The problem-based medical audit program: influence on family practice residents' knowledge and skills.
Family physicians need to possess the skills to conduct audits in their own clinical settings to ensure that their patients receive exemplary clinical care. Residency offers an important opportunity for physicians to develop these auditing skills. This study describes the introduction of a problem-based medical audit program at three teaching units in the Department of Family Medicine at McMaster University and the program's effect on learner knowledge, skills, and attitudes toward the practice audit. A survey designed to assess residents' self-rated knowledge, skills, and attitudes toward practice audits was distributed before and after residents participated in the audit program. Forty-three residents were surveyed; 33 (76.7%) completed the initial questionnaire and follow-up questionnaire. Residents reported significant improvements in their understanding of the relevance of audits, ability to develop a practice audit question, skills in designing methodology, and skills needed to conduct an audit independently. Residents also reported a moderate increase in their knowledge of statistics needed to complete an audit. The practice audit program at McMaster University uses a problem-based model to introduce learners to the concept of the clinical audit. The practice audit program successfully improved the residents' self-reported ability to conduct an audit and heightened their understanding of the importance and relevance of the audit process.


Associations of dietary patterns with hypertension among adults in Jilin Province, China: a structural equation modelling approach.
To explore the direct and indirect associations of dietary patterns with hypertension using structural equation modelling (SEM). Factor analysis with varimax rotation was used to classify different dietary patterns and SEM was employed to investigate the associations of dietary patterns with hypertension. Total cholesterol to HDL-cholesterol (TC:HDL-C) ratio and LDL-cholesterol to HDL-cholesterol (LDL-C:HDL-C) ratio were used as observed indicator variables of the lipid latent variable. Waist circumference, body fat percentage and BMI, which were associated with hypertension, were used as observed indicator variables of the obesity latent variable. International Chronic Disease Cohort (ICDC) that began in 2005 with the purpose of describing the frequency and determinants of chronic diseases in Jilin Province, China. A total of 1492 adults (40-79 years) were enrolled in the baseline study from August 2010 to August 2011. Hypertension prevalence in our study population was 34·9 %. It was found that the wine pattern, condiment pattern, obesity latent variable, lipid latent variable, glucose, age and family history of hypertension were factors that had an association with hypertension via SEM, and the corresponding coefficients were 0·056, 0·011, 0·230, 0·281, 0·098, 0·232 and 0·116, respectively. The wine pattern and lipid latent variable had positive direct associations with hypertension. The condiment pattern had a positive indirect association with hypertension via the obesity latent variable. The vegetables pattern, modern pattern and snack pattern were not associated with hypertension.


Toxoplasma gondii infection in animal-friendly pig production systems.
Consumption of undercooked pork meat products has been considered a major risk factor for contracting toxoplasmosis in humans. Indoor farming and improved hygiene have drastically reduced Toxoplasma infections in pigs over the past decades. Whether introduction of animal-friendly production systems will lead to a reemergence of Toxoplasma infections in pigs is not yet known. Investigating this possibility was the purpose of this study. Blood was obtained from pigs raised for slaughter and tested for Toxoplasma antibodies by using latex agglutination and indirect immunofluorescence testing, with confirmation by immunoblotting. None of the slaughter pigs (n = 621) from conventional farms (n = 30) were positive, whereas 38 (2.9%) of 1295 animals from animal-friendly systems tested positive (n = 33 farms; 13 [39%] farms positive). The following conclusions may be derived from this study: Conventionally (indoors) raised pigs are free from Toxoplasma infection, and (2) animal-friendly production systems may lead to a reemergence of Toxoplasma infections, although many of these farms remain Toxoplasma free. Slaughterhouse monitoring of pigs from animal-friendly production systems combined with on-farm prevention strategies should be applied to ensure safety for consumers of the meat products obtained from these animals.


Ratiometric fluorescent biosensor for hyaluronidase with hyaluronan as both nanoparticle scaffold and substrate for enzymatic reaction.
Hyaluronidases (HAase) are involved in various physiological and pathological processes and have been reported as urinary marker for bladder cancer. In this study, a novel ratiometric fluorescent sensing system based on both aggregation-induced emission (AIE) and aggregation-induced quenching (ACQ) was developed to quantitatively assess hyaluronidase level. First, a tetraphenylethylene derivative with positive charges (TPE-2N(+), typical AIE molecule) at both ends and an anthracene derivative with positive charge at one end (AN-N(+), typical ACQ molecule) was synthesized. These two positively charged compounds were then mixed with a negatively charged hyaluronan (HA), which induced the aggregation of the compounds as well as the nanoparticles formation as a result of electrostatic complexation, with TPE-2N(+) acting as cross-linking agent. The aggregation also caused the efficient quenching of the emission of AN-N(+) due to ACQ effect, as well as the fluorescence enhancement of TPE-2N(+) due to AIE effect. In the presence of HAase, the enzymatic reaction led to the degradation of HA and triggered disassembly of the nanoparticles; as a result, the emission of AN-N(+) was restored and that of TPE-2N(+) was suppressed. This fluorescence variation affords the system a robust ratiometric biosensor for HAase, and the ratio of fluorescence intensity for AN-N(+) (I414) to that for TPE-2N(+) (I474) can be used as the sensing signal for detecting HAase activity. In this system, hyaluronan serves not only as the scaffold for nanoparticle formation but also as the substrate for enzymatic reaction. This assay system is operable in aqueous media with very low detection limit of 0.0017 U/mL and is capable of detecting HAase in biological fluids such as serum and urine. This strategy may provide a new and effective approach for developing other enzyme assays.


Effect of a virtual environment on the development of mathematical skills in children with dyscalculia.
In this study, we show the effectiveness of a virtual environment comprising 18 computer games that cover mathematics topics in a playful setting and that can be executed on the Internet with the possibility of player interaction through chat. An arithmetic pre-test contained in the Scholastic Performance Test was administered to 300 children between 7 and 10 years old, including 162 males and 138 females, in the second grade of primary school. Twenty-six children whose scores showed a low level of mathematical knowledge were chosen and randomly divided into the control (CG) and experimental (EG) groups. The EG participated to the virtual environment and the CG participated in reinforcement using traditional teaching methods. Both groups took a post-test in which the Scholastic Performance Test (SPT) was given again. A statistical analysis of the results using the Student's t-test showed a significant learning improvement for the EG and no improvement for the CG (p≤0.05). The virtual environment allows the students to integrate thought, feeling and action, thus motivating the children to learn and contributing to their intellectual development.


Type I interferon pathway activation in COPA syndrome.
Mutations of the COPA gene cause an immune dysregulatory disease characterised by polyarticular arthritis and progressive interstitial lung disease with pulmonary haemorrhages. We report the case of a young girl that presented at age 3 with polyarticular arthritis, chronic cough and high titer rheumatoid factor. Radiologic imaging showed interstitial lung disease with tree-in-a-bud nodules and air-filled cysts. Targeted genetic analysis of COPA gene showed the reported c.698G>A mutation. The patient was lost to follow up for 3years during which therapy was discontinued with the development of joint damage and deformities. Analysis of peripheral blood showed activation of type 1 interferon pathway, which was also confirmed in 4 previously reported COPA patients. Our observations underline the importance of early treatment in COPA disease to avoid loss of joint function. Furthermore, our results suggest a role for type 1 interferon in disease pathogenesis opening the possibility for targeted therapeutic approaches.


Diagnostic accuracy of 18F-FDG PET/CT in characterizing ovarian lesions and staging ovarian cancer: correlation with transvaginal ultrasonography, computed tomography, and histology.
To (a) assess the accuracy of 18F-FDG PET/CT in distinguishing malignant from benign pelvic lesions, compared to transvaginal ultrasonography (TVUS) and (b) to establish the role of whole-body 18F-FDG PET/CT, compared to contrast enhanced computed tomography (CT), in staging patients with ovarian cancer. Fifty consecutive patients with a pelvic lesion, already scheduled for surgery on the basis of physical examination, TVUS, and serum Ca125 levels, were enrolled in the study. Patients' age ranged between 23 and 89 years (mean 64). All patients underwent TVUS including a colour Doppler study followed by a thorax and abdominal CT scan, and whole-body 18F-FDG PET/CT within 2 weeks prior to surgery. Histological findings obtained at surgery were taken as the 'gold standard' to compare 18F-FDG PET/CT and TVUS, and 18F-FDG PET/CT vs. CT. When tissue analysis showed ovarian cancer, the accuracy of 18F-FDG PET/CT and CT were compared for the purpose of obtaining a precise staging. At surgery, the ovarian lesions were malignant in 32/50 patients (64%) and benign in the remaining 18/50 patients (36%). The sensitivity, specificity, NPV, PPV and accuracy of 18F-FDG PET/CT were 87%, 100%, 81%, 100% and 92%, respectively, compared with 90%, 61%, 78%, 80% and 80%, respectively, for TVUS. In staging ovarian cancer, 18F-FDG PET/CT results were concordant with final pathological staging in 22/32 (69%) patients while CT results were concordant in 17/32 (53%) patients. CT incorrectly down-staged four out of six stage IV patients by missing distant metastasis in the liver, pleura, mediastinum, and in left supraclavicular lymph nodes, which were correctly detected by 18F-FDG PET/CT. PET/CT with 18F-FDG provides additional value to TVUS for the differential diagnosis of benign from malignant pelvic lesions, and to CT for the staging of ovarian cancer patients.


[Study on the ultraviolet spectrum in a series of 2 (1H)-quinoxalin-2-one derivatives].
A series of 2 (1H)-quinoxalin-2-one derivatives: 1-alkyl-3-methyl-2 (1H)-quinoxalin-2-one (AMQ, alkyl = H, CH3, C2H5, n-C3H7, n-C5H11, n-C16H33) have been studied by ultraviolet spectrometry. They may be used as highly active fungicides, compounds inhibiting the growth of plants, neuroprotectant for cerebral ischemia, new fluorescent probes, selective antagonists to alpha-amino-3-hydroxy-5-methly-4-isoxazole propionic acid (AMPA) et al. Results show that as the length of the alky1 chain at the nitrogen on the 1-position increases, little changes have been found in the ultraviolet absorption spectra. All spectra have similar peak shape, a strong shoulder peak appears around 327 and 340 nm with a weaker peak around 280 nm. The peak about 340 nm in the UV spectrum is mainly due to the transition of n-->pi* and pi-->pi*, the intense absorption peak about 327 and 280 nm is as the result of the transition of pi-->pi*.


