressions of NF-κB p65, TGF-β1, Smad2, and Smad7 in lung tissues were detected. Compared with those in the Nor group, the inflammatory response score, PF degree score, HYP, GSH, and MDA contents, NF-κB p65, TGF-β1, and Smad2 expressions were significantly increased in the PF group, but Smad7 expression decreased (P<0.05). The above symptoms were significantly improved in the Mox, BFQY, and Mox+ BFQY groups (P<0.05). The effect was more remarkable in the Mox+BFQY group, and there was no significant difference in each index compared with those in the Nor group (P>0.05). Thus, the combined therapy of Mox and decoction had an effect on PF through the NF-κB/TGF-β1/Smads pathway.


Possible control of subduction zone slow-earthquake periodicity by silica enrichment.
Seismic and geodetic observations in subduction zone forearcs indicate that slow earthquakes, including episodic tremor and slip, recur at intervals of less than six months to more than two years. In Cascadia, slow slip is segmented along strike and tremor data show a gradation from large, infrequent slip episodes to small, frequent slip events with increasing depth of the plate interface. Observations and models of slow slip and tremor require the presence of near-lithostatic pore-fluid pressures in slow-earthquake source regions; however, direct evidence of factors controlling the variability in recurrence times is elusive. Here we compile seismic data from subduction zone forearcs exhibiting recurring slow earthquakes and show that the average ratio of compressional (P)-wave velocity to shear (S)-wave velocity (vP/vS) of the overlying forearc crust ranges between 1.6 and 2.0 and is linearly related to the average recurrence time of slow earthquakes. In northern Cascadia, forearc vP/vS values decrease with increasing depth of the plate interface and with decreasing tremor-episode recurrence intervals. Low vP/vS values require a large addition of quartz in a mostly mafic forearc environment. We propose that silica enrichment varying from 5 per cent to 15 per cent by volume from slab-derived fluids and upward mineralization in quartz veins can explain the range of observed vP/vS values as well as the downdip decrease in vP/vS. The solubility of silica depends on temperature, and deposition prevails near the base of the forearc crust. We further propose that the strong temperature dependence of healing and permeability reduction in silica-rich fault gouge via dissolution-precipitation creep can explain the reduction in tremor recurrence time with progressive silica enrichment. Lower gouge permeability at higher temperatures leads to faster fluid overpressure development and low effective fault-normal stress, and therefore shorter recurrence times. Our results also agree with numerical models of slip stabilization under fault zone dilatancy strengthening caused by decreasing fluid pressure as pore space increases. This implies that temperature-dependent silica deposition, permeability reduction and fluid overpressure development control dilatancy and slow-earthquake behaviour.


Identification of Predictable Biomarkers in Conjunction to Framingham Risk Score to Predict the Risk for Cardiovascular disease (CVD) in Non Cardiac Subjects.
Although the cardiovascular disease (CVD) burden is rising in different countries, the morbidity and mortality rate is not reduced to much extent because of lack of application of the biomarkers for diagnosing CVD. Hence, we aimed to establish the predictable biomarkers in conjunction to framingham risk score in order to predict the risk for CVD in non cardiac patients. Three hundred subjects were screened for the study who came for the master health checkup. Out of them 50 patients were excluded as they were under medication. 23 patients were excluded due to various systemic diseases like fever and infection etc. The remaining of 227 patients with age range of 30-80 y was randomly selected for investigation. These subjects were divided into four different groups: Group I - controls with age range: 30-60 y (n=50) these subjects were free from all the systemic ailments and risk factors. Study groups comprised of Group II - (n=44) with age range: 30-40 y, Group III - (n=50) with age range: 41-50 y and Group IV - (n=83) with age range: 51-80 y. Patients with different risk factors without medication participated as study groups. Routine biochemical parameters were analysed using fully automated analyser and atherosclerotic biomarkers was analysed using ELISA kit. In addition to this, framingham risk scores was calculated in all the groups, for 30 y risk prognosis for CVD. The atherosclerotic biomarkers such as E-selectin, Leptin, osteoprotegerin (OPG) and Ox-LDL were elevated among the study groups as compared to control group. Pearson correlation showed a significant association between the individual risk score (30 y framingham risk for CVD) of individuals, and the above biomarkers. The Receiver operating curve (ROC) analysis also showed a greater area under curve with higher sensitivity and specificity. We conclude the application E-Selectin, leptin, OPG and Ox-LDL as biomarkers along with the framingham risk scores in prediction risk for CVD in the individuals with subclinical atherosclerosis. It is more reliable and predictable as compared to the individual biomarkers alone.


Isolation of smooth muscle cells from swine carotid artery by digestion with papain.
A new method is described for the preparation of viable, elongated smooth muscle cells from the swine carotid artery. Cells were prepared by papain digestion of pressurized arteries in calcium-free solution. After digestion, the arteries were everted, and fine strips were teased from the intimal surface of the media in calcium-free solution, releasing single cells. Viability was assessed by exclusion of trypan blue and by appearance under phase-contrast microscopy. By these criteria, approximately 20% of the isolated cells were viable. The most distinguishing and unexpected characteristic of these cells was their length. Mean length of the relaxed viable cells was 240.4 +/- 47.4 microns (SD, n = 76), which is much longer than previously reported for arterial smooth muscle cells. Calcium (1.6 mM) caused most of the viable cells to contract slightly, and the mean cell length in calcium was 194.4 +/- 57.7 microns. Cells in 1.6 mM calcium contracted substantially in response to 10 microM histamine or the calcium ionophore A23187 (10 microM), demonstrating that histamine receptors and the contractile apparatus were still functional.


Ethanolic extract of Commiphora mukul gum resin attenuates streptozotocin-induced alterations in carbohydrate and lipid metabolism in rats.
The purpose of this study was to investigate the effects of Commiphora mukul gum resin ethanolic extract (CMEEt) administration against altered activities of key enzymes of carbohydrate metabolism, lipid metabolism and changes in glycogen content (liver and muscle) and lipids (liver and heart) in streptozotocin (STZ) induced insulin deficient diabetic Wistar albino rats. Diabetes was induced by intraperitoneal injection of STZ (55 mg/kg body wt) to male Wistar rats. The animals were divided into four groups: Control (C), control-treated (C+CM), diabetic (D) and diabetic-treated group (D+CM). Diabetic-treated and control-treated rats were treated with C. mukul gum resin ethanolic extract (CMEEt) in 2 ml distilled water, orally (200 mg/kg body weight/day for 60 days). At the end of the experimental period, biochemical parameters related to carbohydrate and lipid metabolism were assayed. The significant enhancement in tissue lipids (heart and liver) total cholesterol, triglycerides, phospholipids and free fatty acids of diabetic rats were nearer to normalized in diabetic treated rats (D+CM). Alterations in the activities of enzymes of glucose metabolism (hexokinase, phosphofructokinase, pyruvate kinase, and glucose-6-phosphatase, fructose-1,6-bisphosphatase and glucose-6-phosphate dehydrogenase) and lipid metabolism (fatty acid synthase, malic enzyme and lipoprotein lipase) as observed in diabetic (D) rats were prevented with CMEEt administration. In conclusion, our findings indicate improvement of glucose and lipid metabolisms in STZ induced diabetic rats by treatment with Commiphora mukul and suggest that the plant can be used as an adjuvant for the prevention and/or management of insulin deficiency and disorder related to it.


PIAS adds methyl-bias to HSC-differentiation.
Epigenetic modifications of stem cell genome including DNA methylation and histone modifications are critical for the regulation of stem cell gene expression and maintenance of stem cell pool and their differentiation. Although the importance of epigenetic modifications specifically DNA methylation to adult hematopoietic stem cells (HSC) has been established, the identity of specific modulators and precise mechanism of integration of methylation events remain to be uncovered. In this issue, Shuai and colleagues identify the SUMO E3 ligase PIAS1 (protein inhibitor of activated STAT1) as a key regulator of DNA methylation of HSC required for their maintenance and lineage commitment (Liu et al, 2014).


Methane production and nitrogen balance of dairy heifers grazing palisade grass cv. Marandu alone or with forage peanut.
Livestock production systems are an essential agribusiness activity in Brazil, but a critical challenge of Brazilian farmers is to maintain the equilibrium of the ecosystem, using herbage resources efficiently with a minimum impact on the environment. Nitrogen (N) fertilization and the inclusion of forage legumes into tropical grass pastures are management strategies which increase the productivity and nutritive value of pastures and may also affect methane (CH4) production by ruminants. The objective of this study was to examine the effects of either fertilizing palisade grass pastures with N or including the forage peanut (Arachis pintoi) into grass pastures on enteric CH4 emission, microbial protein production in the rumen via purine derivatives in the urine, and N balance. Twenty-one nonlactating crossbred dairy heifers were used in a completely randomized design with 3 treatments. The treatments consisted of pastures of palisade grass without N fertilization (control), fertilized with urea (fertilized), and palisade grass mixed with forage peanut (mixed). Seven animals (replications) were used to evaluate dry matter intake, digestibility, CH4 emission, urea, purine derivatives, and volume of urine, and N ingestion and excretion. Four paddocks (replications) were used to measure herbage mass; morphological, botanical, and chemical composition of herbage; and herbage allowance. The CH4 emissions were determined using the sulfur hexafluoride (SF6) tracer gas technique. The efficiency of N utilization (ENU) was calculated using the N balance data. Crude protein (CP) concentration of herbage increased with fertilization or legumes inclusion (P < 0.0001) while neutral detergent fiber (NDF) concentration decreased (P = 0.0355). The leaf allowance was higher in the fertilized treatment (P = 0.0294). Only uric acid excretion increased with N fertilization (P = 0.0204). The ENU was not affected by fertilized or mixed compared to control and averaged 55% (P = 0.8945). The enteric CH4 production was similar between treatments and averaged 129 g/d (P = 0.3989). We concluded that the changes in chemical composition of herbage provided by N fertilization or the inclusion of the legume showed no reduction in enteric CH4 emissions, but the ENU was more significant than previous studies with palisade grass, suggesting that different management strategies might alter the ENU under grazing conditions.


