Restrictions on provider access in health plans and socioeconomic status.
To model the socioeconomic determinants of restrictions on provider access and choices in health plans. Data from the 1996-97 Community Tracking Study are used. Publicly available enrollee data including enrollee reports of health care plan characteristics are linked with restricted use data with insurer reports of health plan characteristics. This is an observational study. A mixed multinomial logit model is used to model the enrollees' choice between health plans, each plan being treated as a bundle of attributes formed from restrictions on provider access. There are important differences between the enrollee responses and the insurer reports, which may be due to poor information dissemination on the part of health plans and/or lack of attention on the part of enrollees. There is no evidence of selection into plans with restrictive attributes on the basis of observed health status but there is evidence of selection on the basis of race, ethnicity, gender and other socioeconomic characteristics. Determinants of plan supply, i.e., employment characteristics, are the most important determinants of plan attribute choices. The finding suggests that plan designs optimized using "objective" knowledge and with the best intentions may not receive favorable reviews from enrollees because enrollees have different perceptions of these plans.


Acceptance of technology-based tools in a sample of Parkinson's patients.
Objectives Parkinson's disease is the second most common neurodegenerative movement disorder in the United States. Patients' opinions of technology-based tools for education and communication as related to Parkinson's disease are unclear with little documented research addressing the issue. The goal of this research was to investigate patient opinions about technology-based tools with a focus on differences between patients of different age groups. Methods A cross-sectional survey was used to assess views on using multiple different electronic methods for receiving instructions and communicating with healthcare providers in 109 Parkinson's disease patients. Results Approximately 28% (n = 28) of the subjects reported having unmet needs related to Parkinson's disease. Those 65 and over were less likely to believe that using technology to communicate with the healthcare center would result in themselves having a better understanding of their care (odds ratio = 0.36, 95% confidence interval: 0.14, 0.95). Those over 75 had a lower odds of being willing to use electronic methods (odds ratio = 0.33, 95% confidence interval: 0.14, 0.79), a lower odds of believing that technology would result in better self-understanding of medical needs (odds ratio = 0.27, 95% confidence interval: 0.12, 0.63) and a lower odds of believing that technology would result in their healthcare providers better understanding their needs (odds ratio = 0.32, 95% confidence interval: 0.14, 0.73). Discussion The results of this study indicate that older Parkinson's disease patients report a less favorable view regarding the role of technology in communicating with healthcare providers and for understanding their care.


Bioassay-guided isolation of Poliovirus-inhibiting constituents from Zephyranthes candida.
Plants of the Zephyranthes genus are globally used in folk medicine. In a previous study, Zephyranthes candida Linn. (Amaryllidaceae) was identified as having antiviral properties; this led to anti-poliovirus assay-guided isolation of compounds from crude methanol extract of the plant. Isolation of anti-poliovirus constituents from Z. candida. Active chloroform fraction from crude methanol extract of Z. candida (whole plant) was subjected to bioassay-guided fractionation; repeated column and preparative thin layer chromatography led to isolation of active compounds. Chemical structures were identified using spectroscopic techniques. Using serial two-fold dilution of maximum non-toxic concentration (MNTC) of each compound (0.0625-1 µg/mL for lycorine and 0.625-10 µg/mL for trisphaeridine and 7-hydroxy-3',4'-methylenedioxyflavan), the ability of extracts to inhibit viral-induced cell death in tissue culture was evaluated 72 h post-infection by the colorimetric method using MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) dye. Regression analysis was used to determine 50% inhibitory concentration (IC50) and 50% cytotoxicity concentration (CC50), from which selective index (SI) was calculated. From the chloroform fraction, three compounds were isolated and identified, namely lycorine (1), trisphaeridine (2), and 7-hydroxy-3',4'-methylenedioxyflavan (3) as the anti-polioviral components. Lycorine was the most active, with an IC50 value of 0.058 µg/mL followed by trisphaeridine (2) with an IC50 of 0.1427 µg/mL, and 7-hydroxy-3',4'-methylenedioxyflavan (3) with an IC50 of 0.2384 µg/mL. The antipoliovirus activity of trisphaeridine (2) and 7-hydroxy-3',4'-methylenedioxyflavan (3) is established in this report; these compounds are of moderate toxicity and have very good SI. They could be a potential template for the development of a new antiviral agent.


Beta relaxation versus high frequency wing in the dielectric spectra of a binary molecular glass former.
The binary molecular glass former 2-picoline in tri-styrene is investigated by means of broadband dielectric spectroscopy with the aim of understanding the role of secondary relaxation processes that emerge during the glass transition. It is shown that the "high frequency wing," which is seen in neat picoline, becomes a separate process in the mixture and exhibits all the features of a Johari-Goldstein relaxation. In particular, the previously found relation between activation energy and Tg is recovered. In addition, below Tg the width parameter of this secondary relaxation is shown to be governed by a common temperature dependence, and the time scale is characterized by an isokinetic point. Above Tg pronounced deviations from an Arrhenius behavior are observed.


Conformational analysis of tannic acid: Environment effects in electronic and reactivity properties.
Polyphenols are natural molecules of crucial importance in many applications, of which tannic acid (TA) is one of the most abundant and established. Most high-value applications require precise control of TA interactions with the system of interest. However, the molecular structure of TA is still not comprehended at the atomic level, of which all electronic and reactivity properties depend. Here, we combine an enhanced sampling global optimization method with density functional theory (DFT)-based calculations to explore the conformational space of TA assisted by unsupervised machine learning visualization and then investigate its lowest energy conformers. We study the external environment's effect on the TA structure and properties. We find that vacuum favors compact structures by stabilizing peripheral atoms' weak interactions, while in water, the molecule adopts more open conformations. The frontier molecular orbitals of the conformers with the lowest harmonic vibrational free energy have a HOMO-LUMO energy gap of 2.21 (3.27) eV, increasing to 2.82 (3.88) eV in water, at the DFT generalized gradient approximation (and hybrid) level of theory. Structural differences also change the distribution of potential reactive sites. We establish the fundamental importance of accurate structural consideration in determining TA and related polyphenol interactions in relevant technological applications.


[Alternative approaches to prevention and treatment of postoperative complications by introduction of new models urinary catheter].
and goals. The evaluation of the results of the primary introduction into clinical practice of two new models of the urethral catheter. Considering the advisability was evaluated the efficiency of using new models of urinary catheter for the prevention and treatment of postoperative complications after radical prostatectomy, as well as in the treatment of major pathological conditions accompanied by the infectious-inflammatory complications MATERIALS AND METHODS: The study included 25 patients who underwent radical prostatectomy (the first group) or transurethral resection of the bladder / prostate (the second group). After surgery, the bladder was installed specially designed urethral catheter with controlled filling the balloon is located in the area formed by the anastomosis (the first group) and urinary catheter irrigation urethra drugs (the second group). In the control group (n=22) in the bladder has been established a standard two-way silicone Foley urinary catheter. Hypersensitive of the new model of the urethral catheter none of the patients were observed. The average period when the urinary catheter in the main and control groups, exactly as the incidence of dysuria did not differ. After removal of the urethral catheter in all patients in the study and control groups restored self urination. The preliminary data showed a good tolerability the new models of the urethral catheter. Evaluation of the effectiveness of distant occupy additional time and will require inclusion in the study a larger number of patients.


The influence of ispaghula husk and lactulose on the in vivo and the in vitro production capacity of short-chain fatty acids in humans.
To evaluate factors influencing the short-chain fatty acid (SCFA) concentrations in stools, three different experiments were performed: faecal concentrations of SCFA at defecation were determined by gas liquid chromatography in nine healthy volunteers on a free diet. SCFAs were 114 +/- 15.0 mmol/l (means +/- SD). The coefficient of variation (CV) of the assay was 4-15%, the intraindividual CV 12-33%, and the interindividual CV 11-29%. On incubation of faeces at 37 degrees C concentrations of SCFA doubled in 6 h and rose fourfold in 72 h. In three volunteers the experiments were extended by adding ispaghula husk or lactulose to the diet for two 14-day periods each; no change in faecal SCFA concentrations was seen, either at defecation or after incubation. When ispaghula husk or lactulose was added to faeces in an in vitro incubation system, the concentrations of SCFA were five times higher than those of controls. We conclude that instant handling of faeces is essential for determinations of SCFA concentrations to obtain interpretable and comparable results; that determination of total SCFA output is of limited value; that addition of fibre to the diet does not influence faecal SCFA concentrations; and that the capacity for SCFA production in faeces is large provided a sufficient amount of substrate is available.


[Asthma with hypersensitivity to aspirin].
Aspirin-induced asthma (AIA) is a distinct clinical entity characterised by hypersensitivity to aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) typically occurring in the form of asthma and severe rhinosinusitis. Its prevalence is about 10%, but AIA probably is underdiagnosed. The diagnosis can only be established with certainty by challenge tests, using increasing doses of aspirin. The crucial cell in AIA is the eosinophil, while the role of mast cell is more elusive. At the biochemical level, AIA is distinguished by profound underlying arachidonic acid disturbances. An overproduction of leukotrienes was observed in patients with aspirin hypersensitivity at baseline and following aspirin challenge. In some patients altered prostaglandin release following aspirin was encountered. The inhibition of COX-1, but not COX-2, was shown to precipitate post-challenge symptoms precipitated by aspirin. The new insights into eicosanoid molecular biology and genetics have recently emerged. The patients with aspirin-sensitive asthma require often prolonged oral, inhaled and nasal corticotherapy. Antileukotrienes also can be used. Aspirin and NSAIDs should be avoided. Nevertheless, highly specific COX-2 inhibitors are well tolerated. Aspirin desensitisation, followed by daily aspirin treatment, is a valuable therapeutic option.


Attenuation of toxicity and occurrence of degradation products of the fungicide tebuconazole after combined vacuum UV and UVC treatment of drinking water.
Antifungal azoles are the most frequently used fungicides worldwide and occur as active ingredients in many antifungal pharmaceuticals, biocides, and pesticides. Azole fungicides are frequent environmental contaminants and can affect the quality of surface waters, groundwater, and drinking water. This study examined the potential of combined vacuum UV (185 nm) and UVC (254 nm) irradiation (VUV/UVC) of the azole fungicide tebuconazole and the transformation product 1,2,4-trizole on degradation and changes in ecotoxicity. In vivo ecotoxicity was examined before and after UV treatment using bioassays with test organisms from different trophic levels to integrate changes in biological effect of the parent compound and the degradation products. The test battery included the luminescent bacterium Aliivibrio fischeri, the Gram-positive bacterium Bacillus subtilis, the fungus Fusarium graminearum, the green microalga Raphidocelis subcapitata, and the crustacean Daphnia magna. The combined VUV/UVC treatment of tebuconazole in drinking water efficiently degraded the parent compound at the µg/L-mg/L level and resulted in transformation products with lower toxicity than the parent compound. A direct positive correlation was observed between the applied UV dose (fluence, J/cm2), the disappearance of tebuconazole, and the decrease in ecotoxicity. The combined VUV/UVC process does not require addition of supplementary oxidants or catalysts and our study suggests that VUV/UVC-mediated photolysis of azole fungicides in water can decrease the overall toxicity and represent a potentially environmentally friendly treatment method.


