Public prescription drug plan coverage for antiretrovirals and the potential cost to people living with HIV in Canada: a descriptive study.
Antiretrovirals are expensive and people living with HIV may experience a range of financial burdens when accessing these medications. Our aim was to describe the policy of all Canadian public drug insurance programs for antiretroviral drugs and illustrated how these policies might affect patients' annual out-of-pocket expenditures. In December 2017, we reviewed public drug programs offering antiretroviral coverage in Canada using government websites to summarize eligibility criteria. We estimated the annual out-of-pocket costs incurred by people living with HIV by applying the cost-sharing rules to 2 hypothetical cases, a single man and a married woman with a net household income of $39 000 and $80 000, respectively, receiving identical prescriptions in different jurisdictions. We observed substantial variation in the subsidy provided based mainly on geography, income and age. All 5 federal programs and 6 of 13 provincial and territorial jurisdictions offered universal coverage. In the remaining regions, patients spend up to several thousand dollars annually depending on income (Manitoba), age and income (Ontario, Saskatchewan) and age, income and drug costs (Quebec and Newfoundland and Labrador). We found the greatest variation for our higher income case, with out-of-pocket expenses ranging from 0 to over 50% of the antiretroviral cost. There is considerable inter- and intra-jurisdiction heterogeneity in the cost-sharing policies for antiretrovirals across Canada's public drug programs. Policy reforms that either eliminate or set national standards for copayments, deductibles or premiums would minimize variation and could reduce the risk of cost-associated non-adherence to HIV therapy.


[Accuracy of gestational age assessment in Brazilian Information System on Live Birth (SINASC): a population study].
The prevalence of preterm births has shown a growing trend in many countries, including developed ones. Studies in Brazil have shown that the Information System on Live Births (SINASC, in Portuguese), until 2010, underestimated the prevalence of preterm births, when compared with studies based on primary data. Starting in 2011, gestational age at birth has been calculated in SINASC according to the last menstrual period (LMP), when available. This study sought to evaluate the accuracy of the gestational age assessment using LMP, compared with two other estimates, and correlate it with birth weight. This is a population study with data from SINASC available from Brazilian Health Informatics Department between 2011 and 2015. Definitions of preterm birth, low birth weight and birth asphyxia were taken from the literature. Adequacy of birth weigh to gestational age was calculated based on Fenton and Intergrowth-21 curves. We compared weight means according to the presence or lack of preterm birth. gestational age assessment was based on LMP in 58.5% and 41.5% used another method. We found that the preterm proportion was 12% in the LMP group and 8.4% in the other method group, while low birth weight was 6.5% and 8.4%, respectively. Mean weight of preterm infants was higher in the LMP group. Use of LMP as a gestational age estimator overestimated the proportion of weight equal to or higher than 2,500g among preterm infants, which does not seem compatible with the expected distribution for this group. LMP favored "correction" of prematurity for the parameters that are comparable to those of primary data studies, though the distortions we found between gestational age and birth weigh may indicate that there are still problems with this estimator.


Catheter related thrombosis in hospitalized infants: A neural network approach to predict risk factors.
We sought to investigate the predictors of catheter-related thrombosis (CRT) in a cohort of critically ill hospitalized infants and using a novel approach (the artificial neural network - ANN) in combination with conventional statistics to identify/confirm those predictors. We performed a retrospective analysis of all infants with a central or peripherally inserted central venous catheter (CVC/PICC) between 2015 and 2018. ANN was generated to investigate the predictors of CRT. The predictive variables examined in the ANN were age, gender, weight, co-morbid conditions, line type, use of ultrasound (USG), emergent line placement, location of line tip, any major surgical procedures, use of mechanical ventilation, exposure to cardio-pulmonary bypass (CPB), past-history of CVC/PICC, or thrombosis. Binary logistic regression was performed to calculate odds ratios (ORs) and determine which factors were significant in predicting CRT. Of total of 613 infants, 59.9% of patients had a history of previous CVC or PICC and 12.2% had a history of thrombus as documented by USG in the past three months. CPB exposure was present in 48.1%. The incidence of CRT was 10.7%. Independent predictors of CRT were the line tip in IVC (OR: 2.37, 1.08-5.21, P = 0.032), history of thrombosis (OR: 2.40, 1.16-4.96, P = 0.019), previous CVC/PICC (OR: 2.80, 1.24-6.33, P = 0.014) and exposure to CPB (OR: 2.749, 1.08-6.98, P = 0.034). A sensitivity analysis was performed to determine the normalized importance of each variable used to create the ANN. The most important variables were age (with normalized importance of 100%), history of thrombosis, weight, and exposure to CPB (normalized importance of 68.2%). Nearly 1 in 10 infants developed CRT. We found that catheter tip in IVC, exposure to CPB, history of vein thrombosis and history of CVC/PICC placement in the past 3 months are independently associated with a higher risk of CRT in infants by using conventional and neural network methods.


New perspective of ceria nanodots for precise tumor therapy via oxidative stress pathway.
Ceria-based nanomaterials have aroused major attentions among the biomedical application research field in recent years. Most of the researches have mainly focused on promoting the functional healing therapies of normal cells/organs with cerium oxide compounds, while the applications of ceria-based materials employed on cancer curing processes have been merely mentioned. To explore the possible capabilities of cerium oxide nanomaterials exterminating tumor cells, innovatively, we synthesized the eco-friendly pure cerium oxide nanodots (CNDs), proving the prominent ability of CNDs used in tumor chemotherapy (CDT) via Fenton reaction with the highly presence of H2O2 (acidic pH) in tumor tissues. CNDs reacted with the self-produced H2O2 of tumor cells, which generated piled up toxic hydroxyl radical (·OH). The accumulated virulent ·OH restrained the growth of cancer cells intensively. This peroxidase-like activity, provided a distinguished paradigm for effective cancer curing treatment. We also verified the biosafety of CNDs applied on normal cells. Notably, not only did CNDs be harmless to normal cells, but also it protected them from the damages of reactive oxygen species (ROS). In normal cells/tissues, under the microenvironment of neutral pH and low level of H2O2, the CNDs could effectively function as an annihilator inhibiting ROS. They reduced the damages caused by ROS, exhibiting catalase-like activity. The research we studied, which estimated CNDs thoroughly, has provided a new perspective to the future researches of the cerium oxide biomaterial applications.


Clinical significance of insulin resistance.
Insulin resistance has emerged in the last 20 years as a concept familiar to clinicians in many specialties. No easily performed laboratory test is available to assess insulin action in routine clinical practice. Several rare syndromes of severe insulin resistance are recognized but most clinicians will encounter insulin resistance as a manifestation of common diseases. Physiological and treatment induced changes in insulin sensitivity influence insulin doses required in insulin-dependent diabetes mellitus. In non-insulin-dependent diabetes mellitus insulin resistance is fundamental to pathogenesis but it is also influenced by standard dietary and pharmacological treatment, and probably mediated by changes in prevailing glycaemia. Antihypertensive agents appear to have diverse effects on the insulin resistance of essential hypertension though the long term significance of these remains unclear. The importance of insulin as a risk factor for coronary heart disease and the concept of an insulin resistance syndrome as a common precursor of conditions with increased vascular risk remains controversial.


Assessment of the changes in corneal biomechanical properties after collagen cross-linking in patients with keratoconus.
To assess the changes in biomechanical properties of the cornea after treatment of keratoconus patients with UV-A/riboflavin corneal collagen cross-linking (CXL) using Corvis ST (Oculus, Wetzlar, Germany) and Ocular Response Analyzer (ORA; Reichert Ophthalmic Instruments, Inc., Buffalo, NY, USA) devices. In this prospective, observational case series, 48 eyes from 48 consecutive patients with progressive keratoconus were enrolled. Patients with history or signs of ocular disorders other than keratoconus, previous eye surgery, systemic diseases, or inability to cooperate with any measurement device were excluded. Corvis ST and ORA images were obtained at baseline and 4 months after CXL. The primary outcome measures comprised Corvis ST corneal biomechanical factors [time of highest concavity (T), time of applanation 1 (T1), time of applanation 2 (T2), length of applanation 1 (L1), length of applanation 2 (L2), velocity of applanation 1 (V1), velocity of applanation 2 (V2), deformation amplitude (DA), peak distance (PD), and radius (R)] and the ORA parameters [corneal hysteresis (CH), corneal resistance factor (CRF), Goldmann-related IOP (IOPg), cornea-compensated IOP (IOPcc), and waveform score (WS)]. The mean [± standard deviation (SD)] age of patients was 20 ± 5 years, and 27 (56%) were male. At baseline, the averages of the refraction, mean keratometry, and keratometric astigmatism were -3.0 ± 1.8 diopter (D), 47.0 ± 1.8 D, and 3.5 ± 1.5 D, respectively. According to Corvis ST, L2 increased from 0.83 ± 0.25 mm at baseline to 1.15 ± 0.57 mm after CXL; and V2 decreased from -0.81 ± 0.08 to -0.94 ± 0.26 m/s (P = 0.001 and P = 0.032, respectively). ORA parameters showed significant decrease in the CRF (from 7.82 ± 1.72 to 7.21 ± 1.05 mmHg; P = 0.036) and increase in the WS (from 4.58 ± 2.55 to 6.12 ± 1.92; P = 0.002). According to in vivo observation with Corvis ST and ORA, CXL induces significant changes in corneal biomechanical properties in cases with keratoconus. The parameters with significant changes (L2 and V2) may reflect increased stiffness of the treated cornea. The importance of such observations should be elucidated in future studies.


Transcriptomic fingerprints in human peripheral blood mononuclear cells indicative of genotoxic and non-genotoxic carcinogenic exposure.
For evaluating genotoxic exposure in human populations a number of biomarkers has been successfully applied over the last 30 years to determine early biological effects due to exposure to carcinogens. Despite their success, these early biological effect markers provide limited mechanistic insight, and do not allow detection of exposure to non-genotoxic carcinogens. Gene expression profiling forms a promising tool for the development of new biomarkers in blood cells to overcome these limitations. The aim of our research was to identify novel genomics-based candidate markers for genotoxic and non-genotoxic carcinogen exposure in human peripheral blood cells (PBMC). Whole genome gene expression changes were investigated following 20 h of in vitro exposure to a high and low concentration of eight genotoxic and three non-genotoxic carcinogenic compounds using whole genome microarrays. Per condition, PBMC of five independent donors were exposed, all in the presence of human liver S9. Sets of genes, as well as biological pathways indicative of genotoxic exposure and of non-genotoxic carcinogenic exposure were identified. Furthermore, networks were built using the genotoxic and non-genotoxic gene sets, showing the majority of the genes to be interlinked and revealing distinctive transcription factors for both classes. The identification of these potential candidate marker genes might contribute to the development of genomic based biomarkers of carcinogen exposure.