Early laparoscopic cholecystectomy for acute gangrenous cholecystitis.
Treatment of severe acute cholecystitis by laparoscopic cholecystectomy remains controversial because of technical difficulties and high rates of complications and conversion to open cholecystectomy. We investigated whether early laparoscopic cholecystectomy is appropriate for acute gangrenous cholecystitis. Pathologic diagnoses and outcomes were analyzed in patients who underwent laparoscopic or open cholecystectomy at our hospital, January 2002 to September 2005. Of 30 patients with acute gangrenous cholecystitis, 16 underwent early laparoscopic cholecystectomy, 10 underwent open cholecystectomy, and 4 were converted to open cholecystectomy (conversion rate, 20.0%). There was no significant difference in operation time or intraoperative bleeding. The requirement for postoperative analgesics was significantly lower (6.4+/-7.3 vs. 1.5+/-1.2 doses, P<0.05) and hospital stay significantly shorter (8.6+/-2.1 vs. 15.6+/-6.3 d, P<0.01) after laparoscopic cholecystectomy. There were no postoperative complications in either group. Thus, early laparoscopic cholecystectomy seems appropriate for acute gangrenous cholecystitis. Conversion to open cholecystectomy may be required in difficult cases with complications.


Cellular morphological changes detected by laser scanning in vivo confocal microscopy associated with clinical outcome in fungal keratitis.
HRT3 in vivo confocal microscopy (IVCM) images may indicate clinical outcome, but few studies have analysed this in fungal keratitis (FK). Adults with FK (diameter ≥3 mm) presenting to Aravind Eye Hospital, India from 2012-3 were enrolled prospectively. IVCM was performed at baseline, days 7, 14 and 21 post-enrolment (+/- 3 days where possible). Specific morphologies were identified in IVCM images by a grader masked to microbiology and clinical outcome (defined as good: healed/improving, or poor: enlarged ulcer, perforation or transplant/glue). Associations with final visit outcome assessed using logistic regression. 143 FK participants were enrolled; 87 had good outcome, 56 had poor outcome. Poor outcomes were associated with stellate interconnected cellular processes with no visible nuclei (OR 2.28, 95% CI: 1.03-5.06, p = 0.043) in baseline IVCM images, and fungal filaments (OR 6.48, 95% CI:2.50-16.78, p < 0.001) or honeycomb distribution of inflammatory cells (OR 5.24, 95% CI: 1.44-19.06, p = 0.012) in final visit images. Fungal filaments (OR 3.61, 95% CI:1.64-7.95, p = 0.001), stromal dendritiform cells (OR 2.88, 95% CI:1.17-7.11, p = 0.022), or stellate cellular processes with no visible nuclei (OR 2.09, 95% CI:1.14-3.82, p = 0.017) were associated with poor outcome if not in baseline but present in final visit images. IVCM can reveal morphological changes associated with clinical outcome.


Control of the pulmonary arterial resistance by the use of the oscillated assist flow.
In the clinical application of supporting circulation, the treatment of a patient with pulmonary hypertension is very important. We developed the electromagnetically driven vibrating flow pump (VFP) as a totally implantable type ventricular assist system. The artificial heart driven by electromagnetic forces creates high speed oscillation flow around 10-50 Hz. Assistance by high-speed oscillation flow has an interesting influence on the cardiovascular system. In this study, we carried out research on the influence such oscillation flow had on the pulmonary arterial vessels, and the supporting flow wave-form that controlled pulmonary vascular resistance was considered. Six healthy adult goats of both sexes were used in the experiments. We carried out inhalation anesthesia and performed intubation. The thorax was opened through left fourth rib resection. Right heart bypass was performed from the right atrium to the pulmonary artery. The flow of right heart assistance was maintained within 20-25% of total flow. Our purpose was to add flow of a specific high frequency to the right heart circulation. The hemodynamic parameters were recorded on a magnetic tape data recorder and input into a computer through an A-D converter. A result identified was that the pulmonary vascular resistance changed according to the alteration of the driving frequency of the VFP even during the same flow assistance. The resistance of the pulmonary arterial vessels became smaller when the driving of the VFP of 30 Hz was added to the right heart circulation. This was significant even when compared with continuous flow right heart assist. The characteristics of impedance appeared to have interesting alterations as well. Control of pulmonary vascular resistance by right heart assistance becomes possible if these results are applied. Accordingly, it may become one of the choices for treatment of a patient with pulmonary hypertension.


Emotional intelligence and perceived stress in dental undergraduates: a multinational survey.
This multinational survey investigated the relationship between emotional intelligence (EI) and perceived stress (PS) in seven countries. First-year dental undergraduates attending a dental school in England, Greece, Romania, South Africa, Australia, and the United States and three schools in Malaysia were invited to complete a set of questionnaires on age, gender, academic background, satisfaction with career choice, EI, and PS. Of 860 questionnaires distributed, 596 were fully completed--a response rate of 69.3 percent. Mean EI score was 123.8 (95 percent CI 122.7-124.9), and mean PS score was 19.1 (95 percent CI 18.6-19.7). Significant differences in EI and PS scores were detected between different countries. Females (p<0.05), younger students (p<0.001), those without a previous higher education qualification (p<0.001), and those not satisfied with their decision to study dentistry (p<0.001) were more likely to report PS when compared to their counterparts. A significant inverse relationship (coefficient=-0.29, p=0.001) between EI and PS was detected. Independent significant predictors of PS identified were gender (beta=0.22, t=5.71, p=0.001), previous higher education qualification (beta=-0.14, t=-2.42, p=0.010), satisfaction with decision to study dentistry (beta=-0.20, t=-5.11, p=0.001), and EI (beta=-0.24, t=-6.09, p=0.001), with the latter being relatively the most important predictor. In conclusion, the inverse relationship between EI and PS has been confirmed in this heterogeneous sample representing diverse sociocultural and academic contexts of dental undergraduates.


Complete genome sequences of Lactococcus lactis D1_2, a bacterium with antimicrobial properties isolated from peat soil.
Lactococcus lactis is a beneficial lactic acid bacterium commonly studied for its probiotic properties and role in dairy production. Here, we present a complete genome of Lactococcus lactis D1_2, isolated from peat swamp forests. To discover the potential antimicrobial properties, the complete genome of the strain was sequenced and analyzed.


Applicability of antibody and mRNA expression microarrays for identifying diagnostic and progression markers of early and late stage colorectal cancer.
The exact molecular background and the connection between protein and mRNA expression in colorectal cancer (CRC) development and progression are not completely elucidated. Our purposes were the identification of protein markers of colorectal carcinogenesis and progression using protein arrays and validation on tissue microarrays. The connection between antibody and mRNA expression array results was also examined. Using cancerous and adjacent normal samples from 10 patients with early and 6 with advanced CRC, 67 differentially expressed genes were identified between normal and cancerous samples. A marker set containing 6 proteins (CCNA1, AR, TOP1, TGFB, HSP60, ERK1) was developed which could differentiate normal specimen, early and late stage CRC with high sensitivity and specificity. Dukes D stage samples were analyzed on HGU133plus2.0 microarrays. In these samples, mRNA and protein expression of 143 genes showed strong positive correlations (R2>0.8), while a negative correlation (R2>0.9) was found in case of 95 genes. Based on our results a correlation could be established between transcriptome and antibody array results, hence the former may be used as a high-capacity screening method before applying antibody arrays containing already planned targets. Antibody microarrays may have a fundamental importance in testing of marker combinations and future application in diagnostics of tumorous diseases.


Axillary lymph node dissection in early-stage invasive breast cancer: is it still standard today?
Evaluation of axillary lymph node status by sentinel lymph node biopsy (SLNB) and complete axillary lymph node dissection (ALND) are an inherent part of breast cancer treatment. Increased understanding of tumor biology has changed the prognostic and therapeutic impact of lymph node status. Non-invasive imaging techniques like axillary ultrasound, FDG-PET, or MRI revealed moderate sensitivity and high specificity in evaluation of lymph node status. Therefore, they are not sufficient for lymph node staging. Otherwise, the impact of remaining micrometastases and even macrometastases for prognosis and treatment decisions is overestimated. Considering tumor biology, the distinction of axillary metastases in isolated tumor cells (ITC, pN0(i+)); micrometastases (pN1mi), and macrometastases (pN1a) is not comprehensible. Increasing data support the thesis that remaining axillary metastases neither increase the axillary recurrence rate nor decrease overall survival. It is doubtful that axillary tumor cells are capable to complete the complex multistep metastatic process. If applied, axillary metastases are sensitive to systemic treatment and are targeted by postoperative tangential breast irradiation. Therefore, the controversy about the clinical relevance of tumor cell clusters or micrometastases in SLN is a sophisticated but not contemporary discussion. Currently, there is no indication for axillary surgery in elderly patients with favorable tumors and clinically tumor-free lymph nodes. Nonetheless, a rational and evidence-based approach to the management of clinically and sonographically N0 patients with planned breast-conserving surgery and limited tumor size is needed now.


Zbtb20 promotes astrocytogenesis during neocortical development.
Multipotent neural precursor cells (NPCs) generate astrocytes at late stages of mammalian neocortical development. Many signalling pathways that regulate astrocytogenesis directly induce the expression of GFAP, a marker of terminally differentiated astrocytes. However, astrocyte specification occurs before GFAP expression and essential factors for the specification step have remained elusive. Here we show that Zbtb20 regulates astrocyte specification in the mouse neocortex. Zbtb20 is highly expressed in late-stage NPCs and their astrocytic progeny. Overexpression and knockdown of Zbtb20 promote and suppress astrocytogenesis, respectively, although Zbtb20 does not directly activate the Gfap promoter. Astrocyte induction by Zbtb20 is suppressed by knockdown of Sox9 or NFIA. Furthermore, in the astrocyte lineage, Zbtb20 directly represses the expression of Brn2, which encodes a protein necessary for upper-layer neuron specification. Zbtb20 is thus a key determinant of astrocytogenesis, in which it collaborates with Sox9 and NFIA, and acts in part through direct repression of Brn2 expression.


An ATP-dependent inwardly rectifying potassium channel, KAB-2 (Kir4. 1), in cochlear stria vascularis of inner ear: its specific subcellular localization and correlation with the formation of endocochlear potential.
Cochlear endolymph has a highly positive potential of approximately +80 mV. This so-called endocochlear potential (EP) is essential for hearing. Although pivotal roles of K+ channels in the formation of EP have been suggested, the types and distribution of K+ channels in cochlea have not been characterized. Because EP was depressed by vascular perfusion of Ba2+, an inhibitor of inwardly rectifying K+ (Kir) channels, but not by either 4-aminopyridine or tetraethylammonium, we examined the expression of Kir channel subunits in cochlear stria vascularis, the tissue that is supposed to play the central role in the generation of positive EP. Of 11 members of the Kir channel family examined with reverse transcription-PCR, we could detect only expression of KAB-2 (Kir4.1) mRNA in stria vascularis. KAB-2 immunoreactivity was specifically localized at the basolateral membrane of marginal cells but not in either basal or intermediate cells. Developmental expression of KAB-2 in marginal cells paralleled formation of EP. Furthermore, deaf mutant mice (viable dominant spotting; WV/WV) expressed no KAB-2 in their marginal cells. These results suggest that KAB-2 in marginal cells may be critically involved in the generation of positive EP.