The role of donor and recipient factors in initial renal graft non-function.
ATN is a deleterious problem in the outcome of kidney transplantation. This complication is usually related to multiple factors including donor parameters, surgical technique, ischemic time, and recipient variables. In order to develop prophylactic measures, out of 430 kidney transplants performed in our Department, a series of 90 consecutive cadaveric renal allografts has been considered in this study. The overall incidence of IGNF was 23/90 (25.5%). Kidneys from MOD revealed a lower rate of IGNF (7/35 = 20%) when compared with organs from SOD (16/55 = 29%, P = NS). No difference was noted when kidneys were removed together with heart and/or liver and/or pancreas. Out of the donor factors, only CID was significant (17 +/- 9 hours in IGNF v 11 +/- 10 hours in patients with IGF, P = less than .05). Analysis of data concerning the fate of paired kidneys revealed two cases of IGNF in both kidneys from the same donor v 14 cases of IGNF in only one of the two paired grafts (P = NS). We conclude that: 1. Donor factors are clearly associated with a minority of IGNF. 2. The introduction of multiorgan procurement programs does not complicate early function. 3. Recipient factors (immunological events and intraoperative fluid management) provides important additive effects on initial graft nonfunction.


Speciation in the aqueous H+/H2VO4-/H2O2/picolinate system relevant to diabetes research.
A detailed study of the quaternary aqueous H+/H2VO4-/H2O2/picolinate (Pi-) system has been performed at 25 degrees C in 0.150 M Na(Cl) medium using quantitative 51 V NMR (500 MHz) and potentiometric data (glass electrode). In the ternary H+/H2VO4-/Pi- system, six complexes have been found in the pH region 1-10. In the quaternary H+/H2VO4-/H2O2/Pi- system, eight additional complexes have been found. Generally, equilibria are fast in both systems. The rate of peroxide decomposition depends on the species in solution. Chemical shifts, compositions and formation constants for the species are given. Equilibrium conditions and the fit of the model to the experimental data are illustrated in distribution diagrams. Possible formation of mixed ligand species with imidazole, lactic acid and citric acid have been investigated and ruled out under the same experimental conditions. Structural proposals are given, based on 1)C NMR data and available crystal structures.


Stimulation of phosphorylation of ERK and CREB by phellopterin and auraptene isolated from Citrusjunos.
Bioactive compounds from citrus fruits contribute many benefits to human health. Extracellular signal-regulated kinase (ERK) signaling plays an important role in the regulation of multiple cellular processes. Activation of the ERK-cAMP response element binding protein (CREB) signaling is required for long- term memory formation. In this study, auraptene, phellopterin, thymol, coniferyl alcohol 9-methyl ether and methyl ferulate were isolated from Citrus junos. Among the five compounds isolated, auraptene and phellopterin increased the phosphorylation of ERK and CREB. This study provides, to our knowledge, the first evidence that phellopterin potently stimulates the phosphorylation of ERK and CREB. Phellopterin could be a novel neuroprotective agent.


Malignant peripheral nerve sheath tumors developing multifocally in the central nervous system in a patient with neurofibromatosis type 2.
We describe autopsy findings of multifocal malignant peripheral nerve sheath tumors (MPNSTs) appearing in the central nervous system in a 45-year-old Japanese female with neurofibromatosis type 2. Multiple MPNSTs were detected in both III and VIII, left IV, and V cranial nerves, and a number of nerve roots of the spinal cord. Neurofibromata were on the other hand evident on some nerve roots of the spinal cord and femoral and sciatic nerves. Our results suggest that a mutation of p53 gene may have played a role in the malignant transformation of nerve tumors in this patient since p53 protein was immunohistochemically detected in MPNST cells but not in tumor cells of the neurofibromata.


Intravenous injections in neonatal mice.
Intravenous injection is a clinically applicable manner to deliver therapeutics. For adult rodents and larger animals, intravenous injections are technically feasible and routine. However, some mouse models can have early onset of disease with a rapid progression that makes administration of potential therapies difficult. The temporal (or facial) vein is just anterior to the ear bud in mice and is clearly visible for the first two days after birth on either side of the head using a dissecting microscope. During this window, the temporal vein can be injected with volumes up to 50 μl. The injection is safe and well tolerated by both the pups and the dams. A typical injection procedure is completed within 1-2 min, after which the pup is returned to the home cage. By the third postnatal day the vein is difficult to visualize and the injection procedure becomes technically unreliable. This technique has been used for delivery of adeno-associated virus (AAV) vectors, which in turn can provide almost body-wide, stable transgene expression for the life of the animal depending on the viral serotype chosen.


Potential role for purple acid phosphatase in the dephosphorylation of wall proteins in tobacco cells.
It is not yet known whether dephosphorylation of proteins catalyzed by phosphatases occurs in the apoplastic space. In this study, we found that tobacco (Nicotiana tabacum) purple acid phosphatase could dephosphorylate the phosphoryl residues of three apoplastic proteins, two of which were identified as alpha-xylosidase and beta-glucosidase. The dephosphorylation and phosphorylation of recombinant alpha-xylosidase resulted in a decrease and an increase in its activity, respectively, when xyloglucan heptasaccharide was used as a substrate. Attempted overexpression of the tobacco purple acid phosphatase NtPAP12 in tobacco cells not only decreased the activity levels of the glycosidases but also increased levels of xyloglucan oligosaccharides and cello-oligosaccharides in the apoplast during the exponential phase. We suggest that purple acid phosphatase controls the activity of alpha-xylosidase and beta-glucosidase, which are responsible for the degradation of xyloglucan oligosaccharides and cello-oligosaccharides in the cell walls.


Entanglement detection by local orthogonal observables.
We propose a family of entanglement witnesses and corresponding positive maps that are not completely positive based on local orthogonal observables. As applications the entanglement witness of a 3x3 bound entangled state [P. Horodecki, Phys. Lett. A 232, 333 (1997)] is explicitly constructed and a family of dxd bound entangled states is introduced, whose entanglement can be detected by permuting local orthogonal observables. The proposed criterion of separability can be physically realized by measuring a Hermitian correlation matrix of local orthogonal observables.


Theoretical and practical reflections on sharing transcripts with participants.
This article is a critical reflection on the process of creating transcripts and sharing them with interviewees. It relates to two elements of the research process: first, sharing transcripts with research participants and, second, participants' seeing extracts from transcripts in academic writing. The authors explore participants' experiences of revisiting the interview in written form by reflecting on the interconnections between social research methods and epistemology. They also consider the ethical implications of this process. They consider the relationship between the transcript and the representation (re-presentation) of what participants believe to have occurred within the interview. This leads to a discussion of the importance of developing reflexivity with respect to the practice and processes of sharing transcripts.


Genetic reassortants for identification of the genome segment coding for the bluetongue virus hemagglutinin.
Two bluetongue virus (BTV) serotypes isolated in Australia and two selected reassortants derived from cells coinfected with these viruses have been used to identify the gene coding for the virus hemagglutinin. The parent viruses had characteristic hemagglutination patterns: BTV type 20 agglutinated sheep erythrocytes only; and BTV type 21 agglutinated sheep, bovine, human, and goose erythrocytes. Analysis of the two virus clones that had reassorted in genes coding for the outer capsid polypeptides demonstrated that hemagglutination and hemagglutination inhibition are functions associated with the outer capsid protein (VP2), which is encoded by genome segment 2.


Prognostic Significance of Hematological Markers for Patients with Nasopharyngeal Carcinoma: A Meta-analysis.
Purpose: Hematological parameters are considered to be associated with prognosis in various cancers. We designed a meta-analysis to evaluate the prognostic significance of hematological parameters, including the neutrophil-to-lymphocyte ratio (NLR), C-reactive protein/albumin ratio (CRP/ALB), lymphocyte-to-monocyte ratio (LMR), plasma fibrinogen level, Glasgow prognostic score (GPS), platelet-to-lymphocyte ratio (PLR) and high-density lipoprotein cholesterol (HDL-C) level, on clinical outcomes in nasopharyngeal carcinoma (NPC). Methods: Relevant studies published prior to February 2018 were identified in the PubMed, Web of Science, EMBASE and Cochrane library databases. The primary outcome was overall survival (OS), and the secondary outcome was progression-free survival (PFS). The pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated. Results: In total, 23 studies encompassing 23,417 patients were included in our meta-analysis. An elevated NLR was related to a poor OS (HR=1.46, 95% CI=1.30-1.63, p<0.00001) and PFS (HR=1.67, 95% CI=1.36-2.07, p<0.00001), and a high PLR was associated with a poor OS (HR=1.62, 95% CI=1.32-1.98, p<0.00001). Additionally, a high LMR predicted a significantly favorable OS (HR=0.50, 95% CI: 0.43-0.58, p<0.00001). CRP/ALB, the GPS, HDL-C and plasma fibrinogen levels were also related to OS and PFS. Conclusion: Inflammation-based prognostic scoring systems considering inflammatory cells (lymphocytes, neutrophils, platelets and monocytes) and proteins (ALB, CRP and HDL-C) are essential prognostic factors.


Visual assay of Escherichia coli O157:H7 based on an isothermal strand displacement and hybrid chain reaction amplification strategy.
Here, we describe a simple, sensitive, and enzyme-free method for visual point-of-care detection of 16S rRNA of Escherichia coli O157:H7 based on an isothermal strand displacement-hybrid chain reaction (ISD-HCR) and lateral flow strip (LFS). In this study, the secondary structure of 16S rRNA of E. coli O157:H7 was unwound by two helper oligonucleotides to expose the single-strand-specific nucleic acid sequence. The free specific sequence promoted the toehold-mediated strand displacement reaction to output a large number of FITC-labeled single-stranded DNA probes (capture probe [CP]). The 3'-end sequence of the reporter probe propagated a chain reaction of hybridization events between the two hairpin probes modified with biotin to form long nicked DNA polymers with multiple biotins (RP-HCR complexes); the free CP and RP-HCR complexes then form CP/RP-HCR complexes. The biotin-labeled double-stranded DNA CP/RP-HCR polymers then introduced numerous streptavidin (SA)-labeled gold nanoparticles (AuNPs) on the LFS. The accumulation of AuNPs produced a characteristic red band, which enabled visual detection of changes in the signal of 16S rRNA of E. coli O157:H7. The current approach could detect E. coli O157:H7 at concentrations as low as 102 CFU mL-1 without instrumentation. This approach thus provides a simple, sensitive, and low-cost tool for point-of-care detection of pathogenic bacteria, especially in resource-limited countries.