Micro- and Macromechanical Properties of Thermoelectric Lead Chalcogenides.
Both n- and p-type lead telluride (PbTe)-based thermoelectric (TE) materials display high TE efficiency, but the low fracture strength may limit their commercial applications. To find ways to improve these macroscopic mechanical properties, we report here the ideal strength and deformation mechanism of PbTe using density functional theory calculations. This provides structure-property relationships at the atomic scale that can be applied to estimate macroscopic mechanical properties such as fracture toughness. Among all the shear and tensile paths that are examined here, we find that the lowest ideal strength of PbTe is 3.46 GPa along the (001)/⟨100⟩ slip system. This leads to an estimated fracture toughness of 0.28 MPa m1/2 based on its ideal stress-strain relation, which is in good agreement with our experimental measurement of 0.59 MPa m1/2. We find that softening and breaking of the ionic Pb-Te bond leads to the structural collapse. To improve the mechanical strength of PbTe, we suggest strengthening the structural stiffness of the ionic Pb-Te framework through an alloying strategy, such as alloying PbTe with isotypic PbSe or PbS. This point defect strategy has a great potential to develop high-performance PbTe-based materials with robust mechanical properties, which may also be applied to other materials and applications.


Specific binding of neoglycoproteins to Toxoplasma gondii tachyzoites.
Several studies have shown that protozoa bind to glycoproteins or neoglycoproteins. Here we report that Toxoplasma gondii binds strongly to bovine serum albumin-glucosamide. The binding was rapid, time dependent, partially reversible, saturable, and specific. Scatchard analysis showed about 40,000 molecules of bovine serum albumin-glucosamide per toxoplasma cell. The apparent dissociation constant was found to be 4.46 x 10(-8) M.


Primary closure of deep sternal wound infection following open heart surgery: a safe operation?
Deep median sternotomy wound infection is a significant source of morbidity and mortality after cardiac operations. Management of an infected median sternotomy incision is a subject of controversy. The aim of this study was to assess our experience with primary closure without any irrigation system for infected deep median sternotomy wound. Between January 1994 and December 1997, 4,227 consecutive open heart procedures via a median sternotomy under cardiopulmonary bypass were performed in our department. A total of 27 (0.64%) consecutive patients with deep sternotomy wound infection were identified. The mean age of the patients was 45 years. Six were female and 21 were male. The incidence of deep sternal wound infection was therefore 0.64%. The mean duration between the primary operation and the onset of deep sternal wound infection was 2.5 weeks. Staphylococcus aureus and Staphylococcus epidermidis were the most common pathogen causing postoperative mediastinal infection. Out of the 27 cases, 17 were successfully treated, 8 (30%) died and 2 had a persistent fistula. The mean follow-up time was 18 months (range 4 to 52 months). The mortality in the pediatric group was 4/8 (50%) and 4/19 (21%) in the adult group. The mortality for mediastinitis presenting before one week or after 4 weeks after operation was 63%. In contrast, the mortality for mediastinitis presenting after one week but before 4 weeks after operation was 17%. Mediastinitis after cardiac surgical procedures remains a devastating complication. Primary closure without irrigation-suction system should only be considered in selected patients.


Evaluation of Temporomandibular Disorders and Comorbidities in Patients with Ehler--Danlos: Clinical and Digital Findings.
The objective of this study is to recognize representative cranio-cervico-mandibular features of patients with Ehler-Danlos syndrome and associated temporomandibular disorders (TMDs), to assess a targeted and integrated treatment plan. After a diagnosis of disease, 38 individiuals with Ehler-Danlos syndrome and temporomandibular symptomatology referred were evaluated. Gnathological evaluation, according to the Diagnostic Criteria for TMDs, and radiographic imaging was performed. In addition, digital evaluation of occlusal and muscular balance, using surface electromyography of jaw muscles, was conducted. Statistical software for data analysis - STATA (StataCorp, College station, Texas, USA) - was used. Most common temporomandibular dysfunctions were arthralgia, myalgia, disc displacement with reduction and subluxation. Headache and neck pain were the most frequent comorbidities. Somatization, depression, anxiety, and obsessive-compulsive behavior were the most recurrent psychological disorders. Electromyographic analysis showed out of normal range data. Early diagnosis and interception are requested to avoid injuries and repeated traumatism. Multidisciplinary treatments are available to approach all the aspects of the syndrome.


Taiwanese nurses' cognition and attitudes towards the Magnet Hospitals Recognition Programme.
To explore the relevance and feasibility of using the Magnet Recognition Programme (MRP) at a Taiwanese hospital. Since no hospitals in Taiwan have applied for American Nurses Credentialing Center Magnet Recognition, and the American medical system and customs are different from those in Taiwan, this study explores whether or not the MRP is appropriate for Taiwanese hospitals. This study used a cross-sectional design with data collected from 905 nurses at a 1200-bed Taiwanese military hospital. The authors created the structured questionnaire from a framework based on the 14 Forces of Magnetism. The study used descriptive and inferential statistical analyses to explain the nurses' cognitions and attitudes towards the MRP and to discover if variations in these concepts occurred across nurses' demographics and their job classification. The mean nurses' cognitive score on each item varies from 3.3 to 4.1, and the mean nurses' attitude score on each item varies from 3.0 to 4.0 (both with the highest possible score related to the 14 Forces of Magnetism being 5.0). Using regression analysis, overall cognitive score, working in the operating room, or the sub-critical Neonatal Care Unit, and part-time hours of work explained 42% of the variance in the total attitude score towards the MRP. The findings indicate that when nurses have a higher cognition towards MRP, the more positive are their attitudes towards seeking the MRP. Using these findings and information about the nurses, the authors suggest strategies that hospital executives and nursing supervisors can use to improve nurses' cognition and attitudes when preparing to seek recognition through the MRP.


Progress toward an elusive goal: current status of cytomegalovirus vaccines.
Although infection with human cytomegalovirus (CMV) is ubiquitous and generally asymptomatic in most individuals, certain patient populations are at high risk for CMV-associated disease. These include HIV-infected individuals with AIDS, transplant patients, and newborn infants with congenital CMV infection. Immunity to CMV infection, both in the transplant setting and among women of childbearing age, plays a vital role in the control of CMV-induced injury and disease. Although immunity induced by CMV infection is not completely protective against reinfection, there is nevertheless a sound basis on which to believe that vaccination could help control CMV disease in high-risk patient populations. Evidence from several animal models of CMV infection indicates that a variety of vaccine strategies are capable of inducing immune responses sufficient to protect against CMV-associated illness following viral challenge. Vaccination has also proven effective in improving pregnancy outcomes following CMV challenge of pregnant guinea pigs, providing a 'proof-of-principle' relevant to human clinical trials of CMV vaccines. Although there are no licensed vaccines currently available for human CMV, progress toward this goal has been made, as evidenced by ongoing clinical trial testing of a number of immunization strategies. CMV vaccines currently in various stages of preclinical and clinical testing include: protein subunit vaccines; DNA vaccines; vectored vaccines using viral vectors, such as attenuated pox- and alphaviruses; peptide vaccines; and live attenuated vaccines. This review summarizes some of the obstacles that must be overcome in development of a CMV vaccine, and provides an overview of the current state of preclinical and clinical trial evaluation of vaccines for this important public health problem.


Evaluation of post-procedure changes in aneurysmal lumen following detachable coil-placement using multi-planar reconstruction of high-field (3.0T) magnetic resonance angiography.
Placement of detachable coil(s) for intracranial aneurysms has become one of the standard methods of management. Although detailed analysis of post-procedure changes in aneurysmal lumen is essential, technical difficulties often limit such evaluation. Development of higher magnetic field systems is steadily widening clinical usage of magnetic resonance imaging (MRI) primarily due to its significantly higher signal to noise ratio. In this study, we evaluated a multi-planar reconstruction (MPR) technique of magnetic resonance angiography (MRA) on a 3.0T system in an attempt to develop a routine method of post-procedure evaluation following detachable coil placement. Eleven patients with an intracranial aneurysm following placement of a Guglielmi detachable coil (GDC) participated in the study. Time of flight (TOF) magnetic resonance angiography (MRA) was obtained immediately after, and up to two years after coil embolisation utilising a GE 3.0T system. Data was analysed using standard maximum intensity projection (MIP) as well as the MPR technique and the results were compared to conventional catheter angiography. The study demonstrated that, compared to MIP, MPR can provide further information of alteration in aneurysm lumen, especially in analysis of: 1) jet of blood flow, 2) thrombus formation, 3) neck remnant or re-filling of blood, 4) location and shape of coils including compaction, and 5) coil protrusion into the parent artery. Combined MPR/MIP analysis of high-field MRA appears to be a powerful non-invasive method for evaluating GDC-treatment that can potentially replace conventional catheter angiography in many clinical situations.


Validation of prognostic scores to predict short-term mortality in patients with HBV-related acute-on-chronic liver failure: The CLIF-C OF is superior to MELD, CLIF SOFA, and CLIF-C ACLF.
Acute-on-chronic liver failure (ACLF) in chronic hepatitis B (CHB) patients has a high short-term mortality. Identification of effective models to predict the short-term mortality may enable early intervention and improve patients' prognosis. We aim to assess the performance of the CLIF Consortium Organ Failure score (CLIF-C OFs), CLIF sequential organ failure assessment score (CLIF-SOFAs), CLIF Consortium ACLF score (CLIF-C ACLFs), ACLF grade, and model for end-stage liver disease score (MELDs) in predicting the short-term mortality in CHB patients with ACLF.Among the 155 consecutive adult patients with liver failure as a discharge diagnosis were screened, and all the patients were treated at the Department of Infectious Diseases, Huashan Hospital, Fudan University (Shanghai, China) from January 2010 to February 2016. The diagnosis of ACLF was based on the criteria formalized by the ACLF consensus recommendations of the Asian Pacific Association for the Study of the Liver (APASL). Diagnostic accuracy for predicting short-term (28-day) mortality was calculated for CLIF-C OFs, CLIF-SOFAs, CLIF-C ACLFs, ACLF grade, and MELDs in all patients.One hundred fifty-five consecutive adult liver failure patients were screened and 85 patients including 73 males and 12 females were enrolled. Overall, the 28-day transplant-free mortality was 32% in all patients, and 100% in those with severe early course (ACLF-3). The area under the receiver operating characteristic curve (AUROC) of CLIF-C OFs (AUROC: 0.906, P = .0306, compared with MELDs) was higher than those of CLIF-SOFAs (AUROC: 0.876), CLIF-C ACLFs (AUROC: 0.858), ACLF grade (AUROC: 0.857), and MELDs (AUROC: 0.838) for predicting short-term mortality. The cut-point for baseline CLIF-C OFs in predicting death was 8.5, with 67% sensitivity, 90% specificity, and AUROC of 0.906 (95% CI: 0.8450-0.9679).The results indicate that short-term mortality is high in patients with ACLF and CLIF Consortium Organ Failure score is superior to MELD, CLIF SOFA, and CLIF-C ACLF in predicting its short-term mortality.


