Glibenclamide-induced apoptosis is specifically enhanced by expression of the sulfonylurea receptor isoform SUR1 but not by expression of SUR2B or the mutant SUR1(M1289T).
Sulfonylurea receptor 1 (SUR1) is the regulatory subunit of the pancreatic ATP-sensitive K+ channel (K(ATP) channel), which is essential for triggering insulin secretion via membrane depolarization. Sulfonylureas, such as glibenclamide and tolbutamide, act as K(ATP) channel blockers and are widely used in diabetes treatment. These antidiabetic substances are known to induce apoptosis in pancreatic beta-cells or beta-cell lines under certain conditions. However, the precise molecular mechanisms of this sulfonylurea-induced apoptosis are still unidentified. To investigate the role of SUR in apoptosis induction, we tested the effect of glibenclamide on recombinant human embryonic kidney 293 cells expressing either SUR1, the smooth muscular isoform SUR2B, or the mutant SUR1(M1289T) at which a single amino acid in transmembrane helix 17 (TM17) was exchanged by the corresponding amino acid of SUR2. By analyzing cell detachment, nuclear condensation, DNA fragmentation, and caspase-3-like activity, we observed a SUR1-specific enhancement of glibenclamide-induced apoptosis that was not seen in SUR2B, SUR1(M1289T), or control cells. Coexpression with the pore-forming Kir6.2 subunit did not significantly alter the apoptotic effect of glibenclamide on SUR1 cells. In conclusion, expression of SUR1, but not of SUR2B or SUR1(M1289T), renders cells more susceptible to glibenclamide-induced apoptosis. Therefore, SUR1 as a pancreatic protein could be involved in specific variation of beta-cell mass and might also contribute to the regulation of insulin secretion at this level. According to our results, TM17 is essentially involved in SUR1-mediated apoptosis. This effect does not require the presence of functional Kir6.2-containing K(ATP) channels, which points to additional, so far unknown functions of SUR.


Interference and Impact of Dysmenorrhea on the Life of Spanish Nursing Students.
Dysmenorrhea is a cause of absenteeism in universities which, in the context of nursing studies, may affect mandatory attendance. Moreover, presenteeism is associated with medication errors, patient falls, and a reduced quality of patient care. This study sought to identify the degree of interference of dysmenorrhea on daily life and its impact on academic performance among Spanish nursing students, and to explore the reasons for presenteeism. A cross-sectional descriptive study was conducted on 261 nursing students. Data were collected using a self-administered questionnaire. The chi square tests, chi-square linear trend, Student's t-test, one-way analysis of variance of polynomial contrasts, and post hoc tests for the bi-variate analysis were used to compare the participants' responses regarding their type of dysmenorrhea and pain intensity. In addition, a multivariate regression was performed to predict absenteeism. The answers to the open questions were analyzed using thematic content analysis techniques. We observed 62.8% of absenteeism and 92.7% of presenteeism due to dysmenorrhea. Absenteeism was observed to be 3.079 (confidence interval (CI): 95%1.724-5.499; p < 0.001) times more likely among women with severe menstrual pain, 2.513 (CI 95%1.314-4.807; p = 0.005) times more in those suffering from menstrual nausea and 1.936 (CI 95%1.098-3.411; p = 0.022) times more frequent in those suffering from diarrhea. The reasons for presenteeism were grouped into five categories: the pain was bearable, it is not a reason to be absent, others don't consider it a reason to be absent, responsibility and guilt, and academic consequences. Dysmenorrhea can have a significant impact on academic performance. The concern among students about the academic repercussions and even feelings of guilt and incomprehension from others leads to high rates of presenteeism with potentially negative consequences for patient care.


[Electrocochleographic changes in guinea pigs immunized with type II collagen].
Electrocochleograms (ECoGs) were assessed in guinea pigs with cochlear impairment induced by immunization with type II collagen. Action potential (AP) tuning curves (TCs) were studied using a forward masking technique. Not only AP TCs, but the intensity function of APs and summating potentials (SPs) were assessed. The results were as follows: 1) The TCs displayed the normal pattern in all animals, and the Q10dB values of the curves were within the normal range. 2) Abnormal changes in AP, such as threshold elevation, decrease in amplitude and prolongation of latency were observed. 3) Decreases in +SP were observed in eight of ten animals, but no negative SPs were observed. 4) All animals exhibited degeneration of spiral ganglion cells on light microscopy, despite the preservation of normal hair cells. 5) Levels of antibody against type II collagen were much higher than in controls. This suggests that the normal pattern of TCs may have been the result of only minor hair cell damage. The cause of the decrease in +SP, however, is unknown. Further investigation should be performed to resolve this question. In addition, there may be differences in immune reaction from animal to animal.


Amplitude (vu and rms) and Temporal (msec) Measures of Two Northwestern University Auditory Test No. 6 Recordings.
In 1940, a cooperative effort by the radio networks and Bell Telephone produced the volume unit (vu) meter that has been the mainstay instrument for monitoring the level of speech signals in commercial broadcasting and research laboratories. With the use of computers, today the amplitude of signals can be quantified easily using the root mean square (rms) algorithm. Researchers had previously reported that amplitude estimates of sentences and running speech were 4.8 dB higher when measured with a vu meter than when calculated with rms. This study addresses the vu-rms relation as applied to the carrier phrase and target word paradigm used to assess word-recognition abilities, the premise being that by definition the word-recognition paradigm is a special and different case from that described previously. The purpose was to evaluate the vu and rms amplitude relations for the carrier phrases and target words commonly used to assess word-recognition abilities. In addition, the relations with the target words between rms level and recognition performance were examined. Descriptive and correlational. Two recoded versions of the Northwestern University Auditory Test No. 6 were evaluated, the Auditec of St. Louis (Auditec) male speaker and the Department of Veterans Affairs (VA) female speaker. Using both visual and auditory cues from a waveform editor, the temporal onsets and offsets were defined for each carrier phrase and each target word. The rms amplitudes for those segments then were computed and expressed in decibels with reference to the maximum digitization range. The data were maintained for each of the four Northwestern University Auditory Test No. 6 word lists. Descriptive analyses were used with linear regressions used to evaluate the reliability of the measurement technique and the relation between the rms levels of the target words and recognition performances. Although there was a 1.3 dB difference between the calibration tones, the mean levels of the carrier phrases for the two recordings were -14.8 dB (Auditec) and -14.1 dB (VA) with standard deviations <1 dB. For the target words, the mean amplitudes were -19.9 dB (Auditec) and -18.3 dB (VA) with standard deviations ranging from 1.3 to 2.4 dB. The mean durations for the carrier phrases of both recordings were 593-594 msec, with the mean durations of the target words a little different, 509 msec (Auditec) and 528 msec (VA). Random relations were observed between the recognition performances and rms levels of the target words. Amplitude and temporal data for the individual words are provided. The rms levels of the carrier phrases closely approximated (±1 dB) the rms levels of the calibration tones, both of which were set to 0 vu (dB). The rms levels of the target words were 5-6 dB below the levels of the carrier phrases and were substantially more variable than the levels of the carrier phrases. The relation between the rms levels of the target words and recognition performances on the words was random.


Evaluation of 2 novel approaches for assessing the ability of demineralized freeze-dried bone allograft to induce new bone formation.
Because of the wide variation in the ability of human demineralized freeze-dried bone allograft (DFDBA) to reproducibly induce new bone formation, there is a need for a reliable measure of bone induction activity. In this study we examined an immature osteoprogenitor cell line for its potential utility in measuring the activity of DFDBA in vitro. We characterized the response of 2T9 cells, an immature osteoprogenitor cell line derived from the calvariae of transgenic mice containing the SV40 T-antigen driven by the mouse bone morphogenetic protein (BMP)-2 promoter, to recombinant human BMP-2 by measuring alkaline phosphatase specific activity, osteocalcin production, and matrix mineralization. Responses were compared to those obtained with 1,25-(OH)2D3. In addition, 2T9 cells were cultured with active or inactive human DFDBA in the presence or absence of BMP-2. We also tested the hypothesis that radio-opacity of tissue following implantation of DFDBA in vivo correlates with the ability of human DFDBA to induce new bone. DFDBA from 9 different donors, stratified by age, were implanted subcutaneously in the thorax of 18 nude (nu/nu) mice. Tissue was harvested at 36 days postoperatively and examined histologically and biochemically for calcium and phosphorus uptake. 2T9 cells exhibited a dose- and time-dependent response to soluble BMP-2. Proliferation was decreased and alkaline phosphatase activity, osteocalcin production, and mineralized nodule formation were increased. The effects were dose- and time-dependent. Peak effects on alkaline phosphatase and osteocalcin were noted on day 8, whereas mineral deposition did not begin to occur until day 12. 1,25-(OH)2D3 did not regulate these effects unless used with BMP-2. When the cells were exposed to active or inactive DFDBA in the presence or absence of BMP-2, no effect on 2T9 cell differentiation was observed. This indicated that DFDBA released no soluble factors with bone inductive ability and that if any active factors were adsorbed to the DFDBA, they were inactivated. When DFDBA was implanted subcutaneously in the thorax of nude mice, there was no histologic evidence of new bone formation. However, there was a donor age-dependent decrease in Ca and P uptake of the implanted tissue, reflecting a donor age-dependent decrease in remineralization of DFDBA. These data indicate that cell culture assays like the one used in this study may not be appropriate indicators of bone induction ability by DFDBA since soluble factors may not be responsible for bone induction in vivo. Nonetheless, in vitro assays are still needed. While Ca and P uptake by DFDBA-implanted tissue in the present study correlated with the age-dependent decrease in bone induction at intramuscular sites in a previously reported study, these data show that early x-rays may actually detect remineralization and not new bone formation. Thus, assessment of bone induction ability may still depend on histologic analysis of animal models.


