Religious Leaders' Knowledge of Family Planning and Modern Contraceptive Use and Their Involvement in Family Planning Programmes in Burkina Faso: A Qualitative Study in Dori in the Sahel Region.
It is necessary to understand religious leaders' perceptions of modern contraceptive use and their role in influencing fertility behaviour for the successful adoption of family planning, especially in societies where the religious leaders' opinions can have a significant influence on individuals' reproductive decisions. This study, therefore, aimed to assess religious leaders' knowledge of family planning and their involvement in family planning programmes in the Sahel region of Burkina Faso. This is a qualitative study comprising in-depth individual interviews with twenty-one religious' leaders in the town of Dori in the Sahel region of Burkina Faso. An interview guide was used for data collection. This interview guide was developed based on the central themes and sub-themes determined for the research, namely, the religious leaders' knowledge of modern contraception, the inclusion of information on modern contraception during religious activities and the relationship between religious leaders and reproductive health services. All interviews were recorded and transcribed in French using Microsoft Word. The verbatims were then coded for content analysis. The analysis method chosen was that of thematic analysis. The results of the study showed that religious leaders had good knowledge about family planning including modern contraceptive methods and fertility regulation through birth spacing. Regarding their involvement in family planning programme, religious leaders said they were not involved enough. However, the results of the study showed that leaders are reluctant to promote the use of FP methods. Although religious leaders are knowledgeable about family planning, they are still reluctant to promote the use of modern contraceptive methods in their communities. To do so, efforts are needed to sensitise and mobilise them in family planning programmes. The cooperation of local religious leaders will help promote family planning and improve Burkina Faso's performance on the Sustainable Development Goals through the achievement of the demographic dividend in the country.


Exercise, self-efficacy, and exercise behavior in hypertensive older African-Americans.
Older African-Americans have very high rates of hypertension, and they experience one of the highest hypertension-related death rates of all American ethnic groups. They are also one of the most physically inactive groups, which contributes to their hypertension-related health problems. Interventions are needed to assist them in increasing their exercise activities and thereby gaining better hypertension control. This study evaluated the relationship between physical activity level and exercise self-efficacy for this group. Findings support a strong association and suggest that interventions that address exercise self-efficacy would be helpful for increasing the level of exercise in older African-Americans. Suggested nursing interventions, based on theory, are proposed.


[Fibroblast adhesion to glass and the dynamics of pH change in the medium in the pericellular space].
A study was made of dynamics of pH changes in the pericellular space of the Chinese hamster fibroblasts after the completion of cell sedimentation in three media. With the first medium, the cells were spread over the glass, with the second one they were attached to the glass without spreading and with the third medium the cells were not attached to the glass at all. The pH value of the medium surrounding the cells decreased, mainly, within the first 6 hours after sedimentation was completed, this depended on the cell population density on the glass surface. The outlook of this dependence was different for the three media. Based on the analysis of the results obtained it is concluded that the attachment of cells to glass may lead to the increased efflux of acid metabolic products from the cell.


Approximate inclusion of four-mode couplings in vibrational coupled-cluster theory.
The vibrational coupled cluster (VCC) equations are analyzed in terms of vibrational Mo̸ller-Plesset perturbation theory aiming specifically at the importance of four-mode couplings. Based on this analysis, new VCC methods are derived for the calculation of anharmonic vibrational energies and vibrational spectra using vibrational coupled cluster response theory. It is shown how the effect of four-mode coupling and excitations can be efficiently and accurately described using approximations for their inclusion. Two closely related approaches are suggested. The computational scaling of the so-called VCC[3pt4F] method is not higher than the fifth power in the number of vibrational degrees of freedom when up to four-mode coupling terms are present in the Hamiltonian and only fourth order when only up to three-mode couplings are present. With a further approximation, one obtains the VCC[3pt4] model which is shown to scale with at most the fourth power in the number of vibrational degrees of freedom for Hamiltonians with both three- and four-mode coupling levels, while sharing the most important characteristics with VCC[3pt4F]. Sample calculations reported for selected tetra-atomic molecules as well as the larger dioxirane and ethylene oxide molecules support that the new models are accurate and useful.


Effect of WIN 64338, a B2 bradykinin receptor antagonist on guinea-pig tracheal smooth muscle cells in culture.
This study investigated the effect of the non-peptidic B2 bradykinin (BK) receptor antagonist WIN 64338 on BK binding and BK-induced inositol phosphate formation on guinea-pig tracheal smooth muscle cells in culture. The presence of specific and saturable binding sites for BK was demonstrated using [3H]BK. Scatchard analysis indicates a single population of binding sites for [3H]BK with a maximal density (Bmax) of 245.4 +/- 71 fmol/mg of protein and an equilibrium dissociation constant (Kd) of 87.7 +/- 0.12 pM. The order of potency of] B2 BK receptor ligands was Hoe 140 = NPC 17731 > BK > WIN 64338 > D- Arg0[Hyp3, D-Phe7]-BK > > des-Arg9-BK, while B1 BK receptor antagonist, des-Arg9-[Leu8]-BK, was without effect on [3H]BK binding. These results demonstrate the presence of B2 Bk receptors on cultured tracheal smooth muscle cells. The cells were stimulated by BK, and inositol phosphate formation was determined by anion exchange chromatography. The stimulating effect of BK on inositol phosphate formation was concentration dependent (1 nM to 10 microM). The B1 BK agonist des-Arg9-BK did not induce inositol phosphate formation. The order of potency of B2 antagonists to inhibit BK-induced inositol phosphate formation was Hoe 140 = NPC 17731 > WIN 64338 > D-Arg0[Hyp3, D-Phe7]-BK. This study demonstrates that WIN 64338 is able to displace [3H]BK binding and to inhibit B2-BK-induced inositol phosphate formation on cultured guinea-pig tracheal smooth muscle cells.


Patients with acute heart failure discharged from the emergency department and classified as low risk by the MEESSI score (multiple risk estimate based on the Spanish emergency department scale): prevalence of adverse events and predictability.
To determine the rate of adverse events in patients with acute heart failure (AHF) who were discharged from the emergency department (ED) after classification as low risk according to MEESSI score (multiple risk estimate based on the Spanish ED scale), to analyze the ability of the score to predict events, and to explore variables associated with adverse events. Patients in the EAHFE registry (Epidemiology of Acute Heart Failure in EDs) were stratified according to risk indicated by MEESSI score in order to identify those considered at low risk on discharge. All-cause 30-day mortality and revisits related to AHF within 7 days and 30 days were recorded. The area under the receiver operating characteristic curve (AUC) was calculated for the MEESSI score's ability to predict these events. Associations between 42 variables and 7-day and 30-day revisits to the ED were analyzed by multivariable logistic regression. A total of 1028 patients were included. The 30-day mortality rate was 1.6% (95% CI, 0.9%-2.5%). The 7-day and 30-day revisit rates were 8.0% (95% CI, 6.4%-9.8%) and 24.7% (95% CI, 22.1%-25.7%), respectively. The AUCs for MEESSI score discrimination between patients with and without these outcomes were as follows: 30-day mortality, 0.69 (95% CI, 0.58-0.80); 7-day revisiting, 0.56 (95% CI, 0.49-0.63); and 30-day revisiting, 0.54 (95% CI, 0.50-0.59). Variables associated with 7-day revisits were long-term diuretic treatment (odds ratio [OR], 2.45; 95% CI, 1.01-5.98), hemoglobin concentration less than 110 g/L (OR, 1.68; 95% CI, 1.02-2.75), and intravenous diuretic treatment in the ED (OR, 0.53; 95% CI, 0.31-0.90). Variables associated with 30-day revisits were peripheral artery disease (OR, 1.74; 95% CI, 1.01-3.00), prior history of an AHF episode (OR, 1.42; 95% CI, 1.02-1.98), long-term mineralocorticoid receptor antagonist treatment (OR, 1.71; 95% CI, 1.09-2.67), Barthel index less than 90 points in the ED (OR, 1.48; 95% CI, 1.07-2.06), and intravenous diuretic treatment in the ED (OR, 0.58; 95% CI, 0.40-0.84). Patients with AHF who are at low risk for adverse events on discharge from our EDs have event rates that are near internationally recommended targets. The MEESSI score, which was designed to predict 30-day mortality, is a poor predictor of 7-day or 30-day revisiting in these low-risk patients. We identified other factors related to these events.


[Myelolipoma of the adrenal gland: report of a case].
A 50-year-old male was admitted to our municipal hospital because of his right suprarenal tumor which had been found by ultrasonography by chance at National Toneyama Hospital. His physical examination was normal except for obesity. Hematological examination and blood chemistry were normal and no endocrine disorder was found. Excretory urogram revealed neither deformity of the collecting system nor displacement of the right kidney. Computed tomography visualized sharp marginated in homogeneous structured mass of different densities within the negative range. Angiography revealed hypovascularity of the tumor. Right adrenalectomy was performed and the specimen weighed 72 g. Histopathologically is consisted of adult fat tissue and hematopoietic tissue. In addition to our case, 17 cases of surgically removed myelolipoma reported in the Japanese literature are reviewed.


Bleaching of photodarkening in Tm-doped silica fiber with deuterium loading.
We demonstrate the rapid photodarkening (PD) phenomenon in Tm-doped fiber (TDF) core pumped by a laser at 1080 nm and the bleaching effect of deuterium (${{\rm D}_2}$D2) on PD TDF. By ${{\rm D}_2}$D2 loading for seven days, the PD-induced excess loss (PIEL) in the visible (VIS) and near-infrared (NIR) region have been largely eliminated, and no degradation was observed within 30 days. PD resistance of the ${{\rm D}_2}$D2 pretreated TDF has been investigated as well. The formation of color centers based on defects and precursors in the silica matrix and the mechanism of ${{\rm D}_2}$D2 bleaching are discussed.


[Fibroepithelial polyps of renal pelvis and ureter].
To analyze the results of surgical treatment of patients with long ureteral fibroepithelial polyps (FEP). From 2005 to 2014 three patients (1 man and 2 women) with large FEP were observed in our hospital. In 2 patients the base of the polyp was located in the proximal ureter and in 1 patient in the middle calyx of the single kidney. The fibroepithelial polyps were long and extended down to the lower third of the ureter (2) or protruded into the bladder (1). Endoscopic resection of the polyp was made in 1patient, resection of parenchyma in the middle calyx along with the base of FEP in 1 patient with the single kidney, and another patient underwent laparoscopic nephrectomy due to the absence of kidney function. Endoscopic resection was successful; the operation lasted 45 minutes without complications. In the patients with a single right kidney operative time was 3.5 hours; during the operation, she received a blood transfusion. In the postoperative period, she underwent two hemodialysis sessions due to acute renal failure. Subsequently, her kidney function was restored. No FEP recurrences occurred in cases of organ sparing operations during follow-up. The postoperative period of the third patient submitted to laparoscopic nephrectomy was uneventful, creatinine levels remained in the normal range. For long, large ureteral FEPs with a broad base the choice of surgical option depends on possibility of tumor visualization and functional state of the kidney.