Isolation and characterization of N7-guanyl adducts derived from 1,2-dibromo-3-chloropropane.
1,2-Dibromo-3-chloropropane is a potent renal and testicular toxicant and has been shown to induce tumor formation in laboratory animals. The toxic effects of the compound are thought to be a result of a bioactivation step in which a glutathione conjugate is formed and subsequently reacts with cellular DNA. The L-glutathione conjugate of 1,2-dibromo-3-chloropropane was chemically synthesized and used to alkylate DNA: following incubations of the conjugate with calf thymus DNA and neutral thermal hydrolysis (to release N7-guanyl adducts) four major fluorescent products were observed. Three of these were isolated and characterized, the structures being determined as S-[bis(N7-guanylmethyl)methyl]glutathione and the two diastereomers of S-[1-(hydroxymethyl)-2-(N7-guanyl)ethyl]glutathione. The fourth fluorescent product was unstable and formed in low yield and thus could not be characterized. The formation of these N7-guanyl adducts can be explained by a mechanism that includes the formation of two consecutive episulfonium ion intermediates followed by nucleophilic attack at the unsubstituted methylene carbon. These adducts bear structural and mechanistic similarities to the major adduct derived from 1,2-dibromoethane, S-[2-(N7-guanyl)ethyl]glutathione. The same adducts were also formed when DBCP was incubated with rat liver cytosol, GSH, and DNA. In vivo experiments with DBCP yielded very low levels of the N7-guanyl adducts formed in rat liver compared to the levels seen after treatments with 1,2-dibromoethane. The bis-guanyl adduct represents a cross-linked structure that may be important in the toxicity of this compound. The conjugate was not found to be mutagenic to Salmonella typhimurium TA100 but rather showed a toxic effect toward the bacteria.


Asymmetric glycosylation of soybean seed coat peroxidase.
Reanalysis of the tryptic digests of soybean seed coat peroxidase (SBP) and its carboxyamidated peptide derivatives in the light of more complete sequence data has thrown light on the diglycosylated tryptic peptides, TP13 (Leu[183-205]Arg) and TP15 (Cys[208-231]Arg). Matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) analyses indicate that although all potential sites carry some glycan substituents, not all sites are fully occupied. Tryptic glycopeptide TP13, carrying two N-glycosylation consensus sequons (Asn185 and Asn197), occurs mainly (85-90%) as the diglycosylated species, the remainder (10-15%) being monoglycosylated. In contrast, tryptic peptide TP15, also with two N-glycosylation sites (Asn211 and Asn216), is primarily monoglycosylated (approximately 90%), with the remainder (10%) being diglycosylated. No non-glycosylated TP13 or TP15 was observed. Some artifacts are noted in the reactions of N-terminal cysteine residues and aspartate/asparagines residues in glycopeptide TP15. Mapping the glycans onto the crystal structure of SBP shows that these are asymmetrically distributed on the molecule, occurring primarily on the substrate-channel face of the enzyme. In contrast, the glycans of HRP, isozyme c, are more uniformly distributed over the enzyme surface.


Occupational injuries admitted to the emergency department.
To categorise the characteristics, causes and rates of occupational injuries referred to the Emergency Department of a Turkish hospital. The cross-sectional study was conducted at a university-based hospital in Edirne, Turkey, from January 1, 2010 to May 1, 2011. Parameters evaluated included: gender, age, occurrence mechanism, injury type, injury localisation, sector, season, day of week, injury hours, the types of health insurance, working experience, educational level and outcome. SPSS 15 was used for statistical analysis. A total of 552 patients sustained occupational injuries. The male-to-female ratio was 11.54:1.The mean age of the patients was 36.03 +/- 11.77 years. The injury rate was the highest in the 18-29 age group (n = 418; 75.7%). Most cases occurred in the summers (n = 172; 31.2%). The largest number of injuries occurred on weekdays (n = 184; 33.3%). Most injuries occurred between 8AM and 4PM (n = 343; 62.1%).The construction industry had the highest injury rate (n = 222; 40.2%). The most common mechanism of injuries was penetrating sharp-object injury (n = 224; 40.6%). The most common type of injury in the general injury group was multiple-type (n = 162; 29.4%). Of the total, 379 (71.7%) patients were discharged after treatment in the Emergency Department. Five patients died during the study period. Further studies in the Emergency Department may contribute to the prevention of occupational injuries in the future.


Prenatal and childhood antecedents of suicide: 50-year follow-up of the 1958 British Birth Cohort study.
We aimed to elucidate early antecedents of suicide including possible mediation by early child development. Using the 1958 birth cohort, based on British births in March 1958, individuals were followed up to adulthood. We used data collected at birth and at age 7 years from various informants. Suicides occurring up to 31 May 2009 were identified from linked national death certificates. Multivariable Cox proportional hazard models were used to investigate risk factors. Altogether 12399 participants (n = 44 suicides) had complete data. The strongest prenatal risk factors for suicide were: birth order, with risk increasing in later-born children [p trend = 0.063, adjusted hazard ratio (HR)], e.g. for fourth- or later-born children [HR = 2.27, 95% confidence interval (CI) 0.90-5.75]; young maternal age (HR = 1.18, 95% CI 0.34-4.13 for ⩽19 years and HR = 0.41, 95% CI 0.19-0.91 for >29 years, p trend = 0.034); and low (<2.5 kg) birth weight (HR = 2.48, 95% CI 1.03-5.95). The strongest risk factors at 7 years were externalizing problems in males (HR = 2.96, 95% CI 1.03-8.47, p trend = 0.050) and number of emotional adversities (i.e. parental death, neglected appearance, domestic tension, institutional care, contact with social services, parental divorce/separation and bullying) for which there was a graded association with risk of suicide (p trend = 0.033); the highest (HR = 3.12, 95% CI 1.01-9.62) was for persons with three or more adversities. Risk factors recorded at birth and at 7 years may influence an individual's long-term risk of suicide, suggesting that trajectories leading to suicide have roots in early life. Some factors are amenable to intervention, but for others a better understanding of causal mechanisms may provide new insights for intervention to reduce suicide risk.


HPV vaccine coverage in Australia and associations with HPV vaccine information exposure among Australian Twitter users.
Introduction: Human papillomavirus (HPV) vaccine coverage in Australia is 80% for females and 76% for males. Attitudes may influence coverage but surveys measuring attitudes are resource-intensive. The aim of this study was to determine whether Twitter-derived estimates of HPV vaccine information exposure were associated with differences in coverage across regions in Australia. Methods: Regional differences in information exposure were estimated from 1,103,448 Australian Twitter users and 655,690 HPV vaccine related tweets posted between 6 September 2013 and 1 September 2017. Tweets about HPV vaccines were grouped using topic modelling; an algorithm for clustering text-based data. Proportional exposure to topics across 25 regions in Australia were used as factors to model HPV vaccine coverage in females and males, and compared to models using employment and education as factors. Results: Models using topic exposure measures were more closely correlated with HPV vaccine coverage (female: Pearson's R = 0.75 [0.49 to 0.88]; male: R = 0.76 [0.51 to 0.89]) than models using employment and education as factors (female: 0.39 [-0.02 to 0.68]; male: 0.36 [-0.04 to 0.66]). In Australia, positively-framed news tended to reach more Twitter users overall, but vaccine-critical information made up higher proportions of exposures among Twitter users in low coverage regions, where distorted characterisations of safety research and vaccine-critical blogs were popular. Conclusions: Twitter-derived models of information exposure were correlated with HPV vaccine coverage in Australia. Topic exposure measures may be useful for providing timely and localised reports of the information people access and share to inform the design of targeted vaccine promotion interventions.


Gallstone-induced inflammatory fibrosis: a relentless clinical course of retained gallstones after laparoscopic cholecystectomy.
Multiple reports in the literature confirm that retained gallstones spilled during laparoscopic cholecystectomy perpetuate chronic inflammation and suppuration long after the initial operation. Two patients who had previously undergone laparoscopic cholecystectomy presented to our institution with complications of retained stones. Patient 1 presented with right upper quadrant pain and a mass involving the right hepatic lobe. Patient 2 presented with a draining right flank abscess. Both underwent exploratory laparotomy at which time multiple abscess cavities were found, many of which contained retained gallstones. Patient 1 required reoperation for recurrent abscesses 7 months after the initial procedure and has been disease free for 6 months. Patient 2 had abscess recurrence that required percutaneous drainage 1 year after the original procedure and has not had recurrence for 4 years.


Remembering the Art of Dying: lessons for medical trainees.
In her book The Lost Art of Dying: Reviving Forgotten Wisdom (2020), Lydia Dugdale claims that a deep cultural forgetting process underlies contemporary society's impoverished views of, and practices surrounding, death and dying. Her thesis, and the cultural developments that trace this story of widespread forgetting, offer insight into how medical trainees come to participate in such impoverished views and practices, to the detriment of themselves and the patients they serve. Through better understanding the tacit metaphysical and ethical forces that contribute to this process, trainees might better appreciate the insidious power of such forces on their moral development. Moreover, by turning to traditioned communities outside of medicine and to patients themselves, medical trainees may find the moral resources to reimagine their roles both in providing care and attending to their own mortality.


Comparison of factor analysis models applied to the NCANDA neuropsychological test battery.
The factor structure of neuropsychological functioning among a large sample (N = 831) of American youth (ages 12-21 at baseline) was investigated in order to identify an optimal model. Candidate models were selected based on their potential to provide service to the study of adolescent development and the effects of heavy episodic alcohol consumption. Data on neuropsychological functioning were obtained from the NCANDA study. This is a longitudinal community study of the effects of alcohol exposure on neurodevelopment. Three conceptually motivated and one empirically motivated factor analysis model of neuropsychological domains were compared based on penalized-likelihood selection criteria and model fit statistics. Two conceptually-motivated models were found to have adequate fit and pattern invariance to function as a measurement model for the Penn Computerized Neurocognitive Battery (Penn CNB) anchored neuropsychological battery in NCANDA. Corroboration of previous factor analysis models was obtained, in addition to the identification of an alternative factor model that has higher discriminant capacity for neuropsychological domains hypothesized to be most sensitive to alcohol exposure in human adolescents. The findings support the use of a factor model developed originally for the Penn CNB and a model developed specifically for the NCANDA project. The NCANDA 8-Factor Model has conceptual and empirical advantages that were identified in the current and prior studies. These advantages are particularly valuable when applied in alcohol research settings.