C-kit gene mutation: common and widely distributed in intracranial germinomas.
Of the intracranial germ cell tumors (IGCTs), 10% of germinomas and most nongerminomatous tumors remain refractory to multimodality therapy. The authors investigated the mutation of c-kit and the expression of its product KIT in IGCTs to identify tumors susceptible to imatinib mesylate, a synthetic agent targeting KIT. The authors investigated 26 IGCTs, including 13 germinomas, five mixed germ cell tumors (MGCTs), four immature teratomas (ITs), and two each of yolk sac tumors and choriocarcinomas. These tumors were examined for the expression of KIT and CD34 by immunohistochemical analysis, and for mutations in exons 2, 8 to 11, 13, and 17 of c-kit. Strong KIT expression was found in the cell membrane of germinomas (100%) and germinomatous cells of MGCTs (80%), as well as in the cytoplasm of epithelial and smooth-muscle cells of ITs. The membranous expression of CD34 was found in the nongerminomatous tumor cells and the chondrocytes of MGCTs (60%), ITs (100%), and a choriocarcinoma (50%), but not in germinomas and germinomatous cells. A total of five missense mutations distributed in exons 2, 11, 13, and 17 of c-kit were detected in three (23%) of the 13 germinomas. The novel mutations E73K, T96M (both in exon 2), and A636V (in exon 13) were detected in a single tumor. The presence or type of c-kit mutation was not correlated with patient prognosis. Immunohistochemical analysis of KIT expression is useful for the diagnosis of germinoma. This study may help in clarifying the pathogenesis of IGCTs and in identifying tumors susceptible to drugs targeting KIT.


Potential clinical application of masseter and temporal muscle massage treatment using an oral rehabilitation robot in temporomandibular disorder patients with myofascial pain.
To investigate the safety, suitable treatment regimen, and efficacy of masseter and temporal muscle massage treatment using an oral rehabilitation robot. Forty-one temporomandibular disorder (TMD) patients with myofascial pain (8 men, 33 women, median age: 46 years) were enrolled. The safety, suitable massage regimen, and efficacy of this treatment were investigated. Changes in masseter muscle thickness were evaluated on sonograms. No adverse events occurred with any of the treatment sessions. Suitable massage was at pressure of 10 N for 16 minutes. Five sessions were performed every 2 weeks. Total duration of treatment was 9·5 weeks in median. Massage treatment was effective in 70·3% of patients. Masseter muscle thickness decreased with treatment in the therapy-effective group. This study confirmed the safety of massage treatment, and established a suitable regimen. Massage was effective in 70·3% of patients and appeared to have a potential as one of the effective treatments for myofascial pain.


A survey of digital rectal examination training in Canadian medical schools.
The digital rectal examination (DRE) is important for the diagnosis of a variety of gastrointestinal, urological and gynecological disorders. However, it appears that Canadian medical students may not be adequately taught nor provided the opportunity to practice their skills often enough. The present study was an analysis of the current practices in DRE teaching and evaluation in undergraduate medicine programs across Canada. Clinical skills coordinators from the 14 English-speaking medical schools in Canada were invited to participate in the survey and to respond to questions regarding DRE teaching at their respective schools. Thirteen of the 14 schools (93%) responded to the survey. The DRE is taught in various ways: 69% of schools use anatomical rectal models, 62% use video tutorials and 62% involve physician instruction. Most schools (85%) offer one formal teaching session before clerkship. Generally, there is no formal DRE teaching session during clerkship. Preclerkship students in 62% of the schools perform <=1 DRE during their training, and clinical skills coordinators in 85% of the schools expected that clerkship students perform <=2. The training is evaluated in a variety of ways, with most schools (77%) only requiring mandatory attendance. Although a variety of techniques are used to teach and evaluate DRE training in Canadian medical schools, students are performing very few DREs before graduation. Medical schools should objectively evaluate proficiency to give meaningful feedback and improve competence in their students as well as provide more opportunities for students to obtain the necessary experience performing DREs during their clinical training.


Early gestational choriocarcinoma. A case report.
A focus of choriocarcinoma lying in the intervillous space was an unexpected finding in a 20-week placenta. The mother, after a short admission, died from choriocarcinomatous pulmonary emboli and acute cor pulmonale. A diagnosis of early choriocarcinoma associated with normal villi is therefore tenable.


Colorectal cancers with microsatellite instability display unique miRNA profiles.
microRNAs (miRNA) are small noncoding transcripts that play an important role in carcinogenesis. miRNA expression profiles have been shown to discriminate between different types of cancers. The aim of this study was to analyze global miRNA signatures in various groups of colorectal cancers (CRC) based on the presence of microsatellite instability (MSI). We analyzed genome-wide miRNA expression profiles in 54 CRC tissues [22 with Lynch syndrome, 13 with sporadic MSI due to MLH1 methylation, 19 without MSI (or microsatellite stable, MSS)] and 20 normal colonic tissues by miRNA microarrays. Using an independent set of MSI-positive samples (13 with Lynch syndrome and 20 with sporadic MSI), we developed a miRNA-based predictor to differentiate both types of MSI by quantitative reverse transcriptase PCR. We found that the expression of a subset of nine miRNAs significantly discriminated between tumor and normal colonic mucosa tissues (overall error rate = 0.04). More importantly, Lynch syndrome tumors displayed a unique miRNA profile compared with sporadic MSI tumors; miR-622, miR-1238, and miR-192 were the most differentially expressed miRNAs between these two groups. We developed a miRNA-based predictor capable of differentiating between types of MSI in an independent sample set. CRC tissues show distinct miRNA expression profiles compared with normal colonic mucosa. The discovery of unique miRNA expression profiles that can successfully discriminate between Lynch syndrome, sporadic MSI, and sporadic MSS colorectal cancers provides novel insights into the role of miRNAs in colorectal carcinogenesis, which may contribute to the diagnosis, prognosis, and treatment of this disease.


Evidence from electron-paramagnetic-resonance spectroscopy for a complex of sulphite ions with the molybdenum centre of sulphite oxidase.
Reduction of sulphite oxidase by sulphite at low pH values in Mes (4-morpholine-ethanesulphonic acid) buffer gives rise to a new molybdenum(V) electron-paramagnetic-resonance spectrum different from that obtained by photoreduction of the enzyme in the same medium. The spectrum is attributed to a sulphite complex of the enzyme, showing g-values of about 2.000, 1.972 and 1.963. The complex is analogous to that with the inhibitor phosphate in that it gives rise to no observable hyperfine coupling of Mo(V) to exchangeable protons.


Examining the power of the social imaginary through competing narratives of data ownership in health research.
This article explores the social imaginary in the context of data ownership and the (non-)delivery of the data sharing revolution in biomedicine. We contribute to this special issue on imaginaries by developing a method and paradigm of 'competing narratives'. Despite multiple initiatives to encourage health data sharing, and a strong 'open access' agenda, the data sharing revolution is not yet delivered. Ownership is persistently (though inconsistently) presented as a barrier to data sharing. However, existing literature does not reveal how far appeals to ownership are part of the problem. This paper reports original, interdisciplinary research asking: in health research, in what ways, if at all, do notions of ownership (broadly conceived) of health-related data impact on sharing practices? Doctrinal and empirical research methods are used to expose evidence of drivers behind appeals to ownership in health data sharing. The findings speak to how funders and data custodians can better tailor existing and potential data sharing initiatives to perspectives and behaviors. The concept of 'my data' is important: notions of reward, opportunity, control, and safeguarding establish legitimate, potentially competing 'ownership' interests in data. In particular, this research raises questions about the long-term effectiveness of an open access ideology that ignores these subtleties. In conclusion we find power in the social imaginary of ownership with respect to biomedical data; however, that power emerges and is enacted in unexpected ways by multiple actors within the ecosystem, often driven by competing narratives about what is at stake. Importantly, formal legal property-type appeals to ownership appear to have far less power in the narratives about data than the ethical and social concerns that underpin responsible biomedical research.


Incompleteness of the large-N analysis of the O(N) models: Nonperturbative cuspy fixed points and their nontrivial homotopy at finite N.
We summarize the usual implementations of the large-N limit of O(N) models and show in detail why and how they can miss some physically important fixed points when they become singular in the limit N→∞. Using Wilson's renormalization group in its functional nonperturbative versions, we show how the singularities build up as N increases. In the Wilson-Polchinski version of the nonperturbative renormalization group, we show that the singularities are cusps, which become boundary layers for finite but large values of N. The corresponding fixed points being never close to the Gaussian, are out of reach of the usual perturbative approaches. We find four new fixed points and study them in all dimensions and for all N>0 and show that they play an important role for the tricritical physics of O(N) models. Finally, we show that some of these fixed points are bivalued when they are considered as functions of d and N thus revealing important and nontrivial homotopy structures. The Bardeen-Moshe-Bander phenomenon that occurs at N=∞ and d=3 is shown to play a crucial role for the internal consistency of all our results.


Urolithin A-induced mitophagy suppresses apoptosis and attenuates intervertebral disc degeneration via the AMPK signaling pathway.
Intervertebral disc degeneration (IDD) is a major cause of low back pain (LBP), and effective therapies are still lacking. Previous studies reported that mitochondrial dysfunction contributes to apoptosis, and urolithin A (UA) specifically induces mitophagy. Herein, we aimed to investigate the protective effect of UA-induced mitophagy on tert-butyl hydroperoxide (TBHP)-induced apoptosis in nucleus pulposus (NP) cells in vitro and a rat model of IDD in vivo. Mitochondrial function, apoptosis, and mitophagy were measured in UA-treated NP cells by western blotting and immunofluorescence; the therapeutic effects of UA on IDD were assessed in rats with puncture-induced IDD. The results showed that UA could activate mitophagy in primary NP cells, and UA treatment inhibited TBHP-induced mitochondrial dysfunction and the intrinsic apoptosis pathway. Mechanistically, we revealed that UA promoted mitophagy by activating AMPK signaling in TBHP-induced NP cells. In vivo, UA was shown to effectively alleviate the progression of puncture-induced IDD in rats. Taken together, our results suggest that UA could be a novel and effective therapeutic strategy for IDD.