A Theory-Based mHealth Intervention (Getting Off) for Methamphetamine-Using Men Who Have Sex With Men: Protocol for a Randomized Controlled Trial.
Methamphetamine (meth) use among men who have sex with men (MSM) is associated with increased HIV prevalence and transmission and substandard advancement along the HIV prevention and care continuum. Given the growth of mobile health (mHealth) technologies, it is no longer necessary to limit meth treatment options to physical, brick-and-mortar sites, and administration using generic, nontailored content. In a 2-arm randomized controlled trial (RCT; N=300), we aim to evaluate the use of an mHealth intervention (Getting Off) to assess the impact and noninferiority of a cross-platform app (developed from a manualized meth treatment intervention) to help MSM reduce meth use and HIV sexual risk behaviors and improve their advancement along the HIV prevention and care continuum (HIV testing, pre-exposure prophylaxis uptake and persistence, and antiretroviral therapy uptake and adherence). Participants will be randomized into 2 arms: arm A, with immediate access to the app (immediate delivery: n=150), or arm B, with delayed access to the app after a 30-day period (delayed delivery: n=150). Participants in both arms will use the same Getting Off app and will have 30 days to complete the 24 sessions. Participants will be assessed at the 1-, 2- (delayed delivery arm only), 3-, 6-, and 9-month timepoints to determine observed treatment effects and will be compared with a historical matched sample of participants (n=~600) who received the brick-and-mortar group-based Getting Off intervention. Recruitment began in January 2019 for phase 1, the formative phase. In January and February 2019, 4 focus groups (N=36) were formed to provide input on the adaptation of the group-based manual intervention to a mobile app. Data collection for phase 2, the RCT, is expected to be completed in January 2023. The final results are anticipated in April 2023. By creating a culturally responsive mobile app, Getting Off aims to reduce meth use and improve sexual health outcomes among meth-using MSM. The Getting Off app could have significant public health impact by greatly expanding access to effective, affordable, private, culturally competent, and highly scalable meth treatment for MSM. Clinicaltrials.gov NCT03884946; https://clinicaltrials.gov/ct2/show/NCT03884946. DERR1-10.2196/22572.


Effect of deoxycholate on immunoglobulin G concentration in bile: studies in humans and pigs.
Because an increase in biliary deoxycholate levels seems to be a risk factor for cholesterol gallstone formation, we determined the relationship between deoxycholate levels and levels of the pronucleating protein, immunoglobulin G (Ig) in human gallbladder bile. Patients with cholesterol gallstones had a higher concentration of biliary IgG compared with a pigmented stone group and control patients. This was associated with the simultaneous presence of two conditions in the cholesterol stone group, supersaturated bile and a high deoxycholate/cholate ratio. The other patient groups met only one of the two conditions. Next, animal studies were performed to determine if model biles mimicking the two conditions could affect IgG secretion by the gallbladder. Gallbladders were exposed in vivo and then in an Ussing chamber to model biles. The voltage clamp technique was used to monitor functional integrity of the preparation. Three different model biles were tested: (1) taurodeoxycholate (TDC), 80%; taurocholate (TC), 20%; and cholesterol saturation index (CSI), 1.2; (2) TDC, 20%; TC, 80%; and CSI, 1.2; and (3) TDC, 80%; TC, 20%; and CSI, 0.6. IgG concentrations became significantly higher in group 1 than in the other two groups. The concentration of mucous glycoprotein was also significantly greater in group 1 when compared with group 2. Plasma cells were increased in number in mucosal and submucosal layers in group 1. We conclude that cholesterol supersaturated model bile with high content of TDC induces gallbladder epithelial alterations, which increase the luminal concentration of IgG and mucous glycoprotein.


Regulation of the immune response and inflammation by histamine and histamine receptors.
Histamine is a biogenic amine with extensive effects on many cell types, including important immunologic cells, such as antigen-presenting cells, natural killer cells, epithelial cells, and T and B lymphocytes. Histamine and its 4 receptors represent a complex system of immunoregulation with distinct effects dependent on receptor subtypes and their differential expression. These are influenced by the stage of cell differentiation, as well as microenvironmental influences, leading to the selective recruitment of effector cells into tissue sites accompanied by effects on cellular maturation, activation, polarization, and effector functions, which lead to tolerogenic or proinflammatory responses. In this review we discuss the regulation of histamine secretion, receptor expression, and differential activation of cells within both the innate and adaptive immune responses. It is clear that the effects of histamine on immune homeostasis are dependent on the expression and activity of the 4 currently known histamine receptors, and we also recognize that 100 years after the original identification of this biogenic amine, we still do not fully understand the complex regulatory interactions between histamine and the host immune response to everyday microbial and environmental challenges.


Can you ever collect too many oocytes?
Does the chance of pregnancy keep improving with increasing number of oocytes, or can you collect too many? Clinical pregnancy (CP) and live birth (LB) rates per embryo transfer varied from 10.2 and 9.2% following one oocyte collected to 37.7 and 31.3% when >16 oocytes were collected. Regression modelling indicated success rates increased or at least stayed the same with number of oocytes collected. It has been suggested that if >15 oocytes are collected, the success rate for fresh embryo transfers decreases. As this is counterintuitive, as more oocytes should result in more embryos, with a better choice of quality embryos, we decided to analyse the recent experience in a busy IVF unit. A retrospective analysis of clinical pregnancy and live birth outcome, with respect to number of oocytes collected at Monash IVF for the 2-year period between August 2010 and July 2012, where patients under the age of 45 years underwent a fresh embryo transfer. This included 7697 stimulated cycles for IVF and ICSI. Statistical analysis involved data tables and graphs comparing oocyte number with outcome. Results of women who had their first oocyte collection with an embryo transfer within the reference period were analysed by logistic regression analysis including other covariates that might influence pregnancy outcome. Analysis was also carried out of all the 7679 oocyte collections undertaken, resulting in fresh embryo transfers by generalized estimating equations to allow for the within subject correlation in outcomes for repeated treatments. The number of oocytes collected varied from 1 to 48. Clinical pregnancy and live birth rates per embryo transfer varied from 10.2 and 9.2% when only one oocyte was collected to 37.7 and 31.3% when >16 oocytes were collected. Regression modelling indicated success rates increased or at least stayed the same or with the number of oocytes collected. The percentage of women with embryos cryopreserved increased from under 20% with <4 oocytes collected to over 70% with >16 oocytes collected. There was a slight increase (from 18 to 22%) in oocyte immaturity and a more marked increase (from 0 to 3%) in cancelling fresh transfers to prevent Ovarian Hyperstimulation Syndrome (OHSS) with increase in number of oocytes collected above 16. The results of this study suggest that you cannot collect too many oocytes as both clinical pregnancy and live birth rates do not decrease with high numbers of oocytes collected. However, once >15 oocytes are collected, everything gets quite uncertain. As the data become sparse above 15 oocytes, we could not demonstrate a significant increase in pregnancy rates above this number. Larger studies would be required to answer the question whether there is a plateau, or rates continue to increase. The negative of aggressive stimulation to produce many oocytes is that the risk of OHSS increases, and this is the most serious complication of ovarian stimulation. No funding was required. There is no conflict of interest, except that G.K., V.M. and C.M. are shareholders in Monash IVF Pty Ltd.


Ethnic Comparison of 30-Day Potentially Preventable Readmissions After Stroke in Hawaii.
Ethnic disparities in readmission after stroke have been inadequately studied. We sought to compare potentially preventable readmissions (PPR) among a multiethnic population in Hawaii. Hospitalization data in Hawaii from 2007 to 2012 were assessed to compare ethnic differences in 30-day PPR after stroke-related hospitalizations. Multivariable models using logistic regression were performed to assess the impact of ethnicity on 30-day PPR after controlling for age group (<65 and ≥65 years), sex, insurance, county of residence, substance use, history of mental illness, and Charlson Comorbidity Index. Thirty-day PPR was seen in 840 (8.4%) of 10 050 any stroke-related hospitalizations, 712 (8.7%) of 8161 ischemic stroke hospitalizations, and 128 (6.8%) of 1889 hemorrhagic stroke hospitalizations. In the multivariable models, only the Chinese ethnicity, compared with whites, was associated with 30-day PPR after any stroke hospitalizations (odds ratio [OR] [95% confidence interval {CI}], 1.40 [1.05-1.88]) and ischemic stroke hospitalizations (OR, 1.42 [CI, 1.04-1.96]). When considering only one hospitalization per individual, the impact of Chinese ethnicity on PPR after any stroke hospitalization (OR, 1.22 [CI, 0.89-1.68]) and ischemic stroke hospitalization (OR, 1.21 [CI, 0.86-1.71]) was attenuated. Other factors associated with 30-day PPR after any stroke hospitalizations were Charlson Comorbidity Index (per unit increase) (OR, 1.21 [CI, 1.18-1.24]), Medicaid (OR, 1.42 [CI, 1.07-1.88]), Hawaii county (OR, 0.78 [CI, 0.62-0.97]), and mental illness (OR, 1.37 [CI, 1.10-1.70]). In Hawaii, Chinese may have a higher risk of 30-day PPR after stroke compared with whites. However, this seems to be driven by the high number of repeated PPR within the Chinese ethnic group.


Imbalanced expression of inhibin and activin subunits in primary epithelial ovarian cancer.
Inhibins and activins are related gonadal peptides with opposing biologic actions on gonadotropin regulation, cell differentiation, and proliferation. The previous study of activin in ovarian cancer cell lines suggests that activin may promote growth of ovarian cancer. Elevated serum inhibin levels were also found in ovarian cancer patients; however, the source of elevated inhibin is unknown. This study is designed to examine the expression of inhibin and activin subunits as well as activin receptor in primary ovarian epithelial tumors to explore their role in the process of ovarian epithelial tumorigenesis. The protein and mRNA expression of alpha and betaA subunits of inhibin/activin as well as of activin receptor mRNA were examined with immunohistochemistry (IHC) and reverse transcription-polymerase chain reaction (RT-PCR) in 112 ovarian carcinomas. Cases included 59 serous, 23 endometrioid, 16 mucinous, 9 clear cell, and 5 undifferentiated carcinomas. We also tested normal ovary and benign and borderline ovarian tumors for comparison. These included 17 ovarian surface epithelial samples, 6 serous and 5 mucinous cystadenomas, and 9 serous and 7 mucinous tumors of low malignant potential. A total of 139 ovarian tumors were analyzed by IHC and a total of 63 ovarian tumor samples were tested by RT-PCR. Inhibin alpha subunit expression was found in 47% of ovarian surface epithelia and focal alpha immunoreactivity was seen in tumor stroma, but was not found in the epithelial component of ovarian cystadenomas, tumors of low malignant potential (LMP), or carcinomas. Activin betaA subunit was expressed in 93% of surface epithelia, in the epithelial component of all cystadenomas, in 81% of LMP tumors, and in 72% of carcinomas, but not in tumor stroma. Activin expression did not correlate with histologic grades, tumor types, and surgical stages. Activin receptor type I and II mRNA-amplified products were found in virtually all the surface epithelial samples and ovarian tumors. The data suggest that imbalanced expression of inhibin and activin subunits in ovarian surface epithelium may represent an early event which leads to epithelial proliferation. Unopposed betaA and activin receptor expression in epithelial compartment of ovarian tumors suggest that activin may be available as autocrine and/or paracrine factors in ovarian epithelial tumors. But exact roles of inhibin and activin in ovarian epithelial tumors remain to be defined.