Modulation of HER2 expression by ferulic acid on human breast cancer MCF7 cells.
The molecular mechanisms underlying the mitogenic effect of ferulic acid (FA), an active compound derived from Angelica sinensis, have never been elucidated. It was the aim of this study to investigate the proliferative effect of FA on human breast cancer cell lines and to elucidate its modulation mechanism on HER2 expression in MCF7 line. By using MCF7 (oestrogen receptor-positive; ER+, HER2-low), BT474 (ER+, HER2-high), MDAMB231 (ER-, HER2-low) and SKBR3 (ER-, HER2-high) human breast cancer cell lines as in vitro models, the mitogenic effects of FA were assessed by trypan blue dye exclusion assay and DNA flow cytometry. Ferulic acid-modulated cell signalling and HER2 gene expression were evaluated in MCF7 line by Western blot and real-time RT-PCR analysis. Ferulic acid ER-dependently stimulated cell proliferation on MCF7 cells in a concentration-dependent manner. The HER2 oncogene (one of the prognostic factors of breast cancer) and ESR1 gene (oestrogen receptor-alpha; ERalpha) transcription were markedly up-regulated by FA treatment. Besides, HER2 signalling and its downstream molecules such as AKT and ERK1/2 were involved in FA-modulated ERalpha and cyclin D1 synthesis. Addition of anti-HER2 antibody, trastuzumab, abrogated FA-enhanced proliferative effect on MCF7 cells, indicated a positive feedback control for the action of HER2 in this setting. The fact that the ER antagonist blocked most of the FA-up-regulated HER2 expression, and that trastuzumab down-regulated ERalpha gene expression, suggested a cross-talk between ERalpha and HER2 signalling on MCF7 cells. The authors' conclude that FA causes human breast cancer cell proliferation by up-regulation of HER2 and ERalpha expression.


Autoimmune hemolytic anemia in systemic lupus erythematosus at diagnosis: differences between pediatric and adult patients.
Objective To determine the overall prevalence of autoimmune hemolytic anemia (AIHA), and to compare clinical and laboratory features in a large population of children and adult lupus patients at diagnosis. Methods This retrospective study evaluated the medical charts of 336 childhood-onset systemic lupus erythematosus (cSLE) and 1830 adult SLE (aSLE) patients followed in the same tertiary hospital. Demographic data, clinical features and disease activity were recorded. AIHA was defined according to the presence of anemia (hemoglobin <10 g/dL) and evidence of hemolysis (reticulocytosis and positive direct antiglobulin test (DAT)/Coombs test) at SLE diagnosis. Evans syndrome (ES) was defined by the combination of immune thrombocytopenia (platelet count <100,000/mm3) and AIHA. Results The frequency of AIHA at diagnosis was significantly higher in cSLE patients compared to aSLE (49/336 (14%) vs 49/1830 (3%), p = 0.0001), with similar frequency of ES (3/336 (0.9%) vs 10/1830 (0.5%), p = 0.438). The median of hemoglobin levels was reduced in cSLE vs aSLE patients (8.3 (2.2-10) vs 9.5 (6.6-10) g/dL, p = 0.002) with a higher frequency of multiple hemorrhagic manifestations (41% vs 7%, p = 0.041) and erythrocyte transfusion due to bleeding (24% vs 5%, p = 0.025). cSLE patients also had more often constitutional involvement (84% vs 31%, p < 0.001), fever (65% vs 26%, p < 0.001), weight loss > 2 kg (39% vs 6%, p < 0.001), reticuloendothelial manifestations (48% vs 8%, p < 0.001), hepatomegaly (25% vs 2%, p < 0.001) and splenomegaly (21% vs 2%, p = 0.004). Other major organ involvements were common but with similar frequencies in cSLE and aSLE ( p > 0.05). Median systemic lupus erythematosus disease activity index 2000 (SLEDAI-2 K) was comparable in cSLE and aSLE (p = 0.161). Conclusions We identified that AIHA was not a common condition in cSLE and aSLE, with distinct features characterized by a higher prevalence/severity in children and concomitant constitutional symptoms in the majority of them.


Prevalence of Congenital Anomalies in an Indian Maternal Cohort: Healthcare, Prevention, and Surveillance Implications.
India lacks a national birth defects surveillance. Data on the prevalence of congenital anomalies are available mostly from hospital-based, cross-sectional studies. This is the first cohort study from India, where 2107 women were followed till pregnancy outcome, in order to measure the prevalence and types of congenital anomalies, their contribution to neonatal mortality, implications for surveillance, and the health service needs for prevention and management. The study followed a cohort of 2107 pregnant women till outcome which was miscarriage, termination of pregnancy, live or stillbirth, neonatal and post-neonatal mortality. Case ascertainment of congenital anomalies was done through visual examination, followed by various investigations. Rates of congenital anomaly affected births were reported per 10 000 births. Health service needs were described through retrospective analysis of events surrounding the diagnosis of a congenital anomaly. Among 1822 births, the total prevalence of major congenital anomalies was 230.51 (170.99-310.11) per 10 000 births. Congenital heart defects were the most commonly reported anomalies in the cohort with a prevalence of 65.86 (37.72-114.77) per 10 000 births. Although neural tube defects were two and a half times less as compared to congenital heart defects, they were nevertheless significant at a prevalence of 27.44 (11.73-64.08) per 10 000 births. In this cohort, congenital anomalies were the second largest cause of neonatal deaths. The congenital anomaly prenatal diagnosis prevalence was 10.98 per 1000 births and the congenital anomaly termination of pregnancy rate was 4.39 per 1000 births. This first cohort study from India establishes that the congenital anomaly rates were high, affecting one in forty four births in the cohort. The prevalence of congenital anomalies was identical to the stillbirth prevalence in the cohort, highlighting their public health importance. The results of this study identify the need for a well defined national programme with components of prevention, care and surveillance.


The prevalence and consequences of unmet need. Contrasts between older and younger adults with disability.
This article investigates the prevalence, determinants, and consequences of unmet need for assistance with activities of daily living (ADLs), instrumental activities of daily living (IADLs), and transportation in a randomly selected sample of adults with disability residing in Springfield, Massachusetts. Respondents were contacted through random digit dialing, and eligibility was determined through a disability screen. Eligible individuals were stratified by age; 632 people were interviewed (78% of contacted eligibles). The prevalence of need and unmet need for ADLs, IADLs, and transportation assistance was calculated separately by age strata, as was the prevalence of selected negative consequences attributed to inadequate help with specific activities. The determinants of unmet need were modeled using logistic regression. The prevalence of unmet need for assistance with individual ADLs ranged from 4.1% (eating) to 22.6% (transferring) of the full sample. Unmet need for IADLs assistance was higher, ranging from 15.9% (cooking) to 34.6% (heavy housekeeping). Respondents younger than age 65 reported higher levels of unmet need for IADLs and transportation help than respondents age 65 or older; members of the younger group also were more likely to report five of the seven negative consequences attributed to inadequate help with IADLs and transportation (eg, missing medical appointments). Regression results revealed inability to meet expenses, having few or no reliable helpers, and impairment severity to be key determinants of unmet need. Financial problems, and not age per se, placed working age adults at elevated risk of unmet need in this study. The consequences of inadequate help can impede management of chronic health conditions, and may compromise individuals' ability to maintain a safe and reasonable quality of community living.


Labor of love. A model for planning human resource needs.
Typically, the annual budgeting process is the hospital's only attempt to forecast human resource requirements. In times of rapid change, this traditional ad hoc approach is incapable of satisfying either the Catholic hospital's ethical obligations as an employer or its responsibilities to provide healthcare to the poor and suffering. Assumptions about future activity, including volume projections on admissions, patient days, and other services, influence the budgeting process to a large degree. Because the amount of work to be done and the number of employees required to do it are related, changes in demand for service immediately and directly affect staffing requirements. A hospital cannot achieve ethical human resource management or provide high-quality healthcare if inadequate planning forces management into a cycle of crisis-coping--reacting to this year's nursing shortage with a major recruiting effort and next year's financial crunch with a traumatic reduction in force. The human resource planning approach outlined here helps the hospital meet legitimate business needs while satisfying its ethical obligations. The model has four phases and covers a charge to the planning committee; committee appointments; announcements; the establishment of ground rules, focus, and task forces; and the work of each task force.


Recent progress in the etiopathogenesis of pediatric biliary disease, particularly Caroli's disease with congenital hepatic fibrosis and biliary atresia.
Recent progress in elucidating the etiopathogenesis of pediatric biliary diseases, particularly Caroli's disease with congenital hepatic fibrosis (CHF) and biliary atresia (BA), is reviewed. The former is characterized by multiple saccular dilatations of the intrahepatic bile ducts. An animal model of this disease, the PCK rat, is being extensively studied. PCK rats and Calori's disease with CHF belong to autosomal recessive polycystic kidney disease (ARPKD) with ductal plate malformation. Mutations of PKHD1 have been identified in ARPKD, and fibrocystin, a product of PKHD1 located in the cilia of bile ducts is lacking in the pathologic intrahepatic bile ducts of ARPKD. Disordered cell kinetics, including apoptosis of biliary epithelial cells (BECs), may be significantly related to ductal plate malformation, and laminin and type IV collagen were immunohistochemically reduced in the basement membrane of intrahepatic bile ducts of ARPKD, and such a reduction is an additional factor for the dilatation of bile ducts. Abundant connective tissue growth factor retained diffusely in heparan sulfate proteoglycan in the fibrous portal tracts are responsible for non-resolving hepatic fibrosis. In addition, pathologic BECs of ARPKD may acquire mesenchymal features and participate in progressive hepatic fibrosis by producing extracellular matrix molecules. In an animal model of BA, an initial virus-induced, T-cell mediated autoimmune-mediated cholangiopathy has been reported. In human BA, virus-induced apoptosis of BECs by a TNF-related apoptosis-inducing ligand followed by the progressive obliteration of bile ducts is also suggested, and epithelial mesenchymal transition of BECs induced by viral infection may be involved in the fibrotic process in sclerosing cholangitis. However, the role of viral infections in the affected tissues is controversial. Comprehensive and analytical studies of ARPKD and BA using human materials and animal models may lead to the clarification of their etiopathogenesis and open the way for new therapeutic strategies.


