Reducing surgical site infections after hysterectomy: metronidazole plus cefazolin compared with cephalosporin alone.
Organisms that are isolated from vaginal cuff infections and pelvic abscesses after hysterectomy frequently include anaerobic vaginal flora. Metronidazole has outstanding coverage against nearly all anaerobic species, which is superior to both cefazolin and second-generation cephalosporins. Cefazolin plus metronidazole has been demonstrated to reduce infectious morbidity compared with either cefazolin or second-generation cephalosporins in other clean-contaminated procedures, which include both as colorectal surgery and cesarean delivery. The purpose of this study was to evaluate whether the combination of cefazolin plus metronidazole before hysterectomy was more effective in the prevention of surgical site infection than existing recommendations of cefazolin or second-generation cephalosporin. This was a retrospective cohort study of patients in the Michigan Surgical Quality Collaborative from July 2012 through February 2015. The primary outcome was surgical site infection. Patients who were >18 years old and who underwent abdominal, vaginal, laparoscopic, or robotic hysterectomy for benign or malignant indications were included if they received 1 of the following prophylactic antibiotic regimens: cefazolin, second-generation cephalosporin, or cefazolin plus metronidazole. Multivariate logistic regression modeling was performed to evaluate the independent effect of an antibiotic regimen, and propensity score matching was used to validate the findings. The study included 18,255 hysterectomies. The overall rate of surgical site infection was 1.8% (n=329). The unadjusted rate of surgical site infection was 1.8% (n=267) for cefazolin, 2.1% (n=49) for second-generation cephalosporin, and 1.4% (n=13) for cefazolin plus metronidazole. After adjustment for differences in patient and operative factors among the antibiotic cohorts, compared with cefazolin plus metronidazole, we found the risk of surgical site infection was significantly higher for patients who received cefazolin (odds ratio, 2.30; 95% confidence interval, 1.06-4.99) or second-generation cephalosporin (odds ratio, 2.31; 95% confidence interval, 1.21-4.41). In this large cohort, the use of prophylactic cefazolin plus metronidazole resulted in lower surgical site infection rates after hysterectomy compared with cefazolin or second-generation cephalosporin.


Intraductal papillary neoplasm of the bile duct developing in a patient with primary sclerosing cholangitis: a case report.
We report a case of intraductal papillary neoplasm of the bile duct (IPNB) that developed in a patient with primary sclerosing cholangitis. A 46-year-old woman was admitted to our hospital with obstructive jaundice. The liver function tests demonstrated increased serum liver enzyme levels. Computed tomography showed dilatation of the intrahepatic bile ducts. Abdominal ultrasonography revealed a highly echoic protruding lesion in the posterior bile duct near the right lobe of the liver. The lesion was suspected to be IPNB, but we were unable to confirm whether it was a carcinoma. A right hepatectomy was performed, and this showed that the dilated bile duct was filled with mucin and contained several yellowish papillary tumors. Histologically, the neoplastic biliary epithelium showed papillary growth in the dilated lumen. The tumor was diagnosed as IPNB, high-grade intraepithelial neoplasia secreting abundant mucin. No recurrence has been detected 3 years after surgery.


Influence of the shell thickness and charge distribution on the effective interaction between two like-charged hollow spheres.
The mean-force and the potential of the mean force between two like-charged spherical shells were investigated in the salt-free limit using the primitive model and Monte Carlo simulations. Apart from an angular homogeneous distribution, a discrete charge distribution where point charges localized on the shell outer surface followed an icosahedral arrangement was considered. The electrostatic coupling of the model system was altered by the presence of mono-, trivalent counterions or small dendrimers, each one bearing a net charge of 9 e. We analyzed in detail how the shell thickness and the radial and angular distribution of the shell charges influenced the effective interaction between the shells. We found a sequence of the potential of the mean force similar to the like-charged filled spheres, ranging from long-range purely repulsive to short-range purely attractive as the electrostatic coupling increased. Both types of potentials were attenuated and an attractive-to-repulsive transition occurred in the presence of trivalent counterions as a result of (i) thinning the shell or (ii) shifting the shell charge from the outer towards the inner surface. The potential of the mean force became more attractive with the icosahedrally symmetric charge model, and additionally, at least one shell tended to line up with 5-fold symmetry axis along the longest axis of the simulation box at the maximum attraction. The results provided a basic framework of understanding the non-specific electrostatic origin of the agglomeration and long-range assembly of the viral nanoparticles.


Gender Identity and Gender Role in DSD Patients Raised as Females: A Preliminary Outcome Study.
Gender identity and gender role are expected to be consistent with gender assignment for optimal DSD management outcome. To our knowledge, our study is the first to attempt evaluation of gender related outcomes in Turkish DSD patients. After receiving institutional ethical board approval and subject (or parent) informed consent, subjects with DSD raised as girls (22 patients 46 XX DSD, 11 patients 46 XY DSD) answered 566 questions of the Minnesota Multiphasic Personality Inventory (MMPI) questionnaire including 60-item Masculinity-Femininity (MF) subscale which was the focus in this study. Controls (n: 50) were females similar to the probands in age, level of education, relationship status, and having a job or not also answered all questions. The answers were evaluated by a trained psychologist (Derya Inceoglu) on MMPI. For statistical purposes, seven findings were obtained from the data related to the MF subscale from the patients and controls. Of these seven findings (S1-S7), two were associated with masculinity (S3-S4) and another two were associated with femininity (S5-S6). In DSD patients, the percentages of masculinity findings were significantly higher when compared to controls (p < 0.001 and p < 0.001 for S3 and S4, respectively). In controls, the percentages of femininity findings were significantly higher when compared to DSD females (p < 0.001 and p < 0.001 for S5 and S6 respectively). There was no significant difference between 46 XX DSD patients and 46 XY DSD patients with respect to the percentage of any of the seven findings. Two patients requested gender change to male; only these two patients had the finding stating that sexual impulses could come to existence as actions (S7). In conclusion efforts to identify modifiable factors with negative impact and thus modifying them, and professional guidance may be important in minimizing the encountered gender related problems in DSD patients.


Preoperative intravenous glucocorticoids can decrease acute pain and postoperative nausea and vomiting after total hip arthroplasty: A PRISMA-compliant meta-analysis.
A systematic review and meta-analysis of published randomized controlled trials (RCTs) were performed to assess the efficacy and safety of preoperative intravenous glucocorticoids versus controls for the prevention of postoperative acute pain and postoperative nausea and vomiting (PONV) after primary total hip arthroplasty (THA). A computer literature search of electronic databases, including PubMed, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, China National Knowledge Infrastructure (CNKI), and China Wanfang database, was conducted to identify the relevant RCTs comparing preoperative intravenous glucocorticoids versus placebos for reducing acute pain and PONV in THA patients. The primary outcomes included the use of the visual analog scale (VAS) with rest or mobilization at 6, 24, 48, and 72 hours and the occurrence of PONV. The secondary outcome was total morphine consumption. We calculated the risk ratio (RR) with a 95% confidence interval (95% CI) for dichotomous outcomes, and the weighted mean difference (WMD) with a 95% CI for continuous outcomes. Pooled data from 7 RCTs (411 THAs) favored preoperative intravenous glucocorticoids against acute pain intensity at 4, 24, and 48 hours (P < .05). There was no significant difference between the VAS with rest or mobilization at 72 hours (P > .05). Subsequently, preoperative intravenous glucocorticoids provided a total morphine-sparing effect of 9.36 mg (WMD = -9.36, 95% CI = -12.33 to -6.38, P = .000). In addition, preoperative intravenous glucocorticoids were associated with a significant reduction of the occurrence of PONV (RR = 0.41, 95% CI = 0.30-0.57, P = .000). Intravenous glucocorticoids can decrease early pain intensity and PONV after THA. However, the low number of studies and variation in dosing regimens limits the evidence for its use. Thus, more high-quality RCTs are still needed to identify the optimal drug and the safety of intravenous glucocorticoids.


Kinetic studies with iodine-123-labeled serum amyloid P component in patients with systemic AA and AL amyloidosis and assessment of clinical value.
In systemic amyloidosis, widespread amyloid deposition interferes with organ function, frequently with fatal consequences. Diagnosis rests on demonstrating amyloid deposits in the tissues, traditionally with histology although scintigraphic imaging with radiolabeled serum amyloid P component (SAP) has lately been developed as a specific noninvasive alternative. We report a detailed analysis of the abnormal turnover of SAP in patients with systemic amyloidosis and an assessment of its clinical value. Iodine-123-labeled human SAP (200 MBq) SAP was injected intravenously into 49 patients with histologically proven systemic AA- or AL- amyloidosis and in 7 control subjects. Plasma clearance and whole-body retention of labeled SAP were analyzed over 48 hr using plasma sampling, whole-body gamma camera imaging and measurement of radioactivity in the urine. The rate of SAP synthesis and interstitial exchange were determined, and the size of the amyloid compartment was compared with clinical estimates of whole-body amyloid load and patient survival. All plasma time-activity curves were biphasic. In comparison with control subjects, patients with amyloidosis showed significantly faster plasma disappearance [4-hr value: AA 48% +/- 18%, AL 45% +/- 15% versus 65% +/- 8% (p < 0.05)], higher total-body retention 48 hr p.i. [AA 74% +/- 14%, AL 73% +/- 17% versus 46% +/- 15% (p < 0.01)] and especially higher extravascular retention 48 hr p.i. [AA 59% +/- 16%, AL 58% +/- 19% versus 30% +/- 14% (p < 0.01)]. Extravascular retention correlated with clinical estimation of the amyloid load. If extravascular retention values in patients with AL amyloidosis were over 60%, survival was decreased (median 4 versus 23 mo, p < 0.001). Markedly increased interstitial exchange rates were present in amyloidosis (AA 64 +/- 61, AL 50 +/- 37 versus 18 +/- 8 mg/hr), whereas the SAP synthesis rate did not differ from the control values (AA 5.0 +/- 3.0, AL 5.5 +/- 3.2 versus 4.5 +/- 1.4 mg/hr). The presence of systemic amyloidosis is characterized by accelerated initial clearance of 123I-SAP from the plasma and increased interstitial exchange rate and extravascular retention. These findings reflect reversible binding of radiolabeled SAP to amyloid deposits and provide clinically useful information for diagnosis, monitoring of therapy and prognosis in patients with systemic amyloidosis.