[Pathological study on the relationship between nucleic acid oxidative stress and heart failure with preserved ejection fraction in patients aged over 85 years].
Objective: To investigate the level of nucleic acid oxidation in myocardial tissue of patients aged over 85 with heart failure with preserved ejection fraction (HFpEF) and the correlation with myocardial amyloid deposition. Methods: This was a retrospective case-control study. Data of patients≥85 years old who underwent systematic pathological autopsy in Beijing Hospital from 2003 to 2017 were retrospectively collected. Twenty-six patients were included in the HFpEF group and 13 age-and sex-matched patients who had not been diagnosed with heart failure and died of non-cardiovascular diseases served as the control group. The left ventricular myocardium slices of both groups were semi-quantitatively analyzed using immunohistochemical staining of 8-oxidized guanine riboside (8-oxo-G) and 8-oxidized guanine deoxyriboside (8-oxo-dG) to evaluate the oxidation of RNA and DNA in cardiomyocytes. Using the median of the mean absorbance value of 8-oxo-G immunohistochemical staining as the cut-off value, patients were divided into high-absorbance group and low-absorbance group. Congo red staining was used to compare myocardial amyloid deposition between the two groups. Results: The mean age of patients in HFpEF group was (91.8±3.7) years, 24 (92.3%) were males. The mean age of patients in control group was (91.7±3.7) years old, 11 (84.6%) were males. The median mean optical absorbance value of 8-oxo-G immunohistochemical staining of myocardium was significantly higher in HFpEF patients than in control group (0.313 8 (0.302 2, 0.340 6) vs. 0.289 2 (0.276 7, 0.299 4), Z=-3.245, P=0.001). The median mean absorbance value of 8-oxo-dG immunohistochemical staining of myocardial tissue was similar between the two groups (0.300 0 (0.290 0, 0.322 5) vs. 0.300 0 (0.290 0, 0.320 0), Z=-0.454, P=0.661). Proportion of patients with moderate and severe cardiac amyloid deposition was significantly higher in the high-absorbance group than in the low-absorbance group ((85.0%, 17/20) vs. (31.6%, 6/19), P=0.001). Conclusion: The RNA oxidation degree of myocardium in HFpEF patients is higher than that in elderly people without heart failure. Degree of myocardial amyloid deposits is higher in patients with high levels of RNA oxidation.


A novel nonsense mutation at E106 of the 2B rod domain of keratin 14 causes dominant epidermolysis bullosa simplex.
Epidermolysis bullosa simplex (EBS) is classified into three main types and is caused, in most cases, by missense mutations in the genes encoding keratin (K) 5 and K14. In this study, we clinically, ultrastructurally, immunohistochemically, and molecularly studied a patient with a dominant EBS, Köbner type. Using sequence analysis of genomic DNA, a novel K14 nonsense mutation was identified. A heterozygous mutation G1231T of KRT14 was found to be associated with the disease in the patient. The mutation created a premature stop codon (amino acid codon 411, residue 106 of the 2B helix) in the K14 molecule. This residue lies in a highly conserved region and was recently found to be absolutely required for molecular stability and intermediate filament assembly in K5 and K14. The E411X (E106X) heterozygous ablation, missing the last 16 amino acid residues of the 2B and the entire tail domain of K14, led to disease but did not result in clumping of keratin filaments. It is the first premature stop codon mutation of K14 found in dominant EBS.


Finnish female prisoners - heavy consumers of health services.
Previous prison studies show that female prisoners often have more health problems than male prisoners do and that they have many chronic health conditions. Few studies have been made among offenders concerning the use of health services, and even fewer concerning physical diseases. We studied the self-reported lifetime somatic diseases, the use of health services and the current use of prescription medicines among Finnish female prisoners and compared them with males. The sample consisted of 101 females and 309 male prisoners as controls. The study included several questionnaires and interviews conducted by experienced prison nurses. The women had more commonly genitourinary, virus hepatitis/HIV infections and group "other diseases" than the men. Over 80% of the women and men have had accidents/injuries. Four out of five women, and half of the men, used some medicine regularly. Of the females, 92% (80% of the males) reported lifetime hospital care and 65% (61%) treatment in surgery department, respectively; 70% of the females (53% of the males) reported lifetime use of any psychiatric service; 66% of the women (46% of the men) had received psychiatric out-patient services, and 43% (31%) psychiatric in-patient hospital care and 38% (30%) substance abuse services, respectively. The heavy use of health services among female prisoners resulted mainly from the use of services for substance use and other mental disorders and treatment in surgery department. Compared to men, the difference in using health services was associated with psychiatric services.


Pharmacokinetics and tissue distribution of enrofloxacin after single intramuscular injection in Pacific white shrimp.
The pharmacokinetic properties and tissue distribution of enrofloxacin (EF) were investigated after single intramuscular (i.m.) dose of 10 mg/kg body weight (b.w.) in Pacific white shrimp at 22 to 25°C. EF and its metabolite ciprofloxacin (CF) were determined by high-performance liquid chromatography. After i.m. administration, EF was absorbed quickly, and the peak of EF concentration (Cmax ) reached at first time point in hemolymph. The volume of distribution Vd(area) of EF was 3.84 L/kg, indicating that the distribution of EF was good. The area under the concentration-time curve (AUC) of EF was 90.1 and 274.2 μg hr/ml in muscle and hepatopancreas, respectively, which was higher than 75.8 μg hr/ml in hemolymph. The EF elimination was slow in muscle and hepatopancreas with the half-life (T1/2β ) of 52.3 and 75.8 hr, respectively. CF, the mainly metabolite of EF, was detected in hemolymph, muscle and hepatopancreas. The Cmax was 0.030, 0.013 and 0.218 μg/ml, respectively. Based on a minimum inhibitory concentration (MIC) of 0.006-0.032 μg/ml for susceptible strains, EF i.m. injected at a dose 10 mg/kg could be efficacious against common pathogenic bacteria of Pacific white shrimp.


Brain-derived neurotrophic factor is expressed in a gradient in the superior colliculus during development of the retinocollicular projection.
Abstract Theoretical models of topographic map formation have postulated a gradient of attractant in addition to a gradient of repulsion in the target. In species where many axons grow past their correct positions initially, it has also been argued that a parallel gradient of attractant or branching signal is required to ensure collateral formation at the correct position (O'Leary et al., 1999). Brain-derived neurotrophic factor (BDNF) is a known attractant and promotes branching of retinal axons. We have examined its distribution in the superior colliculus and that of its receptor, trkB, in the retina, using immunohistochemistry and in situ hybridization, respectively, during the development of the topographic retinocollicular projection in the wallaby, a marsupial mammal. The number of glial endfeet expressing BDNF at the surface of the colliculus was found to be in a high caudal-to-low rostral gradient during the time when the retinocollicular projection was developing. When the projection was mature the rostrocaudal gradient had disappeared and the number of detectable endfeet expressing BDNF was very low. Messenger RNA for TrkB was expressed in the retinal ganglion cell layer throughout the time when the retinocollicular projection was developing, with no difference in expression across the nasotemporal axis of the retina. The low rostral to high caudal distribution of BDNF in glial endfeet supports the idea that it is providing a parallel gradient of attractant or branching signal in the colliculus.


Hypersensitivity to heparin; a case report.
Hypersensitivity reactions to heparin are very rare. A generalized hypersensitivity reaction including as fever and skin rash to a porcine- and bovine-derived heparin preparation was observed in a hemodialysis patient due to the nephrotic syndrome. The patient revealed peripheral eosinophilia and normal serum IgE. The results of a drug lymphocyte stimulating test on heparin were positive. Following prednisolone administration and infusion of nafamostat mesilate as anticoagulant therapy during hemodialysis, the high fever and generalized urticaria disappeared. Caution is required when conducting heparin therapy on hemodialysis patients.


[An analysis of immunophenotyping of peripheral lymphocytes in adult patients with infectious mononucleosis and chronic active Epstein-Barr virus infection].
To determine the immunophenotypic features of peripheral lymphocytes in adult patients with Epstein-Barr virus(EBV)-associated infectious mononucleosis(IM) and chronic active EBV infection (CAEBV). Eighteen IM patients, 12 CAEBV patients and 18 healthy donors were included. Lymphocyte subsets including CD3(-)CD19(+) B cells, CD3(-)CD16/56(+) NK cells, CD4(+) and CD8(+) T cells in peripheral blood were measured by flow cytometry. The expression of activation markers (HLA-DR and CD38) on CD8(+) T cells and CD28 expression on T cells were also determined. Kruskal-Wallis H and Mann-Whitney U tests were used to compare variables among groups. IM patients had dramatically increased CD8(+) T cell counts than healthy donors (5.22×10(9)/L vs 0.54×10(9)/L, P<0.001). B cell counts moderately reduced in patients with IM than in healthy donors. No difference was found in absolute CD4(+) T cell and NK cell counts between IM and healthy donors. The levels of HLA-DR and CD38 on CD8(+) T cells significantly increased in IM patients compared with those in healthy controls. The intensity of CD28 on CD8(+) T cells significantly decreased, which was not seen on CD4(+) T cells. The median cell counts of B, NK, CD4(+) T and CD8(+) T subsets in CAEBV patients were 0.02×10(9)/L, 0.06×10(9)/L, 0.26×10(9)/L and 0.21×10(9)/L respectively, which were significantly lower than those in healthy donors (0.22×10(9)/L, 0.38×10(9)/L, 0.78×10(9)/L, 0.54×10(9)/L)and IM patients (0.12×10(9)/L, 0.40×10(9)/L, 0.91×10(9)/L, 5.22×10(9)/L). The positive rates of HLA-DR and CD38 on CD8(+) T cells in CAEBV patients were higher than those in healthy controls, but lower than those in IM patients. The immunophenotypic pattern in adult patients with IM is characterized by a dramatic increase of extensively activated CD8(+) T cells, a moderate reduction of CD19(+) B cells and no significant change of CD4(+) T cells and CD16/56(+) NK cells. CAEBV is featured by an immunosuppression status as demonstrated by significantly decreased B, NK, CD4(+) T and CD8(+) T subsets.