Bulevirtide and emerging drugs for the treatment of hepatitis D.
Hepatitis delta virus (HDV) causes acute and chronic liver disease that requires the co-infection of the Hepatitis B virus and can lead to significant morbidity and mortality. Bulevirtide is a recently introduced entry inhibitor drug that acts on the sodium taurocholate cotransporting peptide, thereby preventing viral entry to target cells in chronic HDV infection. The mainstay of chronic HDV therapy prior to bulevirtide was interferon alpha, which has an undesirable side effect profile. We review bulevirtide data from recent clinical trials in Europe and the United States. Challenges to development and implementation of bulevirtide are discussed. Additionally, we review ongoing trials of emerging drugs for HDV, such as pegylated interferon lambda and lonafarnib. Bulevirtide represents a major shift in treatment for chronic HDV, for which there is significant unmet need. Trials that compared bulevirtide in combination with interferon alpha vs interferon alpha monotherapy demonstrated significant increase in virologic response. Overall, treatment with different doses of bulevirtide were comparable. Bulevirtide was generally well tolerated, and no serious adverse events occurred. Understanding the true prevalence of HDV, as well as continued studies of emerging drugs will prove valuable to the larger goal of eradication of Hepatitis D.


HIV and ZIKA in Pregnancy: Parallel Stories and New Challenges.
On February 1, 2016, the World Health Organization (WHO) declared the Zika virus outbreak a Public Health Emergency of International Concern (PHEIC). Because Zika virus is a relatively new infection with several transmission routes that include mosquito bites, sexual and possibly blood-related, we present the case for a parallel between the Zika epidemic and the AIDS epidemic for issues that relate particularly to pregnancy and epidemic response. We will discuss the many similarities between both epidemics while acknowledging that the viruses are different and the pathophysiology and disease manifestation are also different. What can we learn of the three decades of awareness campaigns, community involvement, clinical, behavior and prevention research, activism and policy-making related to HIV/AIDS? How can the lessons and experience of dealing with the HIV epidemic can help us deal with the ongoing Zika epidemic? Is there a roadmap that we can follow? Our position is that we can and we should. Parallels between the Zika and HIV/AIDS epidemics particularly in relation to pregnancy can be established. Lessons and successes from the HIV/AIDS epidemic control efforts can guide us towards comprehensive approaches to improve the health of women and infants at risk for Zika.


Wood volatiles as attractants of the confused flour beetle, Tribolium confusum (Coleoptera: Tenebrionidae).
Confused flour beetles are serious pests of stored grain products, and therefore, it is important to efficiently monitor and control their populations. Aggregation pheromones are commercially used for monitoring this beetle but their efficacy has been questioned and they may be inadequate for practical use. Food attractants as well as pheromones are commonly used for monitoring stored-product insects. However, food attractants may not be effective in the case of food handling facilities, which are already filled with food odours. The ancestors of flour beetles may have been associated with dead or decomposing woody vegetation, so we investigated the attractiveness of several wood odours to beetles using a pitfall olfactometer. The beetles were strongly attracted to all wood odours tested: Castanea crenata, Magnolia obovata, Paulownia tomentosa, Prunus jamasakura, and Zelkova serrata. The attractiveness of these wood odours was also stronger than that of the odours of the usual food of these beetles. Supercritical CO2 extracts of these species of wood were also attractive to the beetles. The Z. serrata extract was the most attractive among these extracts, and was further analysed by gas chromatography mass spectrometry. One major compound, (-)-mellein, was detected in the extract. Synthetic (±)-mellein attracted the beetles.


Initial regional evaluation of the Cystic Fibrosis Newborn Screening Program: data from the Mediterranean coast of Turkey
Since January 2015, the Cystic Fibrosis Newborn Screening (CFNS) program has been implemented in Turkey. We aimed to evaluate the demographic, clinical, and laboratory data of cases referred from the CFNS program and to determine the most suitable cut-off value for immunoreactive trypsinogen (IRT)-1 and immunoreactive trypsinogen (IRT-2) that are used in the CFNS program in Turkey. A total of 156 Turkish Caucasian subjects were determined as positive cases during 3 years, from January 2015 to January 2018, and were referred to the pediatric pulmonology clinics of Akdeniz University Hospital, Antalya, Turkey, for the national CFNS program. The evaluation was made considering the IRT-1 and IRT-2 values, demographic characteristics, sweat test results, CFTR genotypes, and diagnoses. Nine patients were diagnosed with cystic fibrosis (CF). Eight were diagnosed with CF-related metabolic syndromes and three were determined to be CF carriers. The ratio of CF to CF-related metabolic syndrome was determined as 1.1:1. Considering the limits of the present CFNS program and the IRT method, the positive predictive value (PPV) for the referred cases was determined as 5.8%. When a cut-off value of 105.6 ng/mL was taken for IRT-1, sensitivity was 100%, specificity was 59%, and PPV was 12.8%. For a cut-off value of 88.75 ng/mL for IRT-2, sensitivity was determined as 90%, specificity as 65%, and PPV as 15.2%. This is the first detailed clinical study to evaluate the data from the CFNS program along the Mediterranean coast of Turkey. As false positive results are extremely high in Turkey, there is an urgent need for revision of the IRT-1 and IRT-2 limits by evaluating the data of the whole country.


Kaempferol-3-O-rhamnoside isolated from the leaves of Schima wallichii Korth. inhibits MCF-7 breast cancer cell proliferation through activation of the caspase cascade pathway.
Plants consumed by non-human primates represent potential drug sources for human disease management. In this study, we isolated kaempferol-3-O-rhamnoside as an active compound from the leaves of Schima wallichii Korth., a plant commonly consumed by non-human primates. Its anti-cancer activities, including its ability to induce apoptotic mechanisms, were investigated in MCF-7 breast cancer cells. Results showed that in MCF-7 cells, kaempferol-3-O-rhamnoside inhibits cell proliferation in a dose-dependent manner and promotes apoptosis via the activation of the caspase signaling cascade, which includes caspase-9, caspase-3 and PARP. Our results provide a basis for further exploration of kaempferol-3-O-rhamnoside as an active compound for potential anti-cancer therapeutics.


Projected private hospital expenditure in Ireland, 2018-2035: What role for demographics, cost, and Sláintecare?
Despite private hospitals occupying an important role in the delivery of acute hospital care in Ireland, an understanding of future spending pressures on these services is limited. Particularly, a key dimension of Ireland's ambitious roadmap for healthcare reform (Sláintecare) seeks to remove private practice from public hospitals. However, to date, there has been no examination of how this reform could impact private hospital demand and expenditure, and ultimately, the capacity to treat public patients. Using previously unavailable administrative health insurer data and a healthcare macro-simulation projection model, we project real (volume-based) and nominal expenditure on private hospital services over the medium-term (2018-2035). We develop a number of projection scenarios that vary assumptions in relation to population growth and ageing, healthy ageing, and the future cost of care delivery. Additionally, by developing profiles of private activity in public hospitals, we examine how the removal of private practice from public hospitals could impact on demand and expenditure in private hospitals over time. Findings from this analysis have implications for capital investment and workforce planning in private hospitals, and failure to meet future demand could have implications for access to care in public hospitals. Moreover, should private practice be ended in public hospitals, most complex private in-patient and emergency care is likely to remain within the public hospitals with limited capacity benefits for the public system.


Neutrophil zinc: an indicator of zinc status in man.
At present there is no single laboratory test which establishes the diagnosis of zinc deficiency in human subjects. Neutrophils are rich in zinc and have a short life span in the peripheral blood. The possibility that neutrophil zinc may be a reliable indicator of zinc status was tested in this study. Experiments were carried out in two groups of subjects. The first group of subjects included sickle cell anemia patients, known to be zinc-deficient. Zinc concentrations in the plasma, erythrocytes, and neutrophils were assayed by means of flameless atomic absorption spectrophotometry in 17 males and 7 females between the ages of 14-19 years. Neutrophil zinc in sickle cell anemia subjects correlated significantly with height (r = 0.62, p less than 0.005), weight (r = 0.66, p less than 0.001), and serum testosterone in males (r = 0.71, p less than 0.01). Inasmuch as growth retardation and hypogonadism in male sickle cell anemia patients have been related to a deficiency of zinc, these results indicate that the neutrophil zinc assay may be a good indicator of zinc deficiency in human subjects. Such correlations were not observed with zinc levels in the plasma erythrocytes. In the second experiment, a marginal deficiency of zinc was induced in five healthy human volunteers between the ages of 45-65 years by administering a semipurified soy protein-based diet for 12 weeks with daily zinc intake of 14.3 +/- 1.01 mg according to previously published techniques. Zinc balance (excluding sweat loss) on the soy protein diet at the end of the experiment was negative (-2.39 +/- 0.79 mg/dl). At the end of 4 weeks on the experimental diet, neutrophil zinc (mean +/- S.D.) was 107 +/- 27.2 in comparison to the base line level of 135.33 +/- 3.54 micrograms/10(10) cells (p less than 0.05). Changes in plasma zinc at the end of 4 weeks of dietary treatment were not statistically significant. After 12 weeks on the experimental diet, the neutrophil zinc declined 30.87%. In conclusion, our studies in two human zinc-deficient models suggest that neutrophil zinc levels may be a reliable and sensitive indicator of zinc status.


[The efficacy of the chemotherapy of patients with chronic destructive pulmonary tuberculosis].
The efficacy and tolerance of chemotherapy consisting of 4-6 drugs used intermittently and (or) daily for 3 to 16 months were determined in 100 patients with chronic destructive pulmonary tuberculosis formerly treated without effect. Discharge of Bacteria ceased in 71.4% of patients, the caverns healed in 22% and partially regressed in 67% that was correspondingly 33%, 10.8% and 12.6% higher than in routine regimens of chemotherapy used in 125 patient and consisted of three daily administered drugs. The time of abacillation and healing of the caverns in polychemotherapy were two months shorter. The tolerability of both regimens was satisfactory and approximately similar.