[Primary malignant melanoma of the vagina: a report of 22 cases].
In this paper, 22 patients from 1973 through 1994 with primary malignant melanoma are retrospectively analyzed. Vaginal bleeding, discharge and a tumor mass were the chief complaints. The most common site of the tumor origin was the lower third of the anterior and postrior vaginal wall. The 5-year survival rate of 18 previously untreated patients was 11% (2/18). Of the 18 patients, 9 in stage I treated by surgery and postoperative chemothreoapy and/or radiotherapy survived for an average of 33 months. Two of the 9 patients receiving radical surgery survived for more than 5 years. None of the remaining 9 patients in stage II-IV treated with chemotherapy and/or radiotherapy survived longer than 2 years. The survival time differed significantly in patients with and without pelvic lymph node metastasis (7 versus 41 months) and in those with and without vascular tumor thrombi (13 versus 43 months). Mitotic index of tumor cells and lymphocytic infiltration were of no prognostic value.


Community-based cardiovascular Risk Factors Intervention Strategies (CORFIS) in managing hypertension: A pragmatic non-randomised controlled trial.
Hypertension is the number one cardiovascular risk factor in Malaysia. This study aimed to evaluate the effectiveness of a Community-Based Cardiovascular Risk Factors Intervention Strategies (CORFIS) in the management of hypertension in primary care. This is a pragmatic, non-randomized controlled trial. Seventy general practitioners (GPs) were selected to provide either CORFIS (44 GPs) or conventional care (26 GPs) for 6 months. A total of 486 hypertensive patients were recruited; 309 were in the intervention and 177 in the control groups. Primary outcome was the proportion of hypertensive patients who achieved target blood pressure (BP) of <140/90mmHg (for those without diabetes mellitus) and <130/80mmHg (with diabetes mellitus). Secondary outcomes include change in the mean/median BP at 6-month as compared to baseline. The proportion of hypertensive patients who achieved target BP at 6-month was significantly higher in the CORFIS arm (69.6%) as compared to the control arm (57.6%), P=0.008. Amongst those who had uncontrolled BP at baseline, the proportion who achieved target BP at 6-month was also significantly higher in the CORFIS arm (56.6%) as compared to the control arm (34.1%), p<0.001. There was no difference in the patients who had already achieved BP control at baseline. There were significant reductions in SBP in the CORFIS arm (median -9.0mmHg; -60 to 50) versus control (median -2mmHg; -50 to 48), p=0.003; as well as in DBP (CORFIS arm: median -6.0mmHg; ranged from -53 to 30 versus control arm: median 0.0mmHg; ranged from -42 to 30), p<0.001. Patients who received CORFIS care demonstrated significant improvements in achieving target BP.


Analysis of the peri-implant soft tissues in contact with zirconia abutments: an evidence-based literature review.
The aim of this study is to evaluate through a literature review, the soft tissue response in contact with zirconia abutments, including case reports comparing prosthetics rehabilitations with zirconia and titanium abutments upto 3 years of follow-up as well as the factors that should be considered on implant's abutment selection. Metallic abutments can provide grayish color when in contact with thin soft tissues which may lead the implant prosthetic treatment to failure. In this context, the abutments of zirconia stand out because there is an excellent linking between esthetics and the health of peri-implant soft tissues. A consult of the published researches was made on the PubMed database from 2000 to September 2012. The including criteria were: literature reviews, clinical studies and case reports in English that focused on the response of the soft tissue in contact with zirconia implant abutments. The studies that were not in English and did not match the tackled issue were excluded. A total of 32 articles were found. According to the search strategy, just 16 articles were selected for this review. Three studies affirmed that zirconia abutments have an excellent soft tissue response; one study showed increased gingival recession with zirconia abutments and nine studies do not stand out any difference on biological behavior between titanium and zirconia abutments. Three studies affirmed that zirconia abutments provide natural gingival appearance, anatomic contour and greater esthetics. The use of zirconia abutments is recommended for anterior regions because of their greater optical properties and esthetic results and more studies should be performed and analyzed longitudinally regarding their biological response. The zirconia abutments have been established to be essential in order to achieve great esthetic results in cases of thin peri-implant soft tissues and in regions where the three-dimensional placement of implants is more superficial.


Molecular modeling and molecular dynamics simulation studies of Delta-Notch complex.
Notch is a single-pass transmembrane receptor protein which is composed of a short extracellular region, a single-pass transmembrane domain and a small intracellular region. Notch ligand like Delta, member of the DSL protein family, is also single-pass transmembrane protein. It has been demonstrated that of the 36 EGF repeats of Notch, 11th and 12th are sufficient to mediate interactions with Delta. Crystal structure of mammalian Notch extracellular ligand binding domain contains 11 and 12 EGF-like repeats. Here a portion of the Delta protein of Drosophila, known to interact with Notch extracellular domain (ECD) has been modeled using homology modeling. The structure of the Delta-Notch complex was subsequently modeled by protein docking method using GRAMM. MD simulations of the modeled structures were performed. The structure for Delta-Notch complex has been proposed based on interaction energy parameter and planarity studies.


[Comparison of two score models in predicting prognosis and renal outcome in acute renal failure].
To compare the value of ATN-ISI (acute tubular necrosis-individual severity index) and APACHE II (acute physiology and chronic health evaluation) score models in predicting mortality and renal outcome in patients with acute renal failure (ARF). 422 in-hospital patients with ARF were retrospectively analysed, the value in predicting prognosis and renal outcome of these two score models was compared. Renal outcome was observed three times, i.e. >or= 30 days, >or= 45 days and >or= 60 days after the occurrence of ARF and discriminant analysis was used in the study. The scores of the two models both correlated significantly with the mortality of patients with ARF. When ATN-ISI scores were >or= 0.85, the mortality was 100% and it was the same with APACHE II when the scores were >or= 35. The areas under ROC curve of APACHE II and ATN-ISI were 0.817 +/- 0.021 and 0.880 +/- 0.018 respectively, suggesting good model discriminantion. For the correctly classificated rate of renal outcome, ATN-ISI was better than APACHE II at any time. When ATN-ISI scores were >or= 0.75, patients were dialysis dependent. When the scores were >or= 0.58 but less than 0.75, the patient's renal function did not recover but was not dialysis dependent; when the scores were < 0.58, the patients's renal function would recover. When APACHE II scores were >or= 26, patients were dialysis dependent. There was no cut-off score point to separate renal function recovery from renal dysfunction. However, when APACHE II scores were <or= 22, 19.6% of the patients had renal dysfunction and 80.4% of them had renal function recovered. Both the score models are of value in predicting mortality and renal outcome in patients with ARF. ATN-ISI score model was better than APACHE II.


Changes of creatine kinase secondary structure induced by the release of nucleotides from caged compounds. An infrared difference-spectroscopy study.
Light-induced release of ADP and ATP from their respective caged nucleotides produced small distinct difference infrared spectra of creatine kinase (CK), indicating that ADP and ATP binding to CK promoted different structural alteration. The positive band at 1638-1640 cm-1 and the negative band at about 1650-1652 cm-1 on the reaction-induced infrared difference spectra in the amide I region were insensitive to the deuteration effects. They were assigned to the peptide backbone of the ADP/ATP-binding site. In addition Pi or ATP binding produced another positive band at 1657-1659 cm-1 corresponding to the C = O (amide I band) associated with the gamma-phosphate of ATP. This site was also affected when ADP was added, indicating coupling interactions between both sites. No additional structural changes were observed when creatine and ADP were added, suggesting that the creatine-binding site was uncoupled from the ADP-binding site. The infrared difference spectra of a transition-state-analog complex formed by the addition of ADP, creatine and NO3- (a planar-phosphate-mimicking group) lacked the 1657-1659-cm-1 band indicating that the binding site of gamma-phosphate within CK, was not affected. Infrared changes in the 1560-1590-cm-1 region suggested that carboxylate groups of Asp or Glu were involved in the binding of Pi, ADP and ATP.


Quasi-classical statistico-dynamical description of polyatomic photo-dissociations: state-resolved distributions.
An alternative methodology to investigate indirect polyatomic processes with quasi-classical trajectories is proposed, which effectively avoids any binning or weighting procedure while provides rovibrational resolution. Initial classical states are started in terms of angle-action variables to closely match the quantum experimental conditions and later transformed into Cartesian coordinates, following an algorithm very recently published [J. Chem. Phys. 2009, 130, 114103]. Trajectories are then propagated using the 'association' picture, i.e. an inverse dynamics simulation in the spirit of the exit-channel corrected phase space theory of Hamilton and Brumer [J. Chem. Phys. 1985, 82, 595], which is shown to be particularly convenient. Finally, an approximate quasi-classical formula is provided which under general conditions can be used to add possible rotational structures into the vibrationally-resolved quasi-classical distributions. To introduce the method and illustrate its capabilities, correlated translational energy distributions from recent experiments in the photo-dissociation of ketene at 308 nm [J. Chem. Phys. 2006, 124, 014303] are investigated. Quite generally, the overall theoretical algorithm reduces the total number of trajectories to integrate and allows for fully theoretical predictions of experiments on polyatomics.


Collagenous fibroma (desmoplastic fibroblastoma).
A Collagenous Fibroma (Desmoplastic Fibroblastoma) is a rare, benign, slowly growing, fibroblastic, soft tissue lesion. Here, the case of a 28-year-old woman, who presented with a 1-year history of a slowly growing painless mass in the right anterior aspect of her neck, is described. This type of tumor was first described by Evans in 1995, and named as a Desmoplastic fibroblastoma but was renamed, by Nielsen in 1996 as a Collagenous Fibroma. This type of tumor is frequently reported in men with a mean age at occurance of 50 years. Clinically, a Collagenous fibroma presents as a firm, well-circumscribed subcutaneous, or intramuscular, painless mass of long duration. They are mostly located in the neck and extremities. The tumors range in size from 1 to 20 cm and predominantly occurs within the subcutaneous tissue, but fascial and skeletal muscle involvement is common. The treatment of a Collagenous Fibroma is a total surgical excision. No tumor recurrence has been reported the literature during the follow-up period and no tumor recurrence was observed in our case at the 1-year follow-up.


Lineage switch of a mouse pre-B cell line (SPGM-1) to macrophage-like cells after incubation with phorbol ester and calcium ionophore.
The mouse CD5 positive pre-B cell line SPGM-1 can be induced to switch its lineage commitment towards macrophage differentiation by treatment with a combination of phorbol ester and a calcium ionophore. When cultured with these reagents the pre-B cells ceased to proliferate and rapidly became adherent to plastic surfaces. This morphological change was accompanied by the loss of pre-B cell-specific surface markers, such as PB76 and most prominently the mu heavy chain of the immunoglobulin receptor complex. In addition, the mRNA of the surrogate light chain lambda 5 disappeared while the induction of lysozyme mRNA could be detected. Differentiated SPGM-1 cells phagocytosed latex beads and showed nonspecific esterase activity. The high efficiency and speed of differentiation in this cellular system makes SPGM-1 a highly suitable model for studying the phenomenon of lineage switching during hemopoesis.