The severity of pneumonia and its association with socio-demographic factors among children under five years old in Wasit governorate hospitals, Iraq.
Pneumonia is the leading infectious cause of death among children under five globally. The study aims to determine socio-demographic factors associated with the severity of pneumonia among children under five in Wasit Governorate. A cross-sectional study and convenience sampling (non-probability) were conducted among 477 children admitted to Wasit governorate hospitals. This sample was distributed throughout five hospitals selected using convenience sampling techniques, including AL-Zahra Hospital, AL-Numaniyah General Hospital, AL-Karama Teaching Hospital, Martyr Fairouz General Hospital, and AL-Kut Gynecology Hospital. It was conducted from October 1st, 2022, to May 1st, 2023. Through questionnaires, data were collected and analyzed through descriptive and inferential statistics. The results showed that the participants' distribution according to pneumonia severity was such that the majority of children (81%) included in the study suffered from pneumonia. 14% of children suffered from very severe pneumonia, and 5% suffered from severe pneumonia. The children at risk of developing pneumonia were within the age group of 1-11 months (55.6%), were male (60.6%), and resided in urban areas (63.7%). Both the mother and the father had completed their primary education (50.9% and 47.4%, respectively), and 99.4% and 97.5% of the mothers were married and housewives. More than half of the fathers, 59.5%, were self-employed, and 25.6% suffered from house overcrowding. In addition, 65% had low socioeconomic status. There was a significant relationship between pneumonia severity and the father's occupation and socioeconomic status. This study concludes that pneumonia was the most common diagnosis at admission. Among the risk factors studied, low socioeconomic status and the father's occupation were significant risk factors for pneumonia in children.


A case of carpal tunnel syndrome due to dialysis-related amyloidosis in a patient undergoing long-term hemodialysis.
Carpal tunnel syndrome (CTS) is characterized by burning pain, numbness and tingling sensation in the thumb, index and middle fingers and the lateral half of the palm and progressive atrophy of the thenar muscles by compression of the median nerve within the carpal tunnel due to a variety of etiologic factors. Surgical intervention usually successfully relieves symptoms of CTS. Recently CTS has been regarded as one of the major clinical manifestations of dialysis-related amyloidosis due to beta 2-microglobulin deposition and recognized with increasing frequency in patients undergoing long-term hemodialysis. We report a case of carpal tunnel syndrome due to dialysis-related amyloidosis in patients undergoing long-term hemodialysis, confirmed by electromyography and biopsy in transverse carpal ligament and median nerve.


Comparison of the hemodynamic effects of sevoflurane anesthesia induction and maintenance vs TIVA in CABG surgery.
To compare the hemodynamic effects of sevoflurane when used for induction and maintenance of anesthesia with a total intravenous technique in patients with known coronary artery disease (CAD). Thirty patients undergoing elective coronary artery bypass graft (CABG) were randomly allocated to receive either sevoflurane (S group, n = 15) at a minimal concentration of 4% in oxygen for induction and at 0.5-2 MAC end-tidal concentration for maintenance, or a total intravenous technique (T group, n = 15) consisting of midazolam for induction and propofol for maintenance. In both groups, anesthesia was supplemented with sufentanil and muscle relaxation with cis-atracurium. Hemodynamic measurements included systemic and pulmonary pressures, heart rate, mixed venous oxygen saturation and cardiac output at the following times: pre-induction, 7 and 25 min post-induction, chest closure, one hour after surgery and pre and post tracheal extubation. More patients in the S group (8/15) presented bradycardia in the induction period (T:2/15) (P = 0.05). During maintenance of anesthesia, treatment of hypertension was more frequent in the T group (12/15) than in the S group (6/15) (P = 0.025). All other parameters were comparable. Induction of anesthesia in patients with CAD, VCRII with sevoflurane supplemented by sufentanil provided hemodynamic responses comparable with those of TIVA although bradycardia was observed more often with sevoflurane. Intraoperative control of systemic blood pressure was achieved with fewer interventions with a sevoflurane/sufentanil maintenance than with a propofol/sufentanil technique in CABG surgery.


Marek's disease virus gene clones encoding virus-specific phosphorylated polypeptides and serological characterization of fusion proteins.
Marek's disease virus (MDV) gene clones, RA2 and GA8, constructed in E. coli bacteriophage lambda-gt11 (gt11) were identified by a monoclonal antibody (MAb), H19.47, against a putative transformation-related viral antigen consisting of a complex of three phosphorylated polypeptides, pp41, pp38, and pp24. Both recombinants have a MDV-DNA insert of about 0.5 kb and are mapped to the region of BamHI-H or EcoRI-X fragments of the MDV genome by Southern blot hybridization. Immunoblot and immunoprecipitation with H19.47 identified a recombinant beta-galactosidase-MDV 140-kD fusion protein for RA2 and a 127-kD fusion protein for GA8. Immunoprecipitation of 35S-methionine-labeled, MDV-infected chicken embryo fibroblasts (CEF) with antisera against RA2 and GA8 fusion proteins recognized five polypeptides, of which three (p41, p38, and p24) are specified by H19.47 and the remaining two, p135 and p20, have not been previously identified. Immunoprecipitation of 32P-phosphate-labeled or 3H-glucosamine-labeled, GA-MDV-infected CEF with the antiserum against RA2 fusion protein identified a phosphorylated polypeptide of 38 kD and two glycoproteins of 60 and 49 kD, respectively. The antisera against recombinant fusion proteins thus revealed the existence of epitopes common to the phosphorylated polypeptides and other MDV-specific polypeptides. Sera from chickens or mice hyperimmunized with the purified fusion proteins reacted with serotype 1, MDV-infected CEF in the fluorescent antibody (FA) test to significant titers. These immune sera did not react with either serotype II or III, indicating the serotype specificity of the phosphorylated polypeptides.


Effects of sympathetic nerve stimulation on long posterior ciliary artery blood flow in cats.
A new technique using ultrasonic flowmetry was developed in order to directly measure blood flow in the long posterior ciliary artery (LPCA) of anesthetized cats. Basal LPCA blood flow averaged about 0.6 ml/min and was stable over the experimental period. Electrical stimulation of the cervical preganglionic cervical sympathetic nerve produced frequency-dependent anterior segment ocular vasoconstrictor responses. Ipsilateral nictitating membrane contractions were simultaneously measured as a well-established index of neural sympathetic activation. LPCA frequency-response relationships were shifted to the right in comparison with those for the nictitating membrane. When elicited at two min intervals, submaximal evoked responses of both systems were stable for more than 90 min. Ocular vasoconstrictor and nictitating membrane responses were blocked in a dose-dependent fashion by intravenous treatment with the non-selective a-adrenoceptor antagonist, phentolamine (0.3-3.0 mg/kg), as well as with the selective alpha1-adrenoceptor antagonist, prazosin (3-30 microg/kg). In contrast, neither evoked response was further antagonized by subsequent administration of the alpha2-adrenoceptor antagonist, yohimbine (500 microg/kg). These results demonstrate the usefulness of ultrasonic flowmetry to study mechanisms controlling ocular anterior segment circulation and suggest that, as previously established for the nictitating membrane and anterior choroid, adrenergic neurogenic vasoconstriction in tissues perfused by the LPCA is mediated predominantly by alpha1-adrenoceptors.


The critical spot eraser-a method to interactively control the correction of local hot and cold spots in IMRT planning.
Common problems in inverse radiotherapy planning are localized dose insufficiencies like hot spots in organs at risk or cold spots inside targets. These are hard to correct since the optimization is based on global evaluations like maximum/minimum doses, equivalent uniform doses or dose-volume constraints for whole structures. In this work, we present a new approach to locally correct the dose of any given treatment plan. Once a treatment plan has been found that is acceptable in general but requires local corrections, these areas are marked by the planner. Then the system generates new plans that fulfil the local dose goals. Consequently, it is possible to interactively explore all plans between the locally corrected plans and the original treatment plan, allowing one to exactly adjust the degree of local correction and how the plan changes overall. Both the amount (in Gy) and the size of the local dose change can be navigated. The method is introduced formally as a new mathematical optimization setting, and is evaluated using a clinical example of a meningioma at the base of the skull. It was possible to eliminate a hot spot outside the target volume while controlling the dose changes to all other parts of the treatment plan. The proposed method has the potential to become the final standard step of inverse treatment planning.


Specific DNA duplex formation at an artificial lipid bilayer: fluorescence microscopy after Sybr Green I staining.
The article describes the immobilization of different probe oligonucleotides (4, 7, 10) carrying each a racemic mixture of 2,3-bis(hexadecyloxy)propan-1-ol (1a) at the 5'-terminus on a stable artificial lipid bilayer composed of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine (POPE) and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC). The bilayer separates two compartments (cis/trans channel) of an optical transparent microfluidic sample carrier with perfusion capabilities. Injection of unlabeled target DNA sequences (6, 8, or 9), differing in sequence and length, leads in the case of complementarity to the formation of stable DNA duplexes at the bilayer surface. This could be verified by Sybr Green I double strand staining, followed by incubation periods and thorough perfusions, and was visualized by single molecule fluorescence spectroscopy and microscopy. The different bilayer-immobilized complexes consisting of various DNA duplexes and the fluorescent dye were studied with respect to the kinetics of their formation as well as to their stability against perfusion.


Effect of levamisole as an immunomodulating agent in trophoblastic lesions.
Both cell mediated immunity and humoral immunity was assessed in 16 patients of hydatidiform mole and 6 patients of choriocarcinoma. Fifty percent patients of choriocarcinoma and 11 patients of vesicular mole were given levamisole (LVM) trial and were followed for 2 months. Absolute lymphocyte count (ALC) was significantly increased in vesicular mole after levamisole treatment but in choriocarcinoma no effect was obtained. Marked improvement of T cell rosette count was also seen in LVM treated patient of both vesicular mole (p < 0.001) and choriocarcinoma. Cutaneous DTH response to 2:4 DNCB in vesicular mole was also increased after LVM. Before treatment only 31.25% patients had strong cutaneous response but after treatment 53.35% patients had strong response, while cases of choriocarcinoma were unaffected. LVM also raised all the serum immunoglobulins (IgG, IgM, IgA) in both vesicular mole and choriocarcinoma. Hence, levamisole therapy was found to have a beneficial effect on both cellular and humoral immunity in the lesions of trophoblasts.