Temperature-compensated magnetic field sensing with a dual-ring structure consisting of microfiber coupler-Sagnac loop and fiber Bragg grating-assisted resonant cavity.
A novel temperature-compensated magnetic field sensor based on a ring erbium-doped fiber laser combined with a fiber Bragg grating (FBG) and a Sagnac loop containing a microfiber coupler (MFC) and magnetic fluid is proposed and investigated. Thanks to the dual-ring structure of the MFC-Sagnac loop and the FBG-assisted resonant cavity, the output of the structure has two distinct laser peaks. In addition to the magnetic field sensing capability, the proposed structure can simultaneously provide temperature information. The maximum experimentally demonstrated sensitivity to a magnetic field determined from the spectral shift of one laser peak is 102 pm/mT in the magnetic field range from 0 to 60 mT. The spectral position of the other laser peak is independent of the magnetic field but shifts toward longer wavelengths with temperature with a sensitivity of 18 pm/°C. The proposed magnetic field sensor is advantageous for applications requiring measurement accuracy over a wide magnetic field range with a compensating of temperature information.


Trends in of late-stage squamous cell vulvar carcinomas: analysis of the surveillance, epidemiology, and end results (SEER) database.
To describe the trends in the rate, treatment, and survival of late-stage vulvar carcinomas (LSVCs) over a 20-year period in the United States. Demographic, pathologic, treatment, and survival data were collected from the Surveillance, Epidemiology, and End Results registry between 1988 and 2007. Trends concerning the rate of LSVC (International Federation of Gynecology and Obstetrics [FIGO] stages III and IV), its management, and outcome were studied. Five-year overall and disease-specific survival rates were calculated. The rate of LSVC (32.4%) as compared with early-stage disease (67.6%) did not change significantly from 1988 to 2007 (P = 0.59). Of the 2630 patients with LSVC, the median age at diagnosis was 72 years, with 88.5% of them being white. Surgery and radiation therapy were performed in 73.8% and 60.6% of cases, respectively, with 37% of the patients having no lymph node dissection. A significant trend toward removing fewer lymph nodes (P = 0.02) and offering more radiation therapy (P = 0.02) has been observed across the study period. Five-year overall and disease-specific survival rates did not change (P = 0.44 and P =0.26, respectively) from 1988 to 2007. On multivariate analysis, node positivity (hazard ratio, 3.12 [95% confidence interval, 2.30-4.24]) and surgery (hazard ratio, 0.41 [95% confidence interval, 0.24-0.69]) were found to be the 2 most predictive variables for cancer mortality, followed by age and tumor size. Less extensive surgery and more radiation therapy did not compromise survival of LSVC over the 20-year period.


Depression, falls, and risk of fracture in older women. Study of Osteoporotic Fractures Research Group.
Previous studies have suggested that depression is associated with falls and with low bone density, but it is not known whether depression leads to an increased risk of fracture. We conducted a prospective cohort study in elderly white women who were recruited from population-based listings in the United States. At a second visit (1988-1990), 7414 participants completed the 15-item Geriatric Depression Scale and were considered depressed if they reported 6 or more symptoms of depression. We measured bone mineral density (BMD) in the spine and hip using dual energy x-ray absorptiometry at the second visit, and asked participants about incident falls (yes/no) at 4 follow-up visits. Nonvertebral fractures were ascertained for an average of 6 years following the depression measure, and verified radiologically. We determined incident vertebral fractures by comparing lateral spine films obtained at the first visit (1986-1988) with repeat films obtained an average of 3.7 years later (1991-1992). The prevalence of depression (Geriatric Depression Scale score > or = 6) was 6.3% (467/7414). We found no difference in mean BMD of the hip and lumbar spine in women with depression compared with those without depression. Women with depression were more likely to experience subsequent falls than women without depression (70% vs 59%; age-adjusted odds ratio [OR], 1.6; 95% confidence interval [CI], 1.3-1.9; P<.001), an association that persisted after adjusting for potential confounding variables (OR, 1.4; 95% CI, 1.1-1.8; P=.004). Women with depression had a 40% (age-adjusted hazard ratio [HR], 1.4; 95% CI, 1.2-1.7; P<.001) increased rate of nonvertebral fracture (124 fractures in 3805 woman-years of follow-up) compared with women without depression (1367 fractures in 59 503 woman-years of follow-up). This association remained strong after adjusting for potential confounding variables, including medication use and neuromuscular function (HR, 1.3; 95% CI, 1.1-1.6; P=.008). Further adjustment for subsequent falls appeared to explain part of this association (HR, 1.2; 95% CI, 1.0-1.5; P = .06). Women with depression were also more likely to suffer vertebral fractures than women without depression, adjusting for history of vertebral fracture, history of falling, arthritis, diabetes, steroid use, estrogen use, supplemental calcium use, cognitive function, and hip BMD (OR, 2.1; 95% CI, 1.4-3.2; P<.001). Depression is a significant risk factor for fracture in older women. The greater frequency of falls among individuals with depression partially explains this finding. Other mechanisms responsible for the association between depression and fracture remain to be determined.


A pilot study to determine the normal haematological indices for young Malawian adults in Blantyre, Malawi.
Reference ranges for haematological and other laboratory tests in most African countries are based on populations in Europe and America and, because of environmental and genetic factors, these may not accurately reflect the normal reference ranges in African populations. To determine the distribution of haematological parameters in healthy individuals residing in Blantyre, Malawi. We also examined the effect of sociodemographic and nutritional factors on the haematological variables. We conducted a proof-of-concept cross-sectional study, involving 105 healthy blood donors at Malawi Blood Transfusion Service in Blantyre. Eligible participants were HIV-negative males and females, aged 19 to 35 years, who did not have any evidence of acute or chronic illness, or blood-borne infection. We performed the haematological tests at the Malawi-Liverpool Wellcome Trust laboratory in Blantyre, and the screening tests at Malawi Blood Transfusion Service laboratories. Out of 170 consenting healthy volunteers, haematological results were available for 105 participants. The proportions of results which were below the lower limit of the manufacturer's reference ranges were 35.2% (37/105) for haemoglobin, 15.2% (16/105) for neutrophils, 23.8% (25/105) for eosinophils, and 88.6 % (93/105) for basophils. The proportions of results that were above the upper limit of the manufacturer's reference ranges were 9.5% (10/105) for platelets and 12.4% (13/105) for monocytes. We also observed that the mean leucocyte and basophil counts were significantly higher in males than females (p = 0.042 and p = 0.015, respectively). There were no statistically significant differences in haematological results observed among different ethnic, age, and body mass index groups. Over half of otherwise healthy study participants had at least one abnormal haematological result, using previously established foreign standards. More detailed studies are needed to establish locally relevant normal ranges for different age groups and other demographic characteristics of the Malawian population. This will lead to accurate interpretation of laboratory results.


The problems of delivering neuroactive molecules to the CNS.
At present, the aetiologies of many neurological and neurodegenerative diseases are unknown. However, emergence of a better understanding of these diseases, at both cellular and molecular levels, opens up the possibility of replacement therapies. The presence of the blood-brain barrier complicates the delivery of molecules to the central nervous system. Numerous attempts have been made to bypass this barrier either by delivering the drugs directly into the brain or by transplanting cells to produce the missing molecules in situ. This review explores several methods for delivering bioactive molecules into the CNS, including the use of permeabilizers, osmotic pumps, slow polymer release systems and transplantation of cells with or without the use of the encapsulation technology.


Enterobacteriaceae and Enterococcaceae are the dominant bacterial families translocating to femur heads in broiler chicks.
As a result of rapid growth of broilers, bacterial chondronecrosis with osteomyelitis has emerged in the last decade, with bacterial translocation from the gut to internal organs, including the femur head. In this study, we isolated translocated bacteria in femur heads, blood, and liver, during ageing of broilers, and identified the bacteria using 16S rDNA sequencing. We also provided histopathological descriptions of femur head lesions. Bacteria were isolated from blood, liver, and femoral head samples. In the femoral heads, an age-related presence of bacteria was observed, with high prevalence at 2 days post-hatch, and no bacteria isolated from femoral heads of broilers older than 14 days. Bacterial identification using 16S rRNA gene sequencing demonstrated that bacteria present in blood, liver, and femur belonged to different taxonomic groups. Bacteria isolated from blood and liver samples belonged predominantly to the Enterobacteriaceae, Enterococcaceae, and Staphylococcaceae, while Escherichia/Shigella and Enterococcus spp. were the most prevalent taxa in femoral head samples. No bacteria were isolated from the femoral head of any of the birds with histopathological lesions. All 19-day-old and 22-day-old birds in this study showed cartilage retention in both legs, and had signs of separation between the articular cartilage and the growth cartilage in one or both legs. This study shows that young clinically healthy broilers have a higher prevalence of bacteria in the femoral head compared to older broilers and that presence of bacteria in blood and liver is common during ageing of broilers.RESEARCH HIGHLIGHTSLarge number of bacteria isolated from femoral heads of clinically healthy broilers.The prevailing taxa in femoral heads were Escherichia/Shigella and Enterococcus spp.Continuous presence of bacteria in blood and liver of clinically healthy broilers.Enterobacteriaceae, Enterococcaceae, and Staphylococcaceae prevail in blood and liver.


The extensively restored posteriortooth has a high incidence of tooth fracture.
A multicentred practice based study was established to test the hypothesis that the extensively restored tooth has a high incidence of posterior tooth fracture (PTF). All patients who presented with PTF in 23 general dental practices over a period of 14 weeks were included in the study. 764 PTF restorations were placed out of a total of 7551, an incidence of 10%. A novel classification proposing increased severity of fracture from I-IV was used. Class I = 19%, II = 54%, III = 22% and IV = 5%. Primary PTFs accounted for 67%, secondary 33%. 92% offractured teeth had a Class 2 restoration in situ. The heavily restored tooth has been shown to have a high incidence of PTF and it is suggested that this is a major restorative problem in general dental practice in the UK.