Pulmonary resection for metastases from colorectal cancer.
We reviewed our experience in the surgical treatment of 47 patients with colorectal pulmonary metastases and investigated factors affecting their survival. From September 1986 to December 1999, 47 patients underwent 59 thoracotomies for pulmonary metastases from colorectal cancer. The median interval between colorectal resection and lung resection (disease-free interval [DFI]) was 33 months. Overall, 5-year survival was 48%. Five-year survival was 51% for patients with solitary metastasis (n = 30), 47% for patients with ipsilateral multiple metastases (n = 11), and 50% for patients with bilateral metastases (n = 6), and there were no significant differences. Five-year survival was 80.8% for 14 patients with DFI of < 2 years and 39.7% for 30 patients with a DFI of > 2 years (p = 0.22). Five-year survival for 11 patients with normal prethoracotomy carcinoembryonic antigen (CEA) levels was 70%, and that for 26 patients with elevated prethoracotomy CEA levels (> 5 ng/mL) was 36% (p < 0.05). Eight patients had extrathoracic disease. The median survival time after pulmonary resection was 18.5 months, and the 5-year survival was 60%. A second resection for recurrent metastases was performed in five patients, and a third resection was done in one patient. All six patients are alive. The median survival of five patients who underwent a second thoracotomy was 22 months (range, 2 to 68 months), and one patient is alive 39 months after the third resection. Pulmonary resection for metastases from colorectal cancer may help prolong survival in selected patients, even with bilateral lesions, recurrent metastasectomy, or extrathoracic disease. Prethoracotomy CEA level was found to be a significant prognostic factor.


Chitosan as a removing agent of beta-lactoglobulin from membrane models.
Many chitosan biological activities depend on the interaction with biomembranes, but so far it has not been possible to obtain molecular-level evidence of chitosan action. In this article, we employ Langmuir phospholipid monolayers as cell membrane models and show that chitosan is able to remove beta-lactoglobulin (BLG) from negatively charged dimyristoyl phosphatidic acid (DMPA) and dipalmitoyl phosphatidyl glycerol (DPPG). This was shown with surface pressure isotherms and elasticity and PM-IRRAS measurements in the Langmuir monolayers, in addition to quartz crystal microbalance and fluorescence spectroscopy measurements for Langmuir-Blodgett (LB) films transferred onto solid substrates. Some specificity was noted in the removal action because chitosan was unable to remove BLG incorporated into neutral dipalmitoyl phosphatidyl choline (DPPC) and cholesterol monolayers and had no effect on horseradish peroxidase and urease interacting with DMPA. An obvious biological implication of these findings is to offer reasons that chitosan can remove BLG from lipophilic environments, as reported in the recent literature.


The alpha7 nicotinic receptor agonist 4OH-GTS-21 protects axotomized septohippocampal cholinergic neurons in wild type but not amyloid-overexpressing transgenic mice.
While activation of alpha7 nicotinic receptors protects neurons from a variety of apoptotic insults in vitro, little is known about this neuroprotective action in vivo, especially under amyloidogenic conditions that mimic Alzheimer's disease. We therefore investigated the effects of 4OH-GTS-21, a selective partial agonist for these receptors, on septohippocampal cholinergic and GABAergic neuron survival following fimbria fornix (FFX) lesions in three strains of mice: C57BL/6J wild type mice; human presenilin-1 mutant M146L (PS1) transgenic mice; and mice expressing both mutant PS1 and Swedish mutant K670N/M671L amyloid precursor protein (APP). Initial studies to demonstrated that 4OH-GTS-21 is likely brain permeant based on its ability to improve passive avoidance and Morris water task behaviors in nucleus basalis-lesioned rats. In FFX-lesioned mice, twice per day i.p. injections of 1 mg/kg of 4OH-GTS-21 for 2 weeks promoted the survival and prevented the atrophy of septal cholinergic neurons. Septal parvalbumin-staining GABAergic neurons were not protected by this treatment, although they also express alpha7 nicotinic receptors, suggesting an indirect, nerve growth factor (NGF)-mediated mechanism. No protection of cholinergic neurons was observed in similarly treated PS1 or APP/PS1 transgenic mice. 4OH-GTS-21 treatment actually reduced cholinergic neuronal size in APP/PS1 mice. Hippocampal amyloid deposition was not affected by FFX lesions or treatment with this alpha7 nicotinic receptor agonist in APP/PS1 mice under these conditions. These results indicate that brain alpha7 nicotinic receptors are potential targets for protecting at-risk brain neurons in Alzheimer's disease, perhaps via their effects on NGF receptors; however, this protection may be sensitive under some conditions to environmental factors such as inhibitory amyloid-peptides.


Fast backprojections from the motion to the primary visual area necessary for visual awareness.
Much is known about the pathways from photoreceptors to higher visual areas in the brain. However, how we become aware of what we see or of having seen at all is a problem that has eluded neuroscience. Recordings from macaque V1 during deactivation of MT+/V5 and psychophysical studies of perceptual integration suggest that feedback from secondary visual areas to V1 is necessary for visual awareness. We used transcranial magnetic stimulation to probe the timing and function of feedback from human area MT+/V5 to V1 and found its action to be early and critical for awareness of visual motion.


Porous silicon integrated Mach-Zehnder interferometer waveguide for biological and chemical sensing.
Optical waveguides comprised of nanoporous materials are uniquely suited for on-chip sensing applications, because they allow for a target chemical or analyte to directly infiltrate the optical material that comprises the core of the waveguide. We describe here the fabrication and characterization of nanoporous waveguides, and demonstrate their usefulness in measuring small changes in refractive index when exposed to a test analyte. We use a process of electrochemical etching and laser oxidation to produce channel waveguides and integrated on-chip Mach-Zehnder structures, and we compare the responsivity and interferometric stability of the integrated sensor to that of a fiber-based interferometer. We quantify the detection capability by selectively applying isopropanol to a 200 μm length waveguide segment in one arm of the interferometer, which produces a phase shift of 9.7 π. The integrated interferometer is shown to provide a more stable response in comparison to a comparable fiber-based implementation.


Steroid hormone receptors and dietary ligands: a selected review.
Members of the nuclear steroid hormone superfamily mediate essential physiological functions. Steroid hormone receptors (SHR) act directly on DNA, regulate the synthesis of their target genes and are usually activated by ligand binding. Both endogenous and exogenous compounds and their metabolites may act as activators of SHR and disruptors of endocrine, cellular and lipid homeostasis. The endogenous ligands are generally steroids such as 17beta-oestradiol, androgens, progesterone and pregnenolone. The exogenous compounds are usually delivered through the diet and include non-steroidal ligands. Examples of such ligands include isoflavanoids or phytooestrogens, and food contaminants such as exogenous oestrogens from hormone-treated cattle, pesticides, polychlorinated biphenyls and plasticisers. Certain drugs are also ligands; so nuclear receptors are also important drug targets for intervention in disease processes. The present review summarises recent reports on ligand-activated SHR that describe the selective regulation of a tightly-controlled cross-talking network involving exchange of ligands, and the control of major classes of cytochrome P450 (CYP) isoforms which metabolise many bioactive exogenous compounds. Many CYP have broad substrate activity and appear to be integrated into a coordinated metabolic pathway, such that whilst some receptors are ligand specific, other sensors may have a broader specificity and low ligand affinity to monitor aggregate levels of inducers. They can then trigger production of metabolising enzymes to defend against possible toxic nutrients and xenobiotic compounds. The influence of dietary intakes of nutrients and non-nutrients on the human oestrogen receptors (alpha and beta), the aryl hydrocarbon receptor, the pregnane X receptor, the constitutive androstane receptor, and the peroxisome proliferator-activated receptors (alpha and gamma), can be examined by utilising computer-generated molecular models of the ligand-receptor interaction, based on information generated from crystallographic data and sequence homology. In relation to experimental and observed data, molecular modelling can provide a scientifically sound perspective on the potential risk and benefits to human health from dietary exposure to hormone-mimicking chemicals, providing a useful tool in drug development and in a situation of considerable public concern.


Brain excitatory/inhibitory circuits cross-talking with chromogranin A during hypertensive and hibernating states.
To date, many scientific attempts have been directed towards the development of experimental models for the identification of neuronal mechanisms evoking cardiovascular and hemodynamic dysfunctions. The spontaneously hypertensive rat (SHR), a genetic model of essential hypertension, has become a valuable rodent for the characterization of molecular markers in hypertensive-related diseases. Recently, growing interests have also been directed to a new experimental paradigm i.e. hibernation, a physiological state consenting the hamster (Mesocricetus auratus) to activate protective mechanisms against ischemic-like complications during the arousal phase. With this intention, the present review will focus attention on specific neurosignaling systems involved with the preservation of hemodynamic conditions in those brain areas that play a pivotal role on such a feature. It is widely known that healthy neurons conserve their structural and responsiveness properties in presence of a constant blood supply, which is assured by their coupling to microvessels and perivascular astrocytes as well as by secretory proteins such as chromogranin A (CgA). So, it will be interesting to establish if this protein alone or with the participation of excitatory/inhibitory neurosignals is capable of influencing some brain areas controlling cardiovascular conditions in both SHRs and hibernating hamsters. In this context, the present work will deliver the most important findings regarding neuronal CgA and its cross-talking ability with major inhibitory (GABA/adenosine) and/or excitatory (glutamate) neuroreceptor systems in relation to hypertensive/hypotensive states of both animal models. Indications deriving from such approaches may provide clinically useful insights regarding their role as protective factors of hemodynamic and neurological disorders.