Atmospheric Photoionization Detector with Improved Photon Efficiency: A Proof of Concept for Application of a Nanolayer Thin-Film Electrode.
Atmospheric photoionization is a widely applied soft ionization mechanism in gas sensing devices for the detection of volatile organic compounds in ambient air. Photoionization is typically induced by low-pressure Vacuum Ultraviolet (VUV) lamps with MgF2 or LiF lamp surface windows depending on the gas fill and the required wavelength transmission window. These lamps are known to exhibit gradually reduced VUV transmission due to hydrocarbon contamination. LiF surface windows are known to be especially problematic due to their hygroscopic nature, reducing VUV lamp lifetime to a mere 100 h, approximately. Here, we present a new design for the electrode of a photoionization detector based on thin-film technology. By replacing the commonplace metal grid electrode's VUV lamp surface window with a chromium/gold thin film we obtain a doubling of photon efficiency for photoionization. Replacing the hygroscopic LiF lamp window surface with a metallic layer additionally offers the possibility to vastly increase operational lifetime of low-pressure Argon VUV lamps.


The future of calcium channel blocker therapy in diabetes mellitus.
Diabetes mellitus is associated with significant morbidity and mortality caused by the micro- and macro-vascular complications that all too frequently develop during the lifetime of the diabetic patient. In attempts to treat the complications of diabetes, several different treatment strategies have been investigated. The role of tight blood glucose control in the treatment of diabetic vascular complications has recently been challenged, as the existing data in support of this mode of therapy are currently inconclusive. Perhaps more effective in preventing many of the vascular complications is the rigorous treatment of hypertension that frequently accompanies diabetes mellitus. Epidemiological studies have demonstrated that the presence of hypertension significantly contributes to the development and progression of diabetic nephropathy, retinopathy, cardiovascular disease, and possibly neuropathy. Preliminary clinical studies demonstrate that the progression of diabetic renal disease can be slowed by vigorous antihypertensive therapy. Among the various antihypertensive agents used to treat the hypertension associated with diabetes mellitus, calcium channel blockers are emerging as one of the agents of first choice. This is because of their very low side effect profile and their absence of detrimental effects on serum lipid levels and glucose tolerance. Calcium channel blockers may be of additional potential benefit to the diabetic patient by slowing the progression of atherosclerosis, reversing the intracellular calcium defects that may contribute to the pathogenesis of diabetic cardiomyopathy, and protecting against the progression of chronic renal disease.


[Treatment of hypertension with obsilazin].
Obsilazin was established to have a good to moderate hypotensive effect in 75% of the treated 36 patients with moderate and severe hypertension under the condition of a 6-month open clinical experiment, not changing the heart rate. The adverse effects are often 69.4%), usually transitory but in 11.1% they proved to be the cause for discontinuation of the treatment.


Characteristics of atrial re-entry and meander computed from a model of a rabbit single atrial cell.
A two-dimensional excitable medium model of atrial tissue has been constructed by incorporating the Earm-Hilgemann-Noble excitation equations for membrane voltage-dependent ionic currents and pump exchanger currents, time-dependent changes in intracellular and extracellular ionic concentrations, and storage and release of Ca2+, for an atrial cell in an homogeneous partial differential equation. A diffusion coefficient of 1.25 cm2 sec-1 gives the conduction velocity of a solitary planar wave as 0.6 m sec-1. A spiral wave with a period of 78 msec develops from a broken wavefront, and initially rotates around a circular core of 2 mm diameter. After 1.5 sec of rotation, a biperiodic meander, with 6 epicycles/cycle, develops. This simple meander pattern is reflected in a period-6 modulation of the intervals between successive wavefronts.


Initial experience with a new Yamakawa-type prosthesis for long-term percutaneous transhepatic drainage.
In a previous study evaluating the problems of long-term percutaneous transhepatic biliary drainage (PTBD) using Yamakawa-type prostheses in patients with benign and malignant stenoses, breakage of the tube proved to be a serious problem, occurring in 19.7 % of PTBD exchanges. As a consequence of these results, a new PTBD tube made of Tecothane has been developed. From September 1997 to September 1998, this new PTBD tube was applied in 64 patients (39 men, 25 women; median age: 70, range 29-89) in the treatment of benign (n = 30) or malignant stenoses (n=31; three stenoses remained indeterminate), and the course was followed. A total of 134 stent exchanges were performed, 52 of these being ahead of schedule (39 %). Not a single case of breakage occurred. However, other PTBD-related problems remained unchanged. Patients accepted the new prosthesis very well; among 19 patients who had experience of both the new one and the conventional one, 11 had preferences-eight for the new one and three for the old one. This new Tecothane prosthesis has solved the problem of PTBD breakage, which was often accompanied by serious problems. As was to be expected, other PTBD-related problems were not substantially affected. Nevertheless, this new tube represents progress in the percutaneous treatment of biliary stenoses.


Pentoxifylline, Ciprofloxacin and Dexamethasone Improve the Ineffective Hematopoiesis in Myelodysplastic Syndrome Patients; Malignancy.
Twenty-five patients with a diagnosis of myelodysplastic syndromes (MDS) were randomized to either begin therapy with pentoxifylline, ciprofloxacin and dexamethasone (PCD) immediately (10 patients) or after a 12 week observation period (control arm, 15 patients). PCD was administered with the goal of suppressing cytokine-induced excessive intramedullary apoptosis of hematopoietic cells. No marked fluctuations of blood counts were noted during the period of observation. Twenty-two patients completed at least 12 weeks of therapy: 18/22 showed some type of hematologic response, 9/18 showing an improvement in absolute neutrophil count only (p = < 0.001) and 9/18 showing multi-lineage responses. No unique category of MDS responded better, however 19/25 patients had refractory anemia (RA)/RA with ringed sideroblasts. The median time to response was 6 weeks and 3/18 responding patients maintained their responses beyond a year. We conclude that hematologic improvement in response to PCD therapy supports the validity of this unique anti-cytokine approach. Future trials should combine PCD therapy with established approaches (growth factors/chemotherapy) and also should focus on identifying more effective ways of suppressing the pro-apoptotic cytokines in MDS.


Dimitrios Zambakis' Scientific Hypothesis on the Transmission of Leprosy.
Dimitrios Zambakis was an acclaimed physician at his time, most recognized for his work on leprosy. He theorized that leprosy was a hereditary disease, receiving many awards for his work including the Cholera Medal of Honour (1854), Château-Villard Prize from the Faculty of Medicine in Paris (1898), The Montyon Prize, and the title of Pasha. However, his theory was routinely argued against and was later proven to be invalid. Leprosy is regarded as a contagious disease spread by contact and is not hereditary. The last name appears to be spelled in various ways (Zambakis, Zambaco). For this paper, "Dimitrios Zambakis" will be used.


A Study on the Effect of Nanoscale MgO and Hydrogen Bonding in Nanofiber Mats for the Controlled Drug Release along with In Vitro Breast Cancer Cell Line and Antimicrobial Studies.
Nanosized metal oxide-incorporated drug carriers have received significant attention due to their biocompatibility, mechanical strength, controlled drug release, and biodegradability. Herein, an attempt was made to fabricate polycaprolactone-based electrospun nanofiber mats involving the 5-fluorouracil (5Fu) drug, MgO nanoparticle, methyl cellulose, and polyethylene glycol. The chemical interactions, surface wettability, mechanical properties, structural and morphological changes, and thermal stability were studied by the respective analyses. The ionic interaction between 5Fu, MgO, and polymers were found to be responsible for the controlled drug release. Zero-order kinetic and model data also revealed that a controlled drug release pattern was observed in a period of 16 days. Furthermore, the nanofiber mats were subjected to cytotoxicity studies against MDA-MB-231 cancer cell line and the results showed higher cytotoxicity in a short time of 24 h and less toxicity to normal L929 fibroblast cell line. The apoptosis in cancer cell lines was also tested by AO/PI staining assay and confirmed by fluorescence microscopy. In addition, the growth inhibition of several bacterial and fungal strains was tested for the mats and the results exhibited good inhibition activity. Hence, the reported nanofiber drug carrier was found to be an efficient implant for the controlled release of anticancer drug along with other significant properties.


Polymer conjugates: nanosized medicines for treating cancer.
Interdisciplinary research at the interface of polymer chemistry and the biomedical sciences has produced the first polymer-based nanomedicines for the diagnosis and treatment of cancer. These water-soluble hybrid constructs, designed for intravenous administration, fall into two main categories: polymer-protein conjugates or polymer-drug conjugates. Polymer conjugation to proteins reduces immunogenicity, prolongs plasma half-life and enhances protein stability. Polymer-drug conjugation promotes tumor targeting through the enhanced permeability and retention (EPR) effect and, at the cellular level following endocytic capture, allows lysosomotropic drug delivery. The successful clinical application of polymer-protein conjugates (PEGylated enzymes and cytokines) and promising results arising from clinical trials with polymer-bound chemotherapy (e.g. doxorubicin, paclitaxel, camptothecins) has provided a firm foundation for more sophisticated second-generation constructs that deliver the newly emerging target-directed anticancer agents (e.g. modulators of the cell cycle, signal transduction inhibitors and antiangiogenic drugs) in addition to polymer-drug combinations (e.g. endocrine- and chemo-therapy).


Genetic incompatibility drives mate choice in a parasitic wasp.
Allelic incompatibility between individuals of the same species should select for mate choice based on the genetic make-up of both partners at loci that influence offspring fitness. As a consequence, mate choice may be an important driver of allelic diversity. A complementary sex determination (CSD) system is responsible for intraspecific allelic incompatibility in many species of ants, bees, and wasps. CSD may thus favour disassortative mating and in this, resembles the MHC of the vertebrate immune system, or the self-incompatibility (SI) system of higher plants. Here we show that in the monogamous parasitic wasp Bracon brevicornis (Wesmael), females are able to reject partners with incompatible alleles. Forcing females to accept initially rejected partners resulted in sex ratio distortion and partial infertility of offspring. CSD-disassortative mating occurred independent of kin recognition and inbreeding avoidance in our experiment. The fitness consequences of mate choice are directly observable, not influenced by environmental effects, and more severe than in comparable systems (SI or MHC), on individuals as well as at the population level. Our results thus demonstrate the strong potential of female mate choice for maintaining high offspring fitness in this species.