Validity and Reliability of the Violence Risk Scale-Youth Sexual Offense Version.
The present study examined the validity and reliability of a youth sexual offense risk assessment and treatment planning tool, the Violence Risk Scale-Youth Sexual Offense Version (VRS-YSO), on a sample of 102 court-adjudicated youth referred to assessment and/or treatment outpatient services followed up an average of 11.7 years in the community. VRS-YSO scores demonstrated "good" to "excellent" interrater reliability (intraclass correlation coefficients [ICCs] = .64-.83). Exploratory factor analysis (EFA) of the static and dynamic items identified three latent dimensions consistent with the extant risk literature labeled Sexual Deviance, Antisocial Tendencies, and Family Concerns. VRS-YSO scores showed strong patterns of convergence with scores from the Estimate of Risk for Adolescent Sexual Offense Recidivism (ERASOR), Juvenile Sex Offender Assessment Protocol-II (J-SOAP-II), and the Juvenile Sexual Offense Recidivism Risk Assessment Tool-II (J-SORRAT-II). VRS-YSO scores, in turn, demonstrated moderate to high predictive accuracy for sexual, violent (sexual and nonsexual), and general recidivism (significant areas under curve [AUCs] = .67-.88). Examination of pre-posttreatment change data on the subset of youth who attended treatment services found VRS-YSO change scores to be significantly associated with reductions in general recidivism, but not other recidivism outcomes. Future research and clinical applications of the VRS-YSO in youth sexual offense assessment and treatment planning are discussed.


Serum neuron-specific enolase predicting neurological outcomes post-cardiac arrest: a review of the literature.
Coronary artery disease is a major problem in the United States, affecting 785 000 individuals, with the most serious event being a cardiopulmonary arrest. Families of post-cardiac arrest patients are left with difficult decisions to be made. This article is a comprehensive literature review examining the current research available to health care professionals about the biomarker serum neuron-specific enolase (NSE) and its use in predicting neurological outcomes in comatose post-cardiac arrest patients. Using the bibliographic databases CINAHL, Plus, EBSCOhost, MEDLINE, PubMed, Google Scholar, H. W. Wilson, Cochrane, and NEXUS, from the period 2003 to 2013, revealed there is minimal research or literature on NSE predicting neurological outcomes post-cardiac arrest. Research on this particular biomarker is relatively new, and more research is necessary to establish an adequate amount of support. At this time, an exact NSE cutoff value or its exact ability to help predict neurological outcomes is unable to be established, and further research is necessary. This literature review should provide a basic understanding of NSE and its ability to help predict neurological outcomes of post-cardiac arrest patients earlier. The research provides evidence that NSE should be considered in determining outcomes. However, more research is necessary before nursing practice is changed and implemented into patient care.


Mechanisms underlying excitatory effects of group I metabotropic glutamate receptors via inhibition of 2P domain K+ channels.
Group I metabotropic glutamate receptors (mGluRs) are implicated in diverse processes such as learning, memory, epilepsy, pain and neuronal death. By inhibiting background K(+) channels, group I mGluRs mediate slow and long-lasting excitation. The main neuronal representatives of this K(+) channel family (K(2P) or KCNK) are TASK and TREK. Here, we show that in cerebellar granule cells and in heterologous expression systems, activation of group I mGluRs inhibits TASK and TREK channels. D-myo-inositol-1,4,5-triphosphate and phosphatidyl-4,5-inositol-biphosphate depletion are involved in TASK channel inhibition, whereas diacylglycerols and phosphatidic acids directly inhibit TREK channels. Mechanisms described here with group I mGluRs will also probably stand for many other receptors of hormones and neurotransmitters.


Immunotherapy for metastatic prostate cancer.
Chemotherapy with docetaxel is the standard treatment for men with metastatic prostate cancer, and results in statistically significant improvements in survival, as well as in quality of life. However, the response rate to single-agent docetaxel is approximately 40% to 45%, emphasizing a need for alternative approaches. More significantly, with the onset of early, PSA-based detection of prostate cancer and closer follow-up, many men present with metastatic disease that remains asymptomatic. For such patients, the side effects of chemotherapy would compromise their current performance status and, thus, a nontoxic, early treatment option that could improve overall survival would be highly desirable. Immunotherapy represents one such approach; a number of clinical trials have suggested a survival benefit for immunotherapy in metastatic prostate cancer and confirmed that these agents are generally well-tolerated. As is the case for chemotherapy, it is doubtful that maximal survival benefit will be achieved with single-agent immunotherapy; experimental treatments in which mechanistically distinct immunotherapy approaches are combined, as well as approaches in which immunotherapy is combined with chemotherapy or hormonal therapy are currently under investigation. This review will discuss the mechanisms of action of several immunotherapy approaches for metastatic prostate cancer, focusing on active immunotherapy as opposed to administration of anti-tumor antibodies. The relative advantages and disadvantages of current approaches will be noted, and ongoing clinical trials will be highlighted.


Induced pluripotent stem cells-derived neurons from patients with Friedreich ataxia exhibit differential sensitivity to resveratrol and nicotinamide.
Translation of pharmacological results from in vitro cell testing to clinical trials is challenging. One of the causes that may underlie these discrepant results is the lack of the phenotypic or species-specific relevance of the tested cells; today, this lack of relevance may be reduced by relying on cells differentiated from human pluripotent stem cells. To analyse the benefits provided by this approach, we chose to focus on Friedreich ataxia, a neurodegenerative condition for which the recent clinical testing of two compounds was not successful. These compounds, namely, resveratrol and nicotinamide, were selected because they had been shown to stimulate the expression of frataxin in fibroblasts and lymphoblastoid cells. Our results indicated that these compounds failed to do so in iPSC-derived neurons generated from two patients with Friedreich ataxia. By comparing the effects of both molecules on different cell types that may be considered to be non-relevant for the disease, such as fibroblasts, or more relevant to the disease, such as neurons differentiated from iPSCs, a differential response was observed; this response suggests the importance of developing more predictive in vitro systems for drug discovery. Our results demonstrate the value of utilizing human iPSCs early in drug discovery to improve translational predictability.


A review of common methods to convert morphine to methadone.
When dosed appropriately on carefully chosen patients, methadone can be a very safe and effective choice in managing chronic pain. Many authors have discussed important issues surrounding patient selection, drug interactions, screening for QTc prolongation and monitoring. This article will focus on the dosing dilemma that exists after the patient is deemed an appropriate candidate for methadone and a conversion is necessary from another opioid. Despite many publications dedicated to addressing this challenging topic, there is no consensus on the most appropriate method for converting an opioid regimen to methadone. Given the lack of concrete guidance, clinicians in a community setting are likely to be faced with an increased challenge if there are no available pain specialists to provide clinical support. Common methods for converting morphine to methadone will be reviewed and two clinical patient scenarios used to illustrate the outcomes of applying the methods.


Memory of surface patterns in mixed polymer brushes: simulation and experiment.
The correlation between the morphology of mixed polymer brushes and fluctuations of the grafting points is investigated by single-chain-in-mean-field simulations and experiments. The local topography of two types of mixed polystyrene-polymethylmethacrylate (PS-PMMA) brushes that differ in their modes of attachment has been studied during repeated microphase separation into laterally structured and homogeneous morphologies upon changing solvents. In the first type of brush (conventional), each of the surface-attached initiator groups starts the growth of either a PS or a PMMA chain in a random fashion. In the second case (Y-shaped mixed brushes), two chains of different types are attached to the same anchor group on the substrate. Whereas in the first case statistical fluctuations of the chemical composition occur on a local scale, such composition fluctuations are strongly suppressed in the latter case. The microphase-separated morphology is similar in both cases, but Y-shaped brushes exhibit a significantly weaker domain memory than do conventional PS-PMMA mixed brushes. The results of the experiment are compared with simulations, and a simple phenomenological argument and qualitative agreement are found. The observations demonstrate that small fluctuations in the grafting points are amplified by the microphase separation and nucleate the location of the domains in the mixed brush.


High power multi-color OPCPA source with simultaneous femtosecond deep-UV to mid-IR outputs.
Many experimental investigations demand synchronized pulses at various wavelengths, ideally with very short pulse duration and high repetition rate. Here we describe a femtosecond multi-color optical parametric chirped pulse amplifier (OPCPA) with simultaneous outputs from the deep-UV to the mid-IR with optical synchronization. The high repetition rate of 160 kHz is well suited to compensate for low interaction probability or low cross section in strong-field interactions. Our source features high peak powers in the tens to hundreds of MW regime with pulse durations below 110 fs, which is ideal for pump-probe experiments of nonlinear and strong-field physics. We demonstrate its utility by strong-field ionization experiments of xenon in the near- to mid-IR.


Relationship between the neonatal white blood cell count and histologic chorioamnionitis in preterm newborns.
The aim was to examine the relationship between neonatal white blood cell (WBC) count and the diagnosis of histologic chorioamnionitis (HCA). We measured WBC, a widely used marker of inflammation, to evaluate whether the values at birth were associated with HCA. NICU, Department of Pediatrics of Padua University, Padua, Italy. WBC count was evaluated in 71 preterm neonates (<32 weeks of gestation) with HCA and in a control group without HCA on day 1, 3, and 6 after delivery. Logistic regression analysis and diagnostic accuracy analysis were used to assess the association between WBC counts and HCA. WBC levels were significantly higher in infants with HCA than in those without HCA (Median IQR, WBC (x10(9)/l): day 1, 13.2 (6.2-21.8) vs 8.1 (6-11.4), p < 0.001; day 3, 17.4 (11.4-26.9) vs 6.3 (5.2-8.3), p < 0.001; day 6, 18.4 (11.1-31) vs 6.5 (4.4-9), p < 0.0001). The neonatal WBC count on the third day of life was the most sensitive parameter associated with HCA (sensitivity: 0.80; specificity: 0.88). The cut-off value based on the ROC curve was 10 (x10(9)/l). WBC count in the third day of life is strongly associated with HCA.