The structure of the cytoplasmic matrix preserved by freeze-drying and freeze-substitution.
This paper reports a study of the cytoplasmic matrix in whole cultured cells examined by high voltage electron microscopy. In order to acquaint ourselves with the influence of preparation procedures on the morphology depicted, PtK2 cells were prepared for examination by first freezing in propane at -185 degrees C and then drying while maintained at -95 degrees C. Other cells of the same type were first fixed with glutaraldehyde and OsO4 and then frozen dried. Others were prepared by freeze-substitution and eventually dried by the critical-point method from CO2. And finally, some were preserved by conventional techniques of glutaraldehyde and OsO4 followed by dehydration in alcohol and critical-point drying. The observations are presented in stereo images. The morphologies after these various procedures are quite similar. All show the characteristic three-dimensional lattice or meshwork of slender filaments called microtrabeculae. In cells rapidly frozen and then dried from the frozen state, there is less evidence of shrinkage and probable change in the trabecular structure than in cells first fixed with glutaraldehyde and then frozen dried. The differences we relate to the demonstrable failure of glutaraldehyde to penetrate the cell quickly and fix instantly any component that is in active motion. Other differences that can be observed between all four types of preparation are not recognizably striking and are thought to reflect as much as anything morphological diversity in the original cells. In some instances, the amorphous ice of the initial freezing at -185 degrees C was allowed to crystallize at -80 degrees C. The small crystals that form push aside the microtrabeculae and leave obvious imprints on the structure. The essential message from these experiments is that the cytomatrix is structured.


Multiple brain abscesses in an immunocompetent patient after undergoing professional tooth cleaning.
Dental disorders and dental treatment are among the variety of causes of brain abscess. The authors present the case of a patient who developed multiple brain abscesses after undergoing professional tooth cleaning. The results of a diagnostic work-up ruled out an underlying immunodeficiency. After receiving neurosurgical intervention and intensive care treatment by means of local and intravenous antibiotics for 24 days, the patient was transferred to another hospital for rehabilitation. Six months after the treatment, the patient still had moderate residual paresis of the left leg. Although it happens rarely, professional tooth cleaning may be considered a cause of brain abscesses even in otherwise healthy patients.


Muscle weakness in a girl with autoimmune hepatitis and Graves' disease.
Autoimmune hepatitis (AIH) is a chronic hepatic autoimmune disease of unknown etiology associated with inflammatory changes and autoantibodies. The combination of AIH, Grave's disease, and myasthenia gravis (MG) is rare, with only one other case reported. We report a pediatric patient with AIH type 2 and Grave's disease who developed MG whilst on a treatment with corticosteroids. A 13-year-old girl, diagnosed with thyrotoxicosis, was identified as having AIH type 2. During the course of her therapy, she developed muscle weakness. Investigations revealed increased anti-acetylcholine receptor (AChR) antibodies and her electromyography (EMG) was characteristic for MG. Her course is described here. This case highlights the importance of investigating muscle weakness in severely ill hospitalized patients.


Gut microbe metabolism of small molecules supports human development across the early stages of life.
From birth to adulthood, the human gut-associated microbial communities experience profound changes in their structure. However, while the taxonomical composition has been extensively explored, temporal shifts in the microbial metabolic functionalities related to the metabolism of bioactive small molecules are still largely unexplored. Here, we collected a total of 6,617 publicly available human fecal shotgun metagenomes and 42 metatranscriptomes from infants and adults to explore the dynamic changes of the microbial-derived small molecule metabolisms according to the age-related development of the human gut microbiome. Moreover, by selecting metagenomic data from 250 breastfed and 217 formula-fed infants, we also investigated how feeding types can shape the metabolic functionality of the incipient gut microbiome. From the small molecule metabolism perspective, our findings suggested that the human gut microbial communities are genetically equipped and prepared to metabolically evolve toward the adult state as early as 1 month after birth, although at the age of 4 years, it still appeared functionally underdeveloped compared to adults. Furthermore, in respect of formula-fed newborns, breastfed infants showed enrichment in microbial metabolic functions related to specific amino acids present at low concentrations in human milk, highlighting that the infant gut microbiome has specifically evolved to synthesize bioactive molecules that can complement the human breast milk composition contributing to complete nutritional supply of infant.


O-GlcNAcylation: a novel post-translational mechanism to alter vascular cellular signaling in health and disease: focus on hypertension.
O-Linked attachment of beta-N-acetyl-glucosamine (O-GlcNAc) on serine and threonine residues of nuclear and cytoplasmic proteins is a highly dynamic posttranslational modification that plays a key role in signal transduction pathways. Preliminary data show that O-GlcNAcylation may represent a key regulatory mechanism in the vasculature, modulating contractile and relaxant responses. Proteins with an important role in vascular function, such as endothelial nitric oxide synthase, sarcoplasmic reticulum Ca(2+)-ATPase, protein kinase C, mitogen-activated protein kinases, and proteins involved in cytoskeleton regulation and microtubule assembly are targets for O-GlcNAcylation, indicating that this posttranslational modification may play an important role in vascular reactivity. Here, we will focus on a few specific pathways that contribute to vascular function and cardiovascular disease-associated vascular dysfunction, and the implications of their modification by O-GlcNAc. New chemical tools have been developed to detect and study O-GlcNAcylation, including inhibitors of O-GlcNAc enzymes, chemoenzymatic tagging methods, and quantitative proteomics strategies; these will also be briefly addressed. An exciting challenge in the future will be to better understand the cellular dynamics of this posttranslational modification, as well as the signaling pathways and mechanisms by which O-GlcNAc is regulated on specific proteins in the vasculature in health and disease.


Data set of a representative online survey on search engines with a focus on search engine optimization (SEO): a cross-sectional study.
To gain a better understanding of user knowledge and perspectives of search engines, a fruitful approach are representative online surveys. In 2020, we conducted an online survey with a sample representative of the German online population aged 16 through 69 ( N = 2,012). The online survey included 12 search engine-related sections. The questions cover topics such as usage behavior, self-assessed search engine literacy, trust in search engines, knowledge of ads and search engine optimization (SEO), ability to distinguish ads from organic results, assessments and opinions regarding SEO, and personalization of search results. SEO is the specific focus of the survey, as it was conducted as part of the SEO Effect project, dealing with issues such as the role of SEO from the user perspective. This data set contains complete data from the online survey. On the one hand, the data set will allow further analyses, and, on the other hand, comparisons with follow-up studies.


Development of Peru-15 (CholeraGarde), a live-attenuated oral cholera vaccine: 1991-2009.
Epidemics of severe dehydrating cholera are on the increase in resource-limited settings around the world. Adults, children and young infants are all at risk of these infections. Considerable efforts have been made for the development of safe and efficacious oral cholera vaccines over the last three decades. Whole-cell-inactivated as well as live oral cholera vaccines have been developed and tested in different field settings to determine the efficacy and/or effectiveness of such vaccines for reducing life-threatening disease. This review follows the trail of the development of CholeraGarde, a live-attenuated Vibrio cholerae O1 vaccine candidate of the El Tor biotype and Inaba serotype. CholeraGarde, also well known as Peru-15, was derived from V. cholerae O1 strain C6709, a clinical isolate from Peru. The vaccine has now been tested in over 500 individuals, adults and children and shows a good safety and immunogenicity profile. At a dose of around 10(8) CFU, it is immunogenic in adults in the USA, as well as in adults, children and infants in Bangladesh. The vaccine has been tested in infants of 9 months of age where a single 10(8) CFU dose was safe and immunogenic while a tenfold lower dose was not. Excretion of the strain was higher in adults in the USA and low in Bangladeshi participants in all age groups. Phase II studies of CholeraGarde are ongoing in cholera-endemic countries to concomitantly administer it to infants with the parenteral measles vaccine. Studies on HIV-positive individuals are also ongoing to determine safety, immunogenicity and contraindications, if any. Phase III studies are being targeted to determine the protective efficacy of CholeraGarde and for further development of a single-dose vaccine that will protect infants and also other age groups from endemic and epidemic cholera.


Folding kinetics of a polymer.
We present the results of computer simulations giving a kinetic insight into the liquid-to-solid transition of a homopolymer chain with short-range interactions. By calculating the absolute rates in each direction of the transition, using molecular dynamics employing the forward flux sampling scheme, we provide the phase diagram based on purely kinetic data, and compare it with the results from Monte Carlo simulations. Additionally, we present and discuss a remarkably simple and general relation between the polymer topology and the folding pathway, and show that the eigenvalue spectrum of a matrix defined by non-bonded contacts (the Laplacian matrix) provides an insight into the nonequilibrium ensembles of these trajectories. In particular, the Laplacian matrix seems to identify a large fraction of configurations on the folding pathway at the free energy maximum that have a very low probability of reaching the crystallized state. This implies that the eigenvalues of this matrix may be suitable additional reaction coordinates to describe the folding transition of chain molecules.


Rheumatoid arthritis-like active synovitis with T-cell activation in a case of idiopathic multicentric Castleman disease: A case report.
Idiopathic multicentric Castleman disease (iMCD) is a systemic disease with multiple regions of lymphadenopathy and systemic symptoms and associated with rheumatoid arthritis (RA) and collagen diseases. However, few reported have described the coexistence of iMCD and RA and the mechanisms by which iMCD induces arthritis remain elusive. We experienced a rare case of iMCD, wherein the patient exhibited symptoms of polyarthritis with high-grade fever. A 34-year-old woman was admitted to our hospital for further evaluation of a high fever with polyarthritis. The levels of both rheumatoid factor and anticitrullinated protein antibody were negative. F-fluorodeoxyglucose/positron emission tomography-computed tomography showed lymphadenopathy with increased fluoro-2-deoxy-D-glucose uptake. Magnetic resonance imaging and musculoskeletal ultrasonography revealed active synovitis in the hands which was consistent with RA. We diagnosed iMCD based on human herpesvirus 8 negativity, HIV negativity, systemic lymphadenopathy, and pathologic findings of the lymph nodes. The patient did not satisfy the 2010 American College of Rheumatology and European League Against Rheumatism classification criteria for RA. Cytokine assay showed elevated serum levels of interleukin-17 and CXCL10, comparable to those in patients with RA. We administered 15 mg/d of predonisolone. After this treatment, the patient's symptoms showed improvement. As of this writing, we tapered the prednisolone to 7.5 mg/d, and the patient's remission has been maintained for >4 months. The present case suggests that RA-like active synovitis may coexist in iMCD, resulting from aberrant T-cell activation and histologic examination using lymph node biopsy may help enable early diagnosis of iMCD.