Comparative binding energy COMBINE analysis for understanding the binding determinants of type II dehydroquinase inhibitors.
Herein we report comparative binding energy (COMBINE) analyses to derive quantitative structure-activity relationship (QSAR) models that help rationalize the determinants of binding affinity for inhibitors of type II dehydroquinase (DHQ2), the third enzyme of the shikimic acid pathway. Independent COMBINE models were derived for Helicobacter pylori and Mycobacterium tuberculosis DHQ2, which is an essential enzyme in both these pathogenic bacteria that has no counterpart in human cells. These studies quantify the importance of the hydrogen bonding interactions between the ligands and the water molecule involved in the DHQ2 reaction mechanism. They also highlight important differences in the ligand interactions with the interface pocket close to the active site that could provide guides for future inhibitor design.


Antigen-specific antibody response induced in cultures of human blood lymphocytes in presence of polyethylene glycol.
Human peripheral blood lymphocytes respond in vitro to sheep red blood cells (SRBC) with the appearance of numerous specific plaque-forming cells, if the Epstein-Barr virus (EBV) is added to the cultures together with the antigen. However, it was found that when polyethylene glycol (mol. wt. 6000) is included in the culture medium at a final concentration of 4%, antigen alone is able to induce an anti-SRBC response, with clear hemolytic plaques of regular size. Addition of EBV causes a further increase in the antigen-specific antibody response.


Adverse psychological and coronary risk profiles in young patients with coronary artery disease and benefits of formal cardiac rehabilitation.
Recent data indicate that young patients with coronary artery disease (CAD) have a poor long-term prognosis. Although the benefits of formal cardiac rehabilitation and exercise training programs are well established, most of these data come from middle-aged and older patients. We assessed baseline behavioral data, quality of life, and risk profiles in 635 consecutive patients with CAD before and after cardiac rehabilitation and exercise training, and specifically assessed data in 104 young patients (mean +/- SD age, 48 +/- 6 years; range, 22-54 years) compared with 260 elderly patients (mean +/- SD age, 75 +/- 3 years; range, 70-85 years). Compared with older patients, young patients had higher body mass indexes (12.2%, P<.001), total cholesterol-high-density lipoprotein ratio (14.6%, P<.01), and triglycerides level (27.2%, P<.01), and a lower high-density lipoprotein cholesterol level (-8.8%, P=.045). Young patients also had higher scores for anxiety and hostility (51.5% and 94.4%, respectively; P<.001 for both), a considerably higher prevalence of anxiety (27.9% vs 13.5%; P<.01) and hostility (12.5% vs 4.6%; P<.01) symptoms, and slightly more depression symptoms (23.1% vs 18.8%) compared with elderly patients. Following cardiac rehabilitation and exercise training, young patients had improvements in body mass index (-1.7%, P<.01), percentage body fat (-4.4%, P<.001), high-density lipoprotein cholesterol level (10.2%, P<.001), high-sensitivity C-reactive protein level (-33.3%, P<.01), peak oxygen consumption (11.3%, P<.001), resting heart rate (-4.5%, P=.01), and resting systolic pressure (-2.3%, P=.049), and marked improvements in scores for depression (-58.5%), anxiety (-46.0%), hostility (-45.7%), somatization (-33.8%), and quality of life (15.8%) (P<.001 for all). Young patients also had greater than 50% to greater than 80% reductions in the prevalence of anxiety (P<.001), hostility (P<.01), and depression (P<.001). These data demonstrate the adverse psychological and CAD risk profiles that are present in young patients with CAD following major CAD events, and are consistent with substantial benefit of formal cardiac rehabilitation and exercise training programs in younger adults.


Exploratory study of the underutilization of CTSA module services.
The Clinical and Translational Science Award (CTSA) program aims to enhance the quality, efficiency, and impact of translation from discovery to interventions that improve human health. CTSA program hubs at medical research institutions across the United States develop and test innovative tools, methods, and processes, offering core resources and training for the clinical and translational research (CTR) workforce. Hubs have developed services across different domains, such as informatics and pilot studies, to provide ad hoc expertise and staffing for local research teams. Although these services can provide efficient, cost-effective ways to cover skills gaps and implement rigorous studies, three CTSAs of varying size found the majority of investigators were single domain service users, likely missing opportunities to further enhance their work. Through interviews with CTSA service users and a survey of CTSA service managers, this exploratory study aims to identify barriers to using services from multiple modules and solutions to overcome those barriers. Barriers include challenges in finding information about services, unclear or unknown user needs, and users' lack of funding to engage in services. More issues were identified for the largest CTSA. Although this study represents a small subset of CTSA hubs, we anticipate that our findings and proposed solutions will be relevant to the broader CTSA community. This study provides foundational information can use in their own efforts to increase service utilization and methods that can be used for more comprehensive studies that focus on explaining the relationship between CTSA features and rates of single versus cross-module service use.


FIFRA Subdivision F testing Guidelines: are these tests adequate to detect potential hormonal activity for crop protection chemicals? Federal Insecticide, Fungicide, and Rodenticide Act.
Recently, a major topic of discussion has been the impact of synthetic chemicals that possess the capacity to alter hormonal activity, the so-called "endocrine modulators," with potentially the capacity to alter the reproductive capability of humans. Particularly, various synthetic pesticides and industrial chemicals that persist in the environment and/or bioaccumulate have been implicated. Further, it has been alleged that the standard tests for pesticide registration as required by the U.S. Environmental Protection Agency (EPA) and other regulatory agencies may be inadequate to detect endocrine modulating effects. To address these shortcomings, it has been proposed that very specific tests for estrogen receptor binding, or in vitro cell response to chemicals, be used to identify potential endocrine modulators. However, such approaches have certain flaws that limit their application as screens. First, very specific tests, like receptor binding, evaluate only a single chemical event per test. Such tests do not measure toxicity or biological response. Isolated systems are very important for studying mechanisms of action or structure activity relationships, but can only provide a preliminary screen for a single mechanism of toxicity. Isolated systems can not be used to regulate a chemical without additional information. Second, they fail to test many other parts of the neuroendocrine control of the reproductive system. Testing for adverse effects in highly specific in vitro systems failed to replace whole-animal models in carcinogenesis and will also fail in reproductive toxicology because this system is too complicated for such as in vitro approach to be accurately predictive. Advanced tests, such as the EPA multigeneration study, are more effective, and reliable means for evaluation than any specific and narrowly focused screening tests. Experience has shown that a better approach to testing chemicals is to evaluate their effects on the whole animal. When one part of the system is adversely affected, various processes may be indirectly affected and can be detected in the animal model. For example, a modulation of testosterone synthesis could lead to (1) altered accessory sex organ morphology, size, and function; (2) decreased sperm counts; and (3) even decreased fertility. These and many other effects would be noted in toxicity studies that are already required for the registration of crop protection chemicals. The developmental and reproductive toxicity guidelines were recently reviewed in a hearing that included the representatives from the EPA, the public, and the Scientific Advisory Panel. The EPA kept the basic study design the same, but added a few new endpoints to further assess chemical-induced effects on reproductive development and function. The review presented herein concentrates on the required Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) testing for pesticides, and demonstrates how the massive arrays of sensitive endocrine endpoints that are delineated in FIFRA Subdivision F have been successfully used to detect both weak and potent hormonally modulating chemicals. For example, (1) diethyl-stilbestrol (DES), which is a potent synthetic therapeutic estrogen, (2) DDT, which is weakly estrogenic but persistent and bioaccumulating, and (3) dioxins, which have antiestrogenic properties, were all found as being hormonally active in tests similar or identical to FIFRA tests. All food-use pesticides have been evaluated using a comprehensive multigeneration reproduction test. Hence, the FIFRA testing procedures have been demonstrated to identify endocrine modulators of sufficient potency to represent a concern to human health.


Multicomponent Solvate Crystals of 3,5-Dinitrobenzoic Acid and Acetamide and CSD Analysis of Solvates.
Twelve multicomponent solvate crystals (cocrystal solvates) of 3,5-dinitrobenzoic acid and acetamide were synthesized via slow evaporation method. All crystalline materials were characterized by single-crystal X-ray diffraction. All cocrystal solvates are isostructural, and crystal packing forms continuous channels where some solvent molecules are connected via weak intermolecular interactions with 3,5-dinitrobenzoic acid and acetamide. All multicomponent solvate crystals encompass amide-amide dimer homo synthons and form R22 (8) motifs. Moreover, the phase purity of solvate crystals was analyzed by powder X-ray diffraction. Further, most of the cocrystal solvates were analyzed by nuclear magnetic resonance and differential scanning calorimetry. Cambridge structural database analysis categorizes solvate propensity in single-crystal structures. The importance of hydrogen bond donor/acceptor nature, size, and shape of solvents is also discussed in the context of crystallization and crystal packing.


Electrocardiographic progression of acute Lyme disease.
Lyme carditis poses a challenge to physicians given dramatic clinical presentations like the one presented in this case. Quite frequently, these young patients are implanted with permanent pacemakers; given lack of knowledge on the transient nature of the cardiac conduction system inflammation. This is the first case in the literature that has captured the electrocardiographic evolution of Lyme carditis, day by day until complete resolution.


Crystallization and preliminary X-ray characterization of the genetically encoded fluorescent calcium indicator protein GCaMP2.
Fluorescent proteins and their engineered variants have played an important role in the study of biology. The genetically encoded calcium-indicator protein GCaMP2 comprises a circularly permuted fluorescent protein coupled to the calcium-binding protein calmodulin and a calmodulin target peptide, M13, derived from the intracellular calmodulin target myosin light-chain kinase and has been used to image calcium transients in vivo. To aid rational efforts to engineer improved variants of GCaMP2, this protein was crystallized in the calcium-saturated form. X-ray diffraction data were collected to 2.0 A resolution. The crystals belong to space group C2, with unit-cell parameters a = 126.1, b = 47.1, c = 68.8 A, beta = 100.5 degrees and one GCaMP2 molecule in the asymmetric unit. The structure was phased by molecular replacement and refinement is currently under way.