Validation of a Clinical Tool to Predict Neurological Outcomes in Critically Ill Children-A Prospective Observational Study.
To evaluate the performance of the empiric tool by Gupta et al. in predicting neurological outcomes in children admitted to the pediatric intensive care unit (PICU) and to evaluate the association of biomarkers S100B and NSE with neurological outcomes. This prospective observational study was conducted in 163 critically ill children aged 2 mo to 17 y admitted to the PICU from June 2020 to July 2021. The authors used the prediction tool developed by Gupta et al.; the tool was applied at admission and at PICU discharge/death. Samples for NSE and S100B were collected at admission and discharge. The performance of the new tool was assessed through discrimination and calibration. Risk factors for "unfavorable outcomes" (decline in PCPC score by > 1) were evaluated by multivariate analysis. The PICU mortality was 28% (n = 45). When the tool developed by Gupta et al. was used at the time of admission, favorable neurological outcomes were predicted for 69% (112) children. The area under the curve for the new tool at admission was 0.72 and at discharge/death it was 0.99, and the calibration was excellent at both time points. Independent factors associated with unfavorable neurological outcomes were higher PCPC scores and organ failure. As the number of samples processed for NSE and S100B was less, statistical analysis was not attempted. The new tool by Gupta et al. has good discrimination, calibration, sensitivity, and specificity and can be used as a prediction tool. NSE and S100B are promising biomarkers and need further evaluation.


Non-invasive assessment of pulmonary blood supply after staged repair of pulmonary atresia.
Radionuclide studies were performed to determine pulmonary blood flow in six children who had undergone surgery for pulmonary atresia, ventricular septal defect, and hypoplastic pulmonary arteries with or without major aortopulmonary collateral arteries. Lung blood flow was assessed from both particle perfusion lung scans and the pulmonary and systemic phase of a radionuclide dynamic flow study. Five patients had perfusion defects identified on the particle perfusion lung scan. In three of these, abnormal areas were perfused only during the systemic phase of the flow study, a combination of findings that indicate the presence of perfusion by collateral arteries. In one patient no systemic perfusion was noted and in one an initial particle perfusion study indicated the presence of a lung segment perfused by a collateral artery. In this last patient the particle perfusion scan after total correction showed a reduction in the size of the lung perfusion defect and no evidence of lung perfusion during the systemic phase of the flow study. The particle perfusion lung scan in the sixth patient showed pronounced asymmetry in blood flow to the lungs with no segmental perfusion defect on the particle perfusion scan and no abnormalities on the systemic flow study. It is concluded that radionuclide lung perfusion and flow studies provide useful information on lung perfusion and merit further evaluation to define their role in the management of these patients.


Electron transfer in proteins: in search of preferential pathways.
Electron migration between and within proteins is one of the most prevalent forms of biological energy conversion processes. Electron transfer reactions take place between active centers such as transition metal ions or organic cofactors over considerable distances at fast rates and with remarkable specificity. The electron transfer is attained through weak electronic interaction between the active sites, so that considerable research efforts are centered on resolving the factors that control the rates of long-distance electron transfer reactions in proteins. These factors include (in addition to the distance and nature of the microenvironment separating the reactants) thermodynamic driving force and the configurational changes required upon reaction. Several of these aspects are addressed in this review, which is based primarily on recent work performed by the authors on model systems of blue copper-containing proteins. These proteins serve almost exclusively in electron transfer reactions, and as it turns out, their metal coordination sites are endowed with properties uniquely optimized for their function.


Fat body protein granules and storage proteins in the silkmoth, Hyalophora cecropia.
Fat body cells of silkmoth pupae (Hyalophora cecropia ) contain granules, showing a less dense outer zone and a denser, often crystalline, inner portion appear after cocoon spinning and increase until the larval-pupal ecdysis; more granules are formed in females than in males. Urate granules, appearing fibrous in internal structure, first form about the same time, but their accumulation is more gradual, and continues in the pupa. Both types have been isolated by centrifugation. Protein granules dissolve in buffers to yield proteins 1 and 2, with distinct electrophoretic and antigenic properties. These proteins have been isolated individually from pupal fat body extracts by using their different thermal stabilities in phosphate buffer containing MgCl2 and (NH4)2SO4, respectively, and purification was completed by gel chromatography. Protein 1 has a molecular weight of 480,000 and a subunit of 85,000 daltons, while protein 2 gives values of 530,000 and 89,000, respectively. Their amino acid compositions are similar but distinct. Proteins 1 and 2 accumulate in the hemolymph, beginning 3 days before spinning, reach maximal levels at spinning, and then decline in the hemolymph while granules are formed in the fat body, although the total hemolymph protein concentration does not decline at this time. It is concluded that the fat body of the late, feeding larva synthesizes two related "storage proteins" and secretes them in partially crystalline granules as protein reserves for metamorphosis.


Advantages of prenatal diagnosis and early surgery for congenital cystic disease of the lung.
Prenatal ultrasonography makes possible the diagnosis of congenital cystic lung disease in utero, enabling elective surgery for the lesions early in infancy before development of respiratory distress or potentially life-threatening infection. From 1986 to 1994, ten infants with congenital lung cyst underwent corrective surgery. Nine of them had a prenatal diagnosis of congenital lung cyst confirmed by ultrasound or computed tomography (CT) after birth. In 7 of these infants, congenital adenomatoid malformation (CAM) was found at surgery, and pulmonary sequestration was found and removed in two other infants. Two of the nine infants had respiratory distress at birth; the seven others were asymptomatic when surgery was performed (between 2 and 6 months of age). In 4 out of 9 newborn a plain chest radiography at birth was normal and a CT scan only showed the cysts prenatally observed at ultrasound. Intraoperative measurement of pulmonary function in the asymptomatic infants demonstrated significant improvement after resection of the affected lobe. One other infant had normal lung fields at the time of prenatal diagnosis. However, a severe acute pneumonia with abscess of the lobe became life-threatening at 4.5 months. CT showed a large congenital lung cyst, treated initially with antibiotics and extirpated at age 6 months with great difficulty. Pulmonary function did not improve postoperatively. Examinations on follow-up (8 months-8 years; 5 of 10 infants longer than 4 years) have shown that all 10 of the infants are healthy and have normal pulmonary function. Pneumonia in the controlateral lung was found in 3 children (3-6 years after the operation), one of them had respiratory distress at birth and another had the life-threatening pneumonia preoperatively. Thus, early surgery is indicated when prenatal diagnosis of congenital cystic disease has been confirmed after birth.


Detection of quantitative trait loci affecting lameness and leg conformation traits in Danish Holstein cattle.
Lameness is an important factor for culling animals. Strong legs and feet improve herd life of dairy cows. Therefore, many countries include leg and feet conformation traits in their breeding programs, often as early predictors of longevity. However, few countries directly measure lameness related traits to include these in a breeding program. Lameness indices in 3 different lactations and 5 leg conformation traits (rear legs side view, rear legs rear view, hock quality, bone quality, and foot angle) were measured on granddaughters of 19 Danish Holstein grandsires with 33 to 105 sons. A genome scan was performed to detect quantitative trait loci (QTL) based on the 29 autosomes using microsatellite markers. Data were analyzed across and within families for QTL affecting lameness and leg conformation traits. A regression method and a variance component method were used for QTL detection. Two QTL each for lameness in the first [Bos taurus autosome (BTA); BTA5, BTA26] and second (BTA19, BTA22) lactations were detected. For the 5 different leg conformation traits, 7 chromosome-wise significant QTL were detected across families for rear legs side view, 5 for rear legs rear view, 4 for hock quality, 4 for bone quality, and 1 for foot angle. For those chromosomes where a QTL associated with 2 different traits was detected (BTA1, BTA11, BTA15, BTA26, and BTA27), a multitrait-1-QTL model and a multitrait-2-QTL model were performed to characterize these QTL as single QTL with pleiotropic effects or distinct QTL.


Interaction of platelet-activating factor, spleen and atrial natriuretic peptide in plasma volume regulation during endotoxaemia in rats.
1. We studied endotoxin (lipopolysaccharide, LPS)-induced platelet-activating factor (PAF) production in various visceral organs, and the effect of PAF antagonists or splenectomy on LPS-induced changes. 2. PAF production in response to LPS was highest in the spleen, followed by ileum, heart, lung and kidneys. None was found in the liver. The splenic response was rapid, reaching 10 times the basal level at 30 min. The increased PAF content in each organ was unrelated to the enzyme activity of either macrophages or neutrophils. 3. LPS-induced hypotension and haemoconcentration were largely prevented by PAF antagonists and splenectomy. 4. Plasma volume fell, and plasma atrial natriuretic peptide (ANP) rose, after LPS administration. Splenectomy or pretreatment with PAF antagonists almost completely prevented these LPS-induced changes at 30 min, but only partially reversed them at 90 min. 5. These results suggest that during endotoxaemia: (a) the spleen is the site of the highest endogenous PAF production; (b) the initial release of ANP is dependent on the production of endogenous PAF, and a PAF-ANP interaction mediates the early plasma volume reduction; (c) plasma volume reduction as well as ANP release depend on the spleen; (d) PAF mediated the hypotensive response and its action in the spleen; and (e) sequestered neutrophils are probably not the main source of PAF in the spleen.


Neorectum prolapse after rectal cancer surgery corrected with perineal stapled prolapse resection.
A 61-year-old woman developed neorectal prolapse after laparoscopic low anterior resection, total mesorectal excision with partial intersphincteric resection and handsewn coloanal anastomosis for rectal cancer. She presented with a 3 cm full thickness reducible prolapse, with associated anal pain and bleeding. A perineal stapled prolapse resection was performed to address the rectal prolapse, with satisfactory results.