Effect of Jian-Pi-Zhi-Dong Decoction on the Amino Acid Neurotransmitters in a Rat Model of Tourette Syndrome and Comorbid Anxiety Disorder.
Amino acid neurotransmitters have been shown to correlate with Tourette syndrome (TS) and its comorbidities. In this study, we investigated the effects of Jian-Pi-Zhi-Dong Decoction (JPZDD), a formula containing 10 different Chinese medical herbs, on amino acid neurotransmitters in rats. We established a rat model of Tourette syndrome and comorbid anxiety with an iminodipropionitrile injection plus uncertain empty water bottle stimulation for 3 weeks. Then the rats were randomly divided into four groups: control group and model group were gavaged with saline, while the remaining two treatment groups were gavaged with fluoxetine hydrochloride or JPZDD for four consecutive weeks. We recorded the behaviors of the rats with TS and comorbid anxiety by stereotypy recording, open field test, and elevated plus maze. We observed mitochondrial changes with transmission electron microscopy. We measured the content of glutamate (GLU) and γ-aminobutyric acid (GABA) both in the serum and striatum and the expression of their receptors by Western blot and real-time polymerase chain reaction. The study revealed that JPZDD was effective in alleviating the behavioral symptoms of both tic and anxiety in the rat model groups. These results might be associated with the increase in GABA levels and decrease in GLU levels in the serum, as well as an increase in striatal GABA level by the activation of GABA receptors Type A (GABAAR). JPZDD treatment also reversed the mitochondrial dysfunction both in the striatum and cortex in affected animals.


Quantum Yield Measurements of Fluorophores in Lipid Bilayers Using a Plasmonic Nanocavity.
Precise knowledge of the quantum yield is important for many fluorescence-spectroscopic techniques, for example, for Förster resonance energy transfer. However, to measure it for emitters in a complex environment and at low concentrations is far from being trivial. Using a plasmonic nanocavity, we measure the absolute quantum yield value of lipid-conjugated dyes incorporated into a supported lipid bilayer. We show that for both hydrophobic and hydrophilic molecules the quantum yield of dyes inside the lipid bilayer strongly differs from its value in aqueous solution. This finding is of particular importance for all fluorescence-spectroscopic studies involving lipid bilayers, such as protein-protein or protein-lipid interactions in membranes or direct fluorescence-spectroscopic measurements of membrane physical properties.


Sudden Diplopia at a Pediatric Emergency Department: A Case of Gradenigo Syndrome in a Child.
Otitis media, facial pain in trigeminal region, and ipsilateral abducens nerve palsy clinically define Gradenigo syndrome, a rare but serious complication of suppurative middle ear infection. Radiological investigation is required to confirm petrous apex involvement and to exclude further consequences as sinus thrombosis, meningitis, and intracranial abscess. We report the case of an 8-year-old child referred to our emergency department for recurrent headache and sudden strabismus. Clinical evidence of suppurative otitis media raised the suspicion for Gradenigo syndrome, definitively confirmed at computed tomography and magnetic resonance imaging scans. Conservative treatment alone enabled complete clinical and radiological remission, without long-term sequelae. Despite being a rare condition, Gradenigo syndrome should be taken into account as potential differential diagnosis in children referred to emergency department for recurrent headache and strabismus. An accurate anamnesis to document recent ear infection is mandatory to orientate the diagnosis and focus radiological investigations. Early recognition and timely intervention may allow conservative management to succeed, avoiding the need for surgery and serious sequelae.


Clinical Advances in Treatment Strategies for Obsessive-compulsive Disorder in Adults.
In the present article, we provide a comprehensive review of the treatment strategies for obsessive-compulsive disorder (OCD), a common, chronic, and often debilitating disorder, characterized by overwhelming obsessions and compulsions. OCD typically starts in childhood or adolescence and persists throughout life, causing functional impairment across multiple domains. The article begins by describing the historical concepts of OCD from religious and guilt-based explanations to psychoanalytic perspectives, and then explores the changing understanding of OCD as a treatable condition. Recent advances include the development of evidence-based psychological treatments, such as exposure and response prevention, and pharmacological treatments, such as selective serotonin reuptake inhibitors. The latest version of the Diagnostic and Statistical Manual of Mental Disorders, and the International Classification of Diseases, has removed OCD from the anxiety disorder grouping and regrouped it into obsessive-compulsive and related disorders. We conclude by highlighting the current state of knowledge and development in the clinical management of OCD, including recommendations for first- and second-line treatments, alternative, or augmentative strategies for and novel agents under investigation for OCD. In future, the latest advances in neuroimaging, electrophysiology, digital technology, and data-driven analysis will help elucidate the pathophysiology of OCD and develop personalized intervention strategies.


Cardiac Structural or Functional Changes Associated with CHA2DS2-VASc Scores in Nonvalvular Atrial Fibrillation: A Cross-Sectional Study Using Echocardiography.
CHA2DS2-VASc is the most widely accepted scoring system for atrial fibrillation (AF) to assess stroke risk, although little has been revealed regarding the accompanying cardiac functional/structural changes. This echocardiography study was undertaken to understand the changes related to CHA2DS2-VASc scores. A total of 4,795 nonvalvular AF patients were enrolled for the cohort, from which 591 were excluded as they did not meet the inclusion criteria. Based on the CHA2DS2-VASc scores, the remaining 4,204 patients included in the study were divided into 4 groups: 0 to 1 (n = 991); 2 to 3 (n = 1,642); 4 to 6 (n = 1,407); 7 to 9 (n = 164). Increase in the left ventricular mass index and prevalence of left ventricular hypertrophy (LVH) were observed with elevating CHA2DS2-VASc scores (p < 0.05 for all). Diastolic parameters such as left atrial volume index (LAVI) and the ratio of early diastolic mitral inflow velocity to early diastolic velocity of the mitral annulus (E/E') also increased significantly in the higher CHA2DS2-VASc score groups (p < 0.001 for all), although two-way ANOVA analysis showed that such incremental diastolic impairment was independent of hypertension. LVH (hazard ratio [HR], 3.609; confidence interval [CI], 2.426-5.369; p < 0.001) and E/E' (HR, 1.087; CI, 1.054-1.121; p < 0.001) were independent risk factors for CHA2DS2-VASc scores 2 or higher. Our findings suggest that increasing CHA2DS2-VASc scores are associated with impaired diastolic function that may represent high left atrial pressure favoring thrombogenic propensity.


New exponential functions based on CT density to estimate the percentage of liver that is fat.
In fluorine-18 fludeoxyglucose positron emission tomography/CT, hepatic standardized uptake value (SUV) is reduced through "signal dilution" by hepatic fat. The maximum SUV (SUVmax) is less affected than the mean SUV (SUVmean), therefore SUVmax/SUVmean correlates with hepatic fat. The SUV can be corrected for signal dilution using an equation relating CT density (CTD) to %fat. The objective was to exploit the relationship between SUV indices and CTD to assess the validity of two previously published equations (one linear and one sigmoid) for estimating %fat from CTD and two new exponential equations. Study population comprised 465 patients having routine fluorine-18 fludeoxyglucose positron emission tomography/CT. The SUVmax, SUVmean and CTD were measured from a 3-cm-diameter region of interest over the liver. The exponential equations assumed that 100% fat corresponds to CTD of -50 or -100 HU. The proportion of liver occupied by fat (PF) was estimated from all four equations. Then fat-corrected SUVmean is SUVmean/(1 - PF). The ideal equation should give SUVmean approaching but not exceeding SUVmax and give fat-corrected SUVmean/SUVmax that shows no correlation with CTD. The linear equation failed at CTD values exceeding 55.8 HU because it gave negative PF values. Moreover, fat-corrected SUVmean/SUVmax still correlated with CTD. The sigmoid equation grossly overcorrected SUVmean at low CTD. The exponential equations abolished the correlation between fat-corrected SUVmean/SUVmax and CTD. The sigmoid equation is unsuitable for estimating %fat from CTD. The linear equation performed well, but the exponential equation assuming that 100% fat corresponds to -50 HU performed best. Advances in knowledge: Improved (exponential) equations to estimate hepatic fat from hepatic CTD.


[Renal pathology and ultrasounds (author's transl)].
In our present work we inttend to apply the ultrasounds to the field of child nephrology, by using the Vidoson 635 model. The advantages brought about by this new diagnostic method, which does not exclude others, lyes in its tridimensional vision, of easy handling, the fact of not requiring previous preparation of the patient and very little risk. In this work we present images of normal kidneys, renal agenesia, renal hypoplasia, hydronephrosis, hydrocalcinosis, cystic disease and nephroblastoma, emphasizing its use in the differential diagnosis of liquid and solid renal mass.


Effect of drying methods and blending ratios on dough rheological properties, physical and sensory properties of wheat-taro flour composite bread.
The study was conducted to evaluate the effect of taro drying methods and blending ratios on the physical quality attributes and sensory quality of wheat-taro bread and rheological properties of the blend dough. Farinographic properties like water absorption capacity, dough development time, dough stability time, time to break down, mixing tolerance index, and farinographic quality number were significantly (p < .05) affected by drying methods and blending ratio and their interaction. Increased taro flour (10-20 g) per 100 g of wheat flour resulted in an increased water absorption capacity (57.38%-58.23%) and mixing tolerance index (67.33-70.21 FU). The sensory analysis had revealed that as taro flour blending ratio increased the acceptability of blended breads were reduced. With respect to physical and sensory properties, the control bread had better acceptability than that of 10, 15, and 20 g taro flour-mixed bread. The study revealed that there is possibility of incorporating taro flour up to 15 g per 100 g of wheat flour with acceptable sensory attributes of the composite bread.


Silica-Supported Oligomeric Benzyl Phosphate (Si-OBP) and Triazole Phosphate (Si-OTP) Alkylating Reagents.
The syntheses of silica-supported oligomeric benzyl phosphates (Si-OBP(n)) and triazole phosphates (Si-OTP(n)) using ring-opening metathesis polymerization (ROMP) for use as efficient alkylating reagents is reported. Ease of synthesis and grafting onto the surface of norbornenyl-tagged (Nb-tagged) silica particles has been demonstrated for benzyl phosphate and triazole phosphate monomers. It is shown that these silica polymer hybrid reagents, Si-OBP(n) and Si-OTP(n), can be used to carry out alkylation reactions with an array of different nucleophiles to afford the corresponding benzylated and (triazolyl)methylated products in good yield and high purity.


[Recurrent infarct in a young female diabetic].
A case with repeated myocardial infarction is reported in a 23-year old female diabetic, established at necropsy and not diagnosed while still living. The infarctions had been painless and their electrocardiographic manifestation had not been definite. Generalized atherosclerosis with coronary sclerosis was pathologoanatomically established, with no obturating thrombus in the magistral vessels. Diffuse microangiopathic changes, in myocardium including, were present. The pathogenetic possibilities, associated with the characteristics of the clinical picture were discussed.


Enhancing Parent Consent for School-Based Primary and Reproductive Health Care Among Vulnerable Youth.
This quality-improvement initiative evaluated procedures to increase parental consent for students, 13 to 18+ years old, to access a school-based health clinic that provides primary and reproductive health care in a Hispanic immigrant neighborhood in the U.S. Southwest. Six consent-retrieval procedures were sequentially implemented. Procedures included school registration, competition, hand delivery, PTO meetings, self-consent, and mail. Age, grade, and number of completed consents were calculated and compared. The percentage of students with completed consents increased from 35% to 72%. Lessons learned include increasing the number of completed consents is difficult; however, it is important to increase students' access to health-care services.