[Impact of instantaneous uniformity of SonoVue microbubbles on binding characteristics of a new contrast agent targeted to choriocarcinoma cells in vitro].
At present, the investigation of microbubble contrast agents is a hot spot. Although these contrast agents can increase the ultrasound detection rate of tumor vessels, they lack tissue specificity. This study was to evaluate the impact of instantaneous uniformity of SonoVue microbubbles on binding characteristics, including the adhesion rate and stability, of a new contrast agent targeted to choriocarcinoma cells (JARs) in vitro, in order to establish a foundation to explore targeted ultrasound imaging for localization of tumor cell antigens and increase the early diagnostic rate for tumors. The objects were divided into three groups: the uneven microbubble group (n=10), the uniform microbubble group (n=10) and the tiny microbubble group (n=10). The rosette formation rate was counted. JARs were calculated by flow cytometry (FCM). The shape of the rosette was recorded. The targeted contrast agent was prepared by mixing SonoVue microbubbles of different uniformity with rabbit anti-human chorionic gonadotrophin (HCG) antibody. The binding rates of the contrast agent to JARs before and after PBS rinse were analyzed. The binding rate was significantlylower in the uneven microbubble group (60.4+/-1.5)% than in the uniform microbubble group (84.3+/-5.5)% and the tiny microbubble group (90.6+/-6.8)% (P<0.05). The binding rates of different microbubbles to JARs before and after PBS rinse were different. The uniform microbubbles were the most stable ones, with the binding rate of (84.3+/-5.5)% and (82.4+/-3.7)% before and after PBS rinse (P>0.05). The binding rates of the targeted microbubbles labeled with fluorescence to JARs were 72.9%, 81.03% and 88.5% in the uneven microbubble group, the uniform microbubble group and the tiny microbubble group, respectively (P<0.05). The binding capacity of the targeted SonoVue microbubbles to JARs is related to instantaneous uniformity of the microbubble, which is determined by the shaking method before preparation. Improving instantaneous uniformity of SonoVue microbubbles may increase the binding rate and stability of targeted microbubbles to JARs, thus to improve the image of JARs.


Carcinomas of the lung with neuroendocrine differentiation.
While there are examples of each of the histologic types of bronchogenic carcinoma in which ectopic hormone production has been demonstrated, three groups of lung cancers manifest this type of differentiation with great regularity. These are the carcinoid, atypical carcinoid, and the small cell carcinoma, which have been called neuroendocrine carcinomas of the lung. The carcinoids are neoplasms with a heterogeneous array of histologic appearances that share relatively uniform nuclear features, the absence of both tumor necrosis and mitotic figures, and a good prognosis. Neuroendocrine differentiation is demonstrable with such regularity in carcinoids that the diagnosis is not considered tenable in the absence of at least one of the following features: argyrophilia, the demonstration of neuron-specific-enolase or neuropeptides by immunohistochemistry or other techniques, or the demonstration of numerous dense-core membrane-bound granules, usually 150 to 250 nm in diameter, by electron microscopy. The atypical carcinoids (well or moderately differentiated neuroendocrine carcinomas) share the neuroendocrine differentiation of the carcinoids and many of their histologic features, but are distinguished by the presence of tumor necrosis, more anaplastic large cell nuclei with numerous mitotic figures, and a distinctly worse prognosis. They are a heterogeneous lot with some similarities to carcinoids, small cell carcinomas, and large cell or adenocarcinomas. The demonstration of at least one of the neuroendocrine features listed above is considered necessary for this diagnosis. Small cell carcinoma is also a heterogeneous group of neoplasma primarily distinguished by their finely granular chromatin pattern which correlates with a much worse prognosis but a higher likelihood of response to chemotherapy and radiotherapy. Many small cell carcinomas share the neuroendocrine differentiation of the carcinoids or atypical carcinoids, but some do not and the demonstration of these features is not a requisite for inclusion in the small group. The morphologic demonstration of neuroendocrine differentiation may be more difficult in small cell carcinomas, but they more frequently produce clinically important amounts of ectopic neuropeptides. While the term neuroendocrine carcinoma of the lung includes several quite different entities and does not by itself convey histogenetic or prognostic implications, the demonstration of neuroendocrine differentiation in pulmonary neoplasms is an important procedure when combined with the recognition of other cytologic and histologic features.


Expired carbon monoxide levels in self-reported smokers and nonsmokers in prison.
Breath carbon monoxide (CO) is a convenient, widely used method for abstinence validation, with cutoffs of 8-10 ppm commonly employed. The goal of the present study was to determine an appropriate CO cutoff to differentiate nonsmokers and smokers within a large sample (N = 374) of female prisoners incarcerated at a correctional facility in Virginia. Mean age of the population was 34.5 years, 49.2% were White, and 29% had less than a high school education. Smoking prevalence was 74.1% within the prison population. Examination of CO levels versus smoking self-report using a receiver operator characteristic (ROC) analysis revealed that a CO cutoff of 3 ppm resulted in the best sensitivity (98.1%) and specificity (95.8%). Overall ROC area under the curve was 99% (95% CI = 98.2%-99.9%). This same cutoff was optimal for smoking subgroups including Black and light (<10 cigarettes/day) smokers. Results suggest that CO cutoffs higher than 3 ppm may misclassify some smokers as nonsmokers and underestimate the prevalence of smoking.


[Comparative evaluation of clinical efficacy of drugs remaxol and ademetionine in patients with acute ethanol poisoning complicated by the toxic damage of the liver].
As a result of survey in process of treatment of 100 patients with severe acute poisoning of ethanol on the background of the toxic damage of the liver set that the severity of poisoning depends on the duration abuse of alcohol (Binge drinking). Inclusion in the intensive care infusion hepatoprotector remaxol compared with ademetionine leads to a faster dynamics of improvement of the patients condition, evaluated by the scale assessing the severity APACHE II. Also found, Use of remaxol can reduce development of complications such is alcoholic delirium on the background of long-term abuse of alcohol in percentage from 31.9% to 16%, as well as reduces the time of stay of patients in the departments of the resuscitation and intensive care unit from 7,3±0,6 to 5,6±0,3 days and duration of treatment of patients in the hospital from 11,8±1,1 to 9,0±0,4 days.


Dolichopus nimbatus Parent, 1927 revisited, with two new synonyms (Diptera: Dolichopodidae).
On the basis of comparison between the female holotype of Dolichopus nimbatus Parent and the female paratype of D. balius Meuffels, and comparison of a male paratype of D. balius with the description of D. thalhammeri Knézy, D. balius and D. thalhammeri are designated junior synonyms of D. nimbatus. Dolichopus nimbatus ranges from northern France and Belgium to southern Turkey. Ecological features might explain its rarity in collections.


Group electronegativity for prediction of materials hardness.
We have developed a method to predict the hardness of materials containing ultrastrong anionic polyhedra, dense atomic clusters, and layers stacked through van der Waals bonds on the basis of group electronegativity. By considering these polyhedra, clusters, and layers as groups that behave as rigid unities like superatoms bonding to other atoms or groups, the hardness values of materials such as oxysalts, T-carbon, and graphite were quantitatively calculated, and the results are consistent with the available experiments. We found that the hardness of materials containing these artificial groups is determined by the bonds between the groups and other atoms or groups, rather than by the weakest bonds. This work sheds light on the nature of materials hardness and the design of novel inorganic crystal materials.


Analgesic substances derived from natural products (natureceuticals).
From the first recorded accounts, over 7000 years ago, various forms of natural products have been utilized to treat pain disorders. Prototypical examples of such natural products are the opium poppy (Papaver soniferum) and the bark of the willow tree (Salix spp.). It was not until the 19th century when individual compounds were isolated from these substances and were determined to posses the desired effects. The known sources of these substances have been thoroughly investigated. Over the last several decades, more analgesic substances have been purified from natural products resulting in novel structural classes and mechanisms of actions. Plants and other natural products described in historical ethnobotanical and ethnopharmacological literature have become of more recent interest in drug discovery efforts. These manuscripts and reports are being utilized to aid in the identification of natural products that have been historically employed in the alleviation of pain. A large factor that has highlighted the importance of discovering novel compounds to treat pain has been in the fundamental understanding of the complex mechanisms of pain transmission in the nervous system. Nociceptive processing involves many receptor classes, enzymes and signaling pathways. The identification of novel classes of compounds from natural sources may lead to advancing the understanding of these underlying pharmacological mechanisms. With the potential of uncovering new compounds with idealistic pharmacological profiles (i.e., no side effects, no addictive potential), natural products still hold great promise for the future of drug discovery especially in the treatment of pain disorders and potentially drug addictions.


Calculation of kinetic isotope effects for intramolecular hydrogen shift reactions using semiclassical instanton approach.
Primary H/D kinetic isotope effects for the [1,5] hydrogen shift reaction in 13-atomic 1,3-pentadiene and [1,7] hydrogen shift reaction in 23-atomic 7-methylocta-1,3,5-triene are calculated using the semiclassical instanton approach. All 33 and 63 internal degrees of freedom, respectively, are treated quantum mechanically with multidimensional tunneling automatically accounted for by the instanton approach. Reactive potential energy surfaces are calculated on-the-fly using mPW1K/6-31+G(d,p) and mPWB1K/6-31+G(d,p) electronic structure methods. The calculated kinetic isotope effects agree well with the previously reported experimental measurements. The analytical expressions of the semiclassical instanton approach allow one to determine quantitative contributions of various physical mechanisms to the calculated kinetic isotope effects. Multidimensional tunneling is found to play important role in both studied hydrogen shift reactions.


Biomechanical analysis of gait patterns in children with intellectual disabilities.
Children with intellectual disabilities (ID) typically master walking skills much later than typically developing (TD) children and have poor postural control ability. This study aimed to explore the gait ability and characteristics of children with ID and whether there is any difference in walking ability between them and TD children. In this study, integrating kinematic-biomechanic-dynamic measurement methods and corresponding analysis methods (video analysis, three-dimensional force analysis and electromyography test analysis) were used to characterise and compare the gait patterns between ID children and TD children. ID children's step length/leg length ratio was lower than TD children. The left-leg single-leg support time and step length of ID children were shorter than TD children. While walking, ID children touched the ground with the whole foot pad and could not powerfully thrust against the ground with their toes. Their left legs had obvious disadvantages compared with their right legs. ID children's lower limb muscle strength was lower than TD children, and their thigh muscles had an obvious compensation function. Correcting ID children's gait should be an important teaching goal for physical education institutors and teachers. Muscle-strength and flexibility training can help ID children reinforce core strength and better coordinate lower limbs.