Bovine papillomavirus type 1 genome in hamster sarcoma cells in vivo and in vitro: variation in the level of transcription.
The physical state and expression of the bovine papillomavirus type 1 (BPV-1) genome were analysed in two transplantable hamster sarcomas (HT1 and HT2) after a low number of transplantations, in two tumourigenic cell lines derived from the first transplant of HT2 sarcoma and another transplantable sarcoma (HT3) and in tumours obtained by grafting these cells. Blot hybridization experiments indicated the presence of multiple free copies of the whole viral genome in HT1 and HT2 tumour transplants (100 and 25 copies/cell respectively), irrespective of the number of in vivo or in vitro passages. In contrast, HT3 cells, and tumours induced by these cells, at early and late passages in vitro contained viral sequences probably integrated in the cell genome, in addition to the free viral DNA sequences. Polyadenylated viral transcripts were easily detected in HT1, HT2 and HT3 tumours obtained at early passages in vivo and in vitro, with electrophoretic mobilities corresponding to 1200 to 1400 bases (HT1, HT2 and HT3), 1750 bases (HT1) and 2500 bases (HT2). Homologous sequences of the transcripts were localized in the transforming BamHI-HindIII fragment of BPV-1 DNA, mainly in the BamHI-EcoRI fragment (0.31 to 0.602 map units). In contrast, almost no viral transcription was detected in HT2 and HT3 cells after 50 subcultures and in the tumours induced by these cells. This suggests that the tumourigenicity of the HT2 and HT3 cells is compatible with a very low level of expression of the transforming region of the BPV-1 genome.


The angiotensin-converting enzyme gene I/D polymorphism and heart rate variability following acute myocardial infarction.
Heart rate variability (HRV) is a measure of cardiac autonomic control and is therefore subject to regulation by the renin-angiotensin system. The primary objective of this study was to determine the effect of an insertion/deletion polymorphism within the angiotensin-converting enzyme (ACE) gene on HRV in the early stages after a myocardial infarction at a time when cardiac autonomic control is deranged. The secondary objective was to determine whether this polymorphism affected the HRV response to inhibition of ACE. 149 Caucasian subjects were studied 25 +/- 16 h following MI using time and frequency domain measures of HRV derived from two 5-minute ECG recordings. Recordings were repeated at 182 +/- 65 h following MI, when subjects had been stabilised on ramipril 2.5 mg bd. The study included 46 subjects with the DD genotype, 69 with the ID genotype, and 34 with the II genotype. No effect of the I/D polymorphism on short-term recordings of HRV was found. There was no difference in HRV response to the introduction of ramipril according to the genotypes. The I/D polymorphism within the ACE gene does not influence HRV after MI or the HRV response to ACE inhibitor therapy with ramipril. These findings may reflect the relative lack of importance of the I/D polymorphism and ACE activity in determining plasma and tissue angiotensin II concentration after a major stimulus to the renin-angiotensin system as occurs after myocardial infarction.


[Nutritional management of oncologic patients].
Malnutrition is a common complication in the oncological patient, and this affects his or her quality of life and survival. The majority of these patients show nutritional problems in their evolution, especially anorexia and weight loss. The most severe picture is called neoplastic cachexia. The causes hereof are many and some are not well known as they are related to the tumor metabolism itself, the metabolic response to the release of cytokines, or even to the treatment: surgery, chemotherapy or radiation therapy. The nutritional support will not cure the cancer; the malignant cells must be eradicated by the anti-tumor therapies, but nutrition is a therapy that is complementary to the basic treatment, however, with nutritional intervention we can avoid a greater deterioration of the patient, improve some nutritional and immunological parameters, avoid complications, and improve the quality of life. The nutritional action plan should be based on the knowledge of the specific situation of each patient, assessing his or her nutritional status, type of tumor, expected response to treatment, and the capacity to handle the situation. As in any patient, the access route of the nutritional support may be oral, enteral, or parenteral, depending on the clinical situation. The oral route, supervised by an experienced team, is the safest and the most effective, but this requires an adequately functioning digestive system and that the patient be able to maintain an adequate caloric and proteineic ingestion. When oral feeding is impossible or insufficient, it is necessary to resort to enteral or parenteral nutrition, depending on the functionality of the digestive apparatus. Special attention should be paid to those patients in whom the failure of the oncological therapy leads to an expected fatal outcome. Within the palliative care the nutritional intervention is simple, cheap, and effective with regard to the improvement of the quality of life. Dietary advice and at home enteral nutrition may be of great help.


Comparison of topical glyceryl trinitrate with diltiazem ointment for the treatment of chronic anal fissure: a randomized clinical trial.
The aim of this study was to compare the effect of topical glycerol trinitrate ointment (GTN) with topical diltiazem hydrochloride ointment (DTZ) in the treatment of chronic anal fissure. Prospectively, 102 patients were treated randomly with either GTN ointment (0.2%) or DTZ ointment (2%) a couple of times daily for 12 weeks. Forty-five patients (88.2%) in group DTZ and 36 patients (70.6%) in group GTZ had a reduction of symptoms. The decrease in the symptoms for group DTZ was significantly more than for group GTN (P = 0.02). Mean time for symptom reduction was 2.44 +/- 0.30 in group DTZ and 2.50 +/- 0.28 weeks in group GTN with no significant differences between the two groups (P > 0.05). Complete relief of symptoms was observed in 72.5% and 54.9% patients in groups DTZ and GTN, respectively. The frequency of complete relief of symptoms between the two groups was not significant (P > 0.05). Complete remission of anal fissure occurred in 66.7% patients in group DTZ and 54.9% patients in group GTN, which shows no significant difference. Mean time taken for fissure healing in the GTN group was dramatically less than in the DTZ group (P = 0.001). Finally, 33.3% of patients in the DTZ group and 45.1% of patients in the GTN group underwent operation. The need for operation was not significantly different between the two groups (P > 0.05). Both DTZ and GTN are equally effective and can be the preferred first-line treatment of chronic anal fissure. However, GTN is associated with a higher rate of headache, and should be replaced by DTZ.


Pure red cell aplasia in a patient with chronic granulocytic leukaemia treated with interferon-alpha.
Interferon-alpha has been shown to improve survival in patients with chronic granulocytic leukaemia, therefore it is increasingly becoming part of the standard treatment of this condition. Interferon has a wide variety of side-effects. Pure red cell aplasia has been reported in a few cases of chronic granulocytic leukaemia but this usually heralds the onset of the transformation to the acute phase. This paper reports a possible, and not previously reported, side-effect of interferon-alpha in a patient with chronic granulocytic leukaemia.


Optimal Soil Eh, pH, and Water Management for Simultaneously Minimizing Arsenic and Cadmium Concentrations in Rice Grains.
Arsenic (As) and cadmium (Cd) concentrations in rice grains are a human health concern. We conducted field experiments to investigate optimal conditions of Eh and pH in soil for simultaneously decreasing As and Cd accumulation in rice. Water managements in the experiments, which included continuous flooding and intermittent irrigation with different intervals after midseason drainage, exerted striking effects on the dissolved As and Cd concentrations in soil through changes in Eh, pH, and dissolved Fe(II) concentrations in the soil. Intermittent irrigation with three-day flooding and five-day drainage was found to be effective for simultaneously decreasing the accumulation of As and Cd in grain. The grain As and Cd concentrations were, respectively, linearly related to the average dissolved As and Cd concentrations during the 3 weeks after heading. We propose a new indicator for expressing the degree to which a decrease in the dissolved As or Cd concentration is compromised by the increase in the other. For minimizing the trade-off relationship between As and Cd in rice grains in the field investigated, water management strategies should target the realization of optimal soil Eh of -73 mV and pH of 6.2 during the 3 weeks after heading.


Negative refraction imaging in a hybrid photonic crystal device at near-infrared frequencies.
We present the experimental demonstration of imaging of a point source by negative refraction at near-infrared frequencies using a hybrid photonic crystal device. The photonic crystal device, fabricated by patterning holes in 260nm silicon-on-insulator, integrates a triangular-lattice photonic crystal with a large photonic bandgap and square-lattice photonic crystal with negative refraction. Experimental results show that the output of a line-defect photonic bandgap waveguide provides a nearly ideal point source and then is imaged through the photonic crystal by negative refraction.


Effects of Myopic Orthokeratology on Visual Performance and Optical Quality.
To analyze the changes in visual performance and optical quality after orthokeratology (ortho-k) treatment and its correlation with the magnitude of lens decentration and the diameter of treatment zone (TxZ). A prospective study was conducted in 27 eyes of 27 patients wearing ortho-k contact lens. Area under log contrast sensitivity function (AULCSF), modulation transfer function cutoff values (MTFcutoff), Strehl ratio (SR), and objective scattering index (OSI) were measured and compared before and 1 month after ortho-k lens treatment. Refractive sphere, astigmatism, and diameter and decentration of TxZ were tested against the change in AULCSF, MTFcutoff, SR, and OSI after ortho-k treatment in stepwise multiple linear regression models. Objective scattering index significantly increased and AULCSF, MTFcutoff, and SR significantly decreased after ortho-k lens wear (all P<0.001). The mean TxZ diameter was 3.61±0.26 mm, and the mean magnitude of TxZ decentration was 0.60±0.16 mm. The amount of lens decentration significantly correlated with the change in AULCSF and MTFcutoff (P=0.027 and P=0.005, respectively). The diameter of TxZ significantly correlated with the change in MTFcutoff and SR (P=0.005 and P=0.024, respectively). Visual and optical quality decreases after ortho-k treatment, which can be alleviated by a larger TxZ diameter and a smaller lens decentration.


Zeta potential as a measure of polyelectrolyte flocculation and the effect of polymer dosing conditions on cell removal from fermentation broth.
Characterization of flocculation for cell removal from fermentation broth via polyelectrolyte addition is commonly based on qualitative methods such as physical appearance of the floc. The use of zeta potential as a quantitative measure of floc character was evaluated as an indicator of optimal polymer addition. Zeta potential was found to increase with increasing cationic polyelectrolyte dosage, but never reached zero regardless of the total amount of polymer added, indicating flocculation occurs at least partially through a bridging type mechanism. Experiments were conducted using various polymer concentrations (25-75 g/L) and dosing methods (batch, incremental and continuous addition) that resulted in variable overall polymer requirements to achieve optimum flocculation. Zeta potential was found to be constant at optimal floc character regardless of the total amount of polymer added, polymer concentration, or method of polymer addition. Experiments with two additional types of fermentation broth also showed characteristic zeta potentials at optimal flocculation. Polymer requirements to achieve a particular floc character can vary greatly, depending on polymer dosing conditions and fermentation batch. The effect of polymer dosing conditions on the polymer requirement to obtain optimal floc character was evaluated. Polymer dosing method and calcium concentration were both found to have a significant effect (P < 0.0001) with continuous polymer addition and high calcium concentration requiring less polymer than did batch polymer addition and low calcium concentration, respectively. Polymer dosing concentration did not significantly affect polymer requirement for optimal flocculation.