Expression Patterns of ER, PR, HER-2/neu and p53 in Association with Nottingham Tumour Grade in Breast Cancer Patients.
Recent molecular studies show that breast cancer (BC) is a heterogeneous disease, and several molecular changes may accumulate over time to influence treatment response. As a result, employing reliable molecular biomarkers to monitor these modifications may help deliver personalised treatment. However, this may be unrealistic in the resource-limited parts of the world. Thus, this study aimed to investigate the expression pattern of hormone receptors and p53 tumour suppressor using immunohistochemistry (IHC) in BC compared to the traditional tumour grade. In total, 205 cases were investigated, and the Modified Bloom-Richardson score system was adopted in grading the tumours. The tissue sections of the cases were stained with specific primary antibodies at dilutions of 1:60 for oestrogen receptors (ER) and progesterone receptors (PR), 1:350 for the human epidermal growth factor (HER-2/neu) and 1:50 for p53. Invasive ductal carcinoma of no-specific type (n = 190, 92.7%) was predominant and grade II tumour (n = 146, 71.2%) was the most frequent. Hormone receptors ER (n = 127) and PR (n = 145) had 62.0% and 70.7% positive cases, respectively; 34.1% (n = 70) were positive for HER-2/neu, while 76.1% (n = 156) were positive for p53. Significant associations between Nottingham grade and expression patterns of ER (P <0.01), PR (P <0.001), HER-2/neu (P <0.001) and p53 (P = 0.001) were observed. Nottingham grade had a high degree of concordance with the patterns of expression of hormone receptors, HER-2/neu and p53, suggesting that it may play an important role in connection with the predictive and prognostic biomarkers for BC.


MicroRNAs as possible biomarkers for diagnosis and prognosis of hepatitis B- and C-related-hepatocellular-carcinoma.
Aim of the present review is to summarize the current knowledge about the potential relationship between miRNAs and hepatitis B virus (HBV)-hepatitis C virus (HCV) related liver diseases. A systematic computer-based search of published articles, according to the Preferred Reporting Items for Systematic reviews and Meta-Analysis Statement, was performed to identify relevant studies on usefulness of serum/plasma/urine miRNAs, as noninvasive biomarkers for early detection of HBV and HCV-induced hepatocellular carcinoma (HCC) development, as well as for its prognostic evaluation. The used Medical Subject Headings terms and keywords were: "HBV", "HCV", "hepatocellular carcinoma", "microRNAs", "miRNAs", "diagnosis", "prognosis", "therapy", "treatment". Some serum/plasma miRNAs, including miR-21, miR-122, mi-125a/b, miR-199a/b, miR-221, miR-222, miR-223, miR-224 might serve as biomarkers for early diagnosis/prognosis of HCC, but, to date, not definitive results or well-defined panels of miRNAs have been obtained. More well-designed studies, focusing on populations of different geographical areas and involving larger series of patients, should be carried out to improve our knowledge on the potential role of miRNAs for HCC early detection and prognosis.


Inhibition of aberrant proliferation and induction of apoptosis in HER-2/neu oncogene transformed human mammary epithelial cells by N-(4-hydroxyphenyl)retinamide.
Epithelial cells from non-cancerous mammary tissue in response to exposure to chemical carcinogens or transfection with oncogenes exhibit hyperproliferation and hyperplasia prior to the development of cancer. Aberrant proliferation may, therefore, represent a modifiable early occurring preneoplastic event that is susceptible to chemoprevention of carcinogenesis. The synthetic retinoid N-(4-hydroxyphenyl)retinamide (HPR), has exhibited preventive efficacy in several in vitro and in vivo breast cancer models, and represents a promising chemopreventive compound for clinical trials. Clinically relevant biochemical and cellular mechanisms responsible for the chemopreventive effects of HPR, however, are not fully understood. Experiments were performed on preneoplastic human mammary epithelial 184-B5/HER cells derived from reduction mammoplasty and initiated for tumorigenic transformation by overexpression of HER-2/neu oncogene, to examine whether HPR inhibits aberrant proliferation of these cells and to identify the possible mechanism(s) responsible for the inhibitory effects of HPR. Continuous 7-day treatment with HPR produced a dose-dependent, reversible growth inhibition. Long-term (21 day) treatment of 184-B5/HER cells with HPR inhibited anchorage-dependent colony formation by approximately 80% (P < 0.01) relative to that observed in the solvent control. A 24 h treatment with cytostatic 400 nM HPR produced a 25% increase (P = 0.01) in G0/G1 phase, and a 36% decrease (P = 0.01) in S phase of the cell cycle. HPR treatment also induced a 10-fold increase (P = 0.02) in the sub-G0 (apoptotic) peak that was down-regulated in the presence of the antioxidant N-acetyl-L-cysteine. Treatment with HPR resulted in a 30% reduction of cellular immunoreactivity to tyrosine kinase, whereas immunoreactivity to p185HER remained essentially unaltered. HPR exposure resulted in time-dependent increase in cellular metabolism of the retinoid as evidenced by increased formation of the inert metabolite N-(4-methoxyphenyl)-retinamide (MPR) and progressive increase in apoptosis. Thus, HPR-induced inhibition of aberrant proliferation may be caused, in part, by its ability to inhibit HER-2/neu-mediated proliferative signal transduction, retard cell cycle progression and upregulate cellular apoptosis.


Distinct actions of endothelin A-selective versus combined endothelin A/B receptor antagonists in early diabetic kidney disease.
Selective endothelin A (ET(A)) and combined ET(A) and ET(B) receptor antagonists are being investigated for use in treating diabetic nephropathy. However, the receptor-specific mechanisms responsible for producing the potential benefits have not been discerned. Thus, we determined the actions of ET(A) and ET(B) receptors on measures of glomerular function and renal inflammation in the early stages of diabetic renal injury in rats through the use of selective and combined antagonists. Six weeks after streptozotocin (STZ)-induced hyperglycemia, rats were given 2R-(4-methoxyphenyl)-4S-(1,3-benzodioxol-5-yl)-1-(N,N-di(n-butyl)aminocarbonyl-methyl)-pyrrolidine-3R-carboxylic acid (ABT-627) (5 mg/kg/day), a selective ET(A) antagonist; (2R,3R,4S)-4-(benzo[d][1,3]dioxol-5-yl)-2-(3-fluoro-4-methoxyphenyl)-1-(2-(N-propylpentylsulfonamido)ethyl)pyrrolidine-3-carboxylic acid hydrochloride (A-182086) (10 mg/kg/day), a combined ET(A/B) antagonist; or vehicle for 1 week. Sham controls received STZ vehicle (saline). Hyperglycemia led to significant proteinuria, increased glomerular permeability to albumin (P(alb)), nephrinuria, and an increase in total matrix metalloprotease (MMP) and transforming growth factor-β1 (TGF-β1) activities in glomeruli. Plasma and glomerular soluble intercellular adhesion molecule-1 (sICAM-1) and monocyte chemoattractant protein-1 (MCP-1) were elevated after 7 weeks of hyperglycemia. Daily administration of both ABT-627 and A-182086 for 1 week significantly attenuated proteinuria, the increase in P(alb), nephrinuria, and total MMP and TGF-β1 activity. However, glomerular sICAM-1 and MCP-1 expression was attenuated with ABT-627, but not A-182086, treatment. In summary, both selective ET(A) and combined ET(A/B) antagonists reduced proteinuria and glomerular permeability and restored glomerular filtration barrier component integrity, but only ET(A)-selective blockade had anti-inflammatory and antifibrotic effects. We conclude that selective ET(A) antagonists are more likely to be preferred for the treatment of diabetic kidney disease.


The Efficient Energy Collection of an Autoregulatory Driving Arm Harvester in a Breeze Environment.
Breezes are a common source of renewable energy in the natural world. However, effectively harnessing breeze energy is challenging with conventional wind generators. These generators have a relatively high start-up wind speed requirement due to their large and steady rotational inertia. This study puts forth the idea of an autoregulatory driving arm (ADA), utilizing a stretchable arm for every wind cup and an elastic thread to provide adjustable rotational inertia and a low start-up speed. The self-adjustable rotational inertia of the harvester is achieved through coordinated interaction between the centrifugal and elastic forces. As the wind speed varies, the arm length of the wind cup automatically adjusts, thereby altering the rotational inertia of the harvester. This self-adjustment mechanism allows the harvester to optimize its performance and adapt to different wind conditions. By implementing the suggested ADA harvester, a low start-up speed of 1 m/s is achieved due to the small rotational inertia in its idle state. With the escalation of wind speed, the amplified centrifugal force leads to the elongation of the driving arms. When compared to a comparable harvester with a constant driving arm (CDA), the ADA harvester can generate more power thanks to this stretching effect. Additionally, the ADA harvester can operate for a longer time than the CDA harvester even after the wind has stopped. This extended operation time enables the ADA harvester to serve as a renewable power source for sensors and other devices in natural breeze environments. By efficiently utilizing and storing energy, the ADA harvester ensures a continuous and reliable power supply in such settings.


Angiomyofibroblastoma of the vaginal portion.
Angiomyofibroblastoma is a tumor which is consists of two components: blood vessels and stromal cells, with always prominent vascular component. Angiomyofibroblastoma is benign tumor, but in literature is reported a case of recurrence and one case with sarcomatous transformation, which shoved that these tumors may rarely be associated with malignant component. A 78-year-old multiparous housewife was hospitalized at University Clinical Center because of painless, asymptomatic tumor of vaginal portion (posterior side). Tumor size was 7 millimeters in diameter. Internal genital organs did not present abnormalities. The patient underwent operative removal of the tumor and went to home at some day. At the histological examination the tumor presented as a angiomyofibroblastoma cervices uteri.


Inferior myocardial infarction and right coronary artery occlusive disease. A correlative study.
The present study represents an attempt to correlate the electrocardiogram and coronary arteriogram in patients with an inferior transmural infarct - or total occlusion of the right coronary artery. The influence of the collateral circulation on these findings was also evaluated. Fifty patients with a total occlusion of the right coronary artery had characteristic electrocardiographic changes of an inferior infarct in 44 per cent, very suspicious changes in 32 per cent, and no changes suggesting an inferior infarct in 24 per cent. However, in this latter group who had no evidence of an inferior infarct, we were able to recognize a small number who showed an anterior wall infarct. Collateral circulation was more frequently present and more extensive in those patients whose electrocardiograms did not show changes typical of inferior transmural infarction. This suggested that collateral circulation might minimize some of the electrocardiographic abnormalities which would normally result from occlusive disease of the right coronary artery. Another 50 patients, selected because of definite electrocardiographic evidence of typical inferior transmural infarction, were evaluated by coronary arteriography. Severe obstructive disease of the right coronary artery was present in 86 per cent of the group. In the remaining 7 patients (14 per cent) minimal or no disease was found. Infarction of the inferior wall may have resulted from occlusive disease of the anterior descending artery or have been the result of a right coronary artery occlusion with subsequent recanalization. We conclude from our study that a careful analysis of electrocardiographic abnormalities in theinferior leads will, with certain limitations, permit us to estimate the likelihood of a severe lesion in the right coronary artery, and, in the face of definite electrocardiographic evidence of an inferior infarct, to predict the diseased artery.