Interleukin-2 stimulation activates mesothelial cellular functioning against autologous tumor cells.
The present study was designed to determine the different effects of cytokines or antibodies (IL-2, IL-4, IL-7, IL-10, IL-12, alphaCD3) in stimulating the cellular functions of mesothelial cells isolated from malignant pleural effusion. Mesothelial cells were isolated from 27 patients with malignant pleural effusion. The cultured cellular interferon-gamma (IFNgamma) and IL-10 production, proliferative response, and cytolytic activity against autologous tumors and K-562 cells were measured. Stimulation with IL-2 alone significantly increased the mesothelial cells' proliferative response (p < 0.001) and cytolytic activity against autologous tumors (p = 0.025). The further addition of other cytokines did not increase these functions. The IFNgamma/IL-10 ratio data showed that the T-helper (Th) pathway was shifted from the Th-2 pathway to the Th-1 pathway (increase of IFNgamma/IL-10 ratio) when mesothelial cells were stimulated with IL-2. Further stimulation with IL-2 plus IL-12 or alphaCD3 shifted the Th pathway further in the Th-1 direction, but without statistical significance. The mesothelial cell proliferative response is enhanced with IL-2 stimulation alone. The T-helper pathway is also shifted from the Th-2 to the Th-1 response (increase of IFNgamma/IL-10 ratio) after IL-2 stimulation of mesothelial cells. Mesothelial cells had cytolytic activity against tumor cells, and this activity could be augmented by IL-2 stimulation.


The Relationship Between Depression and Metabolic Syndrome: Systematic Review and Meta-Analysis Study.
Several studies have been conducted on the relationship between depression and metabolic syndrome, which have had conflicting results. The purpose of this study was a meta-analysis of studies that have examined the relationship between these two variables. This meta-analysis systematically reviewed the relationship between depression and metabolic syndrome. Scientific databases including IranMedex, SID, Magiran, Scopus, PubMed, Google Scholar, and Science Direct were searched and 17 articles were extracted from 2000 to 2014. Selected studies data were analyzed using meta-analysis and random effects model. Heterogeneity between the studies was examined using I2. Data were analyzed using STATA software version 12.1. Seventeen studies were analyzed with a sample size of 31880 people. Analysis by the type of studies showed that the relationship between the two variables in cross-sectional studies (OR = 1.51, CI 95% = 1.36 - 1.68) and cohort studies (OR = 1.6, CI 95% = 1.23 - 2.08) was significant. In general, the heterogeneity test results among the studies was not significant (P for heterogeneity = 0.08, I(2) = 39.8%). There is a relationship between depression and metabolic syndrome.


Feeding ecology of a group of buffy-headed marmosets (Callithrix flaviceps): fungi as a preferred resource.
Mycophagy is a relatively rare behavior in primates and has only been recorded in five callitrichid species. Here, we present data on the feeding ecology of a free-ranging group of Callithrix flaviceps, which was studied in the Augusto Ruschi Biological Reserve, Southeastern Brazil, in 2008. In contrast with other marmosets, which are typically gummivorous, the study group was predominantly mycophagous-insectivorous, with fungi corresponding to 64.8% of total feeding records, and gum (6.1%) and fruit (3.3%) together providing only a minor part of the diet. Prey corresponded to 25.8% of the group's diet. The fungi (Mycocitrus spp.) consumed by the marmosets were found attached to the stems of Merostachys bamboo. As the animal component of the group's diet was similar to that recorded in studies of other marmosets, we propose that fungi were exploited primarily as a substitute for plant material, in particular exudates. This highly mycophagous diet may be determined by two principal factors: (1) the abundance of fungi within the study area, and (2) the avoidance of bark gouging, for which C. flaviceps may be less specialized than most other marmosets. These conclusions are supported by comparisons with other marmoset groups, which indicate an ecological specialization for mycophagy in C. flaviceps, and that the species will resort to gummivory in habitats where fungi are scarce.


Effects of transition metal doping on electronic structure of metastable β-Fe2O3 photocatalyst for solar-to-hydrogen conversion.
Metastable β-Fe2O3 is a promising photocatalyst with a band gap of approximately 1.9 eV, while its intrinsic material properties remain rarely studied by theoretical calculations. Here, using density functional theory, we studied the electronic band structure and effective mass of carriers in Zr, Sn, and Ti doped β-Fe2O3. The calculation results show that, through the doping of Zr, Sn, or Ti, the dipole moment of FeO6 octahedra in β-Fe2O3 increases, which favors the separation of photo-excited electron-hole pairs. The electron and hole effective masses in the close-packed orientation [111] in cubic β-Fe2O3 have the smallest absolute values. After doping with Zr, Sn, and Ti, the absolute values of electron and hole effective masses in the [111] orientation are further reduced. Furthermore, the relative ratio (D) mostly became larger after doping with Zr, Sn, and Ti, which indicates that the photoexcited carriers in the doped structure are effectively separated. Construction of Zr, Sn, and Ti doped β-Fe2O3 in the [111] orientation may be effective to improve the photocatalytic efficiency.


Liver aging and pseudocapillarization in a Werner syndrome mouse model.
Werner syndrome is a progeric syndrome characterized by premature atherosclerosis, diabetes, cancer, and death in humans. The knockout mouse model created by deletion of the RecQ helicase domain of the mouse Wrn homologue gene (Wrn(∆hel/∆hel)) is of great interest because it develops atherosclerosis and hypertriglyceridemia, conditions associated with aging liver and sinusoidal changes. Here, we show that Wrn(∆hel/∆hel) mice exhibit increased extracellular matrix, defenestration, decreased fenestration diameter, and changes in markers of liver sinusoidal endothelial cell inflammation, consistent with age-related pseudocapilliarization. In addition, hepatocytes are larger, have increased lipofuscin deposition, more frequent nuclear morphological anomalies, decreased mitochondria number, and increased mitochondrial diameter compared to wild-type mice. The Wrn(∆hel/∆hel) mice also have altered mitochondrial function and altered nuclei. Microarray data revealed that the Wrn(∆hel/∆hel) genotype does not affect the expression of many genes within the isolated hepatocytes or liver sinusoidal endothelial cells. This study reveals that Wrn(∆hel/∆hel) mice have accelerated typical age-related liver changes including pseudocapillarization. This confirms that pseudocapillarization of the liver sinusoid is a consistent feature of various aging models. Moreover, it implies that DNA repair may be implicated in normal aging changes in the liver.


Characterization of Balance Problems and Rehabilitation Needs of Patients with Ménière's Disease.
To explore and characterize balance problems in subjects with Ménière's disease (MD). A total of 539 people with MD with a mean age of 61.9 years, mean disease history of 15.6 years, and 79.5% females were recruited. The online questionnaire, consisting of 39 questions, including both structured and open-ended questions, focused on symptoms of MD, balance problems, impacts of the complaints, and quality of life (QoL). After hearing loss (58%) and tinnitus (50%), balance problems (44%) were among the most commonly reported MD complaints, even higher than the impact of vertigo (40%). However, only 22% reported that those balance problems made obvious impacts in their daily lives. The most common balance problem that significantly reduced QoL was tripping (34%). Swaying (25%) had a limited impact on QoL, whereas rocking (10%) was less common but caused a significant impact on QoL. Non-defined balance problems were reported at 18%; these were occasional and correlated with vertigo attacks. Older participants had more frequent tripping problems. Younger participants more frequently reported swaying and rocking. Risk factors predicting poor postural control were mostly related to complaints reflecting otolith pathology. Different types of postural problems require different strategies to manage balance control and cope with the disease.


Identification of the nukacin KQU-131, a new type-A(II) lantibiotic produced by Staphylococcus hominis KQU-131 isolated from Thai fermented fish product (Pla-ra).
Staphylococcus hominis KQU-131, isolated from Thai fermented marine fish, produces a heat stable bacteriocin. Structural and genetic analysis indicated that the bacteriocin is a variant of nukacin ISK-1, a type-A(II) lantibiotic, and we termed the bacteriocin nukacin KQU-131. There were three different amino acid residues between nukacin ISK-1 and nukacin KQU-131, one residue in the leader peptide and the other two in the mature peptide.


Primary total knee arthroplasty for supracondylar/condylar femoral fracture in osteoarthritic knees.
Supracondylar or condylar femoral fractures require extended treatment and often result in loss of knee range of motion. We present 3 cases in which femoral fractures and preexisting painful knees secondary to osteoarthritis were treated using total knee arthroplasty with a stemmed femoral implant. The patients were all women aged 83, 84, and 87 years old. All fractures united within 3 months, and the patients could walk with 1 cane within 2 months. Primary total knee arthroplasty should be considered as a treatment for supracondylar/condylar femoral fractures in osteoarthritic knees.


Acylphloroglucinolated Catechin and Phenylethyl Isocoumarin Derivatives from Agrimonia pilosa.
Eight new compounds (1-8), including five acylphloroglucinolated catechins (1-5) and three phenylethyl isocoumarin glycosides (6-8), were isolated from Agrimonia pilosa along with six other known compounds (9-14). The new compounds were characterized structurally by NMR, MS, and ECD analyses. Compounds 4 and 5 were assigned as acylphloroglucinolated procyanidin derivatives, which are described for the first time from Nature. The absolute configuration of compound 8 was elucidated by computational analysis of its ECD spectrum. The isolated compounds were evaluated for their inhibitory activity against lipopolysaccharide-induced NO production in BV2 microglial cells.


Preoperative determination of prostate cancer tumor volume: analysis through biopsy fragments.
Preoperative determination of prostate cancer (PCa) tumor volume (TV) is still a big challenge. We have assessed variables obtained in prostatic biopsy aiming at determining which is the best method to predict the TV in radical prostatectomy (RP) specimens. Biopsy findings of 162 men with PCa submitted to radical prostatectomy were revised. Preoperative characteristics, such as PSA, the percentage of positive fragments (PPF), the total percentage of cancer in the biopsy (TPC), the maximum percentage of cancer in a fragment (MPC), the presence of perineural invasion (PNI) and the Gleason score were correlated with postoperative surgical findings through an univariate analysis of a linear regression model. The TV correlated significantly to the PPF, TPC, MPC, PSA and to the presence of PNI (p < 0.001). However, the Pearson correlation analysis test showed an R2 of only 24%, 12%, 17% and 9% for the PPF, TPC, MPC, and PSA respectively. The combination of the PPF with the PSA and the PNI analysis showed to be a better model to predict the TV (R2 of 32.3%). The TV could be determined through the formula: Volume = 1.108 + 0.203 x PSA + 0.066 x PPF + 2.193 x PNI. The PPF seems to be better than the TPC and the MPC to predict the TV in the surgical specimen. Due to the weak correlation between those variables and the TV, the PSA and the presence of PNI should be used together.