Non Uremic Calciphylaxis Post Liver Transplantation: A Case Report and Literature Review of an Unusual Presentation of a Rare Disease.
BACKGROUND Calciphylaxis results from abnormal calcification of small to medium sized vessels, resulting in painful ischemic necrosis of the surrounding tissues. It is most commonly seen in patients with end stage renal disease on dialysis, but has also been reported in patients with preserved renal function. CASE REPORT We report a case of non uremic calciphylaxis in a 65-year-old female who presented with painful skin lesions and ulcerations involving both thighs one month after receiving a liver transplantation. She was treated with sodium thiosulfate along with wound care and hyperbaric oxygen with complete resolution of the lesions, but with residual scarring. CONCLUSIONS Non uremic calciphylaxis is a rare phenomenon that is poorly understood. It should be in the differential of unexplained skin lesions even in the absence of renal insufficiency. Sodium thiosulfate plays a role in treatment, but wound care remains the main focus of treatment.


Chimeric SCID-hu Model as a Human Hematopoietic Stem Cell Host That Recapitulates the Effects of HIV-1 on Bone Marrow Progenitors in Infected Patients.
The chimeric small animal model system wherein the severe combined immunodeficient mouse is transplanted with human fetal thymus and liver tissues (SCID-hu Thy/Liv) has been used in different areas of experimental research [1]. A living model system offers the advantage that studies of longer duration than in vitro can be performed. Here we discuss the importance of experimental in vivo studies and how well the data generated using this model system correlates with epidemiological studies from HIV-positive humans. Patients with HIV-1 infection often suffer from cytopenias, with thrombocytopenia typically having an earlier onset than anemia and neutropenia. The cytopenias in patients may be caused by virus effects at the stem cell level, or the mature blood cell level, or by other factors like medications used to treat the infection. Several studies preformed in SCID-hu animals show that the function of human hematopoietic progenitor stem cells are indirectly affected by HIV-1 infection. Colony forming activity (CFA) assays on hematopoietic progenitor cells derived from SCID-hu animals and human bone marrow have been performed as a measure of progenitor cellular function, and HIV-1 infection decreased CFA in multiple lineages that include megakaryoid, erythroid and myeloid types. Highly active antiretroviral therapy (HAART) partially and transiently reduces the inhibition of multilineage CFA and data suggest that HIV-1 indirectly affects stem cell differentiation into multiple lineages. The cojoint human hematopoietic organ of this small animal model system recapitulates the inhibitory effects of HIV-1 infection on the function of progenitor cells of the human bone marrow. Thus the SCID-hu (Thy/Liv) model is a useful in vivo system for preclinical translational research towards development of stem cell therapies in HIV infection.


Protein kinase C theta is dispensable for suppression mediated by CD25+CD4+ regulatory T cells.
The activation of conventional T cells upon T cell receptor stimulation critically depends on protein kinase C theta (PKCθ). However, its role in regulatory T (Treg) cell function has yet to be fully elucidated. Using siRNA or the potent and PKC family-selective pharmacological inhibitor AEB071, we could show that murine Treg-mediated suppression in vitro is independent of PKCθ function. Likewise, Treg cells of PKCθ-deficient mice were fully functional, showing a similar suppressive activity as wild-type CD25+CD4+ T cells in an in vitro suppression assay. Furthermore, in vitro-differentiated wild-type and PKCθ-deficient iTreg cells showed comparable Foxp3 expression as well as suppressive activity. However, we observed a reduced percentage of Foxp3+CD25+ CD4+ T cells in the lymphatic organs of PKCθ-deficient mice. Taken together, our results suggest that while PKCθ is involved in Treg cell differentiation in vivo, it is dispensable for Treg-mediated suppression.


Anisotropy of magnetic properties of Fe(1+y)Te.
The magnetic properties of Fe(1+y)Te single crystals (y ≃ 0.1 ÷ 0.18) were studied at temperatures 4.2 ÷ 300 K. At an ambient pressure, with decreasing temperature a drastic drop in χ(T) was confirmed at T ≃ 60 ÷ 65 K, which appears to be closely related to the antiferromagnetic (AFM) ordering. It is found that the magnitudes of the anisotropy of magnetic susceptibility Δχ in the AFM phase are close in the studied samples, whereas the sign of the anisotropy apparently depends on the small variations of the excess iron y in Fe(1+y)Te samples. The performed DFT calculations of the electronic structure and magnetic properties for the stoichiometric FeTe compound indicate the presence of frustrated AFM ground states. There are very close energies and magnetic moments for the double stripe configurations, with the AFM axes oriented either on the basal plane or along the [0 0 1] direction. Presumably, both these configurations can be realized in Fe(1+y)Te single crystals, depending on the variations of the excess iron. This can provide different signs of magnetic anisotropy in the AFM phase, presently observed in the Fe(1+y)Te samples. For these types of AFM configuration, the calculations for the FeTe values of Δχ are consistent with our experimental data.


Reasons for interruption of anti-tubercular treatment among the retreatment patients in category II of RNTCP in Chandigarh, north India.
More re-treatment TB patients are notified in India than any other country in the world, and default among this group is a serious public health problem. Adherence to the long course of TB treatment is a complex, dynamic phenomenon with a wide range of factors impacting on treatment taking behaviour. The main aim of the study was to study the basic clinical and demographic profile of the defaulters and the reasons for discontinuation of treatment among these retreatment patients in category II of RNTCP. A longitudinal study was designed and the patients registered under RNTCP category II from June 2010 to December 2011 at various centres in Chandigarh formed the study cohort. Out of total 607 patients registered during this period under category II of RNTCP in Chandigarh, 545 consented to participate in the study. These were followed up to September 2012 till the completion of treatment. 32 patients among the registered 545 defaulted from the treatment during the period. These patients were traced in the community and information regarding reasons for interruption and barriers to treatment was obtained from them using a pre-structured pre-tested questionnaire. Data were analysed using SPSS 18 statistical software package. 32(5.9%) patients defaulted from the treatment under RNTCP category II. 29(90.6%) were pulmonary patients while 3(9.4%) were extra-pulmonary patients. 46.9% of the defaulters were in the age group of 20-35 years, followed by 31.3% in the age group of 36-50 years. 21.9% went to traditional healers for cure while 12.5% tried herbal medicine during the treatment. 25% (eight) patients did not have faith on the DOTS treatment. Most common side effects of treatment complained by the patients were GI upset (62.5%), fatigue (59.4%), drowsiness (34.4%) and itching (31.3%). 46.8% believed that ATT induced side-effects were the main reason for treatment interruption. Maximum treatment interruption was seen at the end of the third month (31.3%). Maximum interruptions were found to occur by end of third month of ATI. AT" induced side-effects were the main reason for treatment interruption. Efforts need to be made to improve the pre-treatment counselling, increase proportion of patients treated by community-based DOTS providers, repeated health education to the patients emphasizing the need to continue treatment.


Poly(ADP-ribose) polymerase activity in proliferating and quiescent murine mammary carcinoma cells.
Previous studies have shown that the well-oxygenated but nutrient-deprived quiescent (QI) cells of the 67 murine mammary carcinoma line are significantly more sensitive to radiation-induced cell killing than the well-oxygenated proliferating (P) cells. These QI cells also sustain more initial strand breaks per radiation dose and repair them more slowly than do P cells. We now report that NAD+ levels and rates of poly(ADP-ribosylation) show a trend similar in that both these metabolic parameters are lower in QI cells by a factor of two or more. NAD+ levels were measured in acid extracts of intact monolayers using an enzymatic cycling assay, while poly(ADP-ribosylation) was followed through the incorporation of radioactive NAD+ into polymer by permeabilized cells. The major proteins labeled by [32P]NAD+ were the same in P and QI cells. However, qualitative differences exist among minor poly(ADP-ribosylated) proteins, with some bands labeled in P cells but not detectably labeled in QI cells. These studies suggest similarities between the physiological state of QI cells and that of mature resting lymphocytes.


Fully atomistic molecular dynamics simulations of the behavior of a simple model of crude oil confined between graphene planes.
We present and discuss the results of molecular dynamics computer simulations of crude oil confined between graphene planes. The crude oil is represented as a mixture of alkanes having 6 </= n </= 30 carbons that contain explicit hydrogen atoms; the confining structure is a floor and ceiling, each comprised of graphene sheets. At low temperature, the system adsorbs completely onto the confining layers, showing an interesting domain structure in its own right. As the temperature increases, various species desorb in order of increasing molecular mass and enter the vapor phase between the confining sheets. Desorption proceeds through a roughening of the adsorbed layers but does not appear to couple to any inter- or intramolecular phase transition on the surfaces for any given species. Allowing the graphene sheets to be flexible affects the rate of adsorption as well as the in-plane order and molecular confirmations of the adsorbate. Cursory simulations with more than one layer show droplet-like adsorption at low temperatures and complicated dynamics, which shift the initial desorption temperatures to lower values than those for the monolayer and cause the desorption temperature and process to be much less defined. The results presented here are suggestive of a method of separating alkane mixtures at temperatures significantly different from those of conventional refining processes.


The use of flumazenil after midazolam-induced conscious sedation.
To investigate the use of flumazenil after midazolam-induced conscious sedation. A prospective audit was carried out in the Department of Sedation and Special Care Dentistry at Guy's Hospital, King's College, London, 2009.Subjects Patients sedated with midazolam for dental treatment. All clinical staff completed the data capture proforma when flumazenil was administered to a patient after sedation with midazolam. Four hundred and fifty-three patients were sedated with midazolam. Flumazenil was used in 32 cases. No cases required flumazenil for the emergency treatment of respiratory depression. The results of the audit confirmed the safe and appropriate use of midazolam for conscious sedation within the Department of Sedation and Special Care Dentistry at Guy's Hospital and demonstrated that flumazenil use was low and in accordance with current best practice. The audit has highlighted distinct indications for the post-operative use of flumazenil in specifically selected cases. Each case should be individually considered, justified and documented within the patient's clinical record.