[From sociology in medicine to the sociology of collective health: contributions toward a necessary reflexivity].
This text looks at the difference between sociology in medicine (collaborator of health institutions) and the sociology of medicine (independent of health institutions). If consistent, sociology in medicine should become a sociology of medicine. As an example, it is shown how the study of the social determinants of health and illness begins by assuming non-problematically the ontological reality of health and illness, but ends up problematizing the very concept of health-disease, demonstrating that the study of health determinants also requires the study of the determinants of the social construction of disease. The urgent necessity of objectifying collective health itself is argued. By applying sociological tools we can examine the so-called objective factors in the determination of health and disease, the socially constructed nature of these categories of knowledge, and the struggles and power relations that determine whether or not such categories are viable.


Effects of Inertial Setting on Power, Force, Work, and Eccentric Overload During Flywheel Resistance Exercise in Women and Men.
Exercise load is a key component in determining end-point adaptations to resistance exercise. Yet, there is no information regarding the use of different inertia (i.e., loads) during isoinertial flywheel resistance exercise, a very popular high-intensity training model. Thus, this study examined power, work, force, and eccentric overload produced during flywheel resistance exercise with different inertial settings in men and women. Twenty-two women (n = 11) and men (n = 11) performed unilateral (in both legs) isolated concentric (CON) and coupled CON and eccentric (ECC) exercise in a flywheel knee extension device employing 6 inertias (0.0125, 0.025, 0.0375, 0.05, 0.075, 0.1 kg·m). Power decreased as higher inertias were used, with men showing greater (p ≤ 0.05) decrements than women (-36 vs. -29% from lowest to highest inertia). In contrast, work increased as higher inertias were employed, independent of sex (p ≤ 0.05; ∼48% from lowest to highest inertia). Women increased CON and ECC mean force (46-55%, respectively) more (p ≤ 0.05) than men (34-50%, respectively) from the lowest to the highest inertia evaluated, although the opposite was found for peak force data (i.e., peak force increased more in men than in women as inertia was increased). Men, but not women, increased ECC overload from inertia 0.0125 to 0.0375 kg·m2. Although estimated stretch-shorting cycle use during flywheel exercise was higher (p ≤ 0.05) in men (6.6%) than women (4.9%), values were greater for both sexes when using low-to-medium inertias. The information gained in this study could help athletes and sport and health professionals to better understand the impact of different inertial settings on skeletal muscle responses to flywheel resistance exercise.


Submicrometer 3D structures fabrication enabled by one-photon absorption direct laser writing.
We demonstrate a new 3D fabrication method to achieve the same results as those obtained by the two-photon excitation technique, by using a simple one-photon elaboration method in a very low absorption regime. Desirable 2D and 3D submicrometric structures, such as spiral, chiral, and woodpile architectures, with feature size as small as 190 nm have been fabricated, by using just a few milliwatts of a continuous-wave laser at 532 nm and a commercial SU8 photoresist. Different aspects of the direct laser writing based on ultralow one-photon absorption (LOPA) technique are investigated and compared with the TPA technique, showing several advantages, such as simplicity and low cost.


Bone-conduction threshold and air-bone gap may predict frequency-specific air-conduction threshold after tympanoplasty.
Postoperative hearing improvement is one of the main expectations for patients receiving tympanoplasty. The capacity to predict postoperative hearing may help to counsel a patient properly and avoid untoward expectations. It is difficult to predict postoperative hearing without knowing the disease process in the middle ear, which can only be assessed intraoperatively. However, the duration and extent of the underlying pathologies may represent in bone-conduction threshold and air-bone gap. Here in patients undergoing tympanoplasty without ossiculoplasty, we sorted and separated the surgery dates into the first group to build the predicting models and the second group to test the predictions. There were 87 and 30 ears, respectively. No specific enrollment or exclusion criteria were based on underlying pathologies such as the perforation size of the tympanic membrane or the middle ear conditions. The results show that bone-conduction threshold and air-bone gap together predicted air-conduction threshold after the surgery, including each frequency of 0.5k, 1k, 2k, and 4k Hz. The discrepancies between the predictions and recordings did not differ among these four frequencies. Of the variance in mean postoperative air-conduction threshold, 56.7% was linearly accounted for by these two preoperative predictors in this sample. The results suggest a trend that, the higher the frequency, the larger the part was accounted for by these two preoperative predictors. These together may help a surgeon to estimate frequency-specific hearing outcome after the surgery, answer patients' questions with quantitative statistics, and counsel patients with proper expectations.


Multiphoton imaging of tumor biomarkers with conjugates of single-domain antibodies and quantum dots.
An ideal multiphoton fluorescent nanoprobe should combine a nanocrystal with the largest possible two-photon absorption cross section (TPACS) and the smallest highly specific recognition molecules bound in an oriented manner. CdSe/ZnS quantum dots (QDs) conjugated to 13-kDa single-domain antibodies (sdAbs) derived from camelid IgG or streptavidin have been used as efficient two-photon excitation (TPE) probes for carcinoembryonic antigen (CEA) imaging on normal human appendix and colon carcinoma tissue. The TPACS for some conjugates was higher than 49,000 GM (Goeppert-Mayer units), considerably exceeding that of organic dyes being close to the theoretical value of 50,000 GM calculated for CdSe QDs. The ratio of sdAb-QD emission to the autofluorescence for 800 nm TPE was 40 times higher than that for 457.9 nm one-photon excitation. TPE ensures a clear discrimination of CEA-overexpressing tumor areas from normal tissue. Oriented sdAb-QD conjugates are bright specific labels for detecting low concentrations of antigens using multiphoton microscopy. This study demonstrates carcinoembryonic antigen imaging on normal human appendix and colon carcinoma tissue utilizing CdSe/ZnS quantum dots conjugated to streptavidin or to 13-kDa single-domain antibodies as efficient two-photon excitation probes.


Peroxiredoxin 6 deficiency and atherosclerosis susceptibility in mice: significance of genetic background for assessing atherosclerosis.
Peroxiredoxin 6 (Prdx6; also called antioxidant protein 2, or Aop2) is a candidate gene for Ath1, a locus responsible for the respective susceptibility and resistance of mouse strains C57BL/6J (B6) and C3H/HeJ (C3H) to diet-induced atherosclerosis. To evaluate if Prdx6 underlies Ath1, we compared the diet-induced atherosclerotic lesions in Prdx6 targeted mutant (Prdx6-/-) mice of different genetic backgrounds: B6, 129, and B6;129. PRDX6 protein and mRNA were expressed in normal and atherosclerotic aortas. B6;129 Prdx6-/- macrophages oxidized LDL significantly more than did controls. Plasma lipid hydroperoxide levels were higher in atherogenic diet-fed Prdx6-/- mice with B6;129 and B6 backgrounds than in controls. Prdx6-/- and controls in a 129 genetic background were equally lesion-resistant, and Prdx6-/- and controls in a B6 background were equally lesion-susceptible. In contrast, Prdx6-/- mice in a B6;129 background had significantly larger aortic root lesions than did littermate wild type controls. Therefore, although PRDX6 protein did not affect atherosclerosis susceptibility in either the resistant 129 background or the susceptible B6 background, it may inhibit atherosclerosis in backgrounds with mixed pro- and anti-atherogenic genes. Thus, genetic background plays an important role in modulating atherogenesis in targeted mutant mice. However, we think it is unlikely that Prdx6 underlies Ath1.


Phenotypic and DNA relatedness between nematode symbionts and clinical strains of the genus Photorhabdus (Enterobacteriaceae).
Bacterial strains isolated from wide ranges of nematode hosts and geographic sources and strains isolated from human clinical specimens were used to assess the taxonomic structure of the genus Photorhabdus. The following two methods were used: DNA relatedness and phenotypic characterization. Analysis of the DNA relatedness data revealed that all of the strains studied were congeneric and that the genus Photorhabdus is, on the basis of DNA relatedness data, more homogeneous than the other genus of nematode-symbiotic bacteria, the genus Xenorhabdus. In contrast to previous reports, only two DNA relatedness groups were identified in the genus Photorhabdus. These groups corresponded to the symbiotic strains and the clinical strains. There appeared to be some subgroups within the symbiotic strain group on the basis of the interactions of the strains with nematodes, which corresponded to some extent with the DNA relatedness data. However, there were significant ambiguities in the DNA relatedness data, and this group could not be subdivided on the basis of DNA relatedness data or phenotypic data. The distinct functional differences within and between the DNA relatedness groups of symbiotic Photorhabdus strains indicated that there are biologically significant sub-groups within the genus Photorhabdus that cannot be defined at this time. Further investigation of the taxonomy of Photorhabdus by using different approaches and a suitably wide range of strains is recommended. However, it is clear that the clinical strains form a recognizable subgroup within the genus even though no formal subtaxon can be defined at this time.


[Histiocytosis X. Clinical aspects and course in 5 patients].
Histiocytosis X developed in five patients (one woman and four men) when aged between 15 and 44 years. The initial sign in four of them was eosinophilic granuloma of the bone, in one it was pulmonary involvement. In three patients the disease remained confined to bone, while in two it involved the lungs and central nervous system, respectively. Osteolysis regressed spontaneously in one of the men, while in the woman there has been no recurrence 8 years after resection of the focus. In another man an osteolytic focus in a rib was noted after a 9-year recurrence-free interval. The man with pulmonary and bone involvement received chemotherapy with vinblastine and prednisone: dyspnoea and cough disappeared, vital capacity improved and the interstitial lung changes regressed. The osteolytic foci were repeatedly irradiated in the man with bone and CNS involvement. This brought about considerable reduction in pain but no significant radiological changes of the foci. Two courses of chemotherapy were given over 12 years, once with vincristine and prednisone, afterwards with cyclophosphamide. This arrested the progression of the osteolytic foci, but each time they recurred when the drugs were stopped.