Understanding WT1 Alterations and Expression Profiles in Hematological Malignancies.
WT1 is a true chameleon, both acting as an oncogene and tumor suppressor. As its exact role in leukemogenesis is still ambiguous, research with model systems representing natural conditions surrounding the genetic alterations in WT1 is necessary. In a cohort of 59 leukemia/lymphoma cell lines, we showed aberrant expression for WT1 mRNA, which does not always translate into protein levels. We also analyzed the expression pattern of the four major WT1 protein isoforms in the cell lines and primary AML blasts with/without WT1 mutations and demonstrated that the presence of mutations does not influence these patterns. By introduction of key intronic and exonic sequences of WT1 into a lentiviral expression vector, we developed a unique tool that can stably overexpress the four WT1 isoforms at their naturally occurring tissue-dependent ratio. To develop better cellular model systems for WT1, we sequenced large parts of its gene locus and also other important myeloid risk factor genes and revealed previously unknown alterations. Functionally, inhibition of the nonsense-mediated mRNA decay machinery revealed that under natural conditions, the mutated WT1 alleles go through a robust degradation. These results offer new insights and model systems regarding the characteristics of WT1 in leukemia and lymphoma.


Complications of pancreaticoduodenectomy after neoadjuvant chemoradiation in patients with and without preoperative biliary drainage.
It has been suggested that preoperative biliary drainage increases the risk of infectious complications of pancreaticoduodenectomy. The aim of this study was to assess complications related to biliary stents/drains and postoperative morbidity in patients undergoing neoadjuvant chemoradiotherapy for periampullary cancer. One hundred and eighty-four patients with periampullary neoplasms were prospectively selected for neoadjuvant external beam radiation therapy and 5-fluorouracil-based chemotherapy between 1995 and 2002. The data were retrospectively completed and analysed with respect to biliary drainage, efficacy and complications of endoscopic biliary stents and postoperative morbidity. Patients who had undergone a surgical biliary bypass were excluded. Data were completed in 168 patients. One hundred and nineteen patients were treated with endoscopic biliary stents, 18 patients had a percutaneous biliary drain and 31 patients did not require biliary drainage. Hospitalisation for stent-related complications was necessary in 15% of the patients with endoscopic biliary stents. Seventy-two patients underwent pancreaticoduodenectomy. There was no significant difference in the rate of wound infections, intra-abdominal abscesses and overall complications between the groups with and without preoperative biliary drainage. Postoperative infectious complications are common in patients both with and without preoperative biliary drainage. A statistically significant difference in complication rates was not observed between these groups.


Developing a mental health care plan in a low resource setting: the theory of change approach.
Scaling up mental healthcare through integration into primary care remains the main strategy to address the extensive unmet mental health need in low-income countries. For integrated care to achieve its goal, a clear understanding of the organisational processes that can promote and hinder the integration and delivery of mental health care is essential. Theory of Change (ToC), a method employed in the planning, implementation and evaluation of complex community initiatives, is an innovative approach that has the potential to assist in the development of a comprehensive mental health care plan (MHCP), which can inform the delivery of integrated care. We used the ToC approach to develop a MHCP in a rural district in Ethiopia. The work was part of a cross-country study, the Programme for Improving Mental Health Care (PRIME) which focuses on developing evidence on the integration of mental health in to primary care. An iterative ToC development process was undertaken involving multiple workshops with stakeholders from diverse backgrounds that included representatives from the community, faith and traditional healers, community associations, non-governmental organisations, Zonal, Regional and Federal level government offices, higher education institutions, social work and mental health specialists (psychiatrists and psychiatric nurses). The objective of this study is to report the process of implementing the ToC approach in developing mental health care plan. A total of 46 persons participated in four ToC workshops. Four critical path dimensions were identified: community, health facility, administrative and higher level care organisation. The ToC participants were actively engaged in the process and the ToC encouraged strong commitment among participants. Key opportunities and barriers to implementation and how to overcome these were suggested. During the workshops, a map incorporating the key agreed outcomes and outcome indicators was developed and finalized later. The ToC approach was found to be an important component in the development of the MHCP and to encourage broad political support for the integration of mental health services into primary care. The method may have broader applicability in planning complex health interventions in low resource settings.


AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY COMPREHENSIVE CLINICAL PRACTICE GUIDELINES FOR MEDICAL CARE OF PATIENTS WITH OBESITYEXECUTIVE SUMMARYComplete Guidelines available at https://www.aace.com/publications/guidelines.
Development of these guidelines is mandated by the American Association of Clinical Endocrinologists (AACE) Board of Directors and the American College of Endocrinology (ACE) Board of Trustees and adheres to published AACE protocols for the standardized production of clinical practice guidelines (CPGs). Recommendations are based on diligent review of clinical evidence with transparent incorporation of subjective factors. There are 9 broad clinical questions with 123 recommendation numbers that include 160 specific statements (85 [53.1%] strong [Grade A], 48 [30.0%] intermediate [Grade B], and 11 [6.9%] weak [Grade C], with 16 [10.0%] based on expert opinion [Grade D]) that build a comprehensive medical care plan for obesity. There were 133 (83.1%) statements based on strong (best evidence level [BEL] 1 = 79 [49.4%]) or intermediate (BEL 2 = 54 [33.7%]) levels of scientific substantiation. There were 34 (23.6%) evidence-based recommendation grades (Grades A-C = 144) that were adjusted based on subjective factors. Among the 1,788 reference citations used in this CPG, 524 (29.3%) were based on strong (evidence level [EL] 1), 605 (33.8%) were based on intermediate (EL 2), and 308 (17.2%) were based on weak (EL 3) scientific studies, with 351 (19.6%) based on reviews and opinions (EL 4). The final recommendations recognize that obesity is a complex, adiposity-based chronic disease, where management targets both weight-related complications and adiposity to improve overall health and quality of life. The detailed evidence-based recommendations allow for nuanced clinical decision-making that addresses real-world medical care of patients with obesity, including screening, diagnosis, evaluation, selection of therapy, treatment goals, and individualization of care. The goal is to facilitate high-quality care of patients with obesity and provide a rational, scientific approach to management that optimizes health outcomes and safety. A1C = hemoglobin A1c AACE = American Association of Clinical Endocrinologists ACE = American College of Endocrinology AMA = American Medical Association BEL = best evidence level BMI = body mass index CCO = Consensus Conference on Obesity CPG = clinical practice guideline CSS = cross-sectional study CVD = cardiovascular disease EL = evidence level FDA = Food and Drug Administration GERD = gastroesophageal reflux disease HDL-c = high-density lipoprotein cholesterol IFG = impaired fasting glucose IGT = impaired glucose tolerance LDL-c = low-density lipoprotein cholesterol MNRCT = meta-analysis of non-randomized prospective or case-controlled trials NE = no evidence PCOS = polycystic ovary syndrome RCT = randomized controlled trial SS = surveillance study U.S = United States.


Argasid and ixodid systematics: Implications for soft tick evolution and systematics, with a new argasid species list.
The systematics of the genera and subgenera within the soft tick family Argasidae is not adequately resolved. Different classification schemes, reflecting diverse schools of scientific thought that elevated or downgraded groups to genera or subgenera, have been proposed. In the most recent classification scheme, Argas and Ornithodoros are paraphyletic and the placement of various subgenera remains uncertain because molecular data are lacking. Thus, reclassification of the Argasidae is required. This will enable an understanding of soft tick systematics within an evolutionary context. This study addressed that knowledge gap using mitochondrial genome and nuclear (18S and 28S ribosomal RNA) sequence data for representatives of the subgenera Alectorobius, Argas, Chiropterargas, Ogadenus, Ornamentum, Ornithodoros, Navis (subgen. nov.), Pavlovskyella, Persicargas, Proknekalia, Reticulinasus and Secretargas, from the Afrotropical, Nearctic and Palearctic regions. Hard tick species (Ixodidae) and a new representative of Nuttalliella namaqua (Nuttalliellidae), were also sequenced with a total of 83 whole mitochondrial genomes, 18S rRNA and 28S rRNA genes generated. The study confirmed the utility of next-generation sequencing to retrieve systematic markers. Paraphyly of Argas and Ornithodoros was resolved by systematic analysis and a new species list is proposed. This corresponds broadly with the morphological cladistic analysis of Klompen and Oliver (1993). Estimation of divergence times using molecular dating allowed dissection of phylogeographic patterns for argasid evolution. The discovery of cryptic species in the subgenera Chiropterargas, Ogadenus and Ornithodoros, suggests that cryptic speciation is common within the Argasidae. Cryptic speciation has implications for past biological studies of soft ticks. These are discussed in particular for the Ornithodoros (Ornithodoros) moubata and Ornithodoros (Ornithodoros) savignyi groups.


Enteric Glia Regulate Gastrointestinal Motility but Are Not Required for Maintenance of the Epithelium in Mice.
When the glial fibrillary acidic protein (GFAP) promoter is used to express cellular toxins that eliminate glia in mice, intestinal epithelial permeability and proliferation increase; this led to the concept that glia are required for maintenance of the gastrointestinal epithelium. Many enteric glia, however, particularly in the mucosa, do not express GFAP. In contrast, virtually all enteric glia express proteolipid protein 1 (PLP1). We investigated whether elimination of PLP1-expressing cells compromises epithelial maintenance or gastrointestinal motility. We generated mice that express tamoxifen-inducible Cre recombinase under control of the Plp1 promoter and carry the diptheria toxin subunit A (DTA) transgene in the Rosa26 locus (Plp1CreER;Rosa26DTA mice). In these mice, PLP1-expressing glia are selectively eliminated without affecting neighboring cells. We measured epithelial barrier function and gastrointestinal motility in these mice and littermate controls, and analyzed epithelial cell proliferation and ultrastructure from their intestinal tissues. To compare our findings with those from previous studies, we also eliminated glia with ganciclovir in GfapHSV-TK mice. Expression of DTA in PLP1-expressing cells selectively eliminated enteric glia from the small and large intestines, but caused no defects in epithelial proliferation, barrier integrity, or ultrastructure. In contrast, administration of ganciclovir to GfapHSV-TK mice eliminated fewer glia but caused considerable non-glial toxicity and epithelial cell death. Elimination of PLP1-expressing cells did not reduce survival of neurons in the intestine, but altered gastrointestinal motility in female, but not male, mice. Using the Plp1 promoter to selectively eliminate glia in mice, we found that enteric glia are not required for maintenance of the intestinal epithelium, but are required for regulation of intestinal motility in females. Previous observations supporting the concept that maintenance of the intestinal epithelium requires enteric glia can be attributed to non-glial toxicity in GfapHSV-TK mice and epithelial-cell expression of GFAP. Contrary to widespread notions, enteric glia are therefore not required for epithelial homeostasis. However, they regulate intestinal motility in a sex-dependent manner.