[The causes of appearance of a double insertion of homogeneously staining regions in the chromosome 1 of house mouse (Mus musculus musculus)].
A high resolution analysis of G-band pattern of normal and aberrant chromosome 1 bearing two linked insertions of homogeneously staining regions (HSRs) in the house mouse (Mus musculus musculus) reveals an inverted pattern of the euchromatic region between the HSRs. On the basis of this analysis, a hypothesis on the causes for appearance of the aberrant chromosome was put forward: the double insertion is a result of inversion of the chromosome 1 of Mus musculus domesticus bearing a single long insertion. The proximal breakpoint is localized inside the HSR and the distal one--between subbands E3 and E4. From the point of view of these data, new symbols for the aberrations are proposed: Ls (HSR, 1C5) 1Icg--for the proximal insertion, Is(HSR, 1D)21cg--for the distal one, In (1) 1Icg--for the inverted region, including the bands D, E1-E3 and the insertion Is(HSR 1D)21cg.


HIV type 1 subtype distribution, multiple infections, sexual networks, and partnership histories in female sex workers in Kampala, Uganda.
We investigated for the first time the subtype distribution, prevalence of multiple HIV-1 infections, sexual networks, and partnership histories in a cohort of women engaged in high-risk sexual behavior such as female sex workers (FSWs) and women employed in entertainment facilities. Viral RNA was extracted from blood samples collected from 324 HIV-1-positive women; the gp-41 and pol-IN genes were directly sequenced. Women found to have closely related viruses and those with recombinant viruses were further analyzed in the pol-IN gene by clonal sequencing to determine HIV-1 multiple infections. Individual partnership histories were used to provide information on when sex work was undertaken and where. Subtyping in both gp-41 and pol-IN was successfully done in 210/324 (64.8%) women. Subtype distribution in these two genes was 54.3% (n=114) A/A, 2.9% (n=6) C/C, 24.3% (n=51) D/D, 11.9% (n=25) A/D, 4.8% (n=10) D/A, 0.5% (n=1) C/A, 1.0% (n=2) B/A, and 0.5% (n=1) B/D. Sexual networks were identified in six pairs and one triplet of women with closely related subtype A viruses. Partnership histories showed that women having phylogenetically similar viruses had worked in the same localities. Five cases of multiple infections were confirmed: four dual infections and one triple infection. In this first molecular epidemiology study among FSWs in Kampala, subtype A was the predominant subtype. About 9% of a subgroup had multiple infections. Partnership histories and multiple infections observed in this population suggest sexual mixing of the FSWs and their clients confirming their high-risk characteristics.


The Pax gene family: Highlights from cephalopods.
Pax genes play important roles in Metazoan development. Their evolution has been extensively studied but Lophotrochozoa are usually omitted. We addressed the question of Pax paralog diversity in Lophotrochozoa by a thorough review of available databases. The existence of six Pax families (Pax1/9, Pax2/5/8, Pax3/7, Pax4/6, Paxβ, PoxNeuro) was confirmed and the lophotrochozoan Paxβ subfamily was further characterized. Contrary to the pattern reported in chordates, the Pax2/5/8 family is devoid of homeodomain in Lophotrochozoa. Expression patterns of the three main pax classes (pax2/5/8, pax3/7, pax4/6) during Sepia officinalis development showed that Pax roles taken as ancestral and common in metazoans are modified in S. officinalis, most likely due to either the morphological specificities of cephalopods or to their direct development. Some expected expression patterns were missing (e.g. pax6 in the developing retina), and some expressions in unexpected tissues have been found (e.g. pax2/5/8 in dermal tissue and in gills). This study underlines the diversity and functional plasticity of Pax genes and illustrates the difficulty of using probable gene homology as strict indicator of homology between biological structures.


A Review of Phosphate Binders in Chronic Kidney Disease: Incremental Progress or Just Higher Costs?
As kidney disease progresses, phosphorus retention also increases, and phosphate binders are used to treat hyperphosphatemia. Clinicians prescribe phosphate binders thinking that reducing total body burden of phosphorus may decrease risks of mineral and bone disorder, fractures, cardiovascular disease, progression of kidney disease, and mortality. Recent meta-analyses suggest that sevelamer use results in lower mortality than use of calcium-containing phosphate binders. However, studies included in meta-analyses show significant heterogeneity, and exclusion or inclusion of specific studies alters results. Since no long-term studies have been conducted to determine whether treatment with any phosphate binder is better than placebo on any hard clinical endpoint (including mortality), it is unclear whether possible benefit with sevelamer represents net benefit of sevelamer, net harm with calcium-containing phosphate binders, or both. Although one meta-analysis suggested that calcium acetate may be more efficacious gram for gram than calcium carbonate as a binder, calcium acetate did not reduce hypercalcemia, and gastrointestinal intolerance was higher. Data are insufficient to determine whether calcium acetate provides lower risk of vascular calcification than calcium carbonate. Fears of lanthanum accumulation in the central nervous system or bone with long-term treatment do not appear to be warranted. Newer iron-containing phosphate binders have potential benefits, such as lower pill burden (sucroferric oxyhydroxide) and improved iron parameters (ferric citrate). The biggest challenge to phosphate binder efficacy is non-adherence. This article reviews the current knowledge regarding safety, effectiveness, and adherence with currently marketed phosphate binders and those in development.


Case Series on DRESS: An Unpredictable Adverse Drug Reaction.
Drug rash with eosinophilia and systemic symptoms syndrome (DRESS) is a potentially life-threatening, drug-induced, multi-organ system reaction. The most frequently involved organ is the liver, followed by the kidneys and lungs. Early detection and diagnosis followed by withdrawal of the offending agent is vital to minimise the associated morbidity and mortality, and a detailed drug history is vital to identify the causative drugs. Although Spanish guidelines were developed by a panel of allergy specialists from the Drug Allergy Committee of the Spanish Society of Allergy and Clinical Immunology (SEAIC) and are available in literature from 2020, many clinicians are still unaware about the management of this syndrome. Framing National guidelines for the early diagnosis and pharmaco-therapeutic management of DRESS will help healthcare professionals to save the patients from unintended vulnerability. We hereby present a case series on DRESS.


Cyclic somatostatin analogues as potent antagonists at mu-, but not delta- and kappa-opioid receptors mediating presynaptic inhibition of neurotransmitter release in the brain.
The opioid receptor antagonist properties of four conformationally constrained cyclic octapeptide analogues of somatostatin were investigated using in vitro functional paradigms of mu-, delta- and kappa-opioid receptors in the rat brain. The analogues examined were D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP), D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2 (CTAP), D-Tic-CTOP (TCTOP) and D-Tic-CTAP (TCTAP). Activation of mu-receptors by the enkephalin analogue Tyr-D-Ala-Gly-(NMe)Phe-Gly-ol (DAGO) inhibited the (electrically evoked) release of [3H]noradrenaline (NA) from superfused cortical slices and this inhibitory effect was antagonized in a competitive fashion by all of the octapeptides tested (pA2 values: CTOP and CTAP 7.9-8.0, TCTOP and TCTAP 8.7-8.8). Selective activation of kappa-opioid receptors by the cyclohexylbenzeneaceamide U69593 (0.02 microM) inhibited (by 40-45%) the release of [3H]dopamine (DA) from striatal slices, whereas selective activation of delta-opioid receptors by [D-Ser2(O-t-butyl),Leu5]enkephalyl-Thr6 (DSTBULET; 0.1 microM) caused an inhibition (by 38-46%) of striatal [14C]acetylcholine (ACh) release. However, these inhibitory effects were not affected by any of the octapeptides in concentrations that caused full antagonism of the inhibitory effect (55-65%) of 0.1 microM DAGO on cortical [3H]NA release. Thus, the cyclic octapeptide somatostatin analogues CTOP, CTAP, TCTOP and TCTAP are potent and highly selective antagonists at the mu-opioid receptors mediating presynaptic inhibition of NA release in the brain. The mu-receptor affinity of the most potent of these antagonists, TCTOP and TCTAP, appears to be similar to that of naloxone but these antagonists have a much greater selectivity than the latter.


[Subareolar injection for sentinel lymph node biopsy in multiple breast cancer].
In this study we performed subdermal injection of 99mTc-labeled albumin combined with subareolar (SA) injection of blue dye to axillary lymphatic mapping and sentinel lymph node biopsy (SNLB) in patients with multifocal and multicentric breast cancer (MC) to evaluate the feasibility and accuracy of this technique. We compared the results with a group of patients with unifocal breast cancer. From January 1999 to March 2006 axillary lymph node mapping and SLNB was performed on 250 patients followed by a complete axillary lymph node dissection. Retrospective analysis showed that 32 (12.8%) of these patients have MC on final histopathologic examination and 218 (87.2%) have unifocal cancer. In statistical analysis tumor size shows a significant difference (p=.01) with largest lesions in MC. In MC often histological type is invasive lobular with or without in situ cancer (p= .001). Metastatic lymph node involvement was significantly higher in the MC group compared to unifocal cancer group (p=.001). False negative (FN) rate was 5.8% in MC and 9.6% in unifocal cancers. The overall accuracy of lymphatic mapping was 96.8% in MC and 97.6% in unifocal cancers. Sensitivity was 94.4% in MC and 91.2% in unifocal cancers. In this study we provide further evidence that lymphatic mapping may be reliable even in patients with MC. SA injection technique demonstrates a high sentinel lymph node identification rate and low FN rate; therefore this technique should been recommended to SLNB in patients with MC of the breast.


[Pathogenesis of Secondary Pulmonary Tuberculosis and Role of Cord Factor in Secondary Infection].
The primary and secondary tuberculosis features two completely different pathogenesis.At present,the pathogenesis of primary tuberculosis has been clear,whereas that of secondary tuberculosis remains unclear.In order to decipher the mechanism of secondary infection of Mycobacterium tuberculosis and provide insights into vaccine research and drug development,this paper reviews the problems of the widely accepted mechanism of secondary infection,the new findings of the research on the mechanism,as well as the role of cord factors.


Bioinformatics for study of autoimmunity.
Recent years have witnessed an explosive growth in available biological data pertaining to autoimmunity research. This includes a tremendous quantity of sequence data (biological structures, genetic and physical maps, pathways, etc.) generated by genome and proteome projects plus extensive clinical and epidemiological data. Autoimmunity research stands to greatly benefit from this data so long as appropriate strategies are available to enable full access to and utilization of this data. The quantity and complexity of this biological data necessitates use of advanced bioinformatics strategies for its efficient retrieval, analysis and interpretation. Major progress has been made in development of specialized tools for storage, analysis and modeling of immunological data, and this has led to development of a whole new field know as immunoinformatics. With advances in novel high-throughput immunology technologies immunoinformatics is transforming understanding of how the immune system functions. This paper reviews advances in the field of immunoinformatics pertinent to autoimmunity research including databases, tools in genomics and proteomics, tools for study of B- and T-cell epitopes, integrative approaches, and web servers.