A case of multiple neonatal haemangiomatosis with favourable outcome following steroid therapy.
A case of multiple neonatal haemangiomatosis is described. A short course of steroid therapy produced rapid and marked improvement of cutaneous lesions, without any effect on testicular involvement. The authors emphasize the value of an early treatment with steroids.


Magnesium Transporter 5 plays an important role in Mg transport for male gametophyte development in Arabidopsis.
During anther development the male gametophyte develops inside the locule and the tapetal cells provide all nutrients for its development. Magnesium Transporter 5 (MGT5) is a member of the MGT family and has dual functions of Mg export and import. Here, we show that male gametophyte mitosis and intine formation are defective in a mgt5 mutant. The transient expression of GFP-MGT5 revealed that MGT5 is localized in the plasma membrane. These findings suggest that in the male gametophyte MGT5 plays a role in importing Mg from the locule and that Mg is essential for male gametophyte development. The expression of MGT5 in the knockout ABORTED MICROSPORES (AMS) mutant (AMS being an essential regulator of tapetum) is tremendously reduced. Chromatin immunoprecipitation and mobility shift assay experiments demonstrated that AMS can directly bind the promoter of MGT5. An immunoelectron microscopy assay revealed that MGT5-His is localized to the plasma membrane of the tapetum. These findings suggest that AMS directly regulates MGT5 in the tapetum and thus induces export of Mg into the locule. The mgt5 plant exhibits severe male sterility while the expression of MGT5 under the tapetum-specific promoter A9 partly rescued mgt5 fertility. mgt5 fertility was restored under high-Mg conditions. These findings suggest that the mgt5 tapetum still has the ability to export Mg and that a sufficient supply of Mg from the tapetum can improve the importation of Mg in the mgt5 male gametophyte. Therefore, MGT5 plays an important role in Mg transport from the tapetum to the microspore.


An update to the cost-effectiveness of posaconazole vs fluconazole or itraconazole in the prevention of invasive fungal disease among neutropenic patients in the United States.
Posaconazole has shown superior clinical efficacy in the prevention of invasive fungal disease (IFD) among neutropenic patients as well as cost-effectiveness in the US healthcare setting vs fluconazole or itraconazole (FLU/ITRA) based on oral suspension formulations of each therapy. This study aims to provide an update on the cost-effectiveness of posaconazole in the current US healthcare setting to reflect bioequivalent tablet formulations of posaconazole and fluconazole, as well as changes in healthcare and drug costs. An existing model was used to assess the cost-effectiveness of posaconazole vs FLU/ITRA in the prevention of IFD among patients with acute myelogenous leukemia (AML) or myelodysplastic syndrome (MDS) and chemotherapy-induced neutropenia. Drug efficacy, mortality related to IFD, and death from other causes were estimated for tablet formulations using data from a randomized clinical trial of oral suspensions based on bioequivalence. IFD treatment costs were updated using the average inflation rate over 8 years (2006-2014) and drug costs were based on 2014 Analysource data. Trial data show a lower IFD probability over 100 days of follow-up with posaconazole compared to standard azole therapy (0.05 vs 0.11). The treatment duration on posaconazole is 29 days compared to 24 days for FLU and 29 days for ITRA. The average cost of prophylaxis is higher in the posaconazole group compared to FLU/ITRA ($4673 vs $353); however, the costs associated with treating the IFD are lower in the posaconazole group compared to FLU/ITRA ($2205 vs $5303). The incremental cost effectiveness ratio of IFD avoided for posaconazole is $18,898 vs FLU/ITRA. In the current healthcare cost environment where both drug costs and overall IFD treatment costs have increased since 2007, posaconazole tablets are a cost-effective alternative to fluconazole or itraconazole in the prevention of IFD among neutropenic patients with AML and MDS in the US.


Evaluation of companion animal behavior knowledge among first-year veterinary students before and after an introductory animal behavior course.
To survey first-year veterinary students' knowledge of companion animal (dog, cat, and horse) behavior and popular-culture (ie, pop-culture) behavior myths related to animal body language, motivations, and learning prior to participation in an introductory animal behavior course; evaluate potential associations between sources of prior behavior knowledge and knowledge on the preclass survey; and determine whether postclass scores on the same survey were predictive of final examination score for the behavior class. 156 first-year veterinary students. Students were invited to participate in an anonymous electronic survey before and after a semester-long, 2-credit introductory animal behavior course. Demographic features, self-assessed animal behavior knowledge, and sources of prior behavior knowledge were evaluated as predictors of preclass survey knowledge scores. Postclass survey knowledge scores were evaluated for association with final examination scores as a measure of validity. Preclass knowledge scores were low (mean ± SD, 49 ± 12.7%; n = 152). Reporting peer-reviewed journal articles as a source of incoming knowledge predicted 9% higher scores, whereas reporting magazines or online pop-culture articles as a source of incoming knowledge predicted 7.6% lower scores for preclass behavior knowledge, compared with scores for students not citing those respective sources. Companion animal ownership was not associated with preclass survey knowledge scores. Postclass knowledge scores were substantially improved (mean ± SD, 84.3 ± 8%) and predictive of final examination scores. Results indicated a profound deficit of behavior knowledge among veterinary students at the start of their curriculum. Students graduating from veterinary institutions without a comprehensive behavior course may be at a disadvantage for day 1 competency in addressing animal behavior problems.


Klotho--a common link in physiological and rheumatoid arthritis-related aging of human CD4+ lymphocytes.
Human CD4(+) T lymphocytes undergo aging-related changes leading to decreased immunity to infections and neoplasms, and to increased frequency of autoimmune diseases including rheumatoid arthritis (RA). Certain changes, observed in the CD4(+) cells of RA patients, resemble those observed during physiological aging, but occur at earlier age. Underlying cellular mechanism(s) of these similarities are so far largely unknown. Here we show that KLOTHO, a beta-glucuronidase gene whose activity changes are associated with aging phenotype, is down-regulated at the mRNA, protein, and enzymatic (beta-glucuronidase) activity levels both in the healthy elderly and especially in RA CD4(+) lymphocytes. Although the exact role of Klotho activity for CD4(+) cell function is unknown, we propose here that it might be involved in anti-inflammatory processes occurring in the young and healthy individuals, but reduced in both healthy elderly and RA patients. To support this hypothesis, we show here that the reduction of Klotho expression and activity in both elderly and patients' lymphocytes occurs in concert with the down-regulation of T cell costimulatory molecule CD28, the latter known to be dependent on increased levels of TNF-alpha. Thus, a common mechanism of KLOTHO down-regulation, but executed at various times in life, may underlie both physiological and disease-related T cell aging. Klotho activity might become a target of anti-RA drug development as well as a tool to help increase the immune system efficiency in the elderly.


Evidence for two distinct phenotypes of chronic kidney disease in individuals with type 1 diabetes mellitus.
In a retrospective, observational, cross-sectional, single-centre study, we assessed the prevalence and correlates of different CKD phenotypes (with and without albuminuria) in a large cohort of patients of white ethnicity with type 1 diabetes. From 2001 to 2009, 408 men and 369 women with type 1 diabetes (age 40.2 ± 11.7 years, diabetes duration 19.4 ± 12.2 years, HbA1c 7.83 ± 1.17% [62.0 ± 12.9 mmol/mol]) were recruited consecutively. Albumin-to-creatinine ratio (ACR) and eGFR (Modification of Diet in Renal Disease) were obtained for all individuals, together with CKD stage. Diabetic retinopathy and peripheral polyneuropathy were detected in 41.5% and 8.1%, respectively, and cardiovascular disease (CVD) occurred in 8.5%. Adjudications of CKD phenotype were made by blinded investigators. Normo- (ACR <3.4), micro- (ACR 3.4-34) or macroalbuminuria (ACR ≥34 mg/mmol) were present in 91.6%, 6.4% and 1.9% of individuals, respectively. eGFR categories 1 (≥90 ml min-1 [1.73 m]-2), 2 (60-89 ml min-1 [1.73 m]-2) and 3 (<60 ml min-1 [1.73 m]-2) were present in 57.3%, 39.0% and 3.7%, respectively. The majority of participants had no CKD (89.4%), while stages 1-2 and ≥3 CKD were detected in 6.8% and 3.7%, respectively. The albuminuric (Alb+) and non-albuminuric (Alb-) phenotypes were present in 12 (41.4%) and 17 (58.6%) individuals with stage ≥3 CKD, respectively. Individuals with an ACR <3.4 mg/mmol were subdivided into those with normal albuminuria (<1.1 mg/mmol; 77.2%) and mildly increased albuminuria (1.1-3.4 mg/mmol; 14.4%), and individuals with stage 2 CKD were subdivided into those with eGFR 75-89 ml min-1 [1.73 m]-2 and 60-74 ml min-1 [1.73 m]-2. ACR <3.4 mg/mmol (88.7%) and even <1.1 mg/mmol (70.4%) were common in individuals with eGFR 60-74 ml min-1 [1.73 m]-2. The prevalence of ACR <1.1 mg/mmol was lower but still significant (34.5%) in those with stage ≥3 CKD. In logistic regression analysis, stages 1-2 and ≥3 CKD were independently associated with age, HbA1c, γ-glutamyltransferase, fibrinogen, hypertension, but not with sex, BMI, smoking, HDL-cholesterol or triacylglycerol. Inclusion of advanced retinopathy removed HbA1c from the model. The CKD Alb+ phenotype correlated with diabetes duration, HbA1c, HDL-cholesterol, fibrinogen and hypertension, while the CKD Alb- phenotype was associated with age and hypertension, but not with diabetes duration, HbA1c and fibrinogen. The Alb- CKD phenotype is present in a significant proportion of individuals with type 1 diabetes supporting the hypothesis of two distinct pathways (Alb+ and Alb-) of progression towards advanced kidney disease in type 1 diabetes. These are probably distinct pathways as suggested by different sets of covariates associated with the two CKD phenotypes.