Imagery deficits in nonverbal learning disabilities.
This study reports the observations gathered from 11 children referred to consulting services because of learning difficulties at school and diagnosed with nonverbal learning disabilities (NVLD). These children had an average verbal IQ, but a WISC-R performance IQ lower than the verbal IQ by at least 15 points and experienced difficulties especially in mathematics and drawing. The children completed a battery of four tasks requiring visuospatial working memory and visual imagery: a memory task composed of pictures and their positions (Pictures task), a task that required them to memorize the positions filled in a matrix (Passive Matrix task), a task that required them to imagine a pathway along a matrix (Active Matrix task) and a task that required them to learn groups made up of three words, using a visual interactive imagery strategy (TV task). In comparison to a control group of 49 children, children with NVLD scored lower in all the tasks, showing deficits in the use of visuospatial working memory and visual imagery. By contrasting subgroups of children of different ages in the control group, it was possible to show that some tasks did not show a clear developmental trend. Thus the deficits shown by the children with NVLD cannot simply be attributed to a developmental delay of these children, but seem to reflect a more severe disability.


Dual location of MAR-binding, filament-like protein 1 in Arabidopsis, tobacco, and tomato.
Matrix attachment region-binding filament-like protein 1 (MFP1) is a plant-specific long coiled-coil protein that binds double-stranded DNA. While originally identified as a component of the tobacco nuclear matrix, it was subsequently shown that the majority of MFP1 resides in mature chloroplast where it is located at the stroma side of the thylakoids and is able to bind to nucleoids. On the other hand, a 90 kDa MFP1-like protein from onion has been convincingly shown to be an intrinsic component of the onion meristematic nuclear matrix. Here, we have expanded the analysis of the subcellular location of MFP1 by using high-resolution confocal immunofluorescence microscopy and immunogold electron microscopy. Two different antisera raised against MFP1 from two species were used on isolated nuclei and chloroplasts from tomato, tobacco, and Arabidopsis. Our data show that both antibodies detect a signal in both compartments in all three species. An Arabidopsis MFP1 T-DNA insertional mutation abolishes both nuclear and chloroplast signals, indicating that the nuclear and plastidic antigens are derived from the same gene. We therefore suggest that MFP1 is a protein with a dual location, in both nuclei and chloroplasts, consistent with prior findings in onion and the dicot species investigated here.


Association between metabolic syndrome and sexual dysfunction among men with clinically diagnosed diabetes.
The worldwide epidemic of diabetes and obesity has resulted in a rapid upsurge in the prevalence of metabolic syndrome (MetS). MetS makes the individual liable to endothelial dysfunction which can initiate sexual dysfunction (SD). This study assessed the association between MetS and SD among clinically diagnosed diabetic subjects in Tema, Greater Accra Region of Ghana. Sexual functioning was assessed using Golombok Rust Inventory of Sexual Satisfaction in 300 consecutive diabetic men visiting the diabetic clinic of Tema General Hospital between November, 2010 and March, 2011. Anthropometric data including waist and hip circumference as well as blood pressure were measured. The levels of fasting blood glucose and serum lipid profile were assessed. All the men had a steady heterosexual relationship for at least 2 years before enrolment in the study. The response rate was 91.3% out of the 300 subjects recruited for the study. Those with SD were significantly older and had diabetes for a longer period as compared to those without SD. The prevalence of MetS as defined by the various criteria was 78.8%, 43.4% and 51.8% for WHO, NCEP ATP III and IDF respectively. Central obesity (p = 0.0482) and raised blood pressure (p = 0.0309) are the significant MetS components when the studied population was stratified according to sexual functioning. Generally, SD as well as its sub-scales correlate positively with age, blood pressure, duration of diabetes and MetS score. Whereas TC and LDL-c correlated positively with non-communication, TG correlates positively with avoidance and infrequency. SD and its sub-scales have a direct relationship with duration of diabetes, blood pressure and MetS score from this study. Central obesity and raised blood pressure seem to be the link between MetS and SD among this clinically diagnosed diabetic subjects.


Maximizing Oxygen Delivery in Portable Ventilators.
Military transport of critically ill/injured patients requires judicious use of resources. Maintaining oxygen (O2) supplies for mechanically ventilated is crucial. O2 cylinders are difficult to transport due to the size and weight and add the risk of fire in an aircraft. The proposed solution is the use of a portable oxygen concentrator (POC) to supply O2 for mechanical ventilation. As long as power is available, a POC can provide an endless supply of O2. Anecdotal evidence suggests that as little as 3 L/min of O2 could manage as many as 2/3 of the mechanically ventilated military aeromedical transport patients. We evaluated two each of the AutoMedx SAVe II, Hamilton T1, Zoll 731, and Ventec VOCSN portable ventilators over a range of settings paired with 1 and 2 Caire SAROS POCs at ground level and simulated altitudes of 8,000 feet, 16,000 feet, and 22,000 feet. The Ventec VOCSN has the capability of utilizing an internal O2 concentrator that uses pulsed dose technology, which was also evaluated. Each ventilator was attached to a Michigan Instruments Training Test Lung. Output from the POC was bled into each ventilator via the mechanism provided with each device. A Fleisch pneumotach was used to measure delivered tidal volume (VT), and a fast-response O2 analyzer was used to measure FiO2 within the simulated lung. Ventilator parameters and FiO2 were continuously measured and recorded at each altitude. One-way analysis of variance was used to determine statistically significant differences (P < .05) in FiO2 between ventilators and among the same ventilator model at each testing condition. Delivered FiO2 varied widely between ventilator models and between devices of the same model with some testing conditions. Differences in FiO2 between ventilators at a majority (98.5%) of testing conditions were statistically significant (P < .05) but not all were clinically important. The Zoll 731 delivered the highest and most consistent FiO2 over all ventilator/POC settings at all altitudes. Differences in FiO2 at a given ventilator/POC setting from ground level to 22,000 feet were not clinically important (<5%) with this device. The VOCSN utilizing the integrated internal O2 concentrator delivered the lowest FiO2 across all ventilator/POC settings and altitudes. Due to the inability of the SAVe II to operate at the minute ventilation and positive end expiratory pressure (PEEP) settings required by the testing protocol, the device was only tested at one ventilator setting. The Hamilton T1 failed to operate appropriately at the highest VT/PEEP setting at 16,000 feet and all but one ventilator setting at 22,000 feet. The delivered FiO2 was not included in the analysis for those ventilator settings. The highest delivered FiO2 was 0.85 ± 0.05 at the 250 mL VT setting using 2 POCs (P < .0001) at ground level with the Zoll 731. Oxygen delivery utilizing POCs is dependent upon multiple factors including ventilator operating characteristics, ventilator settings, altitude, and the use of pulsed dose or continuous flow O2. Careful patient selection would be paramount to provide safe mechanical ventilation using this method of O2 delivery.


Auxin requirements of sycamore cells in suspension culture.
Sycamore (Acer pseudoplatanus L.) cell suspension cultures (strain OS) require 2,4-dichlorophenoxyacetic acid (2,4-D) in their culture medium for normal growth. If the 2,4-D is omitted, rates of cell division are dramatically reduced and cell lysis may occur. Despite this ;auxin requirement,' it has been shown by gas chromatography-mass spectrometry that the cells synthesize indol-3yl-acetic acid (IAA). Changes in free 2,4-D and IAA in the cells during a culture passage have been monitored.There is a rapid uptake of 2,4-D by the cells during the lag phase leading to a maximum concentration per cell (125 nanograms per 10(6) cells) on day 2 followed by a decline to 45 nanograms per 10(6) cells by day 9 (middle of linear phase). The initial concentration of IAA (0.08 nanograms per 10(6) cells) rises slowly to a peak of 1.4 nanograms per 10(6) cells by day 9 then decreases rapidly to 0.2 nanograms per 10(6) cells by day 15 (early declining phase) and 0.08 nanograms per 10(6) cells by day 23 (early stationary phase).


Sleep and eye disease: A review.
There is a growing body of literature on the effects of sleep disorders, in particular obstructive sleep apnoea (OSA), on ocular health, with consistent evidence of an increased risk of floppy eyelid syndrome, non-arteritic anterior ischaemic optic neuropathy, diabetic macular oedema, and other retinal vasculature changes in individuals with OSA. However, reports on OSA's associations with glaucoma, papilloedema, diabetic retinopathy, central serous chorioretinopathy, and keratoconus have been conflicting, while links between OSA and age-related macular degeneration have only been described fairly recently. Despite numerous suggestions that OSA treatment may reduce risk of these eye diseases, well-designed studies to support these claims are lacking. In particular, the ocular hypertensive effects of continuous positive airway pressure (CPAP) therapy for OSA requires further investigation into its potential impact on glaucoma risk and management. Reports of ocular surface complications secondary to leaking CPAP masks highlights the importance of ensuring good mask fit. Poor sleep habits have also been linked with increased myopia risk; however, the evidence on this association remains weak.


Kinematic analyses of air-stepping in normal and decerebrate preweanling rats.
We studied the ability of L-DOPA (100 mg/kg, subcutaneous) to elicit air-stepping in decerebrate and sham-operated Sprague-Dawley rats from postnatal Day 5 through postnatal Day 20. The most common gait consisted of fore- and hindlimb alternation, but between 10 and 20 days of age, patterns of coordination resembling swimming, in which the forelimbs remained adducted, and galloping became more frequent in both decerebrate and sham-operated rats. Because episodes of galloping were rarely more than two or three step cycles in length, our analyses focused on episodes of stepping in which limbs within the girdles stepped in alternation and diagonal pairs of limbs moved in synchrony ("trot"). The rate of stepping of both decerebrate and sham-operated rats increased from about 2.9 steps/s at Day 5 to about 4 steps/s at Day 20. In both groups, this increase was found to result from a decrease in the duration of the retraction phase of the step cycle. Amplitudes of movement at the wrist, knee, and ankle increased with age in both decerebrate and sham-operated neonates, whereas those of the shoulder, elbow, and hip did not change in either group. The timing of movements at joints within each limb also changed similarly with age in sham-operated and decerebrate pups. During development, forelimb movement was increasingly led by the wrist, which was followed by the elbow and then finally by the shoulder. Hindlimb movements were increasingly led by the knee, followed by the ankle, and finally by the hip. At all ages, diagonal limbs moved in synchrony, and heterolateral limbs within each girdle moved in antiphase. However, the phase relationship between hindlimb and forelimb movements changed both in sham-operated rats and in decerebrate rats during ontogeny. On Day 5, movement of each hindlimb was phase-delayed relative to that of the diagonal forelimb whereas on Days 15 and 20, the hindlimb was phase-advanced. The parallel emergence of different gaits and the similarity of coordination during diagonal progression in sham-operated and decerebrate pups show that age-related changes in gait are mediated no more rostrally than the midbrain.