The use of cochlear's SCAN and wireless microphones to improve speech understanding in noise with the Nucleus6® CP900 processor.
The newest Nucleus CI processor, the CP900, has two new options to improve speech-in-noise perception: (1) use of an adaptive directional microphone (SCAN mode) and (2) wireless connection to MiniMic1 and MiniMic2 wireless remote microphones. An analysis was made of the absolute and relative benefits of these technologies in a real-world mimicking test situation. Speech perception was tested using an adaptive speech-in-noise test (sentences-in-babble noise). In session A, SRTs were measured in three conditions: (1) Clinical Map, (2) SCAN and (3) MiniMic1. Each was assessed for three distances between speakers and CI recipient: 1 m, 2 m and 3 m. In session B, the benefit of the use of MiniMic2 was compared to benefit of MiniMic1 at 3 m. A group of 13 adult CP900 recipients participated. SCAN and MiniMic1 improved performance compared to the standard microphone with a median improvement in SRT of 2.7-3.9 dB for SCAN at 1 m and 3 m, respectively, and 4.7-10.9 dB for the MiniMic1. MiniMic1 improvements were significant. MiniMic2 showed an improvement in SRT of 22.2 dB compared to 10.0 dB for MiniMic1 (3 m). Digital wireless transmission systems (i.e. MiniMic) offer a statistically and clinically significant improvement in speech perception in challenging, realistic listening conditions.


Transglutaminase differentiation during maturation of human blood monocytes to macrophages.
There are divergent reports in the literature on the character of transglutaminases in monocytes and macrophages. The aim of the present study was to further elucidate the characteristics and functions of various transglutaminases in monocytes and macrophages. Peripheral human blood monocytes were plated and cultured for up to a month and examined for transglutaminase. Freshly prepared monocytes contained cellular Factor XIII only. Successively during culturing, the monocytes matured into macrophages. Cellular Factor XIII correspondingly disappeared and tissue transglutaminase increased during the same time. After approximately 2 weeks in culture only tissue transglutaminase was detected and this remained for the rest of the culturing period. The tissue transglutaminase content was induced by addition of 2 mumols/l retinoic acid. Addition of retinoic acid was not critical for transglutaminase differentiation. Transglutaminase could be associated with phagocytosis of 125I-trypsin-alpha 2-macroglobulin complexes. The phagocytotic capacity of monocytes was approximately 1/4 compared to macrophages cultured for 14 days. Phagocytosis was measured as cellular complex degradation to monoiodo-tyrosine, released to the culture medium. The monocytes and macrophages were incubated at 4 degrees C and 37 degrees C, with and without addition of the transglutaminase inhibitor monodansylthiacadaverine. Addition of 100 mumols/l monodansylthia-cadaverine caused approximately 2/3 inhibition of phagocytosis. These results suggest that transglutaminase differentiates from cellular Factor XIII into tissue type transglutaminase during maturation of monocytes into macrophages and that the differentiation is associated with transglutaminase-dependent phagocytosis.


A Rare Case of Digital Ischemia and Gangrene in ANCA-Associated Vasculitis with Review of the Literature.
This paper describes one patient with Antineutrophil Cytoplasmic Antibody- (ANCA-) associated vasculitis who initially presented with multiple ischemic fingers and toes. On further evaluation, the patient was also found to have pulmonary-renal involvement and episcleritis. The diagnosis was supported with a positive cANCA (anti-proteinase 3) and a bronchoscopy consistent with diffuse alveolar hemorrhage. Although the patient refused a tissue biopsy, clinical presentation including nasal ulceration, sinus congestion, and epistaxis and anti-proteinase 3 antibody were more consistent with Granulomatosis with Polyangiitis (GPA) rather than Microscopic Polyangiitis (MPA) or Eosinophilic Granulomatosis with Polyangiitis (EGPA) based on the recently presented ACR/EULAR Provisional 2017 Classification Criteria for GPA (Luqmani et al., 2016). The patient responded well to therapy including high dose steroids and cyclophosphamide, with improvement of all organs involved and had no further digital ischemia or gangrene on follow-up. We include a review of the English literature summarizing presentation, management, and outcome of 16 similar cases.


[Response of fine root decomposition to simulated nitrogen deposition in Pleioblastus amarus plantation, rainy area of West China].
As an important contributor to carbon (C) flux in the global C cycle, fine root litter decomposition in forests has the potential to be affected by the elevated nitrogen (N) deposition observed globally. From November 2007 to January 2013, a field experiment involving monthly simulated deposition of N in a Pleioblastus amarus plantation was conducted in the Rainy Area of West China. Four levels of nitrogen deposition were included as control (0 g N x m(-2) x a(-1)), low nitrogen (5 g N x m(-2) x a(-1)), medium nitrogen (15 g N x m(-2) x a(-1)) and high nitrogen (30 g N x m(-2) x a(-1)). After 3 years of simulated N deposition experiment (January 2011) , a two-year fine root decomposition experiment was conducted in the simulated N deposition plots using litterbag method, under monthly experimental N deposition. The decomposition rates of fine roots were fast first and then slow. Mass loss of fine roots in the first year of decomposition was up to 60%, and the change of the remaining mass was very slow in the second year. The time of 50% and 95% mass loss of fine roots was 1.20 and 5.17 years, respectively, under the conditions of no addition N input. In general, decomposition rates were underestimated using negative exponential model. Simulated N deposition significantly inhibited the decomposition of fine roots. The remaining mass in the high nitrogen treatment was 51.0% higher than that in the control, after two years of decomposition. Simulated N deposition increased C, P and K contents in the remaining mass of litter. Compared with the control, soil pH decreased significantly in the medium and high nitrogen treatments, soil organic C, total N, ammonium and nitrate contents and fine root biomass of P. amarus increased significantly in the high nitrogen treatment after simulated N deposition for 4. 5 years. Key words: nitrogen deposition; fine root decomposition; Pleioblastus amarus.


What have we learned from a 10-year experience with the LUMINA (Lupus in Minorities; Nature vs. nurture) cohort? Where are we heading?
Recently, there has been an awareness of the variable phenotypic expression of numerous disorders between individuals from different ethnicities, systemic lupus erythematosus (SLE) one of them. These disparities probably arise from the interaction between genetic and non-genetic (environmental, socioeconomic-demographic, cultural and behavioral) factors. To delineate the influence of these factors on SLE outcome, we established a multiethnic (Hispanic, African American and Caucasian) United States (US) early cohort (<5 years disease duration). Ten years later, interesting data have emerged from the LUMINA (Lupus in Minorities: Nature vs. nurture) cohort. For example, African Americans and Hispanics from Texas have a more severe disease than Caucasians and Hispanics from Puerto Rico. Lack of private insurance, acute SLE onset, expression of HLA-DRB1*01 (DR1) and C4A*3 alleles were associated with higher disease activity, whereas age, the number of American College of Rheumatology criteria met, disease activity, corticosteroid use and abnormal illness behaviors were consistent predictors of damage. In turn, damage and poverty were found to predict mortality. We now plan to apply new approaches (genetic admixture) to deconfound the complex interaction between genetic and non-genetic factors influencing SLE outcome. These data may have impact on the development of policies aimed at eliminating health disparities in the US.


Chronic exposure to dexamethasone may not affect sugammadex reversal of rocuronium-induced neuromuscular blockade: an in vivo study on rats.
Chronic glucocorticoid exposure is associated with resistance to nondepolarizing neuromuscular blocking agents. Therefore, we hypothesized that sugammadex-induced recovery would occur more rapidly in subjects exposed to chronic dexamethasone compared to those who were not exposed. This study evaluated the sugammadex-induced recovery profile after neuromuscular blockade (NMB) in rats exposed to chronic dexamethasone. Sprague-Dawley rats were allocated to three groups (dexamethasone, control, and pair-fed group) for the in vivo study. The mice received daily intraperitoneal dexamethasone injections (500 μg/kg) or 0.9% saline for 15 days. To achieve complete NMB, 3.5 mg/kg rocuronium was administered on the sixteenth day. The recovery time to a train-of-four ratio ≥ 0.9 was measured to evaluate the complete recovery following the sugammadex injection. Among the groups, no significant differences were observed in the recovery time to a train-of-four ratio ≥ 0.9 following sugammadex administration (P = 0.531). The time to the second twitch of the train-of-four recovery following rocuronium administration indicated that the duration of NMB was significantly shorter in Group D than that in Groups C and P (P = 0.001). Chronic exposure to dexamethasone did not shorten the recovery time of sugammadex-induced NMB reversal. However, the findings of this study indicated that no adjustments to sugammadex dosage or route of administration is required, even in patients undergoing long-term steroid treatment.


Macular Microvasculature Is Associated With Total Cerebral Small Vessel Disease Burden in Recent Single Subcortical Infarction.
To assess the retinal microvasculature, choriocapillaris, and choroidal thickness in recent single subcortical infarction (RSSI) patients compared with healthy controls. We also assessed the correlation between the macular microvascular changes and choroidal changes with their clinical implications in RSSI patients. Forty-six RSSI patients and 39 healthy controls (HC) were enrolled in our study. Magnetic resonance imaging (MRI) was done for all RSSI patients, and a total cerebral small vessel disease (CSVD) score was assessed for all patients. Swept-source optical coherence tomography (SS-OCT) was used to image and assess the choroidal thickness and SS-OCT angiography (SS-OCTA) was used to image and assess the macular microvasculature and choriocapillaris in all participants. Clinical information was collected for all participants. RSSI patients showed significantly sparser inner retinal microvasculature (P = 0.003) when compared with healthy controls. RSSI patients showed significantly thinner choroidal thickness (P < 0.001) when compared with HC. No significant difference (P = 0.247) was seen when the choriocapillaris was compared between the two groups. CSVD burden (P = 0.014) and NIHSS score (P = 0.010) showed significant correlation with the inner retinal microvasculature of RSSI patients. The inner retinal microvasculature (P = 0.016) and choroidal thickness (P = 0.018) showed a significant correlation with the MoCA scores in RSSI patients. Our report suggests that retinal and choroidal imaging may serve as useful indicators to expand our understanding of RSSI and its clinical validity.