Perspectives on key principles of generalist medical practice in public service in sub-Saharan Africa: a qualitative study.
The principles and practice of Family Medicine that arose in developed Western countries have been imported and adopted in African countries without adequate consideration of their relevance and appropriateness to the African context. In this study we attempted to elicit a priori principles of generalist medical practice from the experience of long-serving medical officers in a variety of African counties, through which we explored emergent principles of Family Medicine in our own context. A descriptive study design was utilized, using qualitative methods. 16 respondents who were clinically active medical practitioners, working as generalists in the public services or non-profit sector for at least 5 years, and who had had no previous formal training or involvement in academic Family Medicine, were purposively selected in 8 different countries in southern, western and east Africa, and interviewed. The respondents highlighted a number of key issues with respect to the external environment within which they work, their collective roles, activities and behaviours, as well as the personal values and beliefs that motivate their behaviour. The context is characterized by resource constraints, high workload, traditional health beliefs, and the difficulty of referring patients to the next level of care. Generalist clinicians in sub-Saharan Africa need to be competent across a wide range of clinical disciplines and procedural skills at the level of the district hospital and clinic, in both chronic and emergency care. They need to understand the patient's perspective and context, empowering the patient and building an effective doctor-patient relationship. They are also managers, focused on coordinating and improving the quality of clinical care through teamwork, training and mentoring other health workers in the generalist setting, while being life-long learners themselves. However, their role in the community, was found to be more aspirational than real. The study derived a set of principles for the practice of generalist doctors in sub-Saharan Africa based on the reported activities and approaches of the respondents. Patient-centred care using a biopsychosocial approach remains as a common core principle despite wide variations in context. Procedural and hospital care demands a higher level of skills particularly in rural areas, and a community orientation is desirable, but not widely practiced. The results have implications for the postgraduate training of family physicians in sub-Saharan Africa, and highlight questions regarding the realization of community-orientated primary care.


Modeling cannabinoids from a large-scale sample of Cannabis sativa chemotypes.
The widespread legalization of Cannabis has opened the industry to using contemporary analytical techniques for chemotype analysis. Chemotypic data has been collected on a large variety of oil profiles inherent to the cultivars that are commercially available. The unknown gene regulation and pharmacokinetics of dozens of cannabinoids offer opportunities of high interest in pharmacology research. Retailers in many medical and recreational jurisdictions are typically required to report chemical concentrations of at least some cannabinoids. Commercial cannabis laboratories have collected large chemotype datasets of diverse Cannabis cultivars. In this work a data set of 17,600 cultivars tested by Steep Hill Inc., is examined using machine learning techniques to interpolate missing chemotype observations and cluster cultivars into groups based on chemotype similarity. The results indicate cultivars cluster based on their chemotypes, and that some imputation methods work better than others at grouping these cultivars based on chemotypic identity. Due to the missing data and to the low signal to noise ratio for some less common cannabinoids, their behavior could not be accurately predicted. These findings have implications for characterizing complex interactions in cannabinoid biosynthesis and improving phenotypical classification of Cannabis cultivars.


The role of CD150-SH2D1A association in CD150 signaling in Hodgkin's lymphoma cell lines.
To find out what signal transduction pathways are linked to CD150 in Hodgkin's lymphoma (HL) cell lines, how are they regulated, and to examine the expression of different CD150 splice forms and SH2 domain containing protein D1A (SH2D1A) adaptor protein on mRNA level in HD primary tumors and cell lines. The expression of CD150 splicing forms and SH2D1A adaptor protein in HD primary lymphoma tissue and cell lines were analyzed by RT-PCR method. To examine CD150-SH2D1A localization in HD cell lines we performed double immunofluorescent staining of these two proteins. Total amount of SH2D1A, Syk, Lyn, SHP-2, SHIP proteins, and activated/phosphorylated ERK1/2 and Akt proteins were detected by Western blot analysis with specific antibodies. We showed the expression of soluble (sCD150) and full length transmembrane (mCD150) splice forms and SH2D1A adaptor protein on mRNA level in 9 cases of classical HD and three HD lines of B cell origin - L428, KM-H2 and L1236. In spite of CD150 and SH2D1A co-expression in studied HD cell lines, CD150 co-precipitated and co-localized with SH2D1A only in L1236 cells. CD150 ligation induced extracellular signal-regulated kinases (ERK) dephosphorylation in L1236 cell line, but had no effect on ERK pathway in KM-H2 and L428 cells. CD150 crosslinking induced Akt activation also only in L1236 cells. HD cells express sCD150 and mCD150 splice forms and SH2D1A. Association of CD150 and SH2D1A depends at least on their localization pattern. CD150 is linked to ERK and Akt pathways in HD cell lines. Our data suggest that CD150-SH2D1A association play decisive role in Akt signaling upon CD150 ligation in HD cell lines. CD150-mediated Akt activation in HD cell lines, similarly to DT40 model system, is SHIP-independent.


Disulfide bond reconstruction: A novel approach for grafting of thiolated chitosan onto wool.
Chitosan, a natural biopolymer, is used as a multifunctional agent for modification of wool either through chemical crosslinking or physical coating. For the first time, wool fabric has been modified with chitosan through disulfide bond breaking and reforming reactions. The chitosan was thiolated and then grafted onto the reduced wool fibers through disulfide bonds. In order to understand the mechanism of the grafting of thiolated chitosan onto wool, glutathione was used as a model compound for wool in the research. The structures of thiolated chitosan reacted with glutathione and wool fabrics grafted with thiolated chitosan were investigated by FTIR, 13CNMR, XPS, XRD, SEM. The dyeability, shrink-resistance and biocompatibility were also tested. The results suggested that glutathione reacted with thiolated chitosan and formed disulfide bond. The thiolated chitosan-grafted wool fabric had good shrink-resistance and dyeability. Hydrophilicity and antibacterial properties were also improved compared with untreated wool fabric. The results provide a novel approach for modification of wool through fiber-intrinsic groups like disulfide bonds.


High Internal Phase Emulsions Stabilized by a Zeolite-Surfactant Combination in a Composition-Dependent Manner.
As a step toward synthesizing zeolite-based porous materials, this study demonstrates for the first time the feasibility of stabilizing oil-in-water (O/W) high internal phase emulsions (HIPEs) using a cationic surfactant (tetradecyltrimethylammonium bromide, TTAB) and "homemade" submicronic Linde type A zeolite particles. The zeolite particles are hydrophilic and therefore do not attach to dodecane-water interfaces, but surface tension measurements and electrochemical data show that their surface can be activated by the electrostatic and subsequent hydrophobic adsorption of TTAB. Comparing the adsorption isotherm of TTAB and zeta potential of the particles with the droplet sizes and rheological properties of the emulsion shows that the stabilization mechanism depends on the TTAB/zeolite weight ratio. At low TTAB/zeolite weight ratios (≤0.2 wt %), gel-like O/W Pickering HIPEs form, but at intermediate TTAB concentrations, the zeolite particles become more hydrophobic, leading to phase inversion and the stabilization of W/O emulsions. At high TTAB/zeolite weight ratios (>1.25 wt %), a second phase inversion occurs and creamy O/W HIPEs form through a different stabilization mechanism. In this case indeed, the zeolite particles are fully covered by a bilayer of TTAB and remain dispersed in the aqueous phase with no adsorption to the dodecane-water interface. The emulsion is stabilized by electrostatic repulsion between the highly positively charged zeolite particles and the cationic surfactant adsorbed at the dodecane-water interface.


Leptin/adiponectin ratio in obese women with and without binge eating disorder.
Adipose tissue-derived hormones are involved in the pathophysiology of eating disorders and other mental disorders. Studies have suggested that the serum leptin/adiponectin ratio is highly correlated with BMI. Furthermore, it is associated with a number of metabolic processes and inflammatory markers that are involved in obesity and mental disorders, such as the physiopathology of binge eating disorder (BED). We investigated whether variations in leptin and adiponectin serum concentrations differed between adult women with and without BED before and after a meal. The study group was composed of 8 normal weight women (20-25 kg/m2) without BED, 8 obese women (>/=30 kg/m2) with BED, and 7 obese women without BED (non-BED). Blood samples were collected before and after the consumption of a meal composed of 55% carbohydrates, 15% protein, and 30% lipids. Body mass index (p<0.0001), leptin (p<0.0001) and the leptin/adiponectin ratio (p<0.0001) were higher in obese non-BED women than in obese BED and normal weight groups. Adiponectin (p=0.01) concentrations were lower in the obese BED group than in the other groups before and after the meal. The hypoadiponectinemia followed by the altered levels of leptin in obese BED woman may predispose these subjects to an inadequate energy balance, which could promote weight gain and an increased food intake in woman that may contribute to obesity and binge eating in these subjects.


How bad are bacteremia and sepsis? Outcomes in a cohort with suspected bacteremia.
To evaluate the short-term and long-term outcomes of patients with suspected bacteremia, we performed a prospective cohort study. Clinical data were collected within 24 hours of initial culture from a random sample of 1516 episodes in which blood cultures were performed in an urban tertiary care hospital. One hundred forty-two patients with bacteremia were compared with two comparison groups: (1) 142 randomly selected patients with negative cultures, matched in age within 5 years, gender, severity of underlying disease, and presence of major comorbidity, and (2) all 155 patients with contaminant cultures. The main outcome measures were death, death secondary to bacteremia, and major complications. In the 439 patients, there were 142 deaths (32%), 114 at 1 year (26%) and 46 within 30 days (11%). Mortality at 30 days was most highly correlated with predicted fatality of underlying disease: 48% for the 65 patients with a rapidly fatal disease, 9% for the 156 patients with an eventually fatal disease, and 0.5% for the 217 patients with no fatal disease. In a Cox survival analysis, the risk ratio associated with bacteremia was 1.6 (95% confidence interval, 1.0 to 2.4) vs the comparison groups. When we performed time-dependent Cox analyses in which the hazard ratio was allowed to change at 30 days, we found that the risk ratios associated with bacteremia were 2.3 (95% confidence interval, 1.2 to 4.4) for the first 30 days, and 1.3 (95% confidence interval, 0.76 to 2.1) after 30 days. We conclude that this population has a high mortality, which is strongly correlated with severity of underlying disease. Short-term mortality was higher in patients with bacteremia even after controlling for severity of illness, but the increase in risk was present only during the first month and most deaths occurred in patients with a rapidly fatal disease.