Junctional Scotoma and Patterns of Visual Field Defects Produced by Lesions Involving the Optic Chiasm.
Lesions of the optic chiasm (OC) typically produce bitemporal hemianopia (BTH) on visual field (VF) testing, whereas lesions located at the nasal optic nerve-chiasmal (ON-OC) junction have been proposed to produce junctional scotoma (JXS), a central defect in the ipsilateral eye with temporal field loss in the contralateral eye. In this study, we investigated whether the pattern of VF loss in patients with chiasmal compression predicted the appearance of the causative lesion on neuroimaging and described the clinical presentation of these patients with different types of VF defect. Retrospective chart review of patients seen in tertiary neuro-ophthalmology practice over 6 consecutive years with lesions abutting or displacing the OC was performed. Lesion size and location relative to the OC on neuroimaging was determined and correlated with VF defects as well as optical coherence tomography (OCT) of the peripapillary retinal nerve fiber layer and macular ganglion cell complex (GCC). Fifty-three patients were enrolled. VFs demonstrated JXS (n = 18), BTH (n = 14), monocular VF defect (n = 4), and no VF defect (n = 17); 64.7% of cases with normal VFs had radiologic OC compression. Lesion volume was highest in the JXS group, and these patients also had the poorest presenting visual acuity. All patients with JXS showed involvement of the ON-OC junction; however, not all cases showed compression of the OC from the nasal direction (15 of 18), and 17 of 18 also showed compression of one or both prechiasmatic ONs. Compression of the ON-OC junction was also seen in 79% of BTH, 100% of monocular VF defect, and 59% of no VF defect cases. Fifty percent of patients with normal VFs already had thinning of the GCC on OCT. GCC thinning was most pronounced nasally in the BTH group, but diffuse bilateral thinning was found in 38% of cases compared with 60% of JXS. VFs improved in 6 of 6 patients with BTH but only in 5 of 8 JXS cases after treatment. JXS is more often seen with larger lesions and when there is compression of both the prechiasmatic ON and ON-OC junction. These patients have worse presenting visual acuity and poorer outcomes. Not all patients with radiologic compression had VF defects, although 50% of patients with normal VFs had evidence of compression on the macular GCC analysis, emphasizing the importance of macular OCT in the evaluation of patients with lesions involving the OC.


Neuromyelitis optica in a patient with an early onset demyelinating episode: clinical and autoantibody findings.
Recent clinical and laboratory findings have substantially advanced our understanding of neuromyelitis optica (NMO) as a humorally mediated, autoimmune disorder. We report on a patient who suffered a first episode of transverse myelitis at the age of 6 months following diphtheria-pertussis-tetanus (DPT) vaccination which had therefore been considered suggestive of acute disseminated encephalomyelitis (ADEM). Fifteen years later, the further disease course revealed typical NMO meeting all diagnostic criteria. This development points to a broad clinical and temporal heterogeneity of NMO, with ADEM probably occurring in the context of a shared autoimmune diathesis. Despite therapy response following B-cell depletion by rituximab, positive NMO-IgG autoantibody status remained unchanged, whereas direct testing for anti-aquaporin-4 (AQP-4)-antibodies was negative throughout. Our findings challenge the pathogenic relevance of NMO-IgG and indicate a varying diagnostic value of testing for NMO-IgG and AQP-4-autoantibodies.


Transient visuospatial disorder from angiographic contrast.
The blood-brain barrier may be permeable under the clinical settings of uncontrolled hypertension, renal insufficiency, immunosuppressive drugs, and intravascular radiographic contrast. Some reversible neurological complications after angiography are caused by cortical penetration of contrast media detected on brain computed tomographic (CT) scans. To describe the first report of a transient visuospatial disorder having elements of Balint syndrome, and caused by angiographic contrast penetration of the bilateral parieto-occipital cortex; and to review cases published between 1980 and 2001 of cortical contrast penetration, documented by CT. Simultanagnosia, optic ataxia, and ocular apraxia occurred in a 74-year-old woman who received nonionic contrast media during a failed renal angioplasty. Contrast noted in the bilateral parieto-occipital cortex on the initial CT scan disappeared after 4 days with clinical resolution. Angiographic contrast tends to breach the blood-brain barrier of the vertebrobasilar circulation, penetrating the occipital cortex and leading to transient, localizable syndromes of cortical blindness or abnormal visuospatial processing.


Trends in retention on antiretroviral therapy in national programs in low-income and middle-income countries.
To document regional and global trends for patients retained on antiretroviral therapy (ART) 12-48 months after treatment initiation, in low-income and middle-income countries. Data reported by national programs to WHO/UNICEF/UNAIDS in 2008 were aggregated to produce regional and global estimates. The proportion of patients on ART at 12, 24, 36, and 48 months is derived from cohort monitoring systems in ART dispensing facilities. Of 149 countries, 70 (47%) reported on retention at 12 months, 54 (36%) at 24 months, 38 (26%) at 36 months, and 30 (20%) at 48 months. Regional and global trends showed that the majority of attrition from ART programs occurred within the first year and declined thereafter. Among countries in sub-Saharan Africa, retention on ART was estimated at 75.2% at 12 months, 66.8% at 24 months, and remained at a similar level up to 48 months. After high attrition in the first year, retention on ART tends to stabilize. In the literature, attrition in the first year was related to early mortality. Earlier presentation for diagnosis of HIV infection, timely screening, and access to ART are fundamental to reduce it. Countries need support in reporting on outcomes on ART.


[Crohn's disease of the appendix: a rare nosological entity].
In this study, the authors describe a case of Crohn's disease confined to the vermiform appendix out of a total of 1,263 appendectomies performed over the past 10 years in a Clinical Surgery Department (Clinica Chirurgica III) of the Policlinico S. Orsola in Bologna. In agreement with other reports in the scientific literature, the essentially non-specific clinical picture prevents pre-operative identification of the condition, whereas a diagnosis of Crohn's disease can be reached only on the basis of histological characteristics. The extreme rarity of Crohn's disease confined to the appendix is, however, confirmed. Follow-up at 3 years revealed no involvement of other areas of the digestive tract.


Myringoplasty Outcomes From a 5-Year Single Surgeon's Experience and Important Surgical Technical Aspects.
The United Kingdom (UK) national standard for the closure rate for myringoplasty is 89.5% (90.6% and 84.2% for primary and revision surgeries, respectively). The average hearing gains for primary and revision myringoplasty are 9.14 dB and 7.86 dB, respectively. This study compared the myringoplasty outcomes for a single surgeon over 5 years. Data for 68 cases were analyzed retrospectively. The outcome measures were achievement of the tympanic membrane closure and the average hearing gain or loss. The overall and primary closure rates were 97% and 98%, respectively and significantly higher than the UK national standard (p=0.0210 and p=0.0287, respectively). The revision closure rate was 93%; however, it was not significantly higher than the national standard (p=0.1872). The average hearing gain was 5.18 dB. The gains for primary and revision surgeries were 5.15 dB and 5.25 dB, respectively. We propose that these outcomes are a result of our surgical technique, including the simultaneous use of cortical mastoidectomy in ears with discharge.


[Preventive effect of acupoint injection at neiguan (PC 6) on postoperative nausea and vomiting after laparoscopic gynecologic surgery].
To investigate the method for preventing the postoperative nausea and vomiting (PONV) after laparoscopic gynecologic surgery. One hundred and twenty patients being for laparoscopic gynecologic surgery at I- II grade as American Society of anesthesiologists (ASA) were randomly divided into three groups, 40 cases in each group. Twenty minutes before the operation, the mixture of 2. 5 mg Droperidol (1 mL) and 1 mL 0. 9% sodium chloride solution was injected into the bilateral Neiguan (PC 6) in group I , and an intravenous injection with 1 mL Droperidol was used in group II , while there was no treatment carried out in group Ill'. Twenty four hours after the operation, the frequency and degree of nausea and vomiting were observed and scored according to the criteria standard. The incidence rate of nausea was 10. 0% (4/40) in group I , 57. 5% (23/40) in group II , which was significantly different from 80. 0% (32/40) in group III (P<0. 01, P<0. 05, respectively), while it was lower in group I than in group II (P<0. 01). The incidence rate of vomiting was 7. 5% (3/40) in group I , 52. 5% (21/40) in group II , which was significantly different from 75.0% (30/40) in group III (P<0.01, P<0.05 respectively), while it was lower in group I than in group II (P<0.01). No complication, such as obvious drowsiness, anxiety and extracorticospinal tract reaction, was observed among the three groups. Acupoint injection at Neiguan (PC 6) with a small dose of Droperidol can effectively prevent the PONV after laparoscopic gynecologic surgery without other adverse effects.


Nurse Practitioner Fellowship: Developing a Program to Address Gaps in Practice
Formal training is an important mechanism to assist the new generation of nurse practitioners (NPs) entering the complex field of oncology. The growing number of patients with cancer and the expansion of treatment options demand structured oncology training to support the transition of novice advanced practice nurses to the field. Oncology NP fellowships are a potential solution for those seeking training centered on the management of patients with cancer. This article discusses the process of implementing an NP fellowship program at an academic cancer center, including benefits and barriers.


Subspecialization in psychiatry: third-generation programs.
Psychiatry, unlike internal medicine, was slow to develop subspecialty certification. For many years, child and adolescent psychiatry was the only major subspecialty recognized by the American Board of Psychiatry and Neurology (ABPN). The situation changed in the early 1990s with the recognition by the ABPN of additional subspecialties of psychiatry including forensic psychiatry. Using the experience of the American Board of Internal Medicine as a guide, this commentary asks what comes next? What are our options as it becomes clear that there is a deepening of knowledge in the field of forensic psychiatry? Are we ready for, or interested in, the development of so-called third-generation certification programs?


[Cloning and expression of organic solvent tolerant lipase gene from Staphylococcus saprophyticus M36].
Lipases are important biocatalysts that are widely used in food processing and bio-diesel production. However, organic solvents could inactivate some lipases during applications. Therefore, the efficient cloning and expression of the organic solvent-tolerant lipase is important to its application. In this work, we first found out an organic solvent-tolerant lipase from Staphylococcus saprophyticus M36 and amplified the 741 bp Lipase gene lip3 (GenBank Accession No. FJ979867), by PCR, which encoded a 31.6 kD polypeptide of 247 amino acid residues. But the lipase shared 83% identity with tentative lip3 gene of Staphylococcus saprophyticus (GenBank Accession No. AP008934). We connected the gene with expression vector pET-DsbA, transformed it into Escherichia coli BL21 (DE3), and obtained the recombinant pET-DsbA-lip3. With the induction by 0.4 mmol/L of isopropyl beta-D-thiogalactopyranoside at pH 8.0, OD600 1.0, 25 degrees C for 12 h, the lipase activity reached up to 25.8 U/mL. The lipase expressed was stable in the presence of methanol, n-hexane, and isooctane, n-heptane.