Maternal allo-recognition of the fetus.
Immunological adjustments are needed to accommodate the close contact between two genetically different individuals, the mother and her baby, during mammalian pregnancy. Contact occurs between fetal somatic or placental cells that enter the maternal systemic circulation or between uterine immune cells and the invading extravillous trophoblast. Here we discuss two main types of maternal allo-recognition of the fetus. One depends on avoidance of maternal T cells recognizing and responding to paternally-derived non-self human leukocyte antigens class I and class I allotypes. The other is natural killer allo-recognition where maternally-inherited variable killer immunoglobulin-like receptors expressed by uterine natural killer cells bind to polymorphic fetal human leukocyte antigens-C molecules displayed by extravillous trophoblast. Genetic studies indicate that natural killer cell allo-recognition regulates placentation and the allocation of resources to the fetus.


Dressler's syndrome after right ventricular infarction.
Undiagnosed myocardial infarction of the right ventricle presented as Dressler's syndrome. Radioisotopic diagnostic procedures including first-pass and multigated acquisition nuclear angiography ( MUGA ) and thallium-201 perfusion studies enabled a retroactive diagnosis of myocardial infarction, showed it to be in the right ventricle, and clarified the aetiology of the unexplained fever and pleuropericarditis.


Microfluidic processing of synovial fluid for cytological analysis.
Cytological analysis of synovial fluid is widely used in the clinic to assess joint health and disease. However, in general practice, only the total number of white blood cells (WBCs) are available for cytologic evaluation of the joint. Moreover, sufficient volume of synovial aspirates is critical to run conventional analyses, despite limited volume of aspiration that can normally be obtained from a joint. Therefore, there is a lack of consistent and standardized synovial fluid cytological tests in the clinic. To address these shortcomings, we developed a microfluidic platform (Synovial Chip), for the first time in the literature, to achieve repeatable, cost- and time-efficient, and standardized synovial fluid cytological analysis based on specific cell surface markers. Microfluidic channels functionalized with antibodies against specific cell surface antigens are connected in series to capture WBC subpopulations, including CD4+, CD8+, and CD66b+ cells, simultaneously from miniscule volumes (100 μL) of synovial fluid aspirates. Cell capture specificity was evaluated by fluorescent labeling of isolated cells in microchannels and was around 90% for all three WBC subpopulations. Furthermore, we investigated the effect of synovial fluid viscosity on capture efficiency in the microfluidic channels and utilized hyaluronidase enzyme treatment to reduce viscosity and to improve cell capture efficiency (>60%) from synovial fluid samples. Synovial Chip allows efficient and standardized point-of-care isolation and analysis of WBC subpopulations in miniscule volumes of patient synovial fluid samples in the clinic.


ROS-responsive microspheres for on demand antioxidant therapy in a model of diabetic peripheral arterial disease.
A new microparticle-based delivery system was synthesized from reactive oxygen species (ROS)-responsive poly(propylene sulfide) (PPS) and tested for "on demand" antioxidant therapy. PPS is hydrophobic but undergoes a phase change to become hydrophilic upon oxidation and thus provides a useful platform for ROS-demanded drug release. This platform was tested for delivery of the promising anti-inflammatory and antioxidant therapeutic molecule curcumin, which is currently limited in use in its free form due to poor pharmacokinetic properties. PPS microspheres efficiently encapsulated curcumin through oil-in-water emulsion and provided sustained, on demand release that was modulated in vitro by hydrogen peroxide concentration. The cytocompatible, curcumin-loaded microspheres preferentially targeted and scavenged intracellular ROS in activated macrophages, reduced in vitro cell death in the presence of cytotoxic levels of ROS, and decreased tissue-level ROS in vivo in the diabetic mouse hind limb ischemia model of peripheral arterial disease. Interestingly, due to the ROS scavenging behavior of PPS, the blank microparticles also showed inherent therapeutic properties that were synergistic with the effects of curcumin in these assays. Functionally, local delivery of curcumin-PPS microspheres accelerated recovery from hind limb ischemia in diabetic mice, as demonstrated using non-invasive imaging techniques. This work demonstrates the potential for PPS microspheres as a generalizable vehicle for ROS-demanded drug release and establishes the utility of this platform for improving local curcumin bioavailability for treatment of chronic inflammatory diseases.


Intestinal tuberculosis sometimes mimics Crohn's disease.
Intestinal tuberculosis is an uncommon presentation of tuberculosis (TB) and has clinicopathological similarities with Crohn's disease. In regions where TB is endemic clinicians must aware of this condition and fully evaluate their patients when Crohn's disease is diagnosed. We recommend all pathologic specimens be evaluate effectively for TB.Smear,culture and PCR for Mycobacterium.tuberculosis from samples aside the pathological reviews help for better diagnosis. Here we present a case of intestinal tuberculosis which initially diagnosed as Crohn's disease but after starting immunosuppressive agents he presented with disseminated tuberculosis.


Demonstration of heat-labile antigen(s) of Bacteroides fragilis associated with non-homogeneous immunofluorescent staining.
Rabbit hyperimmune sera against nine Bacteroides fragilis strains were tested in indirect immunofluorescence against homologous and heterologous formalin and heat-treated bacterial cells. Strain-specific heat-stable and heat-labile antigens were demonstrated as well as many cross-reactive ones. Besides these findings a striking non-homogeneous fluorescence was noted, inasmuch as varying numbers of the bacterial cells were stained while others were not. Results of absorption experiments indicated that the reactive antigens were heat-labile. Non-homogeneous fluorescence was also demonstrated with sera from patients with clinically significant Bacteroides fragilis infections.


Synthesis of enzymatically noncleavable carbocyclic nucleosides for DNA-N-glycosylase studies.
Carbocyclic nucleosides have been of great interest as antiviral agents and in studies in the area of antisense technology. The recent finding that the replacement of a single 2'-deoxynucleoside in DNA by a carba analogue does not alter the Watson-Crick base pairing, yet at the same time provides a chemically and enzymatically stable "glycosidic" linkage, led us to examine this class of compound as enzyme inhibitors of the DNA-repair enzymes involved in oxidative damage. We now report the synthesis and incorporation into oligomeric DNA via suitable derivatives, the carbanucleosides 8-oxo-7,8-dihydro-2'-deoxycarbainosine, 8-oxo-7,8-dihydro-2'-deoxycarbaguanosine, and 2'-deoxyaristeromycin. Aristeromycin (1) was deoxygenated at the 2'-position as follows. Treatment of 1 with TPDSCl2 gave the 3',5'-protected derivative 3 (76%) which on phenylthiocarbonylation at the 2'-position gave 4 in 51% yield. The latter compound on reduction with Bu3SnH led to the 2'-deoxy derivative 5 (90%). Benzoylation followed by deprotection with TBAF in THF then gave the desired intermediate (6) in 65% yield. N2-Isobutyryl-8-oxo-7,8-dihydro-2'-deoxycarbaguanosine (16) was synthesized from 3-chloro-2'-deoxycarbainosine (9). Treatment of 9, either with hydrazine followed by catalytic reduction of the 2-hydrazino derivative or with 1-(2-nitrophenyl)ethylamine followed by photolysis of the resulting 2-substituted derivative, in both instances gave the desired 2'-deoxycarbaguanosine (12) in approximately 50% overall yield in each case. Bromination of 12 gave 13 (90%) which, when treated with BnONa in DMSO at 65 degrees C, led to the 8-benzyloxy derivative 14 (46%). Isobutyrylation of 14 followed by catalytic reduction then afforded 16. 8-Oxo-7,8-dihydro-2'-deoxycarbainosine (23) was prepared in four steps. Bromination of 2'-deoxyaristeromycin (19) at the 8-position gave 20 (> 95%) which was converted to the 8-benzyloxy derivative 21 (61%) using BnONa/DMSO at 80 degrees C. Reductive debenzylation of 21 then led to 8-oxo-7,8-dihydro-2'-deoxyaristeromycin (approximately 100%) which, when treated with adenosine deaminase, provided the desired carbainosine derivative 23 in quantitative yield. Compounds 6, 16, and 23 were converted to their respective 5'-O-DMT, 3'-O-[(2-cyanoethoxy)-(N,N-diisopropylamino)phosphine] derivatives (8, 18, and 25) in excellent overall yields. The latter were then used to synthesize a series of DNA oligomers by automated procedures.


Conversational patterns of two-year-old twins in mother-twin-twin triads.
This study investigated the general nature of conversational interaction in mother-twin-twin triads. Four sets of firstborn twins (2;3) were videotaped during 15 minutes of free play with their mothers. Analyses revealed that triadic conversations were approximately five times longer, and elicited more turns from all speakers, than dyadic conversations between mother and a single twin. Twins also responded as often to comments and requests made to another person as to those directed to themselves, but responded more often to questions directly to them than to others, indicating reliable monitoring of language not addressed to them. These results largely parallel those reported for mother-infant-sibling triads and indicate the unique effects of triadic exchanges are not due to the relative linguistic levels of the child partners.


Abnormal T2 mapping cardiovascular magnetic resonance correlates with adverse clinical outcome in patients with suspected acute myocarditis.
While most patients recover from suspected acute myocarditis (sAMC) some develop progressive disease with 5-year mortality up to 20%. Recently, parametric Cardiovascular Magnetic Resonance (CMR) approaches, quantifying native T1 and T2 relaxation time, have demonstrated the ability to increase diagnostic accuracy. However, prognostic implications of T2 values in this cohort are unknown. The purpose of the study was to investigate the prognostic relevance of elevated CMR T2 values in patients with sAMC. We carried out a prospective study in 46 patients with sAMC defined by current ESC recommendations. A combined endpoint was defined by the occurrence of at least one major adverse cardiac event (MACE) and hospitalisation for heart failure. Event rate was 24% (n = 11) for 1-year-MACE and hospitalisation. A follow-up after 11 ± 7 months was performed in 98% of the patients. Global T2 values were significantly increased at acute stage of disease compared to controls and decreased over time. During acute disease, elevated global T2 time (odds ratio 6.3, p < 0.02) as well as myocardial fraction with T2 time >80 ms (odds ratio 4.9, p < 0.04) predicted occurrence of the combined endpoint. Patients with clinical recovery revealed significantly decreased T2 relaxation times at follow-up examinations; however, T2 values were still elevated compared to healthy controls. Assessment of myocardial T2 relaxation times at initial presentation facilitates CMR-based risk stratification in patients with acute myocarditis. T2 Mapping may emerge as a new tool to monitor inflammatory myocardial injuries during the course of disease.


Bilateral pseudo-internuclear ophthalmoplegia in myasthenia gravis.
A 38-year-old male with bilateral pseudo-internuclear ophthalmoplegia (-INO) in myasthenia that could have been misdiagnosed as INO in multiple sclerosis is reported. He experienced fluctuating symptoms including double vision, imbalance, and tinnitus. His eye movements simulated bilateral INO, with a downshoot in abduction. After thymectomy, his eye movements became normal. From our case and a review of the literature, we propose that ptosis, downshoot, and fatigability are likely to be signs of pseudo-INO in myasthenia, whereas an impaired vertical smooth pursuit is unlikely. Dissociated nystagmus and monocular overshoot might be the results of central compensation.