The quantitative genetics of phenotypic robustness.
Phenotypic robustness, or canalization, has been extensively investigated both experimentally and theoretically. However, it remains unknown to what extent robustness varies between individuals, and whether factors buffering environmental variation also buffer genetic variation. Here we introduce a quantitative genetic approach to these issues, and apply this approach to data from three species. In mice, we find suggestive evidence that for hundreds of gene expression traits, robustness is polymorphic and can be genetically mapped to discrete genomic loci. Moreover, we find that the polymorphisms buffering genetic variation are distinct from those buffering environmental variation. In fact, these two classes have quite distinct mechanistic bases: environmental buffers of gene expression are predominantly sex-specific and trans-acting, whereas genetic buffers are not sex-specific and often cis-acting. Data from studies of morphological and life-history traits in plants and yeast support the distinction between polymorphisms buffering genetic and environmental variation, and further suggest that loci buffering different types of environmental variation do overlap with one another. These preliminary results suggest that naturally occurring polymorphisms affecting phenotypic robustness could be abundant, and that these polymorphisms may generally buffer either genetic or environmental variation, but not both.


Establishing methods for isolation of stem cells from human exfoliated deciduous from carious deciduous teeth.
This study aims to establish the isolation method of stem cells from pulp tissue of carious deciduous teeth. The teeth were soaked in 1% povidone-iodine solution for about 1 min followed by washing in PBS with 1% antibiotic-antimycotic thrice. Dental pulp tissue was removed by extirpation, and then cultivated in the culture medium. Characterization of mesenchymal stem cell (MSC) was carried out using human MSC analysis kit with positive markers CD90, CD73, and CD105, but negative for expressions of CD45, CD34, CD11b, CD19, and HLA-DR. Differentiation capacity of stem cells from human exfoliated deciduous (SHED) was determined by staining with Alizarin S, Alcian Blue, and Oil Red O. There is no contamination after 3 days of culture. SHED derived from dental pulp were expressions of 99.2% of positive marker and 0.3% of the negative marker. At passage 5, SHED was differentiated into osteocyte, chondrocyte, and adipocyte types of cells in the induction medium. SHED derived from carious deciduous teeth can be used as a source of stem cell for regenerative medicine.


Unicompartmental knee arthroplasty for lateral gonarthrosis: midterm results.
Thirty-eight lateral compartment arthroplasties were performed in 22 years. Eighteen joints in 17 patients with an average age of 64.5 years were evaluated with minimum 5-year follow-up. Using the Hospital for Special Surgery knee score, 16 of 18 joints had satisfactory results in terms of function and pain relief. The average preoperative alignment on standing was 14.9 degrees of valgus angulation, which was corrected to 6.9 degrees of valgus. On radiographic analysis, no radiolucent lines were seen under the tibial component, but the femoral component was loose in 1 joint. Although 5 joints showed slight deterioration of osteoarthritic change in the medial compartment, lateral compartment arthroplasty is a reliable and successful option in the treatment of patients with a low level of physical activity.


Undergraduate Origins of American Scientists.
An analysis of the college attendance or college choice for four high-aptitude, high-school senior samples suggests that the differential institutional productivity of scientists and scholars is a function of the differential college attendance, paternal vocational motivations, and their implied correlates among high-aptitude students. This formulation appears to be more probable for males than for females. The institutional productivity hypothesis proposed in previous studies is not supported by the present evidence (14).


Lipidomic Analysis.
The state-of-art in the lipidomic analysis is summarized here to provide the overview of available sample preparation strategies, mass spectrometry (MS)-based methods for the qualitative analysis of lipids, and the quantitative MS approaches for high-throughput clinical workflows. Major challenges in terms of widely accepted best practices for lipidomic analysis, nomenclature, and standards for data reporting are discussed as well.


[Method of treatment of amblyopia with dynamic color stimuli emerging in polarized light interference].
A method for treating amblyopia by using dynamic color objects (stimuli) influencing simultaneously different channels of the optic system is proposed. Original equipment based on polarized light interference was used, as well as a nomogram permitting rapid assessment of the optimal size of the offered test objects. The method was used in 90 children (99 amblyopic eyes). It reliably improved the efficacy of comprehensive treatment of amblyopia of different degree and origin and may be effectively used as the only method, particularly advisable for cases poorly treated by the traditional methods. The method is simple and interesting for young children.


Bacillus cereus Typhlitis in a Patient with Acute Myelogenous Leukemia: A Case Report and Review of the Literature.
Bacillus cereus is a Gram-positive rod that is now recognized as a rare cause of frank disease in the neutropenic hematologic malignancy patient. Because this pathogen is rarely isolated in clinical specimens, no large studies exist to guide the management of these acutely ill patients. Individual case reports and case series exist in the literature describing various clinical manifestations of B. cereus in the neutropenic patient including bacteremia/septicemia, pneumonia, meningitis/encephalitis, hepatic abscesses, and gastritis. In this report, we describe a case of typhlitis caused by B. cereus in a 74-year-old female with recently diagnosed acute myelogenous leukemia (AML), and we summarize the available English language literature to draw tentative conclusions regarding the clinical manifestations of this organism.


HER2-Targeted Multifunctional Silica Nanoparticles Specifically Enhance the Radiosensitivity of HER2-Overexpressing Breast Cancer Cells.
We investigated the effects of targeted functionalized silica nanoparticles on the radiosensitivity of cancer cells. Better control of the local concentration of silica nanoparticles may facilitate their use as an adjuvant in conjunction with ionizing radiation to target cancer cells while preventing damage to normal cells. Hyperbranched polyamidoamine (PAMAM) was grafted onto the surface of amorphous silica nanoparticles to functionalize them. The PAMAM-coated silica nanoparticles (PCSNs) were then conjugated with fluorescent dyes. Anti-HER2 antibodies were covalently attached to the labeled PCSNs. The HER2-overexpressing SK-BR3 breast cancer cell line was incubated in medium containing the PCSN probes. After incubation; the cells were exposed to X-ray radiation. Cells were counted in all samples using cell proliferation assays; and apoptotic cells were detected. The cell survival results showed that the combination of the targeted PCSN probes and radiation reduced the survival rate of SK-BR3 cells to a greater extent than when either PCSN probes, PCSNs or radiation were applied individually. The results also showed an increase in apoptosis in the SK-BR3 cells that internalized the PCSN probes and were then irradiated. Based on these data, PCSN probes act as specific radiosensitizing agents for HER2-overexpressing cells.


Development of insulin resistance by astronauts during spaceflight.
Human spaceflight is associated with the loss of body protein. On Earth, insulin is an important factor in the regulation of muscle protein synthesis and breakdown. The objectives of this study were to determine whether insulin resistance occurs in spaceflight, and if the development of insulin resistance is related to the protein loss. The urinary C-peptide excretion rate was used as a marker for insulin secretion. The experiment was conducted before, during and after the 1991 9.5-d SLS-1 (Columbia) Space Shuttle mission. Dietary intake and urine output were monitored continuously for the four payload crewmembers from 11 d before launch to 7 d after landing for a total of 27 d. Data were obtained on the four payload crewmembers. Results were as follows: 1) the mean inflight C-peptide excretion rates were significantly lower than either the pre- or postflight rates (p < 0.05); and 2) the inflight nitrogen balance decreased as C-peptide excretion increased.


Ionizing irradiation protection and mitigation of murine cells by carbamazepine is p53 and autophagy independent.
Carbamazepine, a sodium channel blocker and pro-autophagy agent used in the treatment of epilepsy and trigeminal neuralgia, is also an ionizing radiation mitigator and protector. We measured the effect of carbamazepine, compared to other pro-autophagy drugs (i.e. lithium and valproic acid), on irradiation of autophagy incompetent (Atg5(-/-)) and competent (Atg5(+/+)) mouse embryonic fibroblasts, p53(-/-) and p53(+/+) bone marrow stromal cells, and human IB3, KM101, HeLa, and umbilical cord blood cell and in total body-irradiated or orthotopic tumor-bearing mice. Carbamazepine, but not other pro-autophagy drugs, was a radiation protector and mitigator for mouse cell lines, independent of apoptosis, autophagy, p53, antioxidant store depletion, and class I phosphatidylinositol 3-kinase, but was ineffective with human cells. Carbamazepine was effective when delivered 24 hours before or 12 hours after total body irradiation of C57BL/6HNsd mice and did not protect orthotopic Lewis lung tumors. Carbamazepine is a murine radiation protector and mitigator.


The impact of preserved Klotho gene expression on antioxidative stress activity in healthy kidney.
Klotho, which was originally identified as an antiaging gene, forms a complex with fibroblast growth factor 23 receptor in the kidney, with subsequent signaling that regulates mineral metabolism. Other biological activities of Klotho, including antiaging effects such as protection from various types of cellular stress, have been shown; however, the precise mechanism of these effects of Klotho gene in the healthy human kidney is not well understood. In this study, we examined the relationships of Klotho and antioxidative stress gene expression levels in zero-hour biopsy specimens from 44 donors in kidney transplantation and verified them in animal models whose Klotho gene expression levels were varied. The nitrotyrosine expression level in the kidney was evaluated in these animal models. Expression levels of Klotho gene were positively correlated with the p53 gene and antioxidant enzyme genes such as catalase, superoxide dismutase 1 (SOD1), SOD2, peroxiredoxin 3 (PRDX3), and glutathione peroxidase 1 (GPX1) but not clinical parameters such as age and renal function or pathological features such as glomerulosclerosis and interstitial fibrosis tubular atrophy. The expression levels of all genes were significantly higher in mice with Klotho overexpression than in wild-type mice, and those except for catalase, PRDX3, and GPX1 were significantly lower in Klotho-deficient mice than in wild-type littermate mice. Nitrotyrosine-positive bands of various sizes were observed in kidney from Klotho-deficient mice only. The preservation of Klotho gene expression might induce the antioxidative stress mechanism for homeostasis of healthy human kidney independently of its general condition, including age, renal function, and histological findings.


Effect of ascorbic acid on surgical stress response in gynecologic surgery.
Surgical stress may cause neural, endocrine, metabolic and humoral responses depending on the severity of the procedure. In this study, we aimed to study the effect of the preoperatively given ascorbic acid (AA), which is an antioxidant, and its role in the biosynthesis of neuropituitary hormones on the surgical stress response. Twenty-two American Society of Anaesthesiologists I and II patients ageing between 18 and 40, who have no endocrine and metabolic disease, and undergoing abdominal operation for non-malignant diseases were allocated to the study. These non-premedicated patients were divided into two groups in random: Group I, etomidate group; and Group II, AA plus etomidate group. AA was given to patients in Group II 20min before etomidate injection. After monitoring the patient, anaesthetic induction was applied by giving 0.3 mg/kg of etomidate, 2 microg/kg of fentanyl and 0.1 mg/kg of vecuronium. Anaesthesia was continued with 1-0.7% isoflurane and N2O/O2 (67 and 37%, respectively). Tramadol was given for the management of post-operative analgesia. Blood samples were obtained from all patients before the operation and at second, sixth, twelfth and twenty-forth hours after the beginning of operation for cortisol, adrenocorticotropic hormone (ACTH), osteocalcin, insulin and blood glucose level analyses. There was no statistically significant difference in cortisol, osteocalcin, insulin and glucose levels in both groups, when compared to the control levels. Whereas, patients in Group II had higher levels of cortisol than the control group at sixth hour, which were in normal limits, and there was no decrease in osteocalcin concentration. ACTH level was increased at the second and sixth hours, which was statistically significant, but at twelfth and twenty-forth hours, they were close to control group levels. As a result, we conclude that AA given before anaesthesia achieved by etomidate is not sufficient for the prevention of surgical stress response and that AA induction before anaesthesia should be preferred, particularly for the prevention of decrease in osteocalcin levels.