Morphea Profunda with Tertiary Lymphoid Follicles: Description of Two Cases and Review of the Literature.
Morphea profunda or subcutaneous (deep) morphea is a variant of localized morphea, characterized by one or more ill-defined, deep sclerotic plaque. Preferential sites are the abdomen, trunk, sacral area, or extremities. The presence of hyperplastic lymphoid follicles in the context of the sclerotic bands of morphea is rarely described. Localized scleroderma is sustained by a profibrotic inflammatory profile. Transforming growth factor-β (TGF-β), an imbalance between functional subclasses of T-lymphocytes (innate immune cells) has a role in activate collagen deposition. In this case report, we present two cases of morphea profunda with lymphoid follicular hyperplasia. A systematic review of the literature on the pathophysiology of localized scleroderma is also presented, with particular reference to the presence of lymphoid structures.


Combined denitrification and excess biological phosphorus removal in discontinuous operated biofilm systems.
The sorption-denitrification-P-removal (S-DN-P) process combines biological excess P-removal (BEPR) and denitrification using immobilized biomass. The accumulation of denitrifying polyP organisms is achieved by sequencing anaerobic/anoxic conditions. The immobilized biomass is in alternating contact with primary treated wastewater (anaerobic sorption-phase) and nitrified wastewater (denitrification phase). In the sorption phase, P-release takes place and readily biodegradable organic substrate, e.g. volatile fatty acid, is taken up and stored by polyP accumulating organisms (PAO). In addition to this, other organic matter is physically/chemically adsorbed in the biofilm structures. In the denitrification phase, the biomass denitrifies the stored and adsorbed organic substrate and, at the same time, P-uptake and polyP formation occurs. This paper presents results of investigations at laboratory and half-technical scale. At laboratory scale different types of carriers were tested regarding their suitability for the S-DN-P-process. In half-technical scale a biofilter and a moving bed reactor (MBR) were tested. In the biofilter a stable removal of nitrate and phosphate was achieved. However, it was not possible to achieve similar results in the MBR process. Especially the release and uptake of phosphate showed no clear tendency although the uptake of acetate was good. Reasons for this could be the accumulation of glycogen accumulating organisms which impair the metabolism of PAO.


Visual laser ablation of the prostate for patients with acute urinary retention.
To evaluate the efficacy of visual laser ablation of the prostate (VLAP) and bladder neck incision in the treatment of patients with acute urinary retention secondary to benign prostatic hyperplasia (BPH). Twenty-three patients (mean age 62 years, range 50-80) with acute urinary retention due to BPH were treated in a prospective trial of VLAP (using a neodymium: YAG laser) with bladder neck incision carried out using the KTP laser. Patients were assessed before and after treatment using the American Urological Association symptom score, prostate volume and peak urinary flow rates. There was a significant and durable objective improvement in measured urinary flow rates and a subjective improvement of symptoms, with minimal morbidity. VLAP is a promising alternative treatment for patients with acute urinary retention secondary to BPH.


[Mycophenolate mofetil in treatment of childhood nephrotic syndrome--preliminary report].
The management of nephrotic syndrome (NS) in children remains a clinical challenge for pediatricians and pediatric nephrologists. Especially, the treatment of patients with steroid-resistant (SR) and steroid-dependent (SD) nephrotic syndrome, because they are at risk for developing complications from prolonged exposure to steroids, CsA and alkylating agents. Mycophenolate mofetil (MMF) is a selective and reversible inhibitor of inosine monophosphate dehydrogenase used above all in transplantology and recently also in patients with nephrotic syndrome. The aim of this study was to tentatively assess the usefulness and the safety of MMF as an immunosuppressive agent in children with steroid-resistant NS, in whom remission was not obtained with previous treatment regimens, and those with steroid-dependent NS, in whom severe adverse reactions were observed in steroid and cyclosporine therapy. The study included 19 children with NS (11 girls, 8 boys) aged 7 to 19.5 years (a mean of 13.5), treated at the Deptartment of Pediatric Nephrology. The duration of disease was from 1 to 16 years (a mean of 9.3). The patients were divided into 3 groups: I--9 children with steroid-dependent NS; II--6 children with steroid-dependent NS and episodes of steroid-resistance; III--4 children with steroid-resistant NS. All patients in groups II and III required multi-drug therapy (prednisone, cyclosporine A, methylprednisolone, chlorambucil, cyclophosphamide) before MMF was introduced. MMF was administered orally: 180-600 mg/m2 body surface/dose, twice daily. The follow-up period lasted for 4 to 16 months (a mean of 7.7). The clinical outcome analysis included decrease or disappearance of proteinuria, clinical improvement and/or possibility of tapering therapy intensity, especially the dosage of steroids and/or CsA. Also, renal function was monitored with serum cystatine C concentration. Particular attention was paid to adverse effects of MMF upon the gastro- intestinal tract and/or opportunistic infections. All medication (apart from MMF) could be discontinued in 4 patients; in 15 cases, prednizone dose was reduced and in 9 cases CsA dose was reduced or discontinued. In group I (SD) steroid treatment could be reduced from a mean prednisone dose of 22.8 to 3.6 mg/m2/48 hours (p=0.018), in groups II and III, in spite of 50 % reduction of a mean prednisone dose, the difference did not reach statistical significance. During MMF therapy Csa treatment could be reduced from a mean CsA dose 4.3 to 2.9 mg/kg/24 hours (p=0.008). Improvement or preservation of stable renal function was observed in all patients--cystatin C levels decreased significantly from a mean 1.35 to 0.96 mg/l (p=0.007). Adverse reaction to MMF (abdominal pain) was observed in 2 patients (nausea, vomiting, diarrhoea in 1, CMV infection in 1). The initial clinical observation of MMF treatment in nephrotic patients shows its best effect in the group of patients with steroid-dependent NS. MMF can safely be used in children with NS. The introduction of MMF allows for reduction of other chronically used medications, especially CsA and steroids.


Acceleration of glycolysis in erythrocytes by the antidiabetic agent M16209.
The effects of M16209 (1-(3-bromobenzofuran-2-ylsulfonyl)hydantoin), an antidiabetic agent and aldose reductase inhibitor, on glycolysis were studied in rat and human erythrocytes in vitro. M16209 increased lactate production from glucose when incubated with rat and human erythrocytes, and also increased glucose consumption in rat erythrocytes. The rates of production of lactate in rat erythrocytes treated with M16209 at 10, 25 and 50 microM were 113, 118 and 123%, respectively, of those in vehicle treated cells. Sorbinil (aldose reductase inhibitor), tolbutamide (sulfonylurea), and buformine (biguanide) did not increase lactate production in rat erythrocytes when tested at 50 microM. On the other hand, M16209 did not affect lactate production from D-glyceraldehyde in rat erythrocytes. At 100 microM the agent decreased both glucose-6-phosphate and fructose-6-phosphate in rat erythrocytes, and increased fructose-1,6-bisphosphate; at 10 microM it also increased 6-phosphofructokinase activity in rat hemolysates. These findings suggest that M16209 accelerates glycolysis in erythrocytes via activation of 6-phosphofructokinase.


Asthma and gastro-oesophageal reflux: can the response to anti-reflux therapy be predicted?
The aim of the study was to investigate which features predict favourable response to omeprazole therapy in asthmatics with gastro-oesophageal reflux (GER). The study population consisted of 52 outpatient asthmatics with GER who had completed an intervention where they were randomized to receive omeprazole 40 mg once a day or placebo for 8 weeks. After a 2-week washout period the patients were crossed over. Asthma symptoms were found to be relieved > or = 20% in 18 (35%) patients who were thus regarded as responders. A logistic regression analysis was performed in order to identify which features separate the responders from the non-responders. More responders were found among the patients whose body mass index (BMI) was higher (P = 0.02) or whose distal esophageal reflux was more severe [total time (%) pH < 4 (P = 0.01) or time (%) pH < 4 in upright position (P = 0.04)]. Adding other predictors to the total time (%) pH < 4, which was the most significant predictor for response in multi-variate analysis, did not further increase the prediction for favourable outcome. It is concluded that severe distal oesophageal reflux and obesity predict amelioration in asthma symptoms after 8-week omeprazole treatment in asthmatics with GER. Adding more than one predictor does not seem to further increase prediction for favourable asthma response.


Involvement of ATP-sensitive potassium (K(ATP)) channels in the loss of beta-cell function induced by human islet amyloid polypeptide.
Islet amyloid polypeptide (IAPP) is a major component of amyloid deposition in pancreatic islets of patients with type 2 diabetes. It is known that IAPP can inhibit glucose-stimulated insulin secretion; however, the mechanisms of action have not yet been established. In the present work, using a rat pancreatic beta-cell line, INS1E, we have created an in vitro model that stably expressed human IAPP gene (hIAPP cells). These cells showed intracellular oligomers and a strong alteration of glucose-stimulated insulin and IAPP secretion. Taking advantage of this model, we investigated the mechanism by which IAPP altered beta-cell secretory response and contributed to the development of type 2 diabetes. We have measured the intracellular Ca(2+) mobilization in response to different secretagogues as well as mitochondrial metabolism. The study of calcium signals in hIAPP cells demonstrated an absence of response to glucose and also to tolbutamide, indicating a defect in ATP-sensitive potassium (K(ATP)) channels. Interestingly, hIAPP showed a greater maximal respiratory capacity than control cells. These data were confirmed by an increased mitochondrial membrane potential in hIAPP cells under glucose stimulation, leading to an elevated reactive oxygen species level as compared with control cells. We concluded that the hIAPP overexpression inhibits insulin and IAPP secretion in response to glucose affecting the activity of K(ATP) channels and that the increased mitochondrial metabolism is a compensatory response to counteract the secretory defect of beta-cells.


Geometric correlations and infrared spectrum of adenine-uracil hydrogen bonds in CDCl(3) solution.
Hybrid QM/MM molecular dynamics simulations have been carried out for the Watson-Crick base pair of 9-ethyl-8-phenyladenine and 1-cyclohexyluracil in deuterochloroform solution at room temperature. Trajectories are analyzed paying special attention to the geometric correlations within the N-HN and N-HO hydrogen bonds in the base pair. Even though the two hydrogen bonds are only approximately linear and the heterocycles are tilted with respect to each other, hydrogen bond and N-H lengths follow a simple empirical correlation based on Pauling's valence bond order model. In order to describe the IR line shape of the two NH-stretching vibrations, the correlation between their fundamental transition frequencies and the hydrogen bond lengths is exploited. This facilitates efficient evaluation of the fluctuating transition frequencies along the QM/MM trajectory which allows the determination of the line shape function.