Invasive intramedullary melanotic schwannoma: case report and review of the literature.
Melanotic schwannoma (MS) is rare, accounting for less than 1% of primary peripheral nerve sheath tumors, and most often occurs in the paraspinal nerve roots. Intramedullary MS is exceedingly rare, and to the best of our knowledge, only nine cases have been reported in literature. We present a 47-year-old male, who underwent excision of thoracic intraspinal space-occupying lesion 6 years ago, as the 10th known case to date of intradural intramedullary MS that had a more invasive growth pattern than those reported before, and we review the diagnosis, clinicopathologic features, treatment and prognosis of intramedullary MS. Intramedullary MS' behavior is unpredictable and can have an aggressive clinical course such as recurrence and metastasis.


A synopsis of radiation oncology in Australia, with particular reference to New South Wales.
The specialty of radiation oncology had its beginning in Australia in 1896 following the discovery of X-rays by Roentgen. The new technology was eagerly embraced and the use of X-rays and radium for the treatment of cancer, even in the early 1900s, produced results which, although far from satisfactory by today's standards, resulted in cure and palliation of more superficial tumours. In the era immediately prior to World War II the specialty was regarded as having only a limited role to play in cancer management. The introduction of cobalt-60 units and linear accelerators in the 1950s allowed for treatment of deep-seated tumours without the skin, bone and other complications of orthovoltage machines (deep X-rays). But the introduction of radiotherapy treatment into cancer care was blocked by other specialties anxious to preserve their own 'turf and by medical administrators who believed the counter-claims that either cancer was incurable or 'the cure for cancer was just around the comer' and it was therefore foolish to waste money on an expensive technology that had a limited future. With further developments in technology, modern radiotherapy is now a highly sophisticated treatment using sharply focused and deeply penetrating X-rays and electron beams. Specialized treatments, such as automated afterloading brachytherapy, total body irradiation, stereotactic radiosurgery and computerized 3-D planning to improve dose distribution, are now widely available. The outcomes of cancer patients with radiotherapy have also improved considerably and organ preservation (e.g. in breast and larynx cancer) has resulted in improved quality of life. However, the specialty has only recently begun to expand in specialist numbers and profile. This is partly due to the lack of undergraduate training in cancer in general and radiotherapy in particular and also because understaffing has meant that radiation oncologists have occupied a purely service role (in the basement with their machines) rather than being an active part of the treatment 'team'. As a consequence radiation oncology has not been projected as an important component in cancer management and as a challenging and fulfilling career option to medical students and new graduates. The failure to act on the (repeated) recommendations of the 42 reports, inquiries, etc. into radiation oncology in Australia since 1982 (in addition to many more at local level) would suggest that the 'message' has yet to be accepted by Health Departments and health administrators. As a result there has been a totally uncoordinated approach to provision of radiation oncology services. The restriction of services and specialist numbers and training posts has led to radiotherapy being underutilized and undervalued in the treatment of cancer, ultimately to the detriment of cancer patients.


The influence of lithium cations on dynamics and structure of room temperature ionic liquids.
The orientational relaxation dynamics of perylene in the room temperature ionic liquid (RTIL) 1-butyl-3-methylimidazolium bis(trifluoromethyl)sulfonyl imide were studied as a function of lithium ion concentration. Perylene is nonpolar and locates in the alkyl regions of the RTIL. The lithium cation was added as lithium bis(trifluoromethyl)sulfonyl imide, so the addition of Li(+) did not change the anion. The Li(+) concentration ranged from 0 to 0.4 mol fraction. The dynamics were measured by observing the fluorescence anisotropy decay using time correlated single photon counting. The anisotropy experiments and viscosity measurements were performed as a function of temperature for each Li(+) concentration sample. Because perylene has high symmetry, it was possible to independently determine the in-plane and out-of-plane diffusion constants and friction coefficients. With increasing concentration of lithium salt the viscosity increases and both the in-plane and out-of-plane orientational relaxations of perylene become slower. However, the corresponding molecular friction coefficients decreased, with the in-plane coefficient decreasing to a greater extent than the out-of-plane coefficient. The decrease in the friction coefficients demonstrates that lithium ions, which are located in the ionic regions of the RTILs, change the structure of the alkyl regions of the RTIL.


Two-Dimensional MFI-Type Zeolite Flow Battery Membranes.
Vanadium flow battery (VFB) is one of the most reliable stationary electrochemical energy-storage technologies, and a membrane with high vanadium resistance and proton conductivity is essential for manufacturing high-performance VFBs. In this study, a two-dimensional (2D) MFI-type zeolite membrane was fabricated from zeolite nanosheet modules, which displayed excellent vanadium resistance (0.07 mmol L-1 h-1 ) and proton conductivity (0.16 S cm-1 ), yielding a coulombic efficiency of 93.9 %, a voltage efficiency of 87.6 %, and an energy efficiency of 82.3 % at 40 mA cm-2 . The self-discharge period of a VFB equipped with 2D MFI-type zeolite membrane increased up to 116.2 h, which was significantly longer than that of the commercial perfluorinated sulfonate membrane (45.9 h). Furthermore, the corresponding battery performance remained stable over 1000 cycles (>1500 h) at 80 mA cm-2 . These findings demonstrate that 2D MFI-type membranes are promising ion-conductive membranes applicable for stationary electrochemical energy-storage devices.


Mouse bone marrow mesenchymal stem cells acquire CD45-CD106+ immunophenotype only at later passages.
Classically, MSC are identified by a CD45-CD106+ phenotype. In this study, we found that mouse MSC achieve this characteristic phenotype only at later passages. With increasing passages, CD45 (hematopoietic marker) expression shifts to negativity, whereas CD106 (vascular cell adhesion molecule-1) expression becomes increasingly positive. These results demonstrate that MSC cells cultured from mouse bone marrow acquire a classical MSC immunophenotype (CD45-CD106+) in later passages.


Molecular and biopharmaceutical investigation of alginate-inulin synbiotic coencapsulation of probiotic to target the colon.
Colon targeting, as a site-specific delivery for oral formulation, remains a major challenge, especially for sensitive bioactive components such as therapeutic forms of phages, live attenuated virus and prebiotics-probiotics association. Synbiotics could be used to protect encapsulated probiotics during the gastrointestinal tract and control their release in the colon. To achieve these goals, effective prebiotics, such as inulin, could be combined with alginate - the most exploited polymer used for probiotic encapsulation - in the form of beads. This work aimed to study the biopharmaceutical behaviour of alginate beads (A) and inulin-alginate beads of different inulin concentrations (5 or 20%) in 2% alginate (AI5, AI20). Beads were loaded with three probiotic strains (Pediococcus acidilactici Ul5, Lactobacillus reuteri and Lactobacillus salivarius). Dissolution of beads was studied by USP4 under conditions simulating the gastrointestinal condition. The survival rates of the bacterial strains were measured by a specific qPCR bacterial count. Mucoadhesiveness of beads was studied by an ex vivo method using intestinal mucosa. To understand the behaviour of each formulation, the ultrastructure of the polymeric network was studied using scanning electron microscopy (SEM). Molecular interactions between alginate and inulin were studied by Fourier transform infra-red spectroscopy (FTIR). Dissolution results suggested that the presence of inulin in beads provided more protection for the tested bacterial strains against the acidic pH. AI5 was the most effective formulation to deliver probiotics to the colon simulation conditions. FTIR and SEM investigations explained the differences in behaviour of each formula. The developed symbiotic form provided a promising matrix for the development of colonic controlled release systems.


The value of serum mean platelet volume in ischaemic stroke patient.
To investigate the value of serum Mean Platelet Volume in acute ischaemic stroke patients. The retrospective case-control study was conducted at Ankara Numune Training and Research Hospital in Turkey and comprised record of patients of acute ischaemic stroke admitted to the Emergency Department between June 2010 and January 2012. The two groups were statistically compared using SPSS 18.0. Overall, there were 482 stroke patients (Group 1) and 315 subjects as controls (Group 2). The median value in Group 1 was 9.0 (2.1) (fL), while in Group 2 it was 8.80 (2.4) (fL).The difference was statistically significant (Z = -2.80; p < 005). Mean Platelet Volume increased in the stroke patients.


Dynamic allostery in thrombin-a review.
Thrombin is a serine protease that catalyzes a large number of different reactions including proteolytic cleave of fibrinogen to make the fibrin clot (procoagulant activity), of the protease activated receptors (for cell signaling) and of protein C generating activated protein C (anticoagulant activity). Thrombin has an effector binding site called the anion binding exosite 1 that is allosterically coupled to the active site. In this review, we survey results from thermodynamic characterization of the allosteric coupling as well as hydrogen-deuterium exchange mass spectrometry to reveal which parts of the thrombin structure are changed upon effector binding and/or mutagenesis, and finally NMR spectroscopy to characterize the different timescales of motions elicited by the effectors. We also relate the experimental work to computational network analysis of the thrombin-thrombomodulin complex.


Hypotensive effects of the renin inhibitor (RI-78) and the converting enzyme inhibitor (teprotide) in conscious monkeys.
Effects of the pentapeptide renin inhibitor (RI-78; Phe(4Cl)-Phe-Val-Tyr-Lys-NH2) and the angiotensin converting enzyme (ACE) inhibitor (teprotide) on mean arterial pressure (MAP) were examined in conscious monkeys (M. fascicularis). In salt depleted normotensive monkeys with a MAP of 95 +/- 4 mmHg and plasma renin activity (PRA) of 15.9 +/- 2.7 ngAI/ml/h, a bolus injection of a dose of 375 micrograms/kg of RI-78 caused a prompt hypotensive effect. Maximal hypotensive action was seen within 1 min, and MAP returned to the basal level within 15 min. With this dose, MAP was reduced by 20 +/- 6 mmHg. Teprotide (1 mg/kg) decreased MAP and reached a nadir after 13 min. There was no significant difference between maximal hypotensive responses seen with RI-78 (375 micrograms/kg) and with teprotide (1 mg/kg). Hypotensive effects of RI-78 and teprotide were also examined in acute renal hypertensive monkeys with a MAP of 125 +/- 5 mmHg and a PRA of 27.1 +/- 5.7 ngAI/ml/h. Again, similar hypotensive effects were observed. We conclude that antihypertensive effect of RI-78 is comparable to that seen with teprotide.