Self and social identity.
In this chapter, we examine the self and identity by considering the different conditions under which these are affected by the groups to which people belong. From a social identity perspective we argue that group commitment, on the one hand, and features of the social context, on the other hand, are crucial determinants of central identity concerns. We develop a taxonomy of situations to reflect the different concerns and motives that come into play as a result of threats to personal and group identity and degree of commitment to the group. We specify for each cell in this taxonomy how these issues of self and social identity impinge upon a broad variety of responses at the perceptual, affective, and behavioral level.


RhoA affects oral morphine analgesia depending on functional variation in intestinal P-glycoprotein induced by repeated etoposide treatment.
In early palliative care, drug-drug interactions between opioids and anticancer agents may be caused by combined treatment with these drugs. We previously reported that repeated administration of oral etoposide (ETP), an anticancer drug that is a substrate of P-glycoprotein (P-gp), caused attenuation of the analgesic effect of oral morphine through up-regulation of intestinal P-gp. Recent studies have revealed that RhoA, a small G-protein, is involved in the regulation of P-gp expression and activity. Moreover, RhoA is known to be involved in various signaling pathways in response to anticancer drugs. Here, we examined the involvement of RhoA in the changes in ileal P-gp protein expression and activity induced by repeated orally administered ETP. Ileal P-gp and RhoA protein expression levels were analyzed using western blot analysis. The efflux activity of ileal P-gp was measured using the in situ closed loop method. The analgesic effect of oral morphine was determined with a tail-flick test. Repeated oral ETP significantly increased the activity of RhoA in association with up-regulation of P-gp protein expression and activity in the ileum. Interestingly, inhibition of RhoA activation by rosuvastatin prevented these effects. Furthermore, ETP-induced attenuation of the analgesic effect of oral morphine was also suppressed by rosuvastatin. RhoA activation induced by repeated oral ETP administration may be involved in the up-regulation of ileal P-gp protein expression and activity, leading to a decrease in the analgesic effect of oral morphine.


Stable isotopes unravel the feeding mode-trophic position relationship in trematode parasites.
Stable isotopes have been sporadically used over the last two decades to characterise host-parasite trophic relationships. The main reason for this scarcity is the lack of an obvious pattern in the ratio of nitrogen stable isotope values (δ15 N) of parasites in comparison to their host tissues, which would be key to understand any host-parasite system dynamics. To circumvent this, we focused on a single snail host, Zeacumantus subcarinatus, and three of its trematode parasites. We used stable isotopes to investigate each host-trematode trophic relationship and shed light on the mechanisms utilised by the parasite to reroute its hosts' biomass. All our trematodes were found to be 15 N-enriched compared to their host, with their δ15 N values strongly related to their feeding behaviours: passive versus active. It was possible to 'rank' these parasite species and assess their 'relative' trophic position using δ15 N values. We also demonstrated that including a broader range of samples (e.g. host food and faeces, multiple parasite life stages) helped understand the metabolic mechanisms used by the various participants, and that using carbon stable isotope values and C:N ratios allowed to identify an important lipid requirement of these trematode parasites. Finally, we show how critical it is to not ignore parasitic infections as they can have a great influence on their host's trophic position. We have shown that by focussing on a single host species and a single taxonomic group of parasites, we can remove a certain amount of variation recorded by broader isotope studies. We hope that these data will ultimately improve our ability to place parasites in food webs, and thus improve our understanding of the connections and interactions that dictate food web dynamics.


p53 family proteins in thyroid cancer.
At variance with other human malignancies, p53 mutations are not frequent in thyroid cancer and are believed to be responsible mainly for cancer progression to poorly differentiated and aggressive phenotype. p63 and p73, two proteins with a high degree of homology with p53, are overexpressed in thyroid cancer, but their role in cancer initiation or progression is controversial. Regulation of p53 family protein function depends on: (1) the balance between the expression of transcriptionally active (p53, TAp63, and TAp73) and inactive isoforms (DeltaNp63 and DeltaNp73); (2) their interaction and competition at DNA-responsive elements; (3) their interaction with regulatory proteins, either inhibitory or activating. In thyroid cancer, therefore, although mutations of the p53 oncosuppressor protein family are rare, other mechanisms are present, including aberrant expression of p53 family dominant negative isoforms, up-regulation of inhibitory proteins, and functional inhibition of activating proteins. The overall result is a defective oncosuppressor activity. These inactivating mechanisms may be present in the early stages of thyroid cancer and in different cancer histotypes. A better understanding of this complex network may not only ameliorate our comprehension of cancer biology, but also open the possibility of innovative diagnostic procedures and the development of targeted therapies.


Network analysis of England's single parent household COVID-19 control policy impact: a proof-of-concept study.
Lockdowns have been a core infection control measure in many countries during the coronavirus disease 2019 (COVID-19) pandemic. In England's first lockdown, children of single parent households (SPHs) were permitted to move between parental homes. By the second lockdown, SPH support bubbles between households were also permitted, enabling larger within-household networks. We investigated the combined impact of these approaches on household transmission dynamics, to inform policymaking for control and support mechanisms in a respiratory pandemic context. This network modelling study applied percolation theory to a base model of SPHs constructed using population survey estimates of SPH family size. To explore putative impact, varying estimates were applied regarding extent of bubbling and proportion of different-parentage within SPHs (DSPHs) (in which children do not share both the same parents). Results indicate that the formation of giant components (in which COVID-19 household transmission accelerates) are more contingent on DSPHs than on formation of bubbles between SPHs, and that bubbling with another SPH will accelerate giant component formation where one or both are DSPHs. Public health guidance should include supportive measures that mitigate the increased transmission risk afforded by support bubbling among DSPHs. Future network, mathematical and epidemiological studies should examine both independent and combined impact of policies.


Type of wine and risk of lung cancer: a case-control study in Spain.
Few epidemiological studies have examined the effect of wine on the risk of lung cancer. A study was therefore undertaken to estimate the effect of wine consumption, both overall and by type of wine, on the risk of developing lung cancer. A hospital based case-control study was conducted on 319 subjects (132 cases, 187 controls) in 1999-2000. All subjects were interviewed about their lifestyles with particular reference to alcohol consumption and tobacco use. The results were analysed using non-parametric logistic regression. The main outcome measure was the risk of lung cancer associated with consumption of wine and its individual types. A very slight but significant association was observed between the risk of lung cancer and white wine consumption (odds ratio (OR) 1.20 for each daily glass). Red wine consumption, on the other hand, had an OR of 0.43 (95% CI 0.19 to 0.96), with each daily glass of red wine having an inverse association with the development of lung cancer (OR 0.87 (95% CI 0.77 to 0.99)). There was no apparent association between lung cancer and consumption of beer or spirits. These results suggest that the consumption of red wine is negatively associated with the development of lung cancer. Further studies are needed to test this finding in cancer induced laboratory animals.


Highly synergistic activity of melittin with imipenem and colistin in biofilm inhibition against multidrug-resistant strong biofilm producer strains of Acinetobacter baumannii.
The rapid increase of drug resistance and failure of available antibiotics to treat biofilm-associated infections is of great health concern. Accordingly, our study aimed to evaluate the synergistic antibacterial, biofilm inhibitory, and biofilm removal activities of melittin in combination with colistin, imipenem, and ciprofloxacin against multidrug-resistant (MDR) strong biofilm producer Acinetobacter baumannii isolates. The kinetics of biofilm formation were evaluated for the isolates for 144 h. Minimum inhibitory concentrations (MICs), minimum bactericidal concentrations (MBCs), minimum biofilm inhibitory concentrations (MBICs), and biofilm removal activities for melittin and combinations with antibiotics were determined. Inhibition of biofilm-associated protein (bap) expression by melittin was evaluated with real-time polymerase chain reaction (PCR). Field emission scanning electron microscopy (FE-SEM) was used to visualize the effect of synergism on the inhibition of biofilm production. The geometric means of the fractional inhibitory concentration index (FICi) for melittin-colistin, melittin-imipenem, and melittin-ciprofloxacin combinations were calculated as 0.31, 0.24, and 0.94, respectively. Comparing the geometric means of the removal activity for melittin, colistin, imipenem, and combinations of them in both 6 and 24 h showed a significant difference between the groups (p-value < 0.05). Exposure to melittin induced a statistically significant downregulation of bap mRNA levels in all isolates at sub-MIC doses. Analysis of the FE-SEM results demonstrated that the synergism of melittin-colistin at 0.125-0.25 μg inhibited biofilm formation completely. In conclusion, our findings indicate that melittin possesses considerable potential for use in combination with colistin and imipenem to treat infections caused by MDR strong biofilm producer A. baumannii isolates.


Vomiting-induced costal cartilage fracture: a case report.
The use of ultrasonography as a first line imaging test in cases of possible costal cartilage fracture can be pivotal. In this case report, we present the case of a patient with a suspected atraumatic vomiting-induced costal cartilage fracture. The costal cartilage fracture was non-displaced and incomplete, thus not visible in a Computed Tomography scan. When Ultrasound imaging was employed at the area of tenderness, soft tissue edema and hematoma around the cartilage were visualized. High level of suspicion for a cartilage fracture in this case revealed a subtle osseous injury.