Cefcapene Pivoxil Hydrochloride Is a Potentially New Treatment for Palmoplantar Pustulosis with Pustulotic Arthro-Osteitis.
Pustulosis palmaris et plantaris or palmoplantar pustulosis (PPP) is a refractory pustular eruption of the palms and soles with unknown etiology. In addition to skin lesions, PPP patients may present with severe joint pain and pustulotic arthro-osteitis (PAO), especially of the sternoclavicular joint. PAO is sometimes regarded as a variant of synovitis, acne, pustulosis, hyperostosis and osteitis (SAPHO) syndrome. Hence, macrolide and tetracycline antibiotics are used for the treatment of PPP with PAO. We report 3 cases of PPP with PAO that did not improve upon administration of macrolide antibiotics with NSAIDs. After administration of cefcapene pivoxil hydrochloride (CFPN-PI), a third-generation cephalosporin, the swelling and sternoclavicular joint pain were promptly reduced and dramatically improved in all 3 cases. We review the conventional antibiotic treatments used currently and propose CFPN-PI as a potentially new therapy for PPP or PPP + PAO.


Antiretroviral combinations implicated in emergence of the L74I and L74V resistance mutations in HIV-1-infected patients.
Very little is known about the alternative L74I mutation. This lack of knowledge has led to contradictory and confusing attitudes to L74I; although this mutation is not listed by the International AIDS Society - USA, it is increasingly included in several resistance algorithms. To compare and clarify the role of each antiretroviral compound and the resistance background in the emergence of the L74I and L74V mutations. We focused on the treatment used at the exact time of any L74V or L74I emergences in 74 patients, and we compared the use of each nucleoside reverse transcriptase inhibitor (NRTI) separately and in combination between the 74I and the 74V groups. The distribution of other NRTI and non-NRTI mutations between the two groups was also analysed. A majority of L74I mutations is selected under the zidovudine plus abacavir combination or under tenofovir with thymidine analogue mutations in the resistance background. The K103N substitution also plays an important role in the L74I emergence when not associated with the other non-NRTI mutations seen in this study: L100I, G190A and Y181C. Didanosine plays the principal role in the L74V emergence. This study shows that the L74I and the L74V correspond to two different mutation pathways, conferring probably different resistance and replication advantages on HIV depending on the context. Taking into account more systematically the L74I mutation, whose impact is certainly currently underestimated, would increase our understanding of this substitution and its effects on the drug activity in vivo.


A national internet survey on midlife women's attitudes toward physical activity.
Despite an increasing number of studies of midlife women's physical activity, little is known about how attitudes toward physical activity of midlife women from diverse ethnic groups influence the women's physical activity. To explore ethnic differences in midlife women's attitudes toward physical activity and determine the relationships between the attitudes and their actual participation in physical activity while considering other influencing factors. The Midlife Women's Attitudes Toward Physical Activity model was used to guide the study. This was a cross-sectional Internet survey study of 542 midlife women. The instruments included questions on background characteristics and health and menopausal status; the Physical Activity Assessment Inventory; a modified Barriers to Health Activities Scale; the Questions on Attitudes Toward Physical Activity, Subjective Norm, Perceived Behavioral Control, and Behavioral Intention; and the Kaiser Physical Activity Survey. The data were analyzed using ANOVA, correlation, hierarchical multiple regression, and path analyses. There were significant ethnic differences in the attitude scores (F = 2.58, p < .05), but no ethnic differences in the physical activity scores. Interestingly, there were significant ethnic differences in the occupational physical activity scores (F = 5.68, p < .01). Attitude scores accounted for 5% of total variances of the physical activity scores (F(ch) = 43.52, p < .01). The direct paths from the attitude scores (p < .01), the self-efficacy scores (p < .01), and the barrier scores (p < .05) to the physical activity scores were statistically significant. Ethnic differences in the women's attitudes toward physical activity need to be considered in promoting physical activity of midlife women.


AnnoSys-implementation of a generic annotation system for schema-based data using the example of biodiversity collection data.
Biological research collections holding billions of specimens world-wide provide the most important baseline information for systematic biodiversity research. Increasingly, specimen data records become available in virtual herbaria and data portals. The traditional (physical) annotation procedure fails here, so that an important pathway of research documentation and data quality control is broken. In order to create an online annotation system, we analysed, modeled and adapted traditional specimen annotation workflows. The AnnoSys system accesses collection data from either conventional web resources or the Biological Collection Access Service (BioCASe) and accepts XML-based data standards like ABCD or DarwinCore. It comprises a searchable annotation data repository, a user interface, and a subscription based message system. We describe the main components of AnnoSys and its current and planned interoperability with biodiversity data portals and networks. Details are given on the underlying architectural model, which implements the W3C OpenAnnotation model and allows the adaptation of AnnoSys to different problem domains. Advantages and disadvantages of different digital annotation and feedback approaches are discussed. For the biodiversity domain, AnnoSys proposes best practice procedures for digital annotations of complex records. https://annosys.bgbm.fu-berlin.de/AnnoSys/AnnoSys.


Human peripheral blood monocytes versus THP-1 monocytes for in vitro biocompatibility testing of dental material components.
Monocytes play a central role in the response of tissues to biomaterials. Monocytic cell lines such as the THP-1 cell line have been used extensively as models for primary monocytes (directly from blood) in biocompatibility research. However, little information exists about the appropriateness of these cell lines as models. Thus, the current study compared the biological response of both primary peripheral blood monocytes (PBMs) and the THP-1 cell line to four common components of dental materials known to be released into the oral environment: nickel ions, 2-hydroxyethyl methacrylate (HEMA), triethylene glycol dimethacrylate (TEGDMA), and 2,2-bis[4(2-hydroxy-3-methacryloloxy)-phenyl]propane (Bis-GMA). Comparisons were made by constructing dose-response curves for each type of monocyte and the four components. The 50% cytotoxicity values (TC50 values) were then statistically compared. In addition, the response of the monocytes to the materials with and without lipopolysaccharide (LPS) stimulation were assessed by measuring TNF-alpha secretion from the monocytes. The results showed that the PBMs were 5-10 times less sensitive than the THP-1 monocytes to these dental components, but that both cell lines ranked the components identically. TNF-alpha secretion from both types of monocytes often showed similar trends, although some inconsistent results were noted. The current study supports the use of THP-1s as a model for ranking the cytotoxicity of components of dental biomaterials. Furthermore, the secretory activity of PBMs appears to be generally well represented by the THP-1s. However, sufficient differences between these cell types exist to recommend confirmation of any critical results obtained with THP-1s using PBMs.


[An early phase II clinical study of RP56976 (docetaxel) in patients with breast cancer].
An early phase II clinical study of RP56976 (docetaxel), a new anticancer agent of plant origin, was conducted in patients with breast cancer at 20 Japanese collaborative institutions. Docetaxel was administered at two or more doses of 60 mg/m2 by intravenous infusion with dose-free intervals of 3-4 weeks, and the efficacy and safety was evaluated. Of the 51 patients enrolled, 50 patients completed the scheduled course of treatment. Two patients showed a complete response (CR) and 19 showed a partial response (PR) with a response rate of 42.0%. The response rates based on the efficacy for metastatic lesions in soft tissue, liver and lung, were 46.2% (18/39), 37.5% (3/8), and 38.5% (5/13), respectively. Of the 50 patients who completed the study, 48 patients had previously been treated for the present malignancy. Forty-seven patients had previously been treated with chemotherapy and showed a response rate of 40.4% (19/47). The response rate in those who had received chemotherapy composed of anthracyclines and other agents was 44.1% (15/34). Grade 3 or more severe leukopenia and neutropenia developed in 43 patients (84.3%) and 48 patients (94.1%), respectively. Other adverse reactions which occurred in a Grade 3 or more severe form included nausea/vomiting (1 patient), anorexia (5 patients), diarrhea (4 patients), fatigue (2 patients), and alopecia (20 patients). Except for alopecia, most adverse reactions were generally transient and reversible without any specific treatment.


Evidence for a Fe3+-rich pyrolitic lower mantle from (Al,Fe)-bearing bridgmanite elasticity data.
The chemical composition of Earth's lower mantle can be constrained by combining seismological observations with mineral physics elasticity measurements. However, the lack of laboratory data for Earth's most abundant mineral, (Mg,Fe,Al)(Al,Fe,Si)O3 bridgmanite (also known as silicate perovskite), has hampered any conclusive result. Here we report single-crystal elasticity data on (Al,Fe)-bearing bridgmanite (Mg0.9Fe0.1Si0.9Al0.1)O3 measured using high-pressure Brillouin spectroscopy and X-ray diffraction. Our measurements show that the elastic behaviour of (Al,Fe)-bearing bridgmanite is markedly different from the behaviour of the MgSiO3 endmember. We use our data to model seismic wave velocities in the top portion of the lower mantle, assuming a pyrolitic mantle composition and accounting for depth-dependent changes in iron partitioning between bridgmanite and ferropericlase. We find excellent agreement between our mineral physics predictions and the seismic Preliminary Reference Earth Model down to at least 1,200 kilometres depth, indicating chemical homogeneity of the upper and shallow lower mantle. A high Fe3+/Fe2+ ratio of about two in shallow-lower-mantle bridgmanite is required to match seismic data, implying the presence of metallic iron in an isochemical mantle. Our calculated velocities are in increasingly poor agreement with those of the lower mantle at depths greater than 1,200 kilometres, indicating either a change in bridgmanite cation ordering or a decrease in the ferric iron content of the lower mantle.


[How does a surgeon decide that surgery is the best option?Assessing whether or not to operate].
All abdominal surgical procedures have a certain risk/benefit ratio. Recently, the way surgeons come to a decision whether to operate, or not, was discussed in the Annals of Surgery. First, the assessment of the decision for an operative versus a non-operative strategy was addressed on the basis of clinical vignettes. The perceptions concerning risk/benefit balance varied considerably between surgeons and these perceptions predicted the decision to operate. In a second paper, surgeons were randomized to either an arm in which they were exposed to a risk calculator or to a control arm. The decisions of the risk-calculator arm were less varied, but did not alter the likelihood of recommending an operation. Perhaps surgeons decide to operate or not rather intuitively, based on clinical and laboratory information. Alternatively, they may consider the statistically significant difference in risk/benefit to be less relevant. A better insight into surgeons' decision making and the way in which they weigh benefits against risks is very useful, but it is proving to be a considerable research challenge.