Potential advantage of student-run clinics for diversifying a medical school class.
The purpose of this study was to evaluate the influence of a student-run clinic on the diversification of a medical student class. We distributed a two-page, 20-item, paper survey to students of the University of Missouri School of Medicine (MU SOM) class of 2015 in July of 2011. The survey gathered information on general demographics, opinions on the importance of medical education opportunities, and opinions on the importance of medical school characteristics in applying to and attending MU SOM. A total of 104 students responded to the survey. A majority of the students identified the MedZou Community Health Clinic, a student-run, free health clinic affiliated with MU SOM, and simulated-patient encounters as important educational experiences (81% and 94%, respectively). More than half of the self-identified "non-white" students reported MedZou as an important factor in their choice to apply to (60%; 95% confidence interval [CI], 32 to 88) and attend (71%; 95% CI, 44 to 98) MU SOM, over half of the females reported MedZou as important in their choice to apply (59%; 95% CI, 43 to 76) and attend (57%; 95% CI, 40 to 74), and over half of non-Missouri residents reported MedZou as important in their choice to apply (64%; 95% CI, 36 to 93) and attend (71%; 95% CI, 44 to 98). According to the above results, it can be said that students clearly value both MedZou and simulated-patient encounters as important educational experiences. Women, minorities, and non-Missouri residents value MedZou more highly than their peers who are First Year Medical Students who are Missouri residents, suggesting that MedZou may provide a promising opportunity to advance diversity within MU SOM. These results highlight the need for additional research to further explore MedZou's potential to enhance the recruitment of a diverse medical student class.


The relationship between the number of consecutive days with heat stress and milk production of Holstein dairy cows raised in a humid continental climate.
Heat stress is known to affect performance of dairy cows experiencing prolonged periods of high temperature and relative humidity. Less is known about its effects in cooler climates. The goals of the present study were to determine the prevalence of days susceptible to cause mild heat stress in dairy cows living in a humid continental climate and to investigate the relationship between the number of consecutive days of mild heat stress and milk, fat, protein, and lactose production. A 6-yr data set (2010-2015) containing 606,031 milk analysis records for 34,360 Holstein dairy cows at different parities was matched with the corresponding daily maximum temperature-humidity index. Exposure to heat stress conditions was divided into 5 categories corresponding to 0, 1 to 2, 3 to 4, 5 to 6, and 7 to 8 consecutive days before milk test date. On average, cows were exposed to heat stress conditions for 135.8 ± 5.9 d/yr in Southwest Quebec and 95.3 ± 10.2 d/yr in Eastern Quebec. Cows experiencing heat stress conditions produced on average less fat, protein, and energy-corrected milk and lower fat and protein concentrations. The decrease in milk fat reached 6% for category 7 to 8 exposure of cows in parity 3 or more. The association between exposure category and milk yield and lactose yield and concentration was weak. Heat stress lowered milk fat and protein production but had little effect on milk volume output. Further research is necessary to better understand the mechanism underlying the effects of sporadic low- to medium-intensity heat stress on dairy productivity.


MicroRNA-155, induced by FOXP3 through transcriptional repression of BRCA1, is associated with tumor initiation in human breast cancer.
MicroRNA (miR)-155 is upregulated in breast cancer cells and in sera of patients with breast cancer, but its clinical relevance remains uncertain. The objective of the present effort was to address the transcriptional regulation of miR-155. A bioinformatics analysis of public datasets validated upregulation of miR-155 in tumor cells of patients with breast cancer, particularly those who were at early stages and had triple-negative cancers. The expression profiling and clinical relevance of miR-155 in tumor cells and blood cells were characterized by TaqMan miR assays and, in plasma and exosomes, by nest-quantitative PCR analysis. There was a positive correlation between expression of FOXP3 and miR-155 in breast cancer cell lines and primary breast cancers. In breast cancer cells, FOXP3 induced miR-155 through transcriptional repression of BRCA1. Furthermore, in an Alabama cohort, blood and plasma samples were collected from 259 participants, including patients with breast cancer or benign breast tumors, members of breast cancer families, and matched healthy female controls. For patients with early stage or localized breast cancer, there were high levels of miR-155 in both plasma and blood cells. In cultured breast cancer cells, expression of miR-155 was induced by FOXP3 but was not significantly changed in culture medium or exosomes, suggesting that circulating miR-155 originated from blood cells. These findings reveal a transcriptional axis of FOXP3-BRCA1-miR-155 in breast cancer cells and show that plasma miR-155 may serve as a non-invasive biomarker for detection of early stage breast cancer.


[Study of the inhibitory effect of acetylene on the biological methane formation in a paddy soil (author's transl)].
A 0.05 atm partial pressure of acetylene stopped all the CH4 evolution during anaerobic paddy soil incubations when different carbon substances were added. It was shown proof that acetylene did not disturbe the volatil fatty acids yielding but prohibited the methane forming bacteria from doing future use of those. Acetylene does inhibit methane forming bacteria. Besides, the growth of a Methanosarcina strain was stopped by a 0.01 atm partial pressure of acetylene, and resting cells lost 98 per cent of their activity when the acetylene concentration was 0.5 x 10-3 M in the liquid. This acetylene inhibition can be used for studying the metabolism of methane forming bacteria.


Clinical course and outcomes in adults with co-occurring hypertrophic cardiomyopathy and hypertension: a scoping review protocol.
Hypertension affects 40%-60% of adults with hypertrophic cardiomyopathy (HCM), the most common inherited cardiac condition. It can be a diagnostic confounder for HCM, contributing to delayed diagnosis. Clinically, treatment of co-occurring hypertension and HCM poses challenges as first-line and second-line antihypertensive medications are often contraindicated in HCM. The clinical course in adults with hypertension and HCM is also not well understood, and studies examining patient outcomes in this population are equivocal. In this paper, we aim to outline the protocol of a scoping review, a type of literature review, to systematically synthesise existing knowledge on adults with co-occurring HCM and hypertension, highlighting knowledge and evidence gaps, and identifying future research directions to optimise outcomes in this population. This review is guided by Arksey and O'Malley's conceptual framework on conducting scoping reviews. We will search five electronic databases (PubMed, CINAHL, Scopus, Embase and Web of Science) and reference lists of publications to identify eligible articles focusing on medical therapy, clinical course or outcomes in adults with HCM and hypertension, between 2011 and 2023. Our search strategy and presentation of results will be guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses-Scoping Review guideline. First, two independent reviewers will screen articles, by title and abstract, followed by a full-text screen to identify eligible articles. Relevant data will be extracted and synthesised. Ethical approval is not required for this review as it is a secondary data collection of published articles and does not involve human subject participation. We will present results of this review at relevant professional conferences and patient-centred educational events. Results will be published in a peer-reviewed journal. https://osf.io/cy8qb/?view_only=98197f4850584e51807ff9b62533a706.


Deep sequencing of Lotus corniculatus L. reveals key enzymes and potential transcription factors related to the flavonoid biosynthesis pathway.
Lotus corniculatus L. is used worldwide as a forage crop due to its abundance of secondary metabolites and its ability to grow in severe environments. Although the entire genome of L. corniculatus var. japonicus R. is being sequenced, the differences in morphology and production of secondary metabolites between these two related species have led us to investigate this variability at the genetic level, in particular the differences in flavonoid biosynthesis. Our goal is to use the resulting information to develop more valuable forage crops and medicinal materials. Here, we conducted Illumina/Solexa sequencing to profile the transcriptome of L. corniculatus. We produced 26,492,952 short reads that corresponded to 2.38 gigabytes of total nucleotides. These reads were then assembled into 45,698 unigenes, of which a large number associated with secondary metabolism were annotated. In addition, we identified 2,998 unigenes based on homology with L. japonicus transcription factors (TFs) and grouped them into 55 families. Meanwhile, a comparison of four tag-based digital gene expression libraries, built from the flowers, pods, leaves, and roots, revealed distinct patterns of spatial expression of candidate unigenes in flavonoid biosynthesis. Based on these results, we identified many key enzymes from L. corniculatus which were different from reference genes of L. japonicus, and five TFs that are potential enhancers in flavonoid biosynthesis. Our results provide initial genetics resources that will be valuable in efforts to manipulate the flavonoid metabolic pathway in plants.


The effects of CA1 5HT4 receptors in MK801-induced amnesia and hyperlocomotion.
In this study, the effects of 5-HT4 receptors of the CA1 on MK801-induced amnesia and hyperlocomotion were examined. One-trial step-down method was used to assess memory retention and then, the hole-board method to assess exploratory behaviors. The results showed that post-training intra-CA1 administration of RS67333 (62.5 and 625 ng/mouse) and RS23597 (1 and 10 ng/mouse) decreased memory consolidation, but it did not alter head-dip counts, head-dip latency and locomotor activity. Similarly, MK801 (0.5 and 1 μg/mouse) decreased memory consolidation, but had no effect on head-dip counts and head-dip latency. Interestingly, it increased locomotor activity. The results also showed that post-training intra-CA1 injection of a sub-threshold dose of RS67333 (6.25 ng/mouse) or RS23597 (0.1 ng/mouse) could heighten MK801 induced amnesia and decrease locomotor activity, but it did not alter head-dip counts and head-dip latency. In conclusion, our findings suggest that the CA1 5-HT4 receptors are involved in MK801-induced amnesia and hyperlocomotion.


Universal and culturally dependent issues in health care ethics.
Our beliefs about morality are culturally embedded in social, religious, and political ideologies that influence individuals and communities. Ethical issues in health and medical care are often discussed in articles and at international conferences without explicit consideration of cultural assumptions that influence our beliefs about the significance and relevance of ethical concepts and principles. Helping people in need of care or denying people this help is dependent on values related to political decisions and organisational matters as well as professional and personal interpretations of moral obligations. In this paper we argue that explicit self-critical attention to the meaning of concepts and their cultural contexts is crucial in fostering mutual respect and understanding for different cultural frames of reference. This is especially important in the rapid development of international co-operation and globalisation.