New gammaproteobacteria associated with blood-feeding leeches and a broad phylogenetic analysis of leech endosymbionts.
Many monophagous animals have coevolutionary relationships with bacteria that provide unavailable nutrients to the host. Frequently, these microbial partners are vertically inherited and reside in specialized structures or tissues. Here we report three new lineages of bacterial symbionts of blood-feeding leeches, one from the giant Amazonian leech, Haementeria ghilianii, and two others from Placobdelloides species. These hosts each possess a different mycetome or esophageal organ morphology where the bacterial cells are located. DNA sequencing of the bacterial 16S rRNA genes and fluorescent in situ hybridization placed these symbionts in two separate clades in the class Gammaproteobacteria. We also conducted a broad phylogenetic analysis of the herein-reported DNA sequences as well as others from bacterial symbionts reported elsewhere in the literature, including alphaproteobacterial symbionts from the leech genus Placobdella as well as Aeromonas veronii from the medicinal leech, Hirudo medicinalis, and a Rickettsia sp. detected in Hemiclepsis marginata. Combined, these results indicate that blood-feeding leeches have forged bacterial partnerships at least five times during their evolutionary history.


Dynamics of epigenetic modifiers and environmentally sensitive proteins in a reptile with temperature induced sex reversal†.
The mechanisms by which sex is determined, and how a sexual phenotype is stably maintained during adulthood, have been the focus of vigorous scientific inquiry. Resources common to the biomedical field (automated staining and imaging platforms) were leveraged to provide the first immunofluorescent data for a reptile species with temperature induced sex reversal. Two four-plex immunofluorescent panels were explored across three sex classes (sex reversed ZZf females, normal ZWf females, and normal ZZm males). One panel was stained for chromatin remodeling genes JARID2 and KDM6B, and methylation marks H3K27me3, and H3K4me3 (Jumonji Panel). The other CaRe panel stained for environmental response genes CIRBP and RelA, and H3K27me3 and H3K4me3. Our study characterized tissue specific expression and cellular localization patterns of these proteins and histone marks, providing new insights to the molecular characteristics of adult gonads in a dragon lizard Pogona vitticeps. The confirmation that mammalian antibodies cross react in P. vitticeps paves the way for experiments that can take advantage of this new immunohistochemical resource to gain a new understanding of the role of these proteins during embryonic development, and most importantly for P. vitticeps, the molecular underpinnings of sex reversal.


Clinician-assessed poor compliance identifies adults with severe asthma who are at risk of adverse outcomes.
Our aim was to determine whether clinician-identified poor compliance is useful in identifying, from among adults with severe asthma, patients with characteristics likely to put them at risk of adverse outcomes. Patients with severe asthma (previous hospital admissions and/or prescribed step 4-5 treatment according to British Thoracic Society guidelines) considered by clinicians to be either compliant (C, N = 41) or poorly compliant (PC, N = 92) with aspects of their recommended management (attendance at appointments, taking medication, and monitoring asthma) provided data on symptoms, health service use, medication, self-management practices, physical and psychological comorbidities, and sociodemographic/socioeconomic characteristics. Cross-sectional univariate analyses were used to examine whether the groups differed with respect to self-reported indicators of asthma morbidity and self-management. Logistic regressions were additionally used to explore psychosocial factors independently associated with patients being identified as PC. Compared with C patients, PC patients had significantly poorer self-reported asthma control in terms of medication use, symptoms, time off work, asthma-specific quality of life, primary care visits, emergency attendances, and hospital admissions. This was coupled with poorer self-management practices. Patients identified as PC also had higher levels of physical and psychological comorbidities, were younger, and faced more difficult social and economic circumstances. We identified significant psychological (anxiety) and social (younger age, not working, number of benefits, adverse family circumstances) factors independently associated with patients being identified as PC. Among adults with severe asthma, clinician-assessed poor compliance was useful in distinguishing between two groups that differed significantly in terms of asthma morbidity indicators, self-management practices, and psychosocial characteristics, which have been previously shown to be associated with hospital admissions, near-fatal attacks, and fatal asthma. We conclude that clinician-assessed poor compliance is a useful marker for identifying patients at risk of these adverse outcomes.


Diet-induced unresolved ER stress hinders KRAS-driven lung tumorigenesis.
Dietary effects on tumor biology can be exploited to unravel cancer vulnerabilities. Here, we present surprising evidence for anti-proliferative action of high-calorie-diet (HCD) feeding on KRAS-driven lung tumors. Tumors of mice that commenced HCD feeding before tumor onset displayed defective unfolded protein response (UPR) and unresolved endoplasmic reticulum (ER) stress. Unresolved ER stress and reduced proliferation are reversed by chemical chaperone treatment. Whole-genome transcriptional analyses revealed FKBP10 as one of the most downregulated chaperones in tumors of the HCD-pre-tumor-onset group. FKBP10 downregulation dampens tumor growth in vitro and in vivo. Providing translational value to these results, we report that FKBP10 is expressed in human KRAS-positive and -negative lung cancers, but not in healthy parenchyma. Collectively, our data shed light on an unexpected anti-tumor action of HCD imposed before tumor onset and identify FKBP10 as a putative therapeutic target to selectively hinder lung cancer.


Penile Fracture: Our Experience in a Tertiary Care Hospital.
Penile fracture is rare, but it is a urological emergency that always requires immediate attention. Moreover, penile fracture has been reported more frequently in recent years. It may have devastating physical, functional, and psychological consequences if not properly managed in time. The objective of this study was to highlight the causes, clinical presentation, and outcomes of cases of penile fracture. This was a prospective observational study extending from November 2012 to November 2014. Each patient underwent a thorough clinical evaluation and received proper treatment. Twenty patients with penile fracture, aged 19 to 56 years (mean, 28 years) were evaluated in this study. Vaginal intercourse was the most common mechanism of injury. Most of the patients (95%) were diagnosed clinically with a proper history and clinical examination. Nineteen patients were treated surgically. The patients underwent six months of follow-up, and were evaluated with local examinations, questionnaires, and colour Doppler ultrasonography as necessary. Although penile fracture is an under-reported urological emergency, its incidence is increasing. It is usually diagnosed based on a clinical examination, but ultrasonography can be very helpful in diagnosis. Especially in cases where treatment is delayed, surgery is preferable to conservative management, because it is associated with better outcomes and fewer long-term complications.


A short-term study of laparoscopic-dominant individualised levator ani resection in abdominoperineal resection: A retrospective investigation.
The objective is to investigate if laparoscopic-dominant abdominoperineal resection (LDAPR) with individualised levator ani resection inhibits local recurrence (LR) and prolongs survival as compared to laparoscopic abdominoperineal resection (APR). Rectal cancer surgery cases were retrospectively identified from September 2014 to December 2019. LDAPR-treated group (55 patients) and the APR-treated group (71 patients) were included in the study. The operation time, circumferential resection margin (CRM), intraoperative tumor surgery (ITP), post-operative complications, the 2-year overall survival (OS) and LR were compared in the two groups. The CRM and ITP were significantly reduced in the LDAPR as compared to the APR group (3.6% vs. 16.9%, t = 5.522, P = 0.019; 3.6% vs. 14.1%, t = 3.926, P = 0.048). In terms of post-operative complications, the incidence of urinary retention in LDAPR was significantly reduced than the APR group (10.9% vs. 25.4%, χ2 = 4.139, P = 0.041). Similarly, perineal pain at 6 months or 1 year after surgery was significantly down-regulated in LDAPR than in the APR group (72.7% vs. 88.7%, χ2 = 5.320, P = 0.021; 18.2% vs. 43.2%, χ2 = 8.288, P = 0.004). However, there was no statistically significant difference in the post-operative complications between the LDAPR and APR groups. Finally, LDAPR led to a significantly improved 2-year OS and a reduced LR compared to APR. LDAPR reduces CMR, ITP and LR and simplified the perineum operation, subsequently protecting the pelvic autonomic nerves. Compared to the conventional APR, LDAPR is a promising procedure worth adopting for rectal cancer treatment.


A Comparison of Elliptical Mastectomy to Inverted-T Pattern Mastectomy in Two-Stage Prosthetic Breast Reconstruction.
Patients with large or ptotic breasts undergoing mastectomy followed by tissue expander/implant-based reconstruction may benefit from a Wise (inverted-T) pattern reduction mammaplasty incision compared with the traditional horizontal elliptical incision. The authors compared these two groups of patients with regard to complication rates and outcomes. Sixty-nine patients (117 breasts) were identified who underwent Wise pattern mastectomy and two-stage reconstruction. A control group of 89 patients (136 breasts) who underwent reconstruction after horizontal elliptical mastectomy were selected over the same period. Patient demographics, clinical characteristics, and complication rates were recorded and analyzed statistically. Patient demographics (age, body mass index, diabetes, smoking, and irradiation history) and clinical characteristics (laterality, expander size and fill volume, and time to expansion) were similar, with the exception of body mass index (control, 26.7 kg/m; inverted-T, 28.7 kg/m; p = 0.04) and mean intraoperative fill volume (control, 158.7 cc; inverted-T, 196.9 cc; p = 0.02). Of all complications (infection, seroma, flap necrosis, expander loss, and salvage), only the rate of mastectomy flap necrosis was significantly greater (p = 0.002) in patients undergoing inverted-T mastectomy (25.6 percent versus 11.0 percent). This difference did not result in a significantly higher rate of expander loss or need for salvage surgery. The inverted-T mastectomy approach can be performed safely with acceptable complication rates. When compared with an internal control group, complication rates were similar, with the exception of mastectomy flap necrosis. Despite a higher rate of flap necrosis, 91 percent of inverted-T patients successfully completed the expansion process. Therapeutic, III.


Functional and phenotypic alteration of intrasplenic lymphocytes affected by mesenchymal stem cells in a murine allosplenocyte transfusion model.
Previous data have demonstrated that mesenchymal stem cells (MSCs) can exert immunomodulatory activity in vitro, in which of the process nearly all kinds of immune cell subsets are involved. However, there is still a paucity of information about whether and why MSCs inhibit the ongoing immune responses in vivo. Working in a murine splenocyte transfusion model across the major histocompatibility barrier (C57BL/6 -BALB/c, H2b --> H2d), we have found that MSC coinfusion prolongs the mean survival time (MST) of the recipient mice in a dose-dependent manner and reduces graft-versus-host-associated histopathology in comparison to the allosplenocyte transfusion controls. In vivo eGFP tracing with polymerase chain reaction analysis revealed that grafted MSCs could migrate and settle into the lungs, spleen, liver, intestine, and skin shortly after administration. Further investigations into the functional characteristics of intrasplenic lymphocytes showed that their proliferation and cytotoxic activity against P815 cells (H2d) were significantly restrained by MSC cotransfer. FACS analysis demonstrated that MSC infusion not only increased the proportion of CD4+ subset but also decreased that of CD8+ cells at the belated observation points, resulting in the increase of the ratio of CD4+/CD8+ cells. Also, in contrast to the slight increase of the proportion of CD4+CD25+ T regulatory cells (Tregs) in MSC cotransfer mice, the ratio of Tregs/CD8+ cells was dramatically elevated. Furthermore, RT-PCR analysis on the cytokine array of IL-2, IL-4, IL-12, TNF-alpha, and TGF-beta in recipient splenocytes implied the Thl to Th2 polarization. Therefore, it is deducible that alteration in the proportions of different T-lymphocyte subsets may be one of the main mechanisms by which grafted MSCs suppress the ongoing immune responses in vivo. The study here might provide some new clues for the design of therapeutic approaches for MSC transplantation.