Modeling evaluation of carbaryl degradation in a continuously stirred tank reactor by anodic fenton treatment.
Anodic Fenton treatment (AFT) has been shown to be effective in removing pesticides from aqueous solution in batch reactors with the formation of less toxic and more biodegradable products. To facilitate practical application of AFT, carbaryl degradation in a continuously stirred tank reactor (CSTR) by AFT was investigated under different experimental conditions, such as carbaryl inlet concentration, Fenton reagent concentration/ratio, and carbaryl feeding flow rate. A higher Fe2+ delivery rate and H2O2 to Fe2+ ratio (H2O2:Fe2+) were found to favor the carbaryl degradation process, whereas flow rate was shown to be a much less significant factor to influence the degradation rate under the evaluated experimental conditions. A kinetic-based semiempirical model was developed to simulate the experimental data, and a very good fit between the model and the raw data was found (R2 > 0.99). A dimensionless parameter (k/q2) was found to be a good indicator of the degradation rate; that is, the higher the k/q2value is, the faster the degradation process is. The rate parameter (k) can be used to evaluate the degradation rate when the flow rate is invariant for a given pesticide. The shape parameter (beta) is most likely related to the availability and reactivity of Fenton reagents and hydroxyl radicals. To compare the degradation rate of different pesticides, more information other than k/q2, k, and beta values, such as the instantaneous degradation rate vs time relationship, needs to be considered.


The MDR1/ABCB1 gene, a high-impact risk factor for cardiac transplant rejection.
Variations in the expression and activity levels of the multidrug-resistance MDR1/ABCB1 encoded P- glycoprotein (P-gp) have an impact on the therapeutic efficacy of many drugs. C3435T and G2677 polymorphisms of the MDR1/ABCB1 gene correlate with cellular expression levels of P-gp, a membrane-bound efflux pump which removes a multitude of drugs, including chemotherapy drugs and immunosuppressants, from cells. We aimed to investigate whether the phenomenon of drug resistance, mediated by the MDR1/ABCB1 gene and seen in tumor cells to chemotherapeutic agents, is important in the field of transplantation, predisposing some patients to resistance to immunosuppressants. G2677 and C3435T polymorphisms of the ABCB1 gene were determined by PCR in 170 heart transplant recipients. We examined the relationship between MDR1/ABCB1 polymorphisms and endomyocardial biopsy-proven rejection (EBPR) determined by biopsy performed at set intervals according to a standard protocol. A significant relationship was found between a patient's C3435T genotype and freedom from first grade > or =3A rejection episode. 3435-CC recipients were 1.8 times (1.05-3.09; P = 0.03) more likely to undergo a > or =3A rejection episode in the first 12 months. Haplotypes derived from the G2677 and C3435T polymorphisms (GG/CC, GT/CT and TT/TT) amplified this phenomenon further (log rank, P = 0.03; HR 2.18; 1.21-4.26; P = 0.02). ABCB1 polymorphisms correlate with freedom from grade > or =3A EBPR and we believe that this may be attributed to MDR1/ABCB1 encoded P-gp mediating the efflux of immunosuppressants out of leukocytes, with depleted immunosuppressant levels in leukocytes manifesting as increased cellular rejection.


A Comparison of Youth Flag and Tackle Football Head Impact Biomechanics.
Our purpose was to describe the youth flag football head impact burden and make comparisons with youth tackle football. Head impact frequency and magnitude (linear acceleration [g], rotational acceleration [rad/s2]) were collected from 25 tackle and 25 flag youth football players over one season. Athlete exposure (AE) was defined as one player participating in one session. Head impact rates (IR) were calculated and impact rate ratios (IRR) were used to compare youth tackle and flag football. Random-intercept generalized logit models with odds ratios compared the probabilities of sustaining an impact with a linear acceleration of 20.00-29.99g, 30.00-39.99g, and ≥40.00g against the reference of 14.00-19.99g and an impact with a rotational acceleration of 2500.00-7499.99 rad/s2 or ≥7500.00 rad/s2 against the reference of ≤2499.99 rad/s2 between youth flag and tackle football. We observed 1908 tackle football head impacts (735 in games, 38.5%) across 624 AE and 169 flag football head impacts (101 in games, 59.8%) across 255 AE. Youth tackle football players experienced higher overall IR (3.06, 95% confidence interval [CI]: 2.61, 3.58; IRR = 4.61, 95% CI: 3.94, 5.40) compared with flag football (IR = 0.66, 95% CI: 0.57, 0.78). Youth flag football players had lower odds of sustaining impacts >20g but higher odds of sustaining impacts between 2500.00-7499.99 rad/s2 compared with youth tackle players. Our preliminary sample of youth flag football players sustained less frequent head impacts at higher rotational accelerations than tackle football players. Flag football is considered a limited-contact sport, but little is known about the true head impact burden. Our findings may be important for policymakers when debating potential changes to youth football participation.


The association between discontinuing hormonal contraceptives and wives' marital satisfaction depends on husbands' facial attractiveness.
How are hormonal contraceptives (HCs) related to marital well-being? Some work suggests HCs suppress biological processes associated with women's preferences for partner qualities reflective of genetic fitness, qualities that may be summarized by facial attractiveness. Given that realizing such interpersonal preferences positively predicts relationship satisfaction, any changes in women's preferences associated with changes in their HC use may interact with partner facial attractiveness to predict women's relationship satisfaction. We tested this possibility using two longitudinal studies of 118 newlywed couples. Trained observers objectively rated husbands' facial attractiveness in both studies. In study 1, wives reported their marital satisfaction every 6 mo for 4 y and then reported the history of their HC use for their relationship. In study 2, wives reported whether they were using HCs when they met their husbands and then their marital satisfaction and HC use every 4 mo for up to three waves. In both studies, and in an analysis that combined the data from both studies, wives who were using HCs when they formed their relationship with their husband were less satisfied with their marriage when they discontinued HCs if their husband had a relatively less attractive face, but more satisfied if their husband had a relatively more attractive face. Beginning HCs demonstrated no consistent associations with marital satisfaction. Incongruency between HC use at relationship formation and current HC use was negatively associated with sexual satisfaction, regardless of husbands' facial attractiveness. These findings suggest that HC use may have unintended implications for women's close relationships.


Management of Recurrent Pregnancy-Related Pericarditis.
The evidence on recurrent pregnancy-related pericarditis is limited, and management strategies are based on case reports and expert opinion. We describe a patient with myopericarditis complicated by cardiac tamponade presenting shortly after her first pregnancy, which was then complicated by refractory recurrent pericarditis. She was treated with standard first line therapies, such as NSAIDs, corticosteroids, and colchicine, and eventually initiated on the purine analog, azathioprine. Out of fear of teratogenicity, she self-discontinued her maintenance medications and thereafter, her course was complicated by a recurrent flare of pericarditis during a subsequent pregnancy. Our case illustrates the significant burden on our patient due to the incessant nature of her disease and on the providers due to the therapeutic dilemmas associated with family planning and pregnancy. Further data is required on this unique clinical scenario, and patient-centered management by a multidisciplinary team is critical.


[Disease of operated stomach as an aftereffect of resection without sufficient indications and surgical errors].
Poor issues in the most cases concerned were due to gastric resection either not adeqately indicated of performed with technical shortcomings. It is quite possible to reduce considerably the number of poor late results if the resection is performed on strict indications with proper accomplished of its technical details.


Voluntary Folic Acid Fortification Levels and Nutrient Composition of Food Products from the Spanish Market: A 2011-2015 Update.
Folic acid (FA) is a synthetic compound commonly added for voluntary fortification of food products in many European countries. In our country, food composition databases (FCDB) lack comprehensive data on FA fortification practices and this is considered a priority research need when undergoing nutritional assessment of the population. A product inventory was collected and updated by visiting retail stores in Madrid Region, conducting online supermarket searches, and by the provision of food label information by manufacturers. Euro-FIR FCDB guidelines for data compilation and harmonization were used. The FCDB, compiled between 2011 and 2015, includes FA as well as macro and micronutrient data from 338 fortified foodstuffs. As compared to previous FCDB updates (May 2010), 37 products have ceased to declare added FA in their labels, mainly yogurt and fermented milk products. The main food subgroup is 'breakfast cereals' (n = 95, 34% of total). However, the highest average FA fortification levels per recommended serving were observed in the 'milk, milk products, and milk substitutes' group at ≥35% FA Nutrient Reference Values (NRV, 200 µg, EU Regulation 1169 of 2011) (60-76.3 µg FA per 200 mL). Average contribution to the FA NRV per food group and serving ranged between 16%-35%. Our data show a minor decrease in the number of FA fortified products, but vitamin levels added by manufacturers are stable in most food groups and subgroups. This representative product inventory comprises the main FA food source from voluntary fortification in our country. It is therefore a unique compilation tool with valuable data for the assessment of dietary intakes for the vitamin.


A Longitudinal Cohort Study of Precocious Puberty and Autism Spectrum Disorder.
Autism spectrum disorder (ASD) is defined by persistent deficits in communication, socialization, and stereotypic behaviors. It was previously hypothesized that hormone dysfunction is a frequent occurrence among children diagnosed with an ASD. A hypothesis-testing epidemiological study examined the relationship between precocious puberty (PP) (a known disorder of childhood sex hormone dysfunction) and ASD diagnoses. The Independent Healthcare Research Database is composed of de-identified linked eligibility and claims health-care records prospectively generated from the Florida Medicaid system. A cohort of 101,736 children eligible for Florida Medicaid from 1990 to 2009 and continuously eligible with ≥10 outpatient office visits during the 120-month period following birth were examined using SAS and StatsDirect software. There were 1,593 children (15,738 person-years) in the ASD diagnosed cohort utilizing the Diagnostic and Statistical Manual of Mental Disorders, 4th revision criteria (the International Code for Disease, 9th revision [ICD-9] codes: 299.00 or 299.80) and 100,143 children (996,835 person-years) in the undiagnosed cohort. The incidence rate of PP (ICD-9 code: 259.1) was examined using Cox proportional hazards ratio (HR) and frequency models. PP per 10,000 person-years in the ASD cohort (43.2) relative to the undiagnosed cohort (13.7) was significantly increased in frequency modeling (risk ratio = 3.15, p < 0.0001) and Cox proportional HR modeling (adjusted HR = 4.64, p < 0.0001). Further analyses revealed the incidence rate of PP diagnosed after 3 years of age was significantly increased (adjusted HR = 5.16, p < 0.0001) in the ASD cohort relative to the undiagnosed cohort but not for the incidence rate of PP diagnosed before 3 years (adjusted HR = 1.57, p = 0.44). This hypothesis-testing study provides strong evidence of an increased incidence rate of PP among children diagnosed with an ASD.