Comparison of Task Performance, Hand Power, and Dexterity with and without a Cock-up Splint.
[Purpose] The purpose of this study was to investigate the difference in task performance, grip and pinch strength, and dexterity with and without cock-up splints, which are widely used in occupational therapy practice. [Methods] Twenty-three participants performed Jebsen-Taylor hand function test and grooved pegboard for task performance and dexterity. The power grip and pinch strength was measured using Jamar hydraulic hand dynamometer and pinch gauge. [Results] In the result of the Jebsen-Taylor hand function test, task performance with the cock-up splint was slower compared to without the splint for all items. Men's grip power with the cock-up splint was found to be significantly decreased compared to without the splint. Women's grip and palmar pinch strength with the splint decreased significantly compared to without the splint. In the grooved pegboard test, the dexterity of both men and women with the cock-up splint decreased significantly compared to without the splint. [Conclusion] To assist patients to make wise decisions regarding the use of splints, occupational therapists must have empirical knowledge of the topic as well as an understanding of the theoretical, technical, and related research evidence. The results of this study will be useful in the analysis and understanding of changes in hand function in splint applications for people with hand dysfunction.


Liver transplantation for children with biliary atresia in the pediatric end-stage liver disease era: the role of insurance status.
Socioeconomic status influences health outcomes, although its impact on liver transplantation (LT) in children with biliary atresia (BA) is unknown. We hypothesized that governmental insurance [public insurance (PU)], rather than private insurance (PR), would be associated with poorer outcomes for children with BA. Children with BA who underwent first isolated LT between January 2003 and June 2011 were identified from United Network for Organ Sharing Standard Transplant Analysis and Research files. We identified 757 patients with PR and 761 patients with PU. The race/ethnicity distribution was significantly different between the groups (65% white, 12% black, and 10% Hispanic in the PR group and 33% white, 26% black, and 29% Hispanic in the PU group, P < 0.01). Wait-list mortality was higher for the PU group versus the PR group [46/1654 (2.7%) versus 29/1895 (1.5%), P < 0.01]. PR patients were older than PU patients at transplant (2.4 ± 4.5 versus 1.5 ± 3.0 years, P < 0.01). The donor types differed between the groups: 165 children (21.8%) in the PR group received living donor grafts, whereas 79 children (10.4%) in the PU group did (P < 0.01). The 1- and 5-year posttransplant patient survival rates were greater for the PR group versus the PU group (98.0% versus 94.1% at 1 year, P < 0.01; 97.8% versus 92.2% at 5 years, P < 0.01). Cox proportional hazards models revealed that the insurance type (PU), the donor type (deceased), and life support were significant risk factors for death. A separate analysis of deceased donor LT revealed that the PU group still had significantly worse patient and graft survival. In conclusion, PU coverage is an independent risk factor for significantly increased wait-list and posttransplant mortality in children with BA. Further studies are needed to unearth the reasons for these important differences in outcomes.


Topography of CNV and PINV in schizotypal personality.
The topography of the postimperative negative variation (PINV) was analyzed in participants with high and low scores on the German version of the Schizotypal Personality Questionnaire. Scalp amplitude and Laplacian maps of the terminal contingent negative variation (tCNV) and PINV and the time course of the PINV were compared between the two groups. CNV and PINV were induced with a delayed matching-to-sample task, in which the pattern of the imperative stimulus was either clearly or ambiguous matched to one of the two diamonds simultaneously presented as a warning stimulus 4.0 s earlier. Electroencephalograms were recorded with a DC amplifier (32 channels). Negativity increased from tCNV to PINV, especially at frontal sites, and the PINV was larger under ambiguous than under clear matching conditions. Low-scoring participants showed a right-sided predominance of the PINV, which was absent in high-scoring participants. These results resemble differences in the topography of the PINV between healthy control participants and those with schizophrenia under identical experimental conditions and suggest functional differences between tCNV and PINV.


Microglial over-pruning of synapses during development in autism-associated SCN2A-deficient mice and human cerebral organoids.
Autism spectrum disorder (ASD) is a major neurodevelopmental disorder affecting 1 in 36 children in the United States. While neurons have been the focus to understand ASD, an altered neuro-immune response in the brain may be closely associated with ASD, and a neuro-immune interaction could play a role in the disease progression. As the resident immune cells of the brain, microglia regulate brain development and homeostasis via core functions including phagocytosis of synapses. While ASD has been traditionally considered a polygenic disorder, recent large-scale human genetic studies have identified SCN2A deficiency as a leading monogenic cause of ASD and intellectual disability. We generated a Scn2a-deficient mouse model, which displays major behavioral and neuronal phenotypes. However, the role of microglia in this disease model is unknown. Here, we reported that Scn2a-deficient mice have impaired learning and memory, accompanied by reduced synaptic transmission and lower spine density in neurons of the hippocampus. Microglia in Scn2a-deficient mice are partially activated, exerting excessive phagocytic pruning of post-synapses related to the complement C3 cascades during selective developmental stages. The ablation of microglia using PLX3397 partially restores synaptic transmission and spine density. To extend our findings from rodents to human cells, we established a microglial-incorporated human cerebral organoid model carrying an SCN2A protein-truncating mutation identified in children with ASD. We found that human microglia display increased elimination of post-synapse in cerebral organoids carrying the SCN2A mutation. Our study establishes a key role of microglia in multi-species autism-associated models of SCN2A deficiency from mouse to human cells.


Integrated analysis reveals Atf3 promotes neuropathic pain via orchestrating JunB mediated release of inflammatory cytokines in DRG macrophage.
The dorsal root ganglion (DRG) is actively involved in the development of neuropathic pain (NP), serving as an intermediate station for pain signals from the peripheral nervous system to the central nervous system. The mechanism by which DRG is involved in NP regulation is not fully understood. The immune system plays a pivotal role in the physiological and pathological states of the human body. In recent years, the immune system has been thought to play an increasingly important role in the pathogenesis of NP. The immune system plays a key role in pain through specific immune cells and their immune-related genes (IRGs). However, the mechanism by which IRGs of DRG regulate NP action has not been fully elucidated. Here, we performed Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of IRGs in DRG bulk-RNA sequencing data from spared nerve injury (SNI) model mice and found that their IRGs were enriched in many pathways, especially in the immune response pathway. Subsequently, we analyzed single-cell RNA sequencing (scRNA-seq) data from DRGs extracted from the SNI model and identified eight cell populations. Among them, the highest IRG activity was presented in macrophages. Next, we analyzed the scRNA and bulk-sequencing data and deduced five common transcription factors (TFs) from differentially expressed genes (DEGs). The protein-protein interaction (PPI) network suggested that Atf3 and JunB are closely related. In vitro experiments, we verified that the protein and mRNA expressions of Atf3 and JunB were up-regulated in macrophages after lipopolysaccharide (LPS) stimulation. Moreover, the down-regulation of Atf3 reduced the release of inflammatory cytokines and decreased the protein and mRNA expression levels of JunB. The down-regulation of JunB also reduced the release of inflammatory cytokines. Furthermore, overexpression of JunB attenuated the effect of Atf3 down-regulation in reducing the release of inflammatory cytokines. Therefore, we speculated that Atf3 might promote NP through JunB-mediated release of inflammatory factors in DRG macrophages.


Visual and somatosensory evoked potentials in hereditary motor-sensory neuropathies.
Visual (VEP) and somatosensory evoked potentials (SEP) were studied in 31 patients with hereditary motor-sensory neuropathy (HMSN)--in the absolute majority of cases HMSN type I. Prolonged P100 latency was found in the two oldest patients only, though the amplitude of that wave was significantly lower in the adult patients compared with the controls. Typical SEP findings were poorly detectable waves N9,N13 and spinal wave with prominently prolonged N20 und P40 latencies. The amplitude of these cortical components again decreased in proportion to the patients' age. Surprisingly, the greatest involvement of the peripheral sensory and motor nervous systems with the most prominent SEP alteration was found in the youngest generation while in the previous generations there was, in contrast, a more conspicuous component of central affection.


Production of Escherichia coli heat labile toxin (LT) B subunit in soybean seed and analysis of its immunogenicity as an oral vaccine.
The B subunit of the heat labile toxin of enterotoxigenic Escherichia coli (LTB) was used as a model immunogen for production in soybean seed. LTB expression was directed to the endoplasmic reticulum (ER) of seed storage parenchyma cells for sequestration in de novo synthesized inert protein accretions derived from the ER. Pentameric LTB accumulated to 2.4% of the total seed protein at maturity and was stable in desiccated seed. LTB-soybean extracts administered orally to mice induced both systemic IgG and IgA, and mucosal IgA antibody responses, and was particularly efficacious when used in a parenteral prime-oral gavage boost immunization strategy. Sera from immunized mice blocked ligand binding in vitro and immunized mice exhibited partial protection against LT challenge. Moreover, soybean-expressed LTB stimulated the antibody response against a co-administered antigen by 500-fold. These results demonstrate the utility of soybean as an efficient production platform for vaccines that can be used for oral delivery.


Amino acid transporter (AAT) gene family in foxtail millet (Setaria italica L.): widespread family expansion, functional differentiation, roles in quality formation and response to abiotic stresses.
Amino acid transporters (AATs) plays an essential roles in growth and development of plants, including amino acids long-range transport, seed germination, quality formation, responsiveness to pathogenic bacteria and abiotic stress by modulating the transmembrane transfer of amino acids. In this study, we performed a genome-wide screening to analyze the AAT genes in foxtail millet (Setaria italica L.), especially those associated with quality formation and abiotic stresses response. A total number of 94 AAT genes were identified and divided into 12 subfamilies by their sequence characteristics and phylogenetic relationship. A large number (58/94, 62%) of AAT genes in foxtail millet were expanded via gene duplication, involving 13 tandem and 12 segmental duplication events. Tandemly duplicated genes had a significant impact on their functional differentiation via sequence variation, structural variation and expression variation. Further comparison in multiple species showed that in addition to paralogous genes, the expression variations of the orthologous AAT genes also contributed to their functional differentiation. The transcriptomic comparison of two millet cultivars verified the direct contribution of the AAT genes such as SiAAP1, SiAAP8, and SiAUX2 in the formation of grain quality. In addition, the qRT-PCR analysis suggested that several AAT genes continuously responded to diverse abiotic stresses, such as SiATLb1, SiANT1. Finally, combined with the previous studies and analysis on sequence characteristics and expression patterns of AAT genes, the possible functions of the foxtail millet AAT genes were predicted. This study for the first time reported the evolutionary features, functional differentiation, roles in the quality formation and response to abiotic stresses of foxtail millet AAT gene family, thus providing a framework for further functional analysis of SiAAT genes, and also contributing to the applications of AAT genes in improving the quality and resistance to abiotic stresses of foxtail millet, and other cereal crops.