Cumulative minority stress and suicide risk among LGBTQ youth.
Exposure to minority stress is the primary mechanism through which lesbian, gay, bisexual, transgender, queer, and questioning (LGBTQ) youth experience a greater risk for suicide. The current study examines the association of LGBTQ-based cumulative minority stress with suicide risk using online survey data collected from 39,126 LGBTQ youth ages 13-24 in the United States. Youth who reported four types of minority stress had nearly 12 times greater odds of attempting suicide compared to those who reported none. Transgender and nonbinary youth and American Indian/Alaskan Native youth had higher odds of reporting three or more minority stress experiences. The strong association of cumulative risk with attempted suicide and disproportionate exposure among marginalized members of the LGBTQ community highlight the need for suicide prevention to prioritize those at greatest risk and for research examining LGBTQ suicide risk to employ cumulative risk models.


A pragmatic approach to standard setting--the example of coal tar products and asphalt.
This article will outline a pragmatic approach directed to incorporating key elements of a scientific review of the literature and derive a proposal for an occupational exposure standard for coal tar, coal tar pitch, creosote, petroleum pitch, bitumen and asphalt, six substances which contain polynuclear aromatic hydrocarbons. Five approaches to the standard setting process are reviewed and their strengths and weaknesses discussed. Unfortunately there does not exist an acceptable epidemiological data set, other than the coke oven emission studies, on which to base a valid and reliable risk assessment model. Based on comparative potency experiments of complex mixtures, consideration of the state-of-the-art sampling and analytical methods, prevention of acute human health effects, and current existing standards for these substances throughout the world, a set of recommended exposure standards are derived for health policy makers.


Effect of soy drink replacement in a weight reducing diet on anthropometric values and blood pressure among overweight and obese female youths.
Soy drink replacement in the diet might have beneficial effects on anthropometric and blood pressure values for overweight and obese subjects. Therefore, we are going to determine the effects of soy drink replacements on the weight, waist circumference and blood pressure among overweight and obese female youths. This was a cross-over randomized clinical trial on 23 overweight and obese female subjects. All patients were on a weight reducing diet. There were two trial periods for six weeks (soy drink period and cow's milk period) and a washout period for 3 weeks. In the soy drink period only one glass of soy drink (240 cc) was consumed instead of one glass of cow's milk. The mean age of the patients was 22±2 years. Mean of BMI was 28.1±0.5. Weight and waist circumference did not changed significantly after the soy drink period compared to the cow's milk period. Systolic blood pressure reduced significantly following the soy drink period (mean percent change in soy drink period: -4.0±0.9 vs -1.7±0.5 in the cow's milk period; p<0.05). Diastolic blood pressure also reduced in the soy drink period (-0.4±0.1 vs 0.4±0.1; p<0.05). Soy drink replacement could reduce both systolic and diastolic blood pressure among overweight and obese female youths. However, this replacement had no significant results on weight and waist circumference.


Optimizing the surgical instrument tray to immediately increase efficiency and lower costs in the operating room.
Surgical trays are often poorly configured and can be ongoing sources of frustration and excess costs. We conducted an observational study to determine if the use of a customized mathematical inventory optimization model would result in a greater reduction in the number of instruments on a surgical tray than a clinician review of the tray. Utilization of instruments on the major orthopedic tray at a large academic hospital was documented over 80 procedures. Processes in the medical device reprocessing department and operating room were observed to comprehensively quantify all associated costs. Results of the observations were applied to a customized mathematical model to determine the ideal tray configuration. For comparison, a clinician review was also performed. The mathematical model alone produced an ideal tray size of 47 instruments, a reduction of 41 instruments from the original size of 88 instruments (47% reduction). This represented $34 440 in annual savings. In contrast, the clinician review alone suggested an ideal tray size of 67 instruments (23% reduction), representing $17 640 in annual savings. When clinicians were provided with the additional information from the model, they reduced the tray size to 51 instruments (42% reduction), producing $31 870 in savings. The mathematical model yielded an additional 22% instrument reduction and $14 230 in savings compared with clinician review alone. Our mathematical model is generalizable and can be applied to all specialties and hospitals to determine optimal tray configuration. As such, the financial implications are broad; at our institution, application to all surgical trays would result in $205 000 of savings annually. Surgeons and managers looking to streamline surgical trays should consider this evidence-based approach.


An organic donor/acceptor lateral superlattice at the nanoscale.
A precise control of the nanometer-scale morphology in systems containing mixtures of donor/acceptor molecules is a key factor to improve the efficiency of organic photovoltaic devices. Here we report on a scanning tunneling microscopy study of the first stages of growth of 2-[9-(1,3-dithiol-2-ylidene)anthracen-10(9H)-ylidene]-1,3-dithiole, as electron donor, and phenyl-C61-butyric acid methyl ester, as electron acceptor, on a Au(111) substrate under ultrahigh vacuum conditions. Due to differences in bonding strength with the substrate and different interactions with the Au(111) herringbone surface reconstruction, mixed thin films spontaneously segregate into a lateral superlattice of interdigitated nanoscale stripes with a characteristic width of about 10-20 nm, a morphology that has been predicted to optimize the efficiency of organic solar cells.


Nutrition ecology: the contribution of vegetarian diets.
Nutrition ecology is an interdisciplinary scientific discipline that encompasses the entire nutrition system, with special consideration of the effects of nutrition on health, the environment, society, and the economy. Nutrition ecology involves all components of the food chain, including production, harvesting, preservation, storage, transport, processing, packaging, trade, distribution, preparation, composition, and consumption of food, as well as disposal of waste materials. Nutrition ecology has numerous origins, some of which go back to antiquity. The introduction of industrialized agriculture and mass animal production gave rise to various negative influences on the environment and health. Food quality is determined in part by the quality of the environment. The environment, in turn, is influenced by food consumption habits. Research shows that vegetarian diets are well suited to protect the environment, to reduce pollution, and to minimize global climate changes. To maximize the ecologic and health benefits of vegetarian diets, food should be regionally produced, seasonally consumed, and organically grown. Vegetarian diets built on these conditions are scientifically based, socially acceptable, economically feasible, culturally desired, sufficiently practicable, and quite sustainable.


FcepsilonRI- and Fcgamma receptor-mediated production of reactive oxygen species by mast cells is lipoxygenase- and cyclooxygenase-dependent and NADPH oxidase-independent.
We investigated the enzymes responsible for FcepsilonRI-dependent production of reactive oxygen species (ROS) and the influence of ROS on mast cell secretory responses. 5-Lipoxygenase (5-LO) was the primary enzyme involved in ROS production by human mast cells (huMC) and mouse bone marrow-derived mast cells (mBMMC) following FcepsilonRI aggregation because incubation with 5-LO inhibitors (AA861, nordihydroguaiaretic acid, zileuton) but not a flavoenzyme inhibitor (diphenyleneiodonium) completely abrogated Ag-induced dichlorodihydrofluorescein (DCF) fluorescence. Furthermore, 5-LO-deficient mBMMC had greatly reduced FcepsilonRI-dependent DCF fluorescence compared with wild type mBMMC or those lacking a functional NADPH oxidase (i.e., gp91(phox)- or p47(phox)-deficient cells). A minor role for cyclooxygenase (COX)-1 in FcepsilonRI-dependent ROS production was demonstrated by inhibition of Ag-mediated DCF fluorescence by a COX-1 inhibitor (FR122047) and reduced DCF fluorescence in COX-1-deficient mBMMC. Complete abrogation of FcepsilonRI-dependent ROS production in mast cells had no effect on degranulation or cytokine secretion. In response to the NADPH oxidase-stimulating agents including PMA, mBMMC and huMC produced negligible ROS. IgG-coated latex beads did stimulate ROS production in huMC, and in this experiment 5-LO and COX again appeared to be the enzymatic sources of ROS. In contrast, IgG-coated latex bead-induced ROS production in human polymorphonuclear leukocytes occurred by the NADPH oxidase pathway. Thus mBMMC and huMC generate ROS by 5-LO and COX-1 in response to FcepsilonRI aggregation; huMC generate ROS upon exposure to IgG-coated latex beads by 5-LO and COX; and ROS appear to have no significant role in FcepsilonRI-dependent degranulation and cytokine production.


Myocardial viability in ischemic ventricular dysfunction.
In this paper, some controversial points regarding myocardial its definition hibernation are discussed, including its definition (improvement in contractility versus improvement in clinical or functional status or in prognosis), the histology and pathophysiology (dedifferentiation versus cellular degeneration) and the responses to the diagnostic methods more currently utilised, stress echocardiography and myocardial perfusion scintigraphy. The predictor factors for recovering after revascularization are also discussed.


Neonatal meningitis: what is the correlation among cerebrospinal fluid cultures, blood cultures, and cerebrospinal fluid parameters?
Meningitis is a substantial cause of morbidity and mortality in neonates. Clinicians frequently use the presence of positive blood cultures to determine whether neonates should undergo lumbar puncture. Abnormal cerebrospinal fluid (CSF) parameters are often used to predict neonatal meningitis and determine length and type of antibiotic therapy in neonates with a positive blood culture and negative CSF culture. We evaluated the first lumbar puncture of 9111 neonates at > or =34 weeks' estimated gestational age from 150 NICUs, managed by the Pediatrix Medical Group, Inc. CSF culture results were compared with results of blood cultures and CSF parameters (white blood cells [WBCs], glucose, and protein) to establish the concordance of these values in culture-proven meningitis. CSF cultures positive for coagulase-negative staphylococci and other probable contaminants, as well as fungal and viral pathogens, were excluded from analyses. Meningitis was confirmed by culture in 95 (1.0%) neonates. Of the 95 patients with meningitis, 92 had a documented blood culture. Only 57 (62%) of 92 patients had a concomitant-positive blood culture; 35 (38%) of 92 had a negative blood culture. In neonates with both positive blood and CSF cultures, the organisms isolated were discordant in 2 (3.5%) of 57 cases. In each case, the CSF pathogen required different antimicrobial therapy than the blood pathogen. For culture-proven meningitis, CSF WBC counts of >0 cells per mm3 had sensitivity at 97% and specificity at 11%. CSF WBC counts of >21 cells per mm3 had sensitivity at 79% and specificity at 81%. Culture-proven meningitis was not diagnosed accurately by CSF glucose or by protein. Neonatal meningitis frequently occurs in the absence of bacteremia and in the presence of normal CSF parameters. No single CSF value can reliably exclude the presence of meningitis in neonates. The CSF culture is critical to establishing the diagnosis of neonatal meningitis.