Lactobacillus Brevis OPK-3 from Kimchi Prevents Obesity and Modulates the Expression of Adipogenic and Pro-Inflammatory Genes in Adipose Tissue of Diet-Induced Obese Mice.
Our previous study reported that lactic acid bacteria (L. brevis OPK-3) isolated from kimchi ameliorated intracellular lipid accumulation in 3T3-L1 adipocyte. The current study explored potential roles of L. brevis OPK-3 (KLAB) on preventing body weight gain and its effect on the inflammatory response of adipose tissue. Male C57BL/6 mice (n = 10) were divided into four groups: normal diet with distilled water (NDC), high-fat diet with distilled water (HDC), high-fat diet with L-ornithine (OTC) or high-fat diet with KLAB. The KLAB supplement resulted in significantly lower body weight, lower epididymal fat tissue mass, and lower serum and hepatic TG levels than the HDC. KLAB supplementation improved serum cytokines, and real-time polymerase chain reaction (PCR) analysis showed significantly lower inflammatory cytokine mRNA levels in epididymal adipose tissue. These results suggest that the administration of KLAB inhibits the induction of inflammation in adipose tissue along with the inhibition of weight gain. Therefore, this study demonstrates the therapeutic and beneficial value of this strain produced during the fermentation of kimchi.


Radiological imaging findings of a case with vertebral osteoid osteoma leading to brachial neuralgia.
Osteoid osteoma is a small, benign osteoblastic tumor consisting of a highly vascularized nidus of connective tissue surrounded by sclerotic bone. Three-quarters of osteoid osteomas are located in the long bones, and only 7-12% in the vertebral column. The classical clinical presentation of spinal osteoid osteoma is that of painful scoliosis. Other clinical features include nerve root irritation and night pain. Osteoid osteoma has characteristic computed tomography (CT) findings. Because magnetic resonance imaging (MRI) findings of the osteoid osteomas causing intense perinidal edema can be confusing, these patients should be evaluated with clinical findings and other imaging techniques. In this study, we present X-ray, CT, and MRI findings of a case with osteoid osteoma located in thoracic 1 vertebra left lamina and transverse process junction leading to brachial neuralgia symptoms.


Evaluating the role of transrectal ultrasonography and magnetic resonance imaging in prostate carcinoma.
A review of the recent literature on the performance of transrectal ultrasonography and MR imaging in the evaluation of prostate carcinoma demonstrates the typical evolutionary cycle inherent in any technology assessment: increasingly improved methodology has resulted in the tempering of initial enthusiastic reports by more sober observations and realistic expectations. This inevitable and predictable evolution should not be interpreted as a criticism of earlier work; designing and implementing a rigorous study of new and rapidly changing technology is a challenging endeavor. Nevertheless, the most current work has greatly helped to provide a more balanced and convincing perspective that is more useful to the practicing radiologist.


Efficacy of adding interoceptive exposure to intensive interdisciplinary treatment for adolescents with chronic pain: a randomized controlled trial.
Fear of pain plays an important role in the maintenance of chronic pain. It may be reduced through exposure therapy. This 2-arm parallel samples randomized controlled trial aimed to investigate whether interoceptive exposure (IE) therapy enhances reductions in fear of pain (primary outcome), pain (pain intensity, pain-related disability, and school absence), and emotional characteristics (anxiety and catastrophizing) when implemented as an adjunctive treatment in the context of intensive interdisciplinary pain treatment for pediatric chronic pain patients. N = 126 adolescents, aged 11 to 17 years, who were receiving standard intensive interdisciplinary pain treatment were randomly assigned to either receive additional IE (n = 64) or additional relaxation therapy (RT) (n = 62). All patients were assessed at admission, discharge, and 3 months after discharge. The data of N = 104 patients were analyzed. Significant large reductions were found in the total score and subscale scores of the Fear of Pain Questionnaire for Children in both study groups (eg, total score [range 0-60; IE/RT]: admission M = 23.5/24.9; discharge M = 16.0/19.7; P < 0.001, (Equation is included in full-text article.)= 0.27) and mainly large reductions in pain characteristics. There were no greater decreases in the IE group (P > 0.1). The exploratory analyses revealed that the patients with high fear of pain before treatment (P < 0.05, (Equation is included in full-text article.)> 0.03) and the patients with abdominal pain (P < 0.04, (Equation is included in full-text article.)> 0.25) showed greater decreases in their fear of pain (total and subscale score) in the IE group than in the RT group. In conclusion, the results suggest that IE is not particularly effective for all the pediatric chronic pain patients, but the patients with high fear of pain before treatment and with abdominal pain strongly benefit from this intervention.


Analyses of renal outcome following transplantation adjusting for informative right censoring and demographic factors: A longitudinal study.
Demographic factors such as race, vital status, gender, and age could affect the final renal outcome of patients who undergo renal transplantation. These demographic factors could be assessed at the recipient and donor levels. Repeated measures for blood urea nitrogen (BUN) are typically recorded for each patient following renal transplantation, as a biomarker to assess renal progress. However, once a patient develops renal failure due to graft rejection, no measurement of BUN can be registered and the patient goes back to dialysis. This causes loss of follow-up and incomplete data on BUN measurements, a problem referred to as informative right censoring. If this problem is ignored, inaccurate, and biased estimates will be generated. In this study, unbiased estimates for the rate of change of BUN levels over time adjusted for informative right censoring and demographic factors were acquired using a sophisticated model of analysis. Our results demonstrated that BUN levels for Caucasians were decreasing at a greater rate than African Americans (p < 0.0001). When donors are deceased, African American recipients showed an increase instead of a decrease in their BUN levels following transplantation. Moreover, African Americans showed a decrease in their BUN levels when the donors were African Americans compared with when donors were Caucasians (p = 0.03). Our results also showed that BUN levels were decreasing at a greater rate when donors and recipients were of different gender than when they were of the same gender (p = 0.009). These results suggest that the success of renal transplantation is impacted by the donor/recipient demographic factors.


High rate of recurrent venous thromboembolism in patients with myeloproliferative neoplasms and effect of prophylaxis with vitamin K antagonists.
The optimal duration of treatment with vitamin K antagonists (VKA) after venous thromboembolism (VTE) in patients with Philadelphia-negative myeloproliferative neoplasms (MPNs) is uncertain. To tackle this issue, we retrospectively studied 206 patients with MPN-related VTE (deep venous thrombosis of the legs and/or pulmonary embolism). After this index event, we recorded over 695 pt-years 45 recurrences, venous in 36 cases, with an incidence rate (IR) of 6.5 per 100 pt-years (95% confidence interval (CI): 4.9-8.6). One hundred fifty-five patients received VKA; the IR of recurrent thrombosis per 100 pt-years was 4.7 (95% CI: 2.8-7.3) on VKA and 8.9 (95% CI: 5.7-13.2) off VKA (P=0.03). In patients receiving VKA, the IR of recurrent thrombosis per 100 pt-years was 5.3 (95% CI: 3.2-8.4) among 108 patients on long-term VKA and 12.8 (95% CI: 7.3-20.7) after discontinuation among the 47 who ceased treatment (P=0.008), with a doubled risk of recurrence after stopping VKA (hazard ratio: 2.21, 95% CI: 1.19-5.30). The IR of major bleeding per 100 pt-years was 2.4 (95%: CI: 1.1-4.5) on VKA and 0.7 (95% CI: 0.08-2.5) off VKA (P=0.08). In conclusion, in MPN patients with VTE recurrent thrombosis is significantly reduced by VKA and caution should be adopted in discontinuation; however, the incidence of recurrence on treatment remains high, calling for clinical trials aimed to improve prophylaxis in this setting.


The Desirability Optimization Methodology; a Tool to Predict Two Antagonist Responses in Biotechnological Systems: Case of Biomass Growth and Hyoscyamine Content in Elicited Datura starmonium Hairy Roots.
The use of the desirability function approach combined with the response surface methodology (RSM), also called Desirability Optimization Methodology (DOM), has been successfully applied to solve medical, chemical, and technological questions. It is particularly efficient for the determination of the optimal conditions in natural or industrial processes involving different factors leading to the antagonist responses. Surprisingly, DOM has never been applied to the research programs devoted to the study of plant responses to the complex environmental changes, and thus to biotechnological questions. In this article, DOM is used to study the response of Datura stramonium hairy roots (HRs), obtained by genetic transformation with Agrobacterium rhizogenes A4 strain, subjected to the jasmonate treatments. Antagonist effects on the growth and tropane alkaloid biosynthesis are confirmed. With a limited number of experimental conditions, it is shown that 0.06 mM jasmonic acid (JA) applied for 24 h leads to an optimal compromise. Hyoscyamine levels increase by up to 290% after 24 h and this treatment does not significantly inhibit biomass growth. It is thus demonstrated that the use of DOM can efficiently - with a minimized number of replicates - leads to the optimization of the biotechnological processes.


[Meningo-encephalic tuberculosis in childhood. Anatomo pathological study of 10 cases].
The anatomo-pathological study of ten cases of tuberculosis of the central nervous system (CNS) in children under 10 years old is reported. The emphasis is given to the macroscopic and microscopic changes produced by the tuberculosis in the meninges, in the nervous parenchyma and in the vessels. The clinical and pathological findings are discussed and correlated with the literature. The authors concluded that: 1) the lesion in children with tuberculosis of the CNS is generally a proliferative meningoencephalitis; 2) the nervous parenchyma may be affected by the contiguous propagation of the tuberculous process or by the circulatory changes secondary to the arterial lesions; 3) because of the localization of the endocranial vessels in the sub-arachnoidal space they are generally injured by the inflammatory process, which can determine an obliterating endarteritis, which can be observed by a carotid angiography.


Direct effect of endodontic sealers on trigeminal neuronal activity.
Endodontic sealers are selected on the basis of their antimicrobial properties and ability to provide a tight seal. Sealer extrusions, whether intentional or unintentional, are common during obturation procedures. Such events have been correlated with increased postoperative discomfort and persistent pain states. However, the mechanisms underlying this phenomenon are largely unknown. Thus, we sought to evaluate the effect of commonly used endodontic sealers on peripheral nociceptors. We hypothesized that endodontic sealers can directly activate trigeminal nociceptors in a concentration-dependent manner, resulting in release of calcitonin gene-related peptide (CGRP), a potent modulator of neurogenic inflammation. Rat trigeminal sensory neurons were exposed in vitro to vehicle, zinc oxide-eugenol (ZOE)-based sealer, AH Plus, EndoSequence BC sealer, or RealSeal SE. Neuronal activation was measured by quantification of neuropeptide (CGRP) release. In addition, cultured neurons were also subjected to the set form of all 4 sealers. The concentration of CGRP released was quantified by using a radioimmunoassay. Data were analyzed by using one-way analysis of variance with Newman-Keuls multiple comparison post hoc test. Both ZOE-based sealer and AH Plus in their fresh form evoked greater CGRP release than the control groups. Conversely, EndoSequence BC and RealSeal sealers both reduced basal GCRP release at all concentrations tested. Evaluation of the set sealers revealed that only ZOE-based sealer evoked significant CGRP release compared with its control group. Overall, our results suggest that sealers can directly activate trigeminal nociceptors, leading to a robust release of CGRP, and may therefore lead to pain and neurogenic inflammation. This direct activation along with the immunologic response may underlie the symptoms and flare-up occurrences often seen with sealer extrusions.