IkappaBalpha regulates Hes1 in osteoclast differentiation and resorption.
During osteoclast differentiation and resorption, both NF-kappaB and Notch signalling are activated. This study defines the mechanism about the influence of NFkappaB on Notch. To this end, IkappaBalphaM and Wild-type-IkappaBalpha were transfected into RAW 264.7 cells. The number of cells that differentiated into osteoclasts was quantified. The resorption area was measured. NF-kappaB transcriptional activity was determined by EMSA. Hes1, DC-STAMP and MMP-9 mRNA expression levels were determined by RT-PCR. Hes1 protein expression was determined by western blots. ChIP was used to study binding of IkappaBalpha to the Hes1 promoter. NF-kappaB inactivation inhibited the differentiation and resorption ability of osteoclasts. Compared with Wild-type cells, NF-kappaB inactivation resulted in an up-regulation of Hes1 expression, and a down-regulation of DC-STAMP and MMP-9 expression. Moreover, in response to RANKL, NF-kappaB inactivation resulted in a down-regulation of DC-STAMP and MMP-9 expression compared with Wild-type cells. The Hes1 promoter was detected by ChIP using IkappaBalpha antibody. In conclusion, our data suggest IkappaBalpha regulates Hes1-mediated activity in osteoclast differentiation and resorption, which supports a cross-talk between NF-kappaB and Notch in osteoclast activity.


Ontology-Based Querying with Bio2RDF's Linked Open Data.
A key activity for life scientists in this post "-omics" age involves searching for and integrating biological data from a multitude of independent databases. However, our ability to find relevant data is hampered by non-standard web and database interfaces backed by an enormous variety of data formats. This heterogeneity presents an overwhelming barrier to the discovery and reuse of resources which have been developed at great public expense.To address this issue, the open-source Bio2RDF project promotes a simple convention to integrate diverse biological data using Semantic Web technologies. However, querying Bio2RDF remains difficult due to the lack of uniformity in the representation of Bio2RDF datasets. We describe an update to Bio2RDF that includes tighter integration across 19 new and updated RDF datasets. All available open-source scripts were first consolidated to a single GitHub repository and then redeveloped using a common API that generates normalized IRIs using a centralized dataset registry. We then mapped dataset specific types and relations to the Semanticscience Integrated Ontology (SIO) and demonstrate simplified federated queries across multiple Bio2RDF endpoints. This coordinated release marks an important milestone for the Bio2RDF open source linked data framework. Principally, it improves the quality of linked data in the Bio2RDF network and makes it easier to access or recreate the linked data locally. We hope to continue improving the Bio2RDF network of linked data by identifying priority databases and increasing the vocabulary coverage to additional dataset vocabularies beyond SIO.


Fiber Bragg grating sensors in hollow single- and two-core eccentric fibers.
Fiber Bragg gratings (FBGs) in a hollow eccentric fiber (HEF) have been proposed and demonstrated experimentally. The single-core and two-core HEF FBGs have been inscribed successfully using KrF excimer laser (248 nm), respectively. The temperature and axial strain sensing properties of the two samples have been measured. The experimental results indicate that the temperature and axial strain sensitivities of the two samples are similar, but they are smaller than that of conventional SMF-FBGs. Furthermore, the bending characteristics of the two-core HEF-FBG strongly depend on the bending direction due to the asymmetry of the fiber. Therefore, the proposed two-core HEF-FBGs facilitate temperature-compensated vector-bending sensing by measuring the difference between peak shifts of the two gratings. In addition, the two-core HEF-FBG can be a promising candidate for achieving two-channel filter since the signal crosstalk between the two cores can be largely eliminated by the central air hole.


Technique and timing in women's inward two and one half somersault tuck (405C) and the men's inward two and one half somersault pike (405B) 3 m springboard dives.
The purpose of this study was to compare the inward two and one half somersault dive in a tuck position (405C) performed by females (n = 22) and the inward two and one half somersault dive in a pike position (405B) performed by males (n = 24) to determine changes required by females to successfully perform 405B. Key performance variables in inward dives were also compared to those of backward dives. Video data of the dives performed at the 1999 FINA World Diving Cup were captured and digitized to obtain times and postures of the divers at specific events including takeoff and entry. Estimates of flight height and mass-normalised work done on the springboard were obtained from flight times. Some females worked the springboard strongly enough to generate sufficient height and rotation to perform 405B. Males performed 405B comfortably because they achieved better height and rotation than the females. A comparison of backward and inward dives revealed that divers are able to attain greater height in backward dives than inward dives.


Protein Dielectrophoresis with Gradient Array of Conductive Electrodes Sheds New Light on Empirical Theory.
Dielectrophoresis (DEP) is a versatile tool for the precise microscale manipulation of a broad range of substances. To unleash the full potential of DEP for the manipulation of complex molecular-sized particulates such as proteins requires the development of appropriate theoretical models and their comprehensive experimental verification. Here, we construct an original DEP platform and test the Hölzel-Pethig empirical model for protein DEP. Three different proteins are studied: lysozyme, BSA, and lactoferrin. Their molecular Clausius-Mossotti function is obtained by detecting their trapping event via the measurement of the fluorescence intensity to identify the minimum electric field gradient required to overcome dispersive forces. We observe a significant discrepancy with published theoretical data and, after a very careful analysis to rule out experimental errors, conclude that more sophisticated theoretical models are required for the response of molecular entities in DEP fields. The developed experimental platform, which includes arrays of sawtooth metal electrode pairs with varying gaps and produces variations of the electric field gradient, provides a versatile tool that can broaden the utilization of DEP for molecular entities.


The rise of glyphosate and new opportunities for biosentinel early-warning studies.
Glyphosate has become the most commonly used herbicide worldwide and is reputedly environmentally benign, nontoxic, and safe for use near wildlife and humans. However, studies indicate its toxicity is underestimated and its persistence in the environment is greater than once thought. Its actions as a neurotoxin and endocrine disruptor indicate its potential to act in similar ways to persistent organic pollutants such as the organochlorines dichlorodiphenyltrichloroethane (DDT) and dioxin. Exposure to glyphosate and glyphosate-based herbicides for both wildlife and people is likely to be chronic and at sublethal levels, with multiple and ongoing exposure events occurring in urban and agricultural landscapes. Despite this, there has been little research on the impact of glyphosate on wildlife populations, and existing studies appear in the agricultural, toxicology, and water-chemistry literature that may have limited visibility among wildlife biologists. These studies clearly demonstrate a link between chronic exposure and neurotoxicity, endocrine disruption, cell damage, and immune suppression. There is a strong case for the recognition of glyphosate as an emerging organic contaminant and substantial potential exists for collaborative research among ecologists, toxicologists, and chemists to quantify the impact of glyphosate on wildlife and to evaluate the role of biosentinel species in a preemptive move to mitigate downstream impacts on people. There is scope to develop a decision framework to aid the choice of species to biomonitor and analysis methods based on the target contaminant, spatial and temporal extent of contamination, and perceived risk. Birds in particular offer considerable potential in this role because they span agricultural and urban environments, coastal, inland, and wetland ecosystems where glyphosate residues are known to be present.


Tumor suppression by RNA from the 3' untranslated region of alpha-tropomyosin.
NMU2, a nondifferentiating mutant myogenic cell line, gives rise to rhabdomyosarcomas in mice. We show that constitutive expression of RNA from 0.2 kb of the alpha-tropomyosin (Tm) 3' untranslated region (UTR), but not control 3'UTRs, suppresses anchorage-independent growth and tumor formation by NMU2 cells. When beta-galactosidase (beta-gal)-labeled cells were implanted into muscles of adult mouse hindlimbs, Tm 3'UTR expression suppressed the proliferation, invasion, and destruction of muscle tissues characteristic of NMU2. In the rare tumors that developed from Tm 3'UTR transfectants, RNA expression was extinguished. These results suggest that suppression of tumorigenicity is dependent on the continued expression of Tm transcripts lacking a coding region. We conclude that untranslated RNAs can function as regulators (riboregulators) that suppress tumor formation.


Anti-PD1 immune checkpoint inhibitor-induced bullous pemphigoid in metastatic melanoma and non-small cell lung cancer.
Anti-programmed cell death 1 (PD1) targeted immune checkpoint inhibitors such as nivolumab and pembrolizumab are increasingly used to treat advanced malignancies such as melanoma, non-small cell lung cancer, urothelial cancer, and renal cell carcinoma. A rare but increasingly reported adverse effect of anti-PD1 therapy is bullous pemphigoid (BP), an autoimmune blistering disease directed against BP antigen 1 and BP antigen 2 in the basement membrane of the epidermis. We present 3 cases of BP secondary to anti-PD1 immunotherapy in patients with melanoma and non-small cell lung cancer to highlight the diagnosis and treatment of this condition and emphasize the importance of the dermatologist in the care of patients with immunotherapy-related skin disease.


An interoperability test framework for HL7-based systems.
Health Level Seven (HL7) is a prominent messaging standard in the eHealth domain, and with HL7 v2, it addresses only the messaging layer. However, HL7 implementations also deal with the other layers of interoperability, namely the business process layer and the communication layer. This need is addressed in HL7 v3 by providing a number of normative transport specification profiles. Furthermore, there are storyboards describing HL7 v3 message choreographies between specific roles in specific events. Having alternative transport protocols and descriptive message choreographies introduces great flexibility in implementing HL7 standards, yet, this brings in the need for test frameworks that can accommodate different protocols and permit the dynamic definition of test scenarios. In this paper, we describe a complete test execution framework for HL7-based systems that provides high-level constructs allowing dynamic set up of test scenarios involving all the layers in the interoperability stack. The computer-interpretable test description language developed offers a configurable system with pluggable adaptors. The Web-based GUIs make it possible to test systems over the Web anytime, anywhere, and with any party willing to do so.