Digoxin, an Overlooked Agonist of RORγ/RORγT.
Digoxin was one of the first identified RORγT receptor inverse agonists inhibiting the differentiation of Th17 cells. However, this compound exhibits inhibitory activity at relatively high concentrations that mediate cytotoxic effects. We previously identified several cardenolides that are structurally similar to digoxin that were able to induce RORγ/RORγT-dependent transcription. These observations encouraged us to reanalyze the effects of digoxin on RORγ/RORγT-dependent transcription at low, noncytotoxic concentrations. Digoxin induced RORγ/RORγT-dependent transcription in HepG2 and Th17 cells. Furthermore, analysis of the transcriptomes of Th17 cells cultured in the presence of digoxin revealed the induction of the expression of numerous Th17-specific genes, including IL17A/F, IL21, IL22, IL23R, CCR4, and CCR6. Thus, our study, which includes data obtained from intact cells, indicates that digoxin, similar to other cardenolides, is a potent RORγ/RORγT receptor activator and that its structure may serve as a starting point for the design of dedicated molecules that can be used in the development of adoptive cell therapy (ACT).


Assessment of Prevalence and Risk Factors for Diabetic Retinopathy in Patients with Type 1 and Type 2 Diabetes Examined at a Tertiary Care.
Introduction: Diabetic retinopathy (DR) is a microvascular complication of diabetes mellitus and the leading cause of visual impairment and blindness. The aim of the study was to estimate and compare the prevalence of DR and to determine an association between DR and systemic risk factors in hospitalized type 1 (DMT1) and type 2 (DMT2) diabetic patients. Material and methods: We analyzed 260 patients with diabetes, 43 with DMT1 and 217 with DMT2. The following data were collected: age, gender, type and duration of diabetes, glycemic control, blood pressure, estimated glomerular filtration rate, ophthalmologic examinations and routine biochemical parameters. Results: Out of the total number of 260 patients, 77 (29.6%) had non-proliferative DR (NPDR), 21 (8.1%) had proliferative DR (PDR), 29 (11.1%) had diabetic macular edema (DME), and 69 (23.5%) had diabetic cataracts. Forty-three (16.5%) patients were previously diagnosed with DMT1 and 217 (83.5%) with DMT2. The duration of diabetes was not significantly longer in DMT1 (12.8±11.2 years) in comparison to DMT2 (11.07±8.1 years). The prevalence of NPDR and PDR did not differ statistically in either groups. DME was more prevalent in DMT2 than in DMT1 (P<0.05). Diabetic cataract was found in 26.7% vs. 6.7% of patients with DMT2 and DMT1, respectively (p<0.01). The duration of diabetes significantly correlated with NPDR and PDR in DMT1 (r=o.31, p<0.05; r=0.55, p<0.001, respectively). In DMT2, significant correlations were found between the duration of diabetes and cataract, NPDR, PDR and DME (r=0.31, p<0.001; r=0.43 p<0.01, r=0.16 p<0.05 and r=0.20 p<0.01, respectively). Fasting plasma glucose (FPG) significantly correlated with PDR (r=0.258, p<0.05), while HbA1c with DME (r= 0.15 p<0.05). Conclusion: The duration of diabetes and hyperglycemia were associated with DR in both types of diabetes.


Factors affecting tooth loss among rural Khon Kaen adults: analysis of two data sets.
Tooth loss is an oral health problem affecting Thai people and people of other nations as well. Not much of epidemiologic evidence concerning factors affecting tooth loss among Thai people has been reported although severity of tooth loss among Thai people has never been decreased. This study employed two existing data sets to evaluate the role of health behaviors such as tobacco smoking and betel quid chewing (a common habit prevalent among rural Thai females), together with other factors in relation to tooth loss among rural Thai people. The study population in the first (phase I) and second (phase II) data sets included 1484 and 3471 male and female adults residing in rural areas of Khon Kaen province, Thailand during 1990-1991 and 1992-1994, respectively. The data were obtained through oral examination and interview. Employing descriptive, bivariate, and multivariable Poisson regression, key risk indicators of tooth loss were identified for both data sets. The findings from final multivariable Poisson regression models were consistent in that tobacco smoking, betel quid chewing, age, dental caries (defined as decayed plus filled teeth) and periodontitis were significantly related to tooth loss among these rural populations. Therefore, preventive programs aiming at discouraging Thai people from smoking tobacco and/or chewing betel quid should be established so that healthy natural teeth can be maintained.


Chemodiversity of exudate flavonoids in Dionysia (Primulaceae): a comparative study.
More than 60 accessions of various Dionysia spp. were analysed for their exudate flavonoid composition. Many Dionysia spp. accumulate the typical Primula flavonoids with irregular substitution (unsubstituted flavone, its 2',5'-substituted derivatives and corresponding 5-OH-flavones), but flavones, flavonols and flavanones with regular 5,7-diOH-substitution are also encountered in their exudates. The formation of both types of flavonoids is not mutually exclusive. This paper analyses the chemodiversity of Dionysia exudates with respect to infraspecific variability, infrageneric distribution, patterns in hybrid taxa, and comparisons of biogenetic tendencies between Dionysia and closest related species of Primula. The uniqueness of occurrence of Primula-type flavonoids in the family Primulaceae, and their presumed different biosynthetic origin, suggest significance as further character in the Primula-Dionysia assemblage. Principal component analysis was applied to test the significance of variation of flavonoid composition across Dionysia. Comparative analysis of flavonoid profiles against the current taxonomic views yielded correlations, confined to the level of smaller groups, and only in parts at level of the current infrageneric concept. Flavonoid data are further discussed against the background of morphological and biogeographic differentiation of the genus. Increased diversification of flavonoid profiles may be interpreted as a derived status in Dionysia, which agrees with current views on the phylogeny of Dionysia as a specialised group within Primula. Functional aspects of exudate flavonoid formation are shortly addressed.


Top 50 most-cited articles in medicine and science in football.
To conduct a comprehensive mapping analysis to the scientific literature published in football aiming to identify the areas of bigger interest and potential for further exploration. The data were obtained by a search conducted on the Web of Science. Articles were listed based on citation frequency. We used an open-source bibliometrix R-package for the comprehensive bibliometric analyses. The number of citations per article ranged from 251 to 869 (median 323; IQR 125). The yearly number of citations ranged from 8 to 54 (median 26; IQR 11). Most of the articles (76%) were of level III of evidence, 10% were level II and 14% were level IV. Within the top 50 most-cited articles, 40 articles were original research (37 observational and 3 experimental studies), 9 were review articles and 1 was a thesis. From the 40 original research articles, 50% involved elite players, 73% were exclusive to male players and 80% involved adult players only. The topic area with the highest number of articles was sports medicine (44%), followed by training and testing (32%), performance analysis (14%) and physiology (10%). No study within the top 50 was devoted to biomechanics, nutrition, sport psychology, coaching or social sciences. The lack of experimental studies within the top 50 most-cited articles in football clearly underpins how far we still are from establishing the theoretical and methodological guidelines for the applied science and medicine in football.


STRO-1 selected rat dental pulp stem cells transfected with adenoviral-mediated human bone morphogenetic protein 2 gene show enhanced odontogenic differentiation.
Dental pulp stem cells harbor great potential for tissue-engineering purposes. However, previous studies have shown variable results, and some have reported only limited osteogenic and odontogenic potential.Because bone morphogenetic proteins (BMPs) are well-established agents to induce bone and dentin formation,in this study STRO-1-selected rat dental pulp-derived stem cells were transfected with the adenoviral mediated human BMP-2 gene. Subsequently, the cells were evaluated for their odontogenic differentiation ability in medium not containing dexamethasone or other stimuli. Cultures were investigated using light microscopy and scanning electron microscopy (SEM) and evaluated for cell proliferation, alkaline phosphatase(ALP) activity, and calcium content. Real-time polymerase chain reaction (PCR) was performed for gene expression of Alp, osteocalcin, collagen type I, bone sialoprotein, dentin sialophosphoprotein, and dentin matrix acidic phosphoprotein 1. Finally, an oligo-microarray was used to profile the expression of odontogenesis-related genes. Results of ALP activity, calcium content, and real-time PCR showed that only BMP2-transfected cells had the ability to differentiate into the odontoblast phenotype and to produce a calcified extracellular matrix. SEM and oligo-microarray confirmed these results. In contrast, the non-transfected cells represented a less differentiated cell phenotype. Based on our results, we concluded that the adenovirus can transfect STRO-1 selected cells with high efficacy. After BMP2 gene transfection, these cells had the ability to differentiate into odontoblast phenotype, even without the addition of odontogenic supplements to the medium.


Effect of CYP3A4 and CYP3A5 Genetic Polymorphisms on the Pharmacokinetics of Sirolimus in Healthy Chinese Volunteers.
Sirolimus is a promising immunosuppressive drug for preventing the rejection of organ transplants. However, inter-individual variability in sirolimus pharmacokinetics causes adverse drug reactions, compromising therapeutic efficacy. Sirolimus is primarily metabolized by cytochrome CYP3A4 and CYP3A5. This study aimed to clarify the effect of CYP3A genetic polymorphisms, including the CYP3A4*1G and CYP3A5*3 polymorphisms, on the pharmacokinetics of sirolimus. Thirty-one healthy Chinese volunteers were included in this study. Their genotypes were determined using the Sequenom MassARRAY iPLEX platform, and blood sirolimus concentrations at different time points were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The pharmacokinetic parameters were calculated using WinNonlin version 5.2 software. The allele frequencies of CYP3A4*1G and CYP3A5*3 were 25.8% and 71.0%, respectively. In CYP3A4*1G carriers (n = 13), the area under the curve AUC0-144, AUC0-∞, and Cmax were significantly lower (P < 0.05) than CYP3A4*1/*1 homozygous subjects (n = 18). Briefly, the AUC0-144, AUC0-∞, and Cmax of *1G/*1G carrier were 315.2 ± 91.5, 372.0 ± 108.2, and 10.2 ± 1.6 ng/mL, respectively, and those of *1/*1 G*1/*1 G carrier were 440.8 ± 130.6, 537.4 ± 167.5, and 13.7 ± 4.3, respectively, whereas those of CYP3A4*1/*1 homozygous subjects were 540.2 ± 150.6, 626.6 ± 166.9, and 19.8 ± 7.5 ng/mL, respectively. In CYP3A5-nonexpressing subjects (*3/*3 homozygous carriers, n = 15), the AUC0-144 and Cmax were 549.6 ± 137.9 and 19.9 ± 7.9 ng/mL, respectively, and were significantly higher (P < 0.05) than the values in CYP3A5-expressing subjects (*1/*1homozygous carrier, n = 2; 314.2 ± 129.3 and 10.3 ± 2.2 ng/mL; *1/*3 heterozygous carrier, n = 15; 440.2 ± 146.3 and 14.6 ± 5.1 ng/mL, respectively). CYP3A4 and CYP3A5 genetic polymorphisms are important factors affecting pharmacokinetic parameters of sirolimus. Our data support the monitoring of blood sirolimus concentrations, especially in CYP3A5*1 and CYP3A4*1 G carriers, to ensure accurate dosing in the clinical setting.