Sex-Specific and Estrous Cycle-Dependent Antidepressant-Like Effects and Hippocampal Akt Signaling of Leptin.
Sex differences in the incidence of depression and antidepressant treatment responses are well documented. Depression is twice as common in women as in men. Recent studies indicate that low levels of leptin, an adipocyte-derived hormone, are associated with increased symptoms of depression in women. Leptin has been shown to produce antidepressant-like effects in male rodents. In the present study, we examined sex differences and estrous cycle variations in antidepressant-like responses to leptin. Leptin administration significantly reduced immobility, a putative measure of behavioral despair, in the forced swim test in intact female mice in the proestrus phase but not in the diestrus phase of the estrous cycle. Moreover, leptin administration stimulated Akt phosphorylation in the hippocampus of female mice in proestrus but not in diestrus, in correlation with its differential behavioral effects in these two phases of the cycle. Leptin-induced behavioral responses and stimulation of hippocampal Akt phosphorylation in female mice were abolished by ovariectomy. By contrast, the antidepressant-like effect of leptin in male mice was not affected by gonadectomy (castration). Pretreatment with 17β-estradiol restored sensitivity to the effects of leptin on behavior and hippocampal Akt phosphorylation in ovariectomized female mice. These results suggest leptin regulates depression-like behavior and hippocampal Akt signaling in a sex-specific and estrous cycle-dependent manner.


The evolution of antibiotic resistance: insight into the roles of molecular mechanisms of resistance and treatment context.
The widespread use of antibiotics has markedly improved public health over the last 60 years. However, the efficacy of antibiotic treatment is rapidly decreasing as a result of the continual spread of antibiotic resistance in pathogen populations. The evolution of antibiotic resistance is an amazingly simple example of adaptation by natural selection, and there is growing interest among evolutionary biologists in using evolutionary principles to help understand and combat the spread of resistance in pathogen populations. In this article, we review recent progress in our understanding of the underlying evolutionary forces that drive antibiotic resistance. Recent work has shown that both the mechanisms of antibiotic action and resistance, as well as the treatment context in which resistance evolves, influence the evolution of resistance in predictable ways. We argue that developing predictive models of resistance evolution that can be used to prevent the spread of resistance in pathogen populations requires integrating the treatment context and the molecular biology of resistance into the same evolutionary framework.


Right ventricular volumes overestimate left ventricular preload in critically ill patients.
Studies have shown right ventricular end-diastolic volume (RVEDV) to be a more accurate estimate of left ventricular preload than pulmonary artery wedge pressure. We prospectively evaluated the ability of RVEDV to predict left ventricular end-diastolic volume (LVEDV) in critically ill patients. Thirty critically ill patients in the surgical intensive care unit underwent concurrent measurement of RVEDV and LVEDV. RVEDV was measured using a residual fraction Swan-Ganz catheter (RF Swan). LVEDV was measured using transesophageal echocardiography with acoustic quantification. Intracardiac, intra-abdominal, and ventilatory pressures were also measured. RVEDV as measured by the RF Swan was significantly larger (by a factor of 2) than LVEDV (p < 0.0001 analysis of variance). However, the RVEDV and LVEDV were strongly correlated (r = 0.71, p < 0.0001, Pearson's correlation). RVEDV from the RF Swan markedly overestimated left ventricular preload. If RVEDV is used as an absolute value for determining preload, patients may be underresuscitated. Transesophageal echocardiography in conjunction with RF Swan can be used to more accurately determine preload and cardiac performance than RF Swan alone in critically ill patients.


Genetic analysis of an Escherichia coli mutant with a lesion in stable RNA turnover.
A mutant that rapidly degrades more than 80% of its rRNA and tRNA under defined conditions was genetically analyzed. Two genes, srnA and srnB, are separately located, and the mutated alleles of both are required for degradation of stable RNA in cultures treated with rifampicin at 42 degrees . srnA is closely linked to tsx by matings and transduction tests; by P1 transduction, the gene order is lac (9 min) proC (9.55 min) tsx (9.8 min) srnA (about 10 min) purE (12 min) rnsA (14.4 min). srnB is not yet completely mapped, but is outside the lac-rnsA region, probably in the region between 75 and 90 min.-The product of the rnsA gene, RNase I, is a potent endonuclease of E. coli, and the only one known that can attack ribosomes and tRNA. However, not only are the srn lesions genetically separate from rnsA, but also, derivatives of an srn strain were prepared lacking RNase I, and they retain the Srn(-) phenotype. Thus, no correlation of rapid RNA turnover and RNase I activity has been found.


Mapping of the polA locus of Escherichia coli K12: genetic fine structure of the cistron.
The close linkage of the glnA gene with polA was exploited to construct a fine structure map of polA by means of generalized transduction with phage P1. Nine different polA- alleles were mapped by recombinational crosses. The results indicate a gene order consistent with previous observations (KELLEY and GRINDLEY 1976a; MURRAY and KELLEY 1979). Three mutations, polA5, polA6 and polA12 map within the "carboxy-terminal" or "large-fragment" portion of the gene in unambiguous order. Four alleles, known to affect the "amino-terminal" portion of the gene, polA107, polA214, polA480ex and polA4113, appear to be closely linked with certain ambiguities in their exact order. All four of these mutations are known to alter the 5' leads to 3' exonuclease activity of DNA polymerase I and three of them result in the conditional lethal polA- phenotype. The polA1 nonsense mutation maps between these two groups in a position consistent with its known effect, production of an amber fragment that includes the 5' leads to 3' exonuclease. The final allele, resA1, is another nonsense mutation that maps at the extreme "amino-terminus" of the cistron.----A number of control experiments were conducted to determine the effects of polA- mutations on the P1-mediated recombinational event. These experiments indicated that abortive transduction occurs quite frequently, but the formation of abortive transductants and segregation of unselected transduced markers among daughter progeny is like that observed by other investigators. There was no evidence that any individual polA- allele behaved in an exceptional fashion during recombination.


Bacterial induction of TNF-alpha converting enzyme expression and IL-6 receptor alpha shedding regulates airway inflammatory signaling.
Airway epithelial cells have a major role in initiating inflammation in response to bacterial pathogens. Through the immediate induction of CXCL8 and cytokine expression, polymorphonuclear cells are mobilized and activated to eradicate the infecting organisms. However, the influx of polymorphonuclear cells and the effects of their toxic exoproducts impede respiratory function. We postulated that respiratory epithelial cells must also participate in the regulation of their own proinflammatory signaling. Both Staphylococcus aureus and Pseudomonas aeruginosa were found to potently activate IL-6 expression immediately upon contact with epithelial cells, and by 1 h induced TNF-alpha converting enzyme (TACE) transcription. By 4 h of bacterial exposure, TACE colocalized with IL-6Ralpha on the apical surface of airway cells, and by 24 h, soluble IL-6Ralpha accumulated in the cell culture supernatant. Epithelial IL-6 and soluble IL-6Ralpha were shown to participate in trans-signaling, interacting with membrane-associated gp130 to activate CCL-2 expression and inhibit additional CXCL8 production. Thus, bacteria are physiological activators of TACE expression, which provides a mechanism to regulate inflammatory signaling that is initiated by airway epithelial cells.


Neuropsychological results and neuropathological findings at autopsy in a case of mild traumatic brain injury.
Autopsy studies were undertaken in a 47-year-old college-educated male patient who, 7 months prior to an unexpected death, had sustained a mild traumatic brain injury (TBI) as manifested by brief loss of consciousness and an initial Glasgow Coma Scale score of 14. The patient died from cardiac arrest secondary to an undiagnosed and unknown arteriosclerotic cardiovascular disease as assessed by the coroners office at the time of autopsy. Gross inspection of the brain at autopsy was normal; however, microscopic analysis demonstrated what were considered trauma findings of hemosiderin-laden macrophages in the perivascular space and macrophages in the white matter, particularly the section taken from the frontal lobe. The patient had partially returned to work at the time of death, but had encountered problems with diminished cognitive performance in his work as an appraiser. Neuropsychological studies were generally within normal limits although several tests of either speed of processing or short-term memory showed lower than expected performance. This case demonstrates the presence of subtle neuropathological changes in the brain of a patient who sustained a mild TBI and was still symptomatic for the residual effects of the injury 7 months post injury when he unexpectedly died.


Toxicity of binary-metal mixtures (As, Cd, Cu, Fe, Hg, Pb and Zn) in the euryhaline rotifer Proales similis: Antagonistic and synergistic effects.
Data regarding the effects of binary metal mixtures in marine zooplankton are scarce, particularly for rotifers. We examined the toxicity of 21 binary equitoxic mixtures of As, Cd, Cu, Fe, Hg, Pb, and Zn on the euryhaline rotifer Proales similis. The toxic units (TU50) revealed that 20 of these binary mixtures exhibited synergistic effects (TU50 < 1.00). The AsHg mixture showed a strong antagonistic effect (TU50 = 2.39), whereas the HgCu interaction exhibited a significant synergistic effect (TU50 = 0.29) on P. similis. TU50 values were <0.60 in all cases that showed synergism (80 %). Regarding the MIXTOX analysis, 13 binary mixtures presented some level of synergism, while two mixtures presented only additivity. Results emphasize the need for environmental agencies to revise and readjust protection guidelines for marine biota in response to the evident synergistic effects occurring at metal mixtures concentrations below the current permissible limits.


Biosynthesis and supramolecular assembly of procollagen IV in neonatal lung.
The rate of biosynthesis of procollagen IV, the principal collagen of basement membranes, and the concentration of specific RNAs coding for procollagen IV were measured in neonatal rat lungs. Both decreased sharply at birth and then recovered again a few days later. The supramolecular assembly of procollagen IV was followed in neonatal rat, mouse, and chick lungs, which actively elaborate endothelial and alveolar basement membranes, and in chick embryo gizzard which is rich in smooth muscle. The tetramer of four procollagen IV molecules linked covalently through their amino ends was isolated as an assembly intermediate from all these tissues. While noncovalent association of the carboxyl ends of two procollagen IV molecules occurred readily, the subsequent establishment of covalent cross-links was substantially slower in the junctional complexes of the carboxyl ends than of the amino ends. Both disulfide bonds and other, unidentified covalent links formed. The six component carboxyl peptides of a junctional complex became progressively covalently linked into two kinds of carboxyl peptide pairs. We conclude that both amino-linked tetramers and carboxyl-linked dimers of procollagen IV molecules are intermediates in the biological assembly of the collagen networks of these basement membranes.