Celecoxib has Preventive and Therapeutic Benefits against Nephrotoxicity Caused by Gentamicin in Mice.
It's crucial to comprehend the impact of oxidative stress and pro-inflammatory cytokines in the gentamicin-induced kidney injury mechanism. Celecoxib was administered orally either before or after intraperitoneal therapy with gentamicin in mice. The serum levels of creatinine (SCr), blood urea nitrogen (BUN), IL-6, and TNF-α were measured by ELISA test, as well as the levels of the kidney tissue malondialdehyde (MDA), and glutathione (GSH) were also estimated spectrophotometrically. The renal expression of nuclear factor-κB (NF-κB), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and cyclooxygenase 2 (COX-2) mRNAs were evaluated by qPCR. Histopathological evaluation and Immunohistochemical examination of kidney NF-κB, IL-6, and COX-2 were also, performed. Celecoxib successfully prevented gentamicin-induced kidney damage as indicated by reducing blood BUN, SCr, and tissue MDA levels and increasing renal tissue GSH levels as well as lowering the blood IL-6 and TNF-α in comparison to mice received gentamicin. Furthermore, celecoxib has inhibited COX-2, NF-κB, IL-6, and TNF-α expression in the renal tissue. It is noteworthy that celecoxib therapy after gentamicin administration brought about substantially the same results as celecoxib treatment before gentamicin injection in mice. Our results showed the role of celecoxib as a therapeutic tool for gentamicin-induced nephrotoxicity as well as raised its beneficial prophylactic role in this medical challenge by attenuating oxidative stress and inflammation.


Evaluation of commercial ELISA and RIA for measuring porcine C-peptide: implications for research.
Pre-clinical demonstration of porcine islet graft function is necessary to support the clinical transplantation of pig islets. C-peptide concentration is an especially useful marker of insulin secretion, because its measurement is not confounded by the presence of exogenous insulin. To measure porcine C-peptide (PCP), researchers in the field exclusively used the Millipore (previously Linco Research) radioimmunoassay (RIA) until 2011, when Mercodia released an alternative enzyme-linked immunosorbent assay (ELISA). (At the end of 2013, the Millipore RIA was withdrawn from the market for commercial reasons.) In our current study, to directly compare these two assays, we performed validation studies on each. We also performed interlaboratory comparisons. Then, to determine the level of agreement between the assays, we analyzed the porcine serum C-peptide concentration measurement results obtained from each assay. Using pre-established method validation acceptance criteria, we determined and evaluated the detection limit, sensitivity, precision, linearity, and recovery of the two commercially available PCP assays described above (ELISA and RIA). After validation requirements were met, we performed a method comparison by determining C-peptide concentration in 60 serum samples collected from 31 normal, healthy adult Landrace pigs in the fasting state; a subset underwent an intravenous glucose challenge test, to stimulate the typical physiologic range of C-peptide. All analyses were performed according to manufacturer instructions. To compare the assays, we used Deming regression analysis. Both assays met acceptance criteria. The RIA had a sensitivity of 0.1 ng/ml; it was linear to 2.9 ng/ml. The ELISA had a detection limit of 0.03 ng/ml; it was linear to 1.2 ng/ml. Recovery ranged from 89 to 113% with both assays. The coefficient of variability was 8% in interlaboratory comparisons. Deming regression analysis directly comparing both assays revealed significant correlation between them (before log-transformation: R2=0.9803, P<0.0001; after log-transformation: R2=0.9727, P<0.0001). Measured C-peptide concentration was lower with the ELISA than with the RIA; individual measurements plotted against the averages of the pair demonstrated that the variability from the mean strongly depended on increasing concentration. To transform ELISA data, we used the standard regression equation y=2.191x+0.1119 and the log-transformed regression equation y=0.8101x+0.7502. Both the transformed and the log-transformed (exponential) values approximated the measured RIA levels with a high degree of accuracy in the concentration range of 0 to 1.0 ng/ml. Porcine C-peptide concentration can be reliably measured in porcine serum samples with either assay (ELISA or RIA). However, the C-peptide results generated by these two assays are not equivalent. Therefore, assay bias must be considered before directly comparing pre-clinical studies that used either of these assays. We determined that harmonization between the assays is appropriate in a specific concentration range. Outside of that range, we do not know whether a linear correction function can be more broadly applied. The variation between the two assays may be related to calibration or reagent factors. To determine which assay is truly more accurate and to effectively compare interlaboratory results, we will need a traceable reference standard.


Evaluating a smartphone application to increase the quantity and improve the quality of supervised practice driving.
The learner stage of graduated driver licensing (GDL), when teenagers are supervised by an adult driver, represents an opportunity to develop skills that could confer a safety benefit during their years of independent driving. This paper describes the design of a teenage driving study, which aims to evaluate the impact of a smartphone application, the 'DrivingApp,' to increase the quantity and improve the quality of supervised practice driving. This longitudinal intervention study of teenage drivers and a parent/guardian spans the final 6 months of the learner licence and the first year of independent driving. Participants will be assigned to experimental or control groups using block allocation. Parent-teenage dyads assigned to the intervention arm will receive information about their practice driving via a smartphone application, including miles driven and total drive time. Baseline and monthly surveys will be administered to both experimental and control participants to measure the outcome measures during the learner stage: (1) practice driving amount, (2) consistency and (3) variety. Outcomes during independent driving are (1) self-reported number of attempts at the driving test and (2) number of crashes during the first year of independent driving. Improving the quality of teenagers' supervised practice driving is an unmet research need. This study will contribute to the evidence about what can be done during the learner period of GDL to maximise teenage drivers' safety during the first years of independent driving, when crash risk is highest.


Psychosocial determinants of HIV testing across stages of change in Spanish population: a cross-sectional national survey.
The goal of this research is to study the psychosocial determinants of HIV-testing as a function of the decision or change stage concerning this health behavior. The determinants considered in the major ongoing health models and the stages contemplated in the Precaution Adoption Process Model are analysed. A cross-sectional survey was administered to 1,554 people over 16 years of age living in Spain by a computer-assisted telephone interview (CATI). The sample design was randomised, with quotas of sex and age. The survey measured various psychosocial determinants of health behaviors considered in the main cognitive theories, the interviewees' stage of change concerning HIV-testing (lack of awareness, decision not to act, decision to act, action, maintenance, and abandonment), and the signal for the action of getting tested or the perceived barriers to being tested. Approximately two thirds of the population had not ever had the HIV test. The predominant stage was lack of awareness. The most frequently perceived barriers to testing were related to the health system and to the stigma. We also found that the psychosocial determinants studied differed depending on the respondents' stage of change. Perception of risk, perceived self-efficacy, proximity to people who had been tested, perceived benefits of knowing the diagnosis, and a positive instrumental and emotional attitude were positively associated with the decision and maintenance of testing behavior. However, unrealistic underestimation of the risk of HIV infection, stereotypes about the infection, and the perceived severity of HIV were associated with the decision not to be tested. There are various sociocognitive and motivational profiles depending on people's decision stage concerning HIV-testing. Knowing this profile may allow us to design interventions to influence the psychosocial determinants that characterise each stage of change.


Prevalence and identification of fungal DNA in the small intestine of healthy dogs and dogs with chronic enteropathies.
Limited information is available about the prevalence and phylogenetic classification of fungal organisms in the gastrointestinal tract of dogs. Also, the impact of fungal organisms on gastrointestinal health and disease is not well understood. The aim of this study was to evaluate the prevalence of fungal DNA in the small intestine of healthy dogs and dogs with chronic enteropathies. Small intestinal content was analyzed from 64 healthy and 71 diseased dogs from five different geographic locations in Europe and the USA. Fungal DNA was amplified with panfungal primers targeting the internal transcriber spacer (ITS) region. PCR amplicons were subjected to phylogenetic analysis. Fungal DNA was detected in 60.9% of healthy dogs and in 76.1% of dogs with chronic enteropathies. This prevalence was not significantly different between the two groups (p=0.065). Fungal DNA was significantly more prevalent in mucosal brush samples (82.8%) than in luminal samples (42.9%; p=0.002). Sequencing results revealed a total of 51 different phylotypes. All sequences belonged to two phyla and were classified as either Ascomycota (32 phylotypes) or Basidiomycota (19 phylotypes). Three major classes were identified: Saccharomycetes, Dothideomycetes, and Hymenomycetes. The most commonly observed sequences were classified as Pichia spp., Cryptococcus spp., Candida spp., and Trichosporon spp. Species believed to be clinically more important were more commonly observed in diseased dogs. These results indicate a high prevalence and diversity of fungal DNA in the small intestine of both healthy dogs and dogs with chronic enteropathies. The canine gastrointestinal tract of diseased dogs may harbor opportunistic fungal pathogens.


Exploring Dried Blood Spot Cortisol Concentrations as an Alternative for Monitoring Pediatric Adrenal Insufficiency Patients: A Model-Based Analysis.
Congenital adrenal hyperplasia (CAH) is the most common form of adrenal insufficiency in childhood; it requires cortisol replacement therapy with hydrocortisone (HC, synthetic cortisol) from birth and therapy monitoring for successful treatment. In children, the less invasive dried blood spot (DBS) sampling with whole blood including red blood cells (RBCs) provides an advantageous alternative to plasma sampling. Potential differences in binding/association processes between plasma and DBS however need to be considered to correctly interpret DBS measurements for therapy monitoring. While capillary DBS samples would be used in clinical practice, venous cortisol DBS samples from children with adrenal insufficiency were analyzed due to data availability and to directly compare and thus understand potential differences between venous DBS and plasma. A previously published HC plasma pharmacokinetic (PK) model was extended by leveraging these DBS concentrations. In addition to previously characterized binding of cortisol to albumin (linear process) and corticosteroid-binding globulin (CBG; saturable process), DBS data enabled the characterization of a linear cortisol association with RBCs, and thereby providing a quantitative link between DBS and plasma cortisol concentrations. The ratio between the observed cortisol plasma and DBS concentrations varies highly from 2 to 8. Deterministic simulations of the different cortisol binding/association fractions demonstrated that with higher blood cortisol concentrations, saturation of cortisol binding to CBG was observed, leading to an increase in all other cortisol binding fractions. In conclusion, a mathematical PK model was developed which links DBS measurements to plasma exposure and thus allows for quantitative interpretation of measurements of DBS samples.