[Anti-fall plan for the elderly in France 2022-2024: objectives and methodology].
Falls and fall-related injuries are a major public health problem in industrialized countries. Faced with this challenge, a French national plan was launched in 2022 aiming to reduce by 20% the incidence of falls-related hospitalizations or deaths. To describe the main pillars of the 2022-2024 French national plan against falls in older persons. Methods and assessment: The six pillars of the plan are: 1) screening and monitoring risks of falls and alert health and care workers; 2) home safety assessment and getting out safely; 3) developing technical aids for mobility and the use of assistive technologies at home; 4) appropriate physical activity, best weapon against falls; 5) tele-assistance devices for all older persons; 6) a cross-cutting pillar: Informing, raising awareness, training, and involving local actors. The plan, deployed in the 18 French regions, will provide a unique opportunity to determine the best strategies to achieve the objectives and the barriers encountered. The deployment of the French national plan will bring useful data for considering a long-term strategy in France and helping countries or regions wishing to implement a fall prevention plan on their territory.


Comparison of long-term outcomes between older Asian and white patients with non-ST-segment elevation myocardial infarction: findings from CRUSADE-CMS database.
In the United States as well as globally, Asians are a growing proportion of patients presenting with non-ST-segment elevation myocardial infarction (NSTEMI), yet little is known about their longitudinal outcomes. We linked Centers for Medicare & Medicaid claims data to detailed clinical data for 37,702 NSTEMI patients ≥65 years old treated at 444 CRUSADE hospitals between 2003 and 2006 to examine longitudinal outcomes. We used Cox proportional hazards modeling to compared outcomes between Asian and white patients, adjusting for differences in baseline patient characteristics. Compared with white NSTEMI patients, Asians (n = 307) were younger; more frequently had hypertension, diabetes and renal insufficiency; and were less likely to have had a prior myocardial infarction, but there were no significant differences in rates of cardiac catheterization or revascularization during the index hospitalization between the 2 groups. At 30 days, Asian and white patients had a similar risk-adjusted mortality (9.5% vs 9.9%, P = .77), but by 1 year, Asian patients had a significantly lower risk-adjusted mortality (20.9% vs 24.5%, adjusted hazard ratio 0.64, 95% CI 0.50-0.82). Compared with white patients, Asians also had a lower adjusted 1-year cardiovascular readmission risk (37.1% vs 42.1%, adjusted hazard ratio 0.79, 95% CI 0.64-0.98). Despite similar inhospital treatments, Asian NSTEMI patients had lower mortality and cardiovascular readmission risks at 1 year, compared with white patients. Further study is needed to determine whether intrinsic ethnic differences or differential longitudinal prevention strategies explain these differences in long-term outcomes.


[Coding R.M.EcoR1-plasmids derived from R-factor].
Bacteriophages P1vir and Mu-1 have been used for transductional shortening of recombinant R factor coding for R.M.EcoR1 isolated by Yoshimori et al. P1 shortening made possible the isolation of transmissive isogenic plasmids coding R.M.EcoR1 and differing in antibiotic resistances, as well as isolation of plasmids differing only in R.M.EcoR1 genes. Mu-1 mediated shortening favoured the isolation of transmissive R plasmids having lost the resistance to chloramphenicol but having all other markers of recombinant R factor intact. The data are interpreted in support of Yoshimori et al. supposition concerning the existence of R.M.EcoR1 coding recombinant R factor of Escherichia coli.


Expression analysis of desmosomal components of the novel canine epidermal keratinocyte cell line (MSCEK).
A novel canine epidermal keratinocyte cell line, MSCEK, was developed from skin of a healthy dog. The aim of this study was to determine its expression of desmosomal components and to evaluate its use as a detection tool for circulating autoantibodies in canine pemphigus. Immunofluorescence and western blotting analyses revealed that MSCEK expresses desmoglein (Dsg) 1, Dsg2, Dsg3, desmoplakin, plakoglobin and cytokeratins. Moreover, positive fluorescent reactions on the surface of MSCEK cells were observed when the cells were incubated with sera obtained from four dogs diagnosed with pemphigus complex. These findings indicate that MSCEK should be a useful tool for future research to characterize circulating autoantibodies that recognize desmosomal components in dogs with pemphigus.


'Irritants' increase the response to an allergen in allergic contact dermatitis.
We studied the effect of "irritants" on the response to an allergen in 15 patients. Dilutions of allergens were applied in duplicate, and 24 hours later they were removed and sodium lauryl sulfate (11 subjects) or anthralin (dithranol) (four subjects) was applied for a further 24 hours to one set of patches. Control dilutions of irritants alone were applied. Responses were measured objectively at 72 hours. The response to both allergen and irritant was greater than to either alone. Doses of allergen, which did not produce a response when applied alone, produced a response when an irritant was added. Irritants therefore increase the allergic contact dermatitis response and may explain the presence of contact dermatitis in patients with negative patch tests.


Professional values, value conflicts, and assessments of the duty-hour restrictions after six years: a multi-institutional study of surgical faculty and residents.
the aim of this study was to explore professional values, value conflicts, and assessments of the Accreditation Council for Graduate Medical Education's duty-hour restrictions. questionnaires distributed at 15 general surgery programs yielded a response rate of 82% (286 faculty members and 306 residents). Eighteen items were examined via mean differences, percentages in agreement, and significance tests. Follow-up interviews with 110 participants were explored for main themes. residents and faculty members differed slightly with respect to core values but substantially as to whether the restrictions conflict with core values or compromise care. The average resident-faculty member gap for those 13 items was 35 percentage points. Interview evidence indicates consensus over professional values, a gulf between individualistic and team orientations, frequent moral dilemmas, and concerns about the assumption of responsibility by residents and "real-world" training. the divide between residents and faculty members over conflicts between the restrictions, core values, and patient care poses a significant issue and represents a challenge in educating the next generation of surgeons.


Mutual information between input and output trajectories of biochemical networks.
Biochemical networks can respond to temporal characteristics of time-varying signals. To understand how reliably biochemical networks can transmit information we must consider how an input signal as a function of time--the input trajectory--can be mapped onto an output trajectory. Here we estimate the mutual information between input and output trajectories using a Gaussian model. We study how reliably the chemotaxis network of E. coli can transmit information on the ligand concentration to the flagellar motor, and find the input power spectrum that maximizes the information transmission rate.


Liposomal nanoparticles control the uptake of ciprofloxacin across respiratory epithelia.
Liposomal ciprofloxacin nanoparticles were developed to overcome the rapid clearance of antibiotics from the lungs. The formulation was evaluated for its release profile using an air interface Calu-3 cell model and further characterised for aerosol performance and antimicrobial activity. Liposomal and free ciprofloxacin formulations were nebulised directly onto Calu-3 bronchial epithelial cells placed in an in vitro twin-stage impinger (TSI) to assess the kinetics of release. The aerosol performance of both the liposomal and free ciprofloxacin formulation was characterised using the next generation impactor. Minimum inhibitory and bactericidal concentrations (MICs and MBCs) were determined and compared between formulations to evaluate the antibacterial activity. The liposomal formulation successfully controlled the release of ciprofloxacin in the cell model and showed enhanced antibacterial activity against Pseudomonas aeruginosa. In addition, the formulation displayed a respirable aerosol fraction of 70.5 ± 2.03% of the emitted dose. Results indicate that the in vitro TSI air interface Calu-3 model is capable of evaluating the fate of nebulised liposomal nanoparticle formulations and support the potential for inhaled liposomal ciprofloxacin to provide a promising treatment for respiratory infections.


Cerebral blood flow changes in acute subarachnoid hemorrhage.
Delayed vasospasm and secondary injury due to ischemia occur frequently in the setting of subarachnoid hemorrhage (SAH), and these changes have been well characterized within the last decades. Considerable effort has also been put into the development of therapeutic strategies and appropriate monitoring modalities. However, although in particular acute injury is known to contribute significantly to overall outcome in SAH, these immediate alterations still remain largely neglected in current research. Few studies exist to date which mainly describe rapid alterations in perfusion and metabolism. As the main characteristic of the very first minutes and hours after SAH, an immediate phase of CPP-independent hypoperfusion has been observed repeatedly both experimentally and clinically, and it has mostly been attributed to the development of acute vasospasm. Endothelin and nitric oxide, prime suspect in the pathogenesis of chronic vasospasm, may play a pivotal role in this early scenario, possibly being promoted by the drastic ICP increase and extravasation of blood compounds. The much disputed concept of inflammation in chronic vasospasm may not be applicable this early after the ictus, but mechanisms of cellular and structural changes causing microvascular platelet aggregation and immediate disruption of the basal lamina, however, are thought to contribute significantly to the imminent cascade of disturbances in perfusion and metabolism. This review is intended to summarize current insights and illustrate recent efforts to better understand alterations in cerebral perfusion in these very first minutes and hours after SAH which--at some point--may also be amenable to early therapeutic intervention.


Astrocytic insulin receptor controls circadian behavior via dopamine signaling in a sexually dimorphic manner.
Mammalian circadian clocks respond to feeding and light cues, adjusting internal rhythms with day/night cycles. Astrocytes serve as circadian timekeepers, driving daily physiological rhythms; however, it's unknown how they ensure precise cycle-to-cycle rhythmicity. This is critical for understanding why mistimed or erratic feeding, as in shift work, disrupts circadian physiology- a condition linked to type 2 diabetes and obesity. Here, we show that astrocytic insulin signaling sets the free-running period of locomotor activity in female mice and food entrainment in male mice. Additionally, ablating the insulin receptor in hypothalamic astrocytes alters cyclic energy homeostasis differently in male and female mice. Remarkably, the mutants exhibit altered dopamine metabolism, and the pharmacological modulation of dopaminergic signaling partially restores distinct circadian traits in both male and female mutant mice. Our findings highlight the role of astrocytic insulin-dopaminergic signaling in conveying time-of-feeding or lighting cues to the astrocyte clock, thus governing circadian behavior in a sex